PREVALENCE OF HELICOBACTER PYLORI IN PATIENTS WITH PARKINSON DISEASE DETECTED BY RAPID DIAGNOSTIC TEST

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICINE FACULTY

PREVALENCE OF HELICOBACTER PYLORI IN PATIENTS WITH PARKINSON DISEASE DETECTED BY RAPID DIAGNOSTIC TEST

AUTOR: VICTOR POZUETA SANGRONES

SUPERVISOR: Assoc. prof. DAIVA JANULAITYTE-GUNTHER, MD, PhD

2015/2016

TABLE OF CONTENTS

SUMMARY………..3

CONFLICTS OF INTEREST……….………..4

CLEARANCE ISSUED BY THE ETHICS COMMITTEE……….4

ABBREVIATIONS ………...……….………..5

TERMS………..5

INTRODUCTION………….………6

AIM AND OBJECTIVES……….7

LITERATURE REVIEW……….….8

RESEARCH METHODOLOGY AND METHODS ……….15

RESULTS………17

DISCUSSION OF THE RESULTS………20

CONCLUSION………...23

REFERENCES………26

ANEXES....………..………...28

SUMMARY

Victor Pozueta Sangrones. Prevalence of Helicobacter pylori in patients with Parkinson’s disease detected by a rapid diagnostic test.

Aim: To evaluate the possible relationship between H. pylori and Parkinson‘s disease.

Objectives: To determine the prevalence of H. pylori in Parkinson’s disease patients and in age and sex matched controls; to assess the H. pylori effect on symptom severity in Parkinson’s disease patiens; to assess the H. pylori effect on the quality of life in Parkinson’s disease patients; to detect the risk factors for H. pylori infection.

Methods: There were 28 consecutive patients (age range 48 – 83 years median age 58,) with Parskinson’s disease and 24 controls age and sex matched (age range 54 -87 years, median age 66,5) involved into this study. Sociodemographic characteristics, previous antibiotic use, medical and medication history, and presence of gastrointestinal symptoms have been recorded. Parkinson‘s disease severity has been assessed by using Hoehn and Yahr (H & Y) and Unified Parkinson‘s Disease Rating Scale (UPDRS) . The quality of life has been assessed by 39-item Parkinson‘s Disease Questionnaire (PDQ-39). The whole-blood finger stick antibody test (a rapid diagnostic test) has been used to detect H. pylori. Approval from the LSMU research ethics committee has been obtained prior the study.

Results: There were 11 (39%) patients with Parkinson‘s disease infected with H. pylori and 12 (50%) controls infected with H. pylori. The prevalence of H. pylori in the IV Parkinson‘s disease stage has been detected to be higher (100%) as compared to the prevalence of H. pylori infection in the parkinson‘s disease stages I (14%) and II (25%). There is no significant risk factors for the prevalence of H. pylori in a Parkinson‘s disease patients group. The smoking seems to be a risk factor for H.

pylori infection in controls.

Conclusions: there is no relationship between H. pylori and Parkinson‘s disease identified in

Lithuania.

CONFLICT OF INTEREST

The research had been conducted using H.pylori blood test, which had been acquired by the University at Interlux pharmaceutical company in Vilnius.

Other than that no conflicts had been created.

ETHICS COMMITTEE CLEARANCE

The ethics committee in the bioethics center at Lithuanian University of Health Sciences allows to the medical student Victor Pozueta Sangrones, from VI course, on 2015-09-28 by his request Nr. BEC- MF-33, to proceed with his scientific research “ THE PREVALENCE OF HELICOBACTER PYLORI IN PATIENTS WITH PARKINSON DISEASE” which consist on: form of information to the patient on what the research consists of, form of allowance of the patient to be tested, a questionner is performed and a blood test is performed as well in order to check if the patient has H. Pylori or not.

All the research will be under the supervision of Dr. Daiva Janulaityte-Gunther, from Microbiology

and Virusology Institute,LSMU. (Anex 3).

ABBREVIATIONS LIST:

H. pylori Helicobacter Pylori

PD Parkinson Disease

PUD peptic ulcer disease

GC gastric cancer

OMP outer membrane protein

IgG inmunoglobulin G

CagA cytotoxin-associated gene A

VacA Vacuolating cytotoxin A

DBS deep brain stimulation

TERMS

-Bradykinesia: slowness of movement.

-Cag A: cytotoxin-associated gene A.

-Carbidopa: an inhibitor of decarboxylation of levodopa in extracerebral tissues, used in combination with levodopa as an antiparkinsonian agent.

-Dopamine: compound present in the body as a neurotransmitter and a precursor of other substances including adrenaline.

-Gastritis: inflammation of the lining of the stomach.

-Hypokinesia: partial or complete loss of muscle movement due to a disruption in the basal ganglia.

-Levodopa: synthetic substance, that is converted in the brain to dopamine.

-Lewy bodies: abnormal aggregates of protein that develop inside nerve cells in Parkinson's disease.

-Peptic ulcer disease: break in the lining of the stomach, first part of the small intestine, or occasionally the lower esophagus.

-Substantia nigra: layer of large pigmented nerve cells in the midbrain that produce dopamine.

INTRODUCTION

H. pylori is a Gram-negative bacteria found on the gastric epithelium, discovered in 1983 by Warren and Marshall. H. pylori is usually contracted in the first years of live and it persists indefinitely unless its treated, leading to a chronic inflamation of the gastric mucosa. It was discovered that causes diseases such as gastritis, peptic ulcer disease(PUD) and gastric cancer(GC), but with the pass of time it has been discovered that H. pylori is present in extragastrointestinal diseases such as hematological disorders, cardiovascular diseases and neurological diseases.

PD is a neurodegenerative disease that occurs due to loss of dopaminergic neurons in the substantia nigra of the brain, it was discovered by James Parkinson in 1817, its etiology is unknown. However, recent studies have found that infection plays a role in the etiology of PD, such as bacterial

overgrowth and involving cytomegalovirus, Epstein Barr virus, herpes simplex virus type-1 and H.

pylori in the small intestine. The main symptons are directly related with the motor

system(bradykinesia/hypokinesia, rigidity, tremor and postural abnormality), but non related motor symptoms such as depression, autonomic dysfunction, cognitive abnormalities, dementia and gastrointestinal dysfunction are also seen.

Some studies had found that the prevalence of H. pylori in patients with PD is high, through this study

we want to analyze the prevalence of H. pylori in Lithuanian population and compare its prevalence

between people with PD and people without PD. Asses the effect of H. pylori in the severity of

symptoms and quality of life of patients with PD and detect the risk factors for H. pylori infection.

AIM AND OBJECTIVES OF THE THESIS

The Aim of the present thesis is to evaluate the possible relationship between H. pylori and

Parkinson’s disease, by testing patients with PD and a control group with a Western blood H. pylori test. And see the prevalence of H. pylori in patients with PD.

Objectives:

1. To determine the prevalence of H. pylori in Parkinson’s disease patients and in age and sex matched controls

2. To assess the H. pylori effect on symptom severity in Parkinson’s disease patients

3. To assess the H. pylori effect on the quality of life in Parkinson’s disease patients

4. To detect the risk factors for H. pylori infection

LITERATURE REVIEW

Helicobacter pylori HISTORY

H. pylori is a spiral- shaped, Gram-negative, microaerophilic bacterium, which has been discovered in 1982 by Robin Warren and Barry Marshall[1].

MICROBIOLOGICAL CHARACTERISTICS

This organisms are 2.5 - 5.0 microns long and 0.5 -1.0 micron wide, on one end they have 4 to 6 flagella, allowing him to attach into the gastric mucosa and be free to travel over the mucous

membrane in the outer skin [2]. H. pylori produces urease enzyme that breaks down urea to ammonia releasing nitrogen used in the synthesis of amino acids. Ammonia surrounds the bacteria of the alkaline layer that protects H. Pylori against the acid pH effects, this is crucial for the colonization of the stomach [3].

PATHOGENICITY FACTORS

Cytotoxin-associated gene A(CagA) Is the most extensively studied H. pylori virulence factor. There are two types of clinical H. pylori isolate: CagA-producing (cagA positive) strains and CagA-

nonproducing (cagA negative) strains. These data have led to increasing knowledge of CagA as a bacteria derived carcinogen. In Western countries, it has been reported that individuals infected with cagA-positive strains of H. Pylori are at a higher risk of PUD or GC than those infected with cagA- negative strains[4].

Vacuolating cytotoxing A (VacA): is the second most extensively studied H. pylori virulence factor.

In addition to inducing vacuolation, VacA can induce multiple cellular activities, including membrane- channel formation, cytochrome c release from mitochondria leading to apoptosis, and binding to cell- membrane receptors followed by initiation of a proinflammatory response[5].

EPIDEMIOLOGY

-Smoking. Studies have assessed the possible association between H. pylori infection and smoking.

Whereas some found that H. pylori seropositive subjects were overall more likely than seronegative subjects to be current smokers[6]. Results were often not consistent by race or gender.

-Alcohol consumption. None of several recent epidemiologic studies of the relation between alcohol consumption and H. pylori infection found a positive association[7].

-Diet. Studies have also looked at dietary associations with H. pylori. Although the studies cover many different types of populations and include both adults and children, some consistent associations suggest that nutritional status may be related to H. pylori infection [8]. Found significantly reduced odds ratios and negative gradients in risk of H. pylori infection with increased consumption of fruits and/or vegetables.

-Waterborne exposures. Water has been suggested as a possible source of H. pylori infection. Studies in Colombia, rural China, Lima and Peru [9]. Found that water source may be related to risk of H.

pylori infection. Three waterborne factors were linked to higher risks of H. pylori infection in

Colombian children: drinking water from a stream, swimming in a stream, and swimming in a

swimming pool [10] found that the water supply in Lima, Peru, may be vulnerable to bacterial

contamination, especially if it is stored in a cistern or obtained through central community water taps.

-Hygiene practices. Studies also have assessed the relation between H. pylori infection and various hygiene practice indicators. Overall, poor hygiene practices, especially during childhood, appear to be related to a higher seroprevalence of H. pylori. Some of these practices include having no water closet

or bathroom or no hot water supply in the house when the subject was a child among others [11].

-Oral-oral route. Many scientists have hypothesized that the oral-oral route of H. pylori transmission is the most likely, especially in developed countries. An elevated prevalence of H. pylori within families and institutionalized populations provides support for this route of transmission. However, it is not

clear whether H. pylori is a constant or an intermittent inhabitant of the oral cavity [12].

-Fecal-oral route. Another possible method of H. pylori transmission is the fecal-oral route. H. pylori DNA has been detected in feces of infected subjects by some researchers.

Studies of H. pylori prevalence among adults have generally been cross-sectional in design and have included random surveys of the general population. Comparison of prevalence rates by age 55 suggests that acquisition of H. pylori is decreasing in recent cohorts. This finding is most apparent in developed countries and may be linked to improvements in hygiene practices [13]

In children: a prevalence of Helicobacter-like organisms of 79% was found in a paediatric population.

IgG antibodies against H. Pylori were detected in 57% of the children [14].

DIAGNOSIS

Acute infection with H. pylori is generally asymptomatic, it is not possible to ascertain when infection occurs on the basis of symptoms or clinical findings[15].

1.Microscopy: gastric brushings followed by examination with phase-contrast microscopy in the endoscopy suite allow a quick diagnosis ,

2.Bacterial culture: The best specimens to culture H. pylori are biopsy samples obtained during endoscopy[16]. A single biopsy specimen taken from the antrum (2 cm from the pylorus) gives good sensitivity but is not sufficient for a reliable diagnosis. Indeed, H. pylori may have a patchy

distribution, and the more biopsy specimens analyzed, the higher the chance of organism detection.

The recommendation is, therefore, to take two biopsy specimens from the antrum as well as two specimens each from the anterior and posterior corpus. The media components include an agar base, growth supplements, and selective supplements. [17]. The optimal culture temperature is 37°C,

testifying to the adaptation of this bacterium to humans. Certain strains can, nevertheless, grow at 30°C or 42°C. Colonies may appear after 3 days and are at their optimum on day 4. However, in the case of negative culture, a 7 to 10 day incubation is recommended to ensure that the result is negative[18].

3.Histology:The usual recommendation is to obtain 2 biopsy specimens from the antrum and 2 specimens from the corpus[19]. Biopsy specimens are immediately introduced into a fixative of 10%

formaldehyde. It is usually necessary to cut three thin sections (3 to 5 µm) at different levels. The accuracy of this technique is very much dependent on the quality of the histological preparation, which must allow observation of the surface epithelium and the crypts. The routine hematoxylin-eosin stain is not well suited for H. pylori detection because of the weak contrast between the bacteria and the

mucus. The Warthin Starry stain allows an excellent visualization of the bacteria, but the procedure is

difficult to carry out. This technique is time consuming and costly and requires extemporaneous

preparation of the reagents to be used. The Giemsa stain is probably one of the most popular stains

because of its simplicity and good contrast[20]. A special stain has been proposed for H. pylori: the

Genta stain with which both the bacteria and gastritis lesions can be observed. The typical morphology

of H. pylori in biopsy specimens is a comma or S-shaped bacillus (2.5 to 4 µm long and 0.5 to 1 µm thick). The bacteria are observed on the epithelial surface at high magnification. They adhere to the gastric mucus cells or are free in the mucus and may eventually be present in the intercellular spaces;

very few bacteria, if any, are intracellular. [21]

4.Urea breath test:

C and

C tests: Both tests are affordable and can provide real time results. Some physicians may prefer the

C test as it is non-radioactive compared to

C which uses a radioactive isotope, especially in young children and pregnant women, though dose of radians is very

minimal[22]. the dose of radiation is the dose of

C-urea breath test with the mini dose equals to 1 microCi (37 kbq) which has a high diagnostic accuracy[23].

5.Immunological (serological) techniques-rapid test: A no quantitative enzyme-linked immunosorbent assay detects H. pylori antibodies in serum. A major advantage of this serologic test is that it enables large numbers of subjects to be screened quickly and relatively inexpensively; thus, it is a good test to use in epidemiologic studies [24]. The prevalence of H. pylori is usually found by using serologic tests that detect immunoglobulin G antibodies to H. pylori infection, although IgA and IgM antibodies have also been used[25]. There are two main pathogenic factors: the cag A and the polymorphism of the vacA gene. It is possible to look for antibodies directed against the CagA protein or to detect the cagA gene. The first studies were performed on H. pylori strains by polymerase chain reaction. The

variability in cagA sequences favors the successive use of two polymerase chain reactions. The same Polymerase chain reaction can be applied directly on DNA isolated from gastric biopsy specimens and gives similar results with bacterial colonies The former is the preferred technique because it gives a picture of what exists in vivo[26].

TREATMENT

Administer triple therapies for 10-14 days. The treatment regimens are omeprazole, amoxicillin, and clarithromycin for 10 days; bismuth subsalicylate, metronidazole, and tetracycline for 14 days; and lansoprazole, amoxicillin, and clarithromycin, which has been approved for either 10 days or 14 days of treatment.

H. pylori eradication rates were higher for a 7-day antibiotic regimen containing lansoprazole, amoxicillin and clarithromycin, when used as first-line therapy compared with levofloxacin, amoxicillin, and lansoprazole . Additionally, lansoprazole, amoxicillin, and clarithromycin did not achieve a higher rate of eradication than levofloxacin, amoxicillin, and lansoprazole as second-line therapy; thus, consideration of the sequence of administering antibiotic regimens for H. pylori is important [27].

Antibiotic-resistant strains

-a) Prevalence of H. pylori resistance to clarithromycin. Resistance to clarithromycin is the prevalence which has been the most widely studied so far. It ranges from 20 to 25%. In the United States, a prevalence of 10 to 15% was found based on strains isolated during clinical trials, regardless of the region studied. In Canada, a systematic review of the studies published before the year 2000 estimated this resistance to be less than 4% [28]. A multicenter European study carried out in 1998 in 17

countries found a global prevalence of 9.9% (95% confidence interval, 8.3 to 11.7) with a significant

difference between Northern Europe (9.3%) and Southern Europe (18%) [29].

-b) Prevalence of H. pylori resistance to metronidazole. A global resistance in the range of 20 to 40%

is observed in the United states [30]. As well as in Europe . It was 33.1% in the European multicenter study previously cited, with no significant difference between the North and the South [31]. In

developing countries, the prevalence is much higher (50 to 80%).Again, metronidazole consumption appears to be an important risk factor for this resistance[32].

-c) Prevalence of H. pylori resistance to other antibiotics. The prevalence of H. pylori resistance to amoxicillin is very low (<1%), as is the prevalence of H. pylori resistance to tetracycline[33]. The prevalence of H. pylori resistance to rifampins is virtually absent, given that these antibiotics have a limited use. In contrast, fluoroquinolones, which have shown an increasing consumption over the past few years, are leading to a higher prevalence[34].

H. pylori and GASTROINTESTINAL DISEASES

Effects of H. pylori infection vary depending on the location within the stomach.

Antral predominant infection results in increased gastrin production, probably via local impairment of somatostatin release. Resultant hypersecretion of acid predisposes to prepyloric and duodenal ulcer.

Body-predominant infection leads to gastric atrophy and decreased acid production, possibly via increased local production of IL-1β. Patients with body-predominant infection are predisposed to gastric ulcer and adenocarcinoma.

Some patients have mixed infection of both antrum and body with varying clinical effects. Many

patients with H. pylori infection have no noticeable clinical effects.

Ammonia produced by H. pylori enables the organism to survive in the acidic environment of the stomach and may erode the mucus barrier. Cytotoxins and mucolytic enzymes produced by H. pylori

may play a role in mucosal damage and subsequent ulcerogenesis.

Infected people are 3 to 6 times more likely to develop stomach cancer. H. pylori infection is associated with intestinal-type adenocarcinoma of the gastric body and antrum but not cancer of the gastric cardia.

H. pylori-related diseases and disorders include:

-Ulcers: Bleeding sores in the stomach and duodenal (upper small intestine).

-Gastritis: Inflammation of the stomach lining that can cause nausea, vomiting or aching, burning stomach pain -Stomach cancer: H. pylori infection is a strong risk factor for some types of stomach cancer -Mucosa-associated-lymphoid-type lymphoma: A cancerous tumor that develops from white blood cells (lymphocytes) in the stomach lining -Nonulcer dyspepsia: Stomach pain or discomfort not caused by an ulcer or another identifiable disorder [35].

Prevalence of H. pylori in Lithuania

In gastric cancer a study has been conducted between Taiwan, Latvia and Lithuania in order to analyce the prevalenve of H. pylori in GC of which 99 persons from Lithuania with gastrics cancer were assessed and out of those 99, 69(69,7%) were positive for this bacteria [36].

In PUD a study at the gastroenterology department of LSMU ligonine was conducted, 57 patients in

whom eradication of H. pylori was confirmed 1 year after eradication treatment both by histology and

by rapid urease test. Were invited in order to evaluate the prevalence of reinfection. There were 45

(78.9%) patients with duodenal ulcer and 12 (21.1%) with gastric ulcer. H. pylori was established in 17

patients (29,8%)[15].

H. pylori and EXTRAGASTROINTESTINAL DISEASES Parkinson Disease

a. Classification (Hoehn and Yahr Staging of Parkinson's Disease) -Stage 1: mild signs and symptoms on one side only, not disabling but friends notice.

–Stage 2: symptoms are bilateral, minimal disability, posture and gait affected.

–stage 3: significant slowing, dysfunction that is moderately severe.

–stage 4: severe symptoms, walking limited, rigidity, bradykinesia, unable to live alone.

–stage 5: cachectic, complete invalidism, unable to stand, walk, require nursing care. [37]

b.Epidemiology

Crude prevalence of PD has been reported to vary from 15 (per 100,000 population) in China to 657 in Argentina in door-to-door surveys,[38]and to vary from 100 to 250 in North America and Europe. The prevalence estimates derived by this method are greater than those derived from other methods for comparable populations. Prevalence is easily affected by socioeconomic factors and factors that affect survival rate.

Incidence is a better estimate frequency, and it quantifies the number of new subjects with PD occurring in a given time period for a population of individuals at risk. During the last 4 decades, the crude annual incidence rates of PD ranged from 1.5 per 100,000 population in China in 1986 to 14.8 in

Finland through 1968 to 1970 [39].

Age distribution: Both prevalence and incidence of PD vary greatly across age groups. PD is less common before 50 years of age and increases steadily with age thereafter up to the ninth decade. The decline among the most elderly seen in some studies probably results from the very few people in this age group and may also reflect diagnostic and ascertaining difficulties.

Gender differences: Although gender specific differences reveal more variability than association with increasing age, PD appears to be slightly more common in men than in women in most studies.

Prevalence

The prevalence and incidence of PD vary in different countries, partly reflecting variations in racial composition of the population surveyed. Generally, white people in Europe and North America have a higher prevalence, around 100 to 350 per 100,000 population. Asians in Japan and China and black Africans have lower rates, around one fifth to one tenth of those in whites[40].

Geographic distribution

Geographic variations in the frequency of PD have been reported. For instance, in door-to-door

surveys, crude prevalence is 15 per 100,000 in China, 328 per 100,000 in India, 131 per 100,000 in

Mississippi, USA, and 657 per 100,000 in Argentina[41]. A recent study examining geographic

variation in reporting of PD mortality in the United States showed strong north-to-south decreasing

gradients for mortality rates for whites, regardless of gender, but no clear west-to-east gradient was

demonstrated [42].

c. Causes: Certain nerve cells (neurons) in the brain gradually breakdown or die. Many of the symptoms are due to a loss of neurons that produce a chemical messenger in the brain called dopamine. When dopamine levels decrease, it causes abnormal brain activity, leading to signs of Parkinson's disease.

The cause of Parkinson's disease is unknown, but several factors appear to play a role, including:

-Genes. Researchers have identified specific genetic mutations that can cause PD, but these are uncommon except in rare cases with many family members affected by PD.

-Environmental triggers. Exposure to certain toxins or environmental factors may increase the risk of later PD, but the risk is relatively small.

Researchers have also noted that many changes occur in the brains of people with PD, although it's not clear why these changes occur. These changes include:

-The presence of Lewy bodies. Clumps of specific substances within brain cells are microscopic markers of PD. These are called Lewy bodies. Although many substances are found within Lewy bodies, scientists believe an important one is the natural and widespread protein, Alpha-synuclein.

[43].

d. Diagnosis

Currently,it is difficult to make a nearly diagnosis for premotor PD. Molecular imaging with position emission tomography or single-photon emission tomography offers a wide variety of tools for

overcoming this difficulty. Molecular imaging technique is capable of detecting the dysfunction of serotonergic, noradrenergic, and cholinergic systems that are typically associated with premotor manifestations. [44].

e. Treatment

PD can't be cured, but medications can help control the symptoms. Doctors may also recommend lifestyle changes, especially ongoing aerobic exercise. In some cases, physical therapy that focuses on balance and stretching also is important. A speech-language pathologist may help improve the speech problems.

Medications may help to manage problems with walking, movement and tremor. These medications increase or substitute dopamine, there may be an improvement on the symptoms after beginning the treatment of PD. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms usually can continue to be fairly well controlled.

Medications that doctor may prescribe include:

Carbidopa-levodopa. Levodopa, the most effective PD medication, is a natural chemical that passes into your brain and is converted to dopamine. Levodopa is combined with carbidopa, which protects levodopa from premature conversion to dopamine outside your brain, which prevents or lessens side effects such as nausea. After years, as your disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). Also, you may experience involuntary movements (dyskinesia) after taking higher doses of levodopa. Your doctor may lessen your dose or adjust the times of your doses to control these effects.

Dopamine agonists. Unlike levodopa, dopamine agonists don't change into dopamine. Instead, they mimic dopamine effects in your brain. They aren't as effective as levodopa in treating your symptoms.

However, they last longer and may be used with levodopa to smooth the sometimes off-and-on effect

of levodopa. Some of the side effects of dopamine agonists are similar to the side effects of carbidopa- levodopa, but also include hallucinations, sleepiness and compulsive behaviors such as hypersexuality, gambling and eating.

MAO-B inhibitors. They help prevent the breakdown of brain dopamine by inhibiting the brain enzyme monoamine oxidase B (MAO-B). This enzyme metabolizes brain dopamine. Side effects may include nausea or insomnia.

Catechol-O-methyltransferase inhibitors. This medication mildly prolongs the effect of levodopa

therapy by blocking an enzyme that breaks down dopamine.

Side effects, including an increased risk of involuntary movements, mainly result from an enhanced levodopa effect.

Anticholinergics. This medication had been used for many years to help control the tremor associated with PD. Several anticholinergic medications are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, hallucinations, constipation, dry mouth and impaired urination.

Amantadine. Prescribed to provide short-term relief of symptoms of mild, early stage PD. It may also be given with carbidopa-levodopa therapy during the later stages of PD to control involuntary

movements induced by carbidopa-levodopa.

Surgical procedures

Deep brain stimulation DBS). In deep brain stimulation, surgeons implant electrodes into a specific part of your brain. The electrodes are connected to a generator implanted in your chest near your collarbone that sends electrical pulses to your brain and may reduce your Parkinson's disease

symptoms. DBS is most often offered to people with advanced Parkinson's disease who have unstable medication responses. DBS is effective in controlling erratic and fluctuating responses to levodopa or for controlling dyskinesias that don't improve with medication adjustments. However, DBS isn't helpful for problems that don't respond to levodopa therapy apart from tremor. A tremor may be controlled by DBS even if the tremor isn't very responsive to levodopa.

f. Prevention

Because the cause of PD is unknown, proven ways to prevent the disease also remain a mystery.

However, some research has shown that caffeine which is found in coffee, tea and cola and regular aerobic exercise may reduce the risk of developing PD[43].

PARKINSON DISEASE AND H.pylori

H.pylori has a high relevance on PD since It turns out that if left untreated, H. pylori may affect the

absorption of PD medications, and consequently affect the overall response to treatment[45]. In 2006

researchers, based in Rome, identified and treated patients with H. pylori infection, either with an anti-

oxidant pill, or with an antibiotic regimen known to eradicate H. pylori in the gut. The absorption of

levodopa in these patients improved, as did the number of hours of on time[46]

RESEARCH METHODOLOGY AND METHODS

The object of study is to see if H. pylori is having any effect in patients with PD in order to see the prevalence of H. pylori and see the difference in the prognosis, treatment and outcomes of PD patients positive for H. pylori and negative patients for H. pylori.

In this study we investigate 28 patients with PD and 24 persons without PD who had been submitted to a serological rapid test for detection of H. pylori, all PD patients and non PD people were familiarized with the test substance and procedure, explained the procedure of the test and its characteristics, and after their allowance the test was performed,.

Criteria for inclusion of patients:

All patients with PD were included in the study since they are the object of the research, in the control group were included all the people who are not diagnostised with PD and havent taken antibiotics in the last month or specific treatment for H. pylori.

Criteria for exclusion of patients:

Patients with parkinson syndrome, and resting tremor due to any other neurological problems were not admited in the study.

In the control group, people who had taken antiobiotics in the last month or taken medication to treat H. pylori previously were not included in the study

Research methods and methods of data analysis.

H. pylori inmunochromatography test were used for the detention of H. pylori is a quick

chromatographic immunoassay test for the qualitative determination of antibodies against H. pylori in blood serum. Test is based on nitro-cellulose membrane on a test zone (T) which has already been immobilized anti-human IgG. The membrane itself is packed in a plastic cartridge. During the investigation, the capillary tube was filled with a fingertip blood sample taken. 50 ml of blood was transferred into the cassette sample. It was then added few drops of buffer. After the sample is droped in place, it reacts with H. pylori antigen coated gold particles located on the cassette test strip. The sample is chromatographed migrate towards the top strip of test zone (T) which responds to the immobilized antibody. The samples then migrate to the target area (C) where the rest of the antigen coated gold particles reacted with anti-H. pylori antibody. After no more than 10 minutes of results.

If there is antibodies for H. pylori a line on the test zone (T) will appear, if there isn’t antibodies for H.

pylori a line in the test zone will not appear. Positive result (Fig,2a)-it shows two color lines. One red

line is found on the control zone (C), and the other line is found in the test zone (T), the intensity of the

line’s colours can vary according to the amount of H. pylori antibody concentration that the subject

has, there for the waiting will be prolonged as well due to the amount of concentration. Negative

result(Fig. 2a)-it shows only one red line in the control zone (C).

Fig.2 test results. A: positive, B: negative

RESULTS

Assessing the prevalence of H. pylori in PD patients in Lithuania there were 11( 39%) patients with PD infected with H. pylori and there were 12(50%) people in a control group infected with H. pylori.

There were 4(33%) males and 7(43%) females in PD group and 4(50%)males and 8(50%) females in a control group infected with H. pylori.

Table I epidemiological characteristics PD group (n=28)

Controls (n=24)

Mean Age 67 years 61 years

Males 12 8

Females 16 16

Elementary education 16 11

High education 12 13

Town 9 6

City 19 18

House 8 12

Apartment 20 12

Work with few people 8 3

Work with more people 20 21

Smokes 2 4

Drinks 1 8

Water from the tap 26 19

Water from a bottle 2 5

Table 2. Comparison between PD patients and controls infected with H. pylori PD infected with H. pylori

(n=11)

Controls infected with H.

pylori (n=12

Mean Age 66 years 60 years

Males 4 (33%) 4(50%)

Females 7 (43%) 8(50%)

Elementary education 7 (43%) 5(45%)

High education 4 (33%) 7(53%)

Town 4 (44%) 3(50%)

City 7 (36%) 9(50%)

House 3 (37%) 6(50%)

Apartment 8 (40%) 6(50%)

Work with few people 2 (25%) 3(100%)

Work with more people 9(45%) 9(42%)

Smokes 0 3(75%)

Drinks 0 4(50%)

Water from the tap 11(42%) 9(47%)

Water from a bottle 0 3(60%)

Assessing the H. pylori effect on symptom severity in PD patients we observed that the patients in a higher stage of PD are the ones who are more prone to get infected with H. pylori, stage IV shows a prevalence of 2(100%)patients, against stages I and II that have a prevalence of 1(14%) and 2(25%) patients.

Table 3. Relationship between staging and average of years in patients with PD and H. pylori infection stage Prevalence of H.

pylori

Sex

Males females

Average of years with the disease

1 1(14%) 1 0 6 years

2 2(25%) 1 1 3,5 years

3 2(66%) 0 2 6 years

4 2(100%) 1 1 9,5 years

5 4(50%) 1 3 8 years

Assessing the H. pylori effect on the quality of life in PD patients we saw that patients with H. pylori infection have a worse quality of life -8(72%) patients with H. pylori said that cant do their daily house work by themselves against

10(58%) patients without H. pylori.

-4(36%) patients with H. pylori said that cant carry bags by themselves against 5(29%) patients

without H. pylori.

-8(72%) patients with H. pylori said that cant walk 100 meters by themselves against 10(58%) patients

without H. pylori.

-11(100%) patients with H. pylori said that cant get dress by themselves against 10(58%) patients

without H. pylori.

-9(81%) patients with H. pylori said that cant writte against 15(88%) patients without H. pylori.

-9(81%) patients with H. pylori said that cant prepare food by themselves against 9(53%) patients

without H. pylori.

-9(69%) patients with H. pylori said that feel depress against 9(60%) patients without H. pylori.

-5(45%) patients with H. pylori said that need help of someone close against 2(11%) patients without

H. pylori that need help of someone.

-6(54%) patients with H. pylori said that have memory fails against 3(17%) patients without H. pylori.

-4(36%) patients with H. pylori said that have musle pains against 2(11%) patients without H. pylori.

-7(63%) patients with H. pylori said that its hard to comunicate against 4(23%) patients without H.

pylori.

-4(36%) patients with H. pylori said that its hard to speak against 2(11%) patients without H. pylori.

-4(36%) patients with H. pylori said that its hard to walk in the house by themselves against 6(35%)

patients without H. pylori.

-7(63%) patients with H. pylori said that felt tied at home against 8(47%) patients without H. pylori.

-7(58%) patients with H. pylori said that cant leave the house alone against 6(35%) patients without H.

pylori.

-7(63%) patients with H. pylori said that cant wash up by themselves against 7(41%) patients without

H. pylori.

Table4. Comparison of Daily living quality in patients with PD with and without H. pylori infection

activity Patients with H. pylori

who cant do the activity

Patients with out H. pylori who cant do the activity

Daily homework, house work 8(72%) 10(58%)

Carry bags 4(36%) 5(29%)

Walk 100 meters 8(72%) 10(58%)

Get dress 11(100%) 10(58%)

Write 9(81%) 15(88%)

Prepare food 9(81%) 9(53%)

Feel depress 9(69%) 9(60%)

Need help of someone close 5(45%) 2(11%)

Memory fails 6(54%) 3(17%)

Muscle pains 4(36%) 2(11%)

Hard to communicate 7(63%) 4(23%)

Hard to speak 4(36%) 2(11%)

Walk in the house 4(36%) 6(35%)

Feel tied at home 7(63%) 8(47%)

Leave the house alone 7(58%) 6(35%)

Wash up 7(63%) 7(41%)

Assessing the risk factor for infection of H. pylori, we observed that in the PD group there is no

significant risk factors, everyone can be randomly infected by H. pylori, while in the control group we

observed that patients who smoke have higher chances of getting infected, 3(75%) controls were

infected, and controls who drink mineral water from bottles have a prevalence of H. pylori of 60%,

being these two the most significant risk factors.

DISCUSSION OF THE RESULTS

The statistical analysis consist of two parts, a first one which consist on analyze the epidemiology and risk factors for H. pylori infection, and a second part which consists of analyze the difference of quality of life between patients with PD with H. pylori and without H. pylori. For our study we have interviewed 52 patients. Total data analysis has been performed with the statistical data collection analysis program R- project.

When we study the prevalence of H. pylori in different sex, we don’t find any significant difference, which would make us think that either men or women are more prone to be infected with H. pylori, seeing in our study that 50% of males and 50% of females are infected in the control group. And 33% of males and 43%

of females are infected in the PD group showing a small predisposition for infection for males. Studies conducted in Sweden [47] where 70 PD patients were investigated showed a prevalence of H. pylori in 35%

females and 65% males, results different to our study. Nevertheless a study in the university of Seoul, Korea [48] with 65 patients with PD showed a prevalence of H. pylori in 57%males and 43% females, these studies are similar to the prevalence found in Lithuanian control group.

Other studied parameter is the prevalence of H. pylori according to the amount of people with whom we spend the day. For what we analyzed:

-The place where they live.

-The type of residency -Work with more people or few people

After analyze the three parameters we have concluded that none of them is a determinant factor to be infected by H. pylori. In fact the percentages on each group resulted similar, to the 50% of infected patients that the WHO calculates that exists now a day.

We see that 47% of the population who lives in the city are infected. As the infected amount of people in towns was about 50%. On the PD group 44% of the patients with PD living in town were infected against the 36% of patients with PD infected who live in the city, demonstrating a higher prevalence for infection in town. A study by Daiva Janulaityte-Gunther in 2015 analyzed 116 childs, among them 78% lived in the city and were infected with H. pylori and 81% of the ones who live in rural areas were infected by H. pylori [14].

When we compare the place of living, the results are similar. Regardless if the person lives in a house 50%

or apartment 50% in the control group and 37% lives in a house and 40% lives in an apartment in the PD group. In the same manner when we compare the people who work in environments with more people and people who work in more solitary environments the data shows that H. pylori differs in the different groups, in the control group 100% of persons who work with few people are infected while 42% of the people who work with more people is infected, different results are obtained in the PD group where 25% of the patients who work with few people are infected and 45%of the patients who work with more people are infected.

This way we observe that H. pylori transmission doesn’t depend on the amount of people with whom we

have direct contact, neither the amplitude of the place where we live and do our daily basis. R. P. Jackman

[49] made an study to the tripulation of an US navy submarine in order to see the prevalence of H. pylori in

persons who work on a close space concluding that only 47 out of 451 submariners (9.4%) were H. pylori

positive.

One of the most revealing factors in the study is the comparison between smokers and non smokers, we observe that 75% of smokers are infected with H. pylori, against a 45% of infected patients who don’t smoke in the control group. Similar results obtained Gamal. A [50] in a research conducted in Yemen to study the risk factors for H. pylori where he saw a prevalence of H. pylori in patients who usually smokes 55%, against 37% patients infected who don’t smoke.

Its needed to mention that other parameters that were thought that would be statistically significant as risk factors such as alcohol consumption and drinking water from the tap or bottle haven’t revealed any significant data which would make us think that this activities are related with H. pylori infection, the amount of H. pylori infected patients who drink alcohol is 50% which is the same amount of non drinkers with H. pylori 50%. 47% of the patients who drink water from the tap are H. pylori infected as the ones who drink water from the bottle 50% of them are infected.

One of the most fascinating data obtained is the relationship between H. pylori infected patients and the antecedents of gastritis in the parents. 57% of the patients who claimed that there are antecedents of gastritis in their parents were H. pylori positive. Analyzing deeply this situation we see that patients who doesn’t claim any antecedents of gastritis in their family are a lower amount of patients 40%.

Nevertheless if we try to find a relationship between family members, it’s evident in persons who have antecedents of gastritis. Being not so evident in persons with ulcers. The reason for this is that not all H.

pylori infected patients develop ulcers, only 25%, but gastritis is a very common disease developed by 50%

of the persons with HP.

A study by Laimas Jonaitis [36] compared patients from Lithuania, Latvia and Taiwan. A total of 322 patients were included in the study and H. pylori was established in 69% patients, among those, atrophy either in the corpus or in the antrum of the stomach was detected in 60.5% TW patients, in 35.7% LV patients, and in 52.2% LT patients, Severe atrophy (grade 2 or 3) detected in 18.6% TW patients, in, 15.2%LV patients, and in 26.1% LT patients, Intestinal metaplasia was detected in 51.2% TW patients, in 33.0% LV patients and in 44.9% LT patients among countries, There were no significant differences in proportions of different degrees of both atrophy and intestinal metaplasia among countries.

Daiva Janulaityte-Gunther [14], analyzed 116 childs, H. pylori was seen in 79% children of whom 18%

children had gastritis and duodenal ulcer disease and 81% children had only gastritis. There was a strong association between H. pylori infection and gastritis, as its seen in our study.

By this means that part of the ancestors who didn’t have ulcers may had H. pylori, even those ancestors who didn’t have gastritis could hade had H. pylori, both hypothesis would mean the same, a bigger relationship between ancestors with H. pylori and actual infected. And we could relate a more direct relationship between ancestors and the offspring if we would know if they had the bacteria instead of the symptoms.

The second part of our study wants to compare the quality of life of PD patients with and without H. pylori infection. This part of the study has been very reveling, and we see an evident relationship between the H.

pylori infection and a worse quality of life.

On our study we see that when we analyze the patients H. pylori negative, 58% gets tired against the H.

pylori positive patients of whom 72,72% of them gets tired. From this data we can conclude that the

antiparkinsonian drugs are not being absorbed properly in the stomach.

Similar data is observed when we ask about the fear of leaving their house alone, parameter which is the

less feared by the patients.

The patients H. pylori negative only 35% avoid to leave their house against the 58% H. pylori positive patients who avoids to leave their house, the results in this field make us think that the prevalence of H.

pylori reduces the efficacy of the antiparkinsoian medication by 50%.

Same results are obtain from activities such as wash up where we observe a percentage of 63% against 41%, or in dress up, parameter in which all the patients with PD and H. pylori have difficulties against the H. pylori negative patients whom only 58% have difficulties dressing up, observing again a better

absorption of the antiparkinsonian drugs.

A study by Kang MY [51] Maintained that usual life and physical ability is the major concern among the people with PD, and they can have a good quality of life if they have a state of health as similar as without the disease, this is exactly what we had analyzed and it seems that are the main key points that control the quality of life of PD patients The hardest task for PD patients is to write, and no difference is observed between positive and negative H.

pylori infection, since in both groups about 85% of the patients have difficulties.

Cooking is other of the parameters where we see a big difference, with 81% of the patients with H. pylori having difficulties to cook, against 53% of the patients without H. pylori having problems cooking.

Vaineta Valeikiene [52] showed that the patients with PD scored lower in a test to assess the quality of life since mobility, activities in daily living, and working capacity were worse than in other patients tested. This study matches our results, the patients with Parkinson have a lower quality of life than the control group, and in the case of patients with PD, the ones infected with H. pylori has even worse quality of life than those non infected with H. pylori

Other analyzed parameter in which case the medication doesn’t have a direct repercussion, which is the

facility to feel depress, 69% of H. pylori positive feel often depress against 60% of H. pylori non infected.

A study by Galit Kleiner-Fisman [53], made 5 sessions with 17 persons with PD in order to analyze what are the needs for these patients in order to improve their quality of life (diagram 1) and all agreed that the emotional and social aspects are the more importants for them which need more involvement.

Diagram 1.

CONCLUSIONS

-There is a higher prevalence of H.pylori in the control group than in the PD group, in PD group there is a higher prevalence on females, while in the control group the prevalence is the same for man and woman

-Patients in a higher stage of PD show a higher prevalence of H. Pylori and higher severity on symptoms.

-Patients with PD infected with H.pylori have a worse quality of life.

-There is no risk factors for H.pylori infection in the PD group but the control group showed a higher

prevalence of H. Pylori in smokers

REFERENCES

1 Mohammed Mahdy Khalifa, Radwa Raed Sharaf, Ramy Karam Aziz. Helicobacter pylori: a poor man’s gut pathogen? Gut Pathogens 2010, 2:2

2 Goodwin CSR, Armstrong JA. Microbiological aspects of Helicobacter pylori (Campylobacter pylori) Eur J Clin Microbiol. 1990;9(1):1–13)

3 Duane T. Smoot, Harry L. T. Mobley, Gwynn R. Chippendale, et al. Helicobacter Pylori Urease Activity Is Toxic To Human Gastric Epithelial Cells. Infection And Immunity, June 1990:58(6):1992- 1994)

4 Van Doorn LJ, et al. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori.

Gastroenterology. 1998;115:58–66.

5 Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol Mech Dis. 2006;1:63–96

6 Lin SK, Lambert JR, Nicholson L, et al. Prevalence of Helicobacter pylori in a representative Anglo- Celtic popula- tion of urban Melbourne. J Gastroenterol Hepatol 1998;13: 505-10

7 Epidemiology of, and risk factors for, Helicobacter pylori infection among 3194 asymptomatic subjects in 17 populations. The EUROGAST Study Group. Gut 1993;34:1672-6.

8 Goodman KJ, Correa P, Tengana AH, et al. Nutritional factors and Helicobacter pylori infection in Colombian children. J Pediatr Gastroenterol Nutr 1997;25:507-15

9 Zhang L, Blot WJ, You WC, et al. Helicobacter pylori anti- bodies in relation to precancerous gastric lesions in a high- risk Chinese population. Cancer Epidemiology Biomarkers Prev 1996;5:627- 30

10 Goodman KJ, Correa P, Tengana Aux HJ, et al. Helicobacter pylori infection in the Colombian Andes: a population-based study of transmission pathways. Am J Epidemiol 1996; 144: 290-9.

11 Peach HG, Pearce DC, Farish SJ. Helicobacter pylori infection in an Australian regional city:

prevalence and risk fac- tors. Med J Aust 1997;167:31O-13

12 Nguyen AM, el-Zaatari FA, Graham DY. Helicobacter pylori in the oral cavity. A critical review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:705-9.

13 Vincent P. Transmission and acquisition of Helicobacter pylori infection: evidences and hypothesis. Biomed Pharmacother 1995;49:11-18

14 Daiva Janulaityte-Gunther , Ruta Kucinskiene Limas Kupcinskas et al. The humoral

immuneresponse to Helicobacter pylori infection in children with gastrointestinal symptoms. FEMS Immunology and Medical Microbiology 44 (2006) 205–212.

15 Laimas Jonaitis, Gediminas Kiudelis, Paulius Slepavicius. High rate of Helicobacter pylori reinfection in Lithuanian peptic ulcer patients World J Gastrointest Pathophysiol 2016 February 15;

7(1): 181-185

16 Parsonnet J. The incidence of Helicobacter pylori infection. Aliment Pharmacol Ther 1995;9(suppl

2):45-51

17 Megraud, F., L. Boyanova, and H. Lamouliatte. 1991. Activity of lansoprazole against Helicobacter pylori. Lancet337:1486

18 Westblom, T. U., E. Madan, and B. R. Riff. 1991. Improved growth of Helicobacter pylori using a liquid medium supplemented with human serum. Ital. J. Gastroenterol.29(Suppl. 2):48.

19 Van Der Hulst, R. W. M., S. B. Verheul, J. F. L. Weel, et al. 1996. Effect of specimen collection techniques, transport media, and incubation of cultures on the detection rate of Helicobacter pylori.

Eur. J. Clin. Microbiol. Infect. Dis.15:211-215

20 Bayerdorffer, E., H. Oertel, N. Lehn, et al. 1989. Topographic association between active gastritis and Campylobacter pylori colonisation. J. Clin. Pathol.42:834-839

21 Fallone, C. A., V. G. Loo, J. Lough, et al. 1997. Hematoxylin and eosin staining of gastric tissue for the detection of Helicobacter pylori. Helicobacter2:32-35.

22 Ota, H., T. Katsuyama, S. Nakajima, et al. 1998. Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features. Hum. Pathol.29:846-850.

23 Leide-Svegborn S, Stenström K, Olofsson M, et al. Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test. Eur J Nucl Med.

1999;26:573–580

24 Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808–1825

25 Taylor DN, Blaser MJ. The epidemiology of Helicobacter pylori infection. Epidemiol Rev 1991;13:42-59

26 Andersen LP, Rosenstock SJ, Bonnevie O, et al. Seroprevalence of immunoglobulin G, M, and A antibodies to Helicobacter pylori in an unselected Danish population. Am J Epidemiol 1996;

143:1157-646

27 Gunn, M. C., J. C. Stephens, J. D. Stewart, et al. 1998. Detection and typing of the virulence determinants cagA and vacA of Helicobacter pylori directly from biopsy DNA: are in vitro strains representative of in vivo strains? Eur. J. Gastroenterol. Hepatol.10:683-687

28 Luigi Santacroce, Manoop S Bhutani, medscape, March 15

http://emedicine.medscape.com/article/176938-treatment

29 Fallone, C. A., S. J. O. V. van Zanten, and N. Chiba. 2000. The urea breath test for Helicobacter pylori infection: taking the wind out of the sails of endoscopy. Can. Med. Assoc. J.162:371-372 30 Megraud, F. 2004. H. pylori antibiotic resistance: prevalence, importance, and advances in testing.

Gut53:1374-1384

31 States Duck, W. M., J. Sobel, J. M. Pruckler, et al. 2004. Antimicrobial resistance incidence and

risk factors among Helicobacter pylori-infected persons, United States. Emerg. Infect. Dis.10:1088-

1094

32 Glupczynski, Y., F. Megraud, M. Lopez Brea, et al. 2001. European Multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur. J. Clin. Microbiol. Infect. Dis.20:820-823

33 Heep, M., M. Kist, S. Strobel, et al. 2000. Secondary resistance among 554 isolates of Helicobacter pylori after failure of therapy. Eur. J. Clin. Microbiol. Infect. Dis.19:538-541

34 Kim, J. J., R. Reddy, M. Lee, et al2001. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J. Antimicrob. Chemother.47:459-461

35 Michael C. DiMarino, MD Helicobacter pylori Infection, Last full review/revision May 2014, merck manual, available from: http://www.merckmanuals.com/professional/gastrointestinal- disorders/gastritis-and-peptic-ulcer-disease/helicobacter-pylori-infection

36 Laimas Jonaitis, Audrius Ivanauskas, Dainius Jančiauskas Precancerous gastric conditions in high Helicobacter pylori prevalence areas: comparison between Eastern European (Lithuanian, Latvian) and Asian (Taiwanese) patients Medicina (Kaunas) 2007; 43(8)

37 Emad N. Eskandar, M.D., Hoehn and Yahr Staging of Parkinson's Disease, Unified Parkinson Disease Rating Scale (UPDRS), and Schwab and England Activities of Daily

Livinghttp://neurosurgery.mgh.harvard.edu/functional/pdstages.htm

38 Melcon MO, Anderson DW, Vergara RH, et al. Prevalence of Parkinson’s disease in Junin, Buenos Aires Province, Argentina. Mov Disord 1997; 12:197-205

39 Marttila RJ, Rinne UK. Epidemiology of Parkinson’s disease in Finland. Acta Neurol Scand 1976;53:81-102

40 Schoenberg BS, Anderson DW, Haerer AF. Prevalence of Parkinson’s disease in the biracial population of Copiah County, Mississippi. Neurology 1985;35: 841-84

41 Bharucha NE, Bharucha EP, Bharucha AE, et al. Prevalence of Parkinson’s disease in the Parsi community of Bombay, India. Arch Neurol 1988;45:1321-1323

42 Lanska DJ. The geographic distribution of Parkinson’s disease mortality in the United States. J Neurol Sci 1997;150:63-70

43 mayo clinic, diseases and conditions parkinson’s disease,

http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/basics/causes/con-20028488 44 JingZou,1Rui-HuiWeng,1Zhao-YuChen et al. PositionEmissionTomography/Single-

PhotonEmission TomographyNeuroimagingforDetectionofPremotor Parkins on’sDisease.doi:

10.1111/cns.12493

45 Michael S. Okun, What's Hot in PD? More Evidence Linking Gut Bacteria to Parkinson’s Disease:

A Guide for Patients. January 2015, http://www.parkinson.org/find-help/blogs/whats-hot/january-2015

46 Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology. 2006 Jun 27;66(12):1824-9.

47 Karl Erik Rahne, Carl Tagesson, Ddag Nyholm. Motor fluctuations and helicobacter pylori in

parkinsons disease. J. neurology. (2013) 260:2974-2980

48 Wong Yon Lee, Won Tae Yoon, Hee Young Shin. Helicobacter pylori infection and motor

fluctuations in patients with Parkinson disease.movement diseorders. Vol 23. No. 12. 2008. Pp. 1696- 1700

49 R.P. Jackman, C.. Schlichting. Prevalence of Helicobacter pylori in United States Navy submarine crews. Epidemiol Infect. 2006 June; 134(3): 460–464.

50 Gamal A, A-Ameri, Mawhoob Noman Alkadasi, the prevalence of helicobacter pylori and risk factors infection associated in taiz city, yemen, int.j.current microbiology. App. Sci (2013) pp 226-233 51 Kang MY, Ellis-Hill C. How do people live life successfully with Parkinson's disease? J Clin Nurs.

2005 Aug;24(15-16):2314-22. doi: 10.1111/jocn.12819. Epub 2015 May 4

52 Vaineta Valeikiene, Jelena Ceremnych, vidmantas alekna, Differences in WHOQOL-100 domain scores in Parkinson's disease and osteoarthritis, Medical science monitor: international medical journal of experimental and clinical research 14(4):CR221-7 · May 2008

53 Galit Kleiner-Fisman, Matthew B Stern, and David N Fisman, Health-Related Quality of Life in Parkinson disease: Correlation between Health Utilities Index III and Unified Parkinson's Disease Rating Scale (UPDRS) in U.S. male veterans, Health Qual Life Outcomes. 2010; 8: 91. doi:

10.1186/1477-7525-8-91

ANEXES

ANEX 1.

KLAUSIMYNAS (H. pylori) (savo teisingą atsakymą – apveskite) Anketos Nr. ____________

Lytis: Vyras Moteris amžius_____ svoris_____ Ūgis_____

Kur Jūs gyvenate? Mieste Kaime

Kokio tipo Jūsų būstas? Namas Butas Bendrabutis

Koks Jūsų išsilavinimas? Profesinis Vidurinis Aukštasis Apibūdinkite savo (šeimos) materialinę padėtį: Gera Vidutinė Bloga

Ar Jūs rūkote? Taip Ne

Ar Jūs vartojate alkoholį? Taip Ne

Ar Jūs vartojate kavą? Taip Ne

Ar Jūs dirbate (dirbote) su fizine veikla susijusį darbą? Taip Ne Ar Jūs dirbate (dirbote) su protine veikla susijusį darbą? Taip Ne

Kokia yra (buvo) Jūsų darbo aplinka? Su daug žmonių Su keletu žmoniu

Ar Jūsų darbas susijęs su nervine įtampa? Taip Ne

Kokį vandenį Jūs naudojate buityje? Vandentiekio Šulinio

Ar Jūs visada geriate tik virintą vandenį? Taip Ne

Ar Jūs laikote namuose gyvūnų? Šunį Katę Nelaika

Ar valgote greitą maistą (bulviųtraškučius, kebabus, mėsainius)? Taip Ne Ar Jūs geriate gazuotus gėrimus (Coca-cola, Sprite, Fanta)? Taip Ne Ar Jūs valgote citrusinius vaisius (apelsinai, citrinos)? Taip Ne

Ar Jūs papildomai vartojate vitaminą C? Taip Ne

Ar Jūs sergate (sirgote)gastritu Taip Ne

Ar Jūs sergate (sirgote) opalige? Taip Ne

Ar serga (sirgo) Jūsų artimieji opalige? Mama Tėtis Nesirgo Nežinau Ar serga (sirgo) Jūsų artimieji skrandžio vėžiu? Mama Tėtis Nesirgo Nežinau Ar Jūs per paskutiniuosisu 3 mėn. vartojote vaistų nuo skausmo ar temperatūros?

(aspirinas, ibuprofenas) Taip Ne Nežinau

Ar per paskutinįjį mėnesį vartojote antibiotikus ? Taip Ne Nežinau

Ar Jums anksčiau buvo nustatyta Helicobacter pylori bakterija? Taip Ne Nežinau

Ar Jūsų šeimos nariui buvo nustatyta Helicobacter pylori bakterija? Taip Ne Nežinau

ANEX 2

PDQ – 39 klausimynas

Kiek dažnai per praėjusį mėnesį DĖL PARKINSONO LIGOS, KURIA SERGATE, patyrėte toliau išvardytus sunkumus?

Prie kiekvieno klausimo varnele pažymėkite tik vieną langelį

Niekada Retai Kartais Dažnai Visada arba apskritai

negalite to daryti 1. Buvo sunku užsiimti mėgstama

kasdiene veikla

q q q q q

2. Buvo sunku tvarkytis namuose, pvz., meistrauti, atlikti namų ūkio darbus, gaminti maistą

q q q q q

3. Buvo sunku nešti pirkinių krepšius

q q q q q

4. Buvo sunku nueiti 800 metrų q q q q q

5. Buvo sunku nueiti 100 metrų q q q q q

6. Buvo sunku judėti po namus taip lengvai, kaip norėtumėte

q q q q q

7. Buvo sunku judėti viešose vietose

q q q q q

8. Kad galėtumėte išeiti iš namų, Jus turėjo lydėti kitas asmuo

q q q q q

9. Buvo baisu arba neramu, kad viešoje vietoje pargriūsite

q q q q q

10. Buvote „pririštas“ prie namų labiau, negu norėtumėte

q q q q q

11. Buvo sunku nusiprausti q q q q q

12. Buvo sunku apsirengti q q q q q

13. Buvo sunku užsisagstyti drabužius arba užsirišti batų raištelius

q q q q q

14. Buvo sunku aiškiai rašyti q q q q q

15. Buvo sunku susipjaustyti maistą

q q q q q

16. Buvo sunku laikyti stiklinę skysčio, jo neišlaisčius

q q q q q

17. Jautėtės prislėgtas q q q q q

18. Jautėtės izoliuotas ir vienišas q q q q q

19. Jautėtės verksmingas ar liūdnas

q q q q q

20. Jautėtės piktas ar paniuręs q q q q q

21. Jautėte nerimą q q q q q

22. Jautėtės susirūpinęs dėl ateities q q q q q

23. Jautėte, kad Parkinsono ligą turite slėpti nuo kitų žmonių

q q q q q

24. Vengėte valgyti arba gerti viešumoje

q q q q q

25. Viešumoje drovėjotės dėl to, kad sergate Parkinsono liga

q q q q q

26. Jautėte nerimą dėl to, kaip į Jus reaguos kiti žmonės

q q q q q

27. Patyrėte sunkumų dėl artimų asmeninių santykių

q q q q q