Antimyenteric neuronal antibodies in scleroderma.

The pathogenesis of gastrointestinal (GI) dysmotility in scleroderma is incompletely understood, although previous studies have proposed a neuropathic mechanism. We studied patients with scleroderma as compared with other connective tissue disease patients and normal controls for the presence of circulating antibodies to myenteric neurons. Serial dilutions of sera were overlaid on rat intestine, double-labeled with antineurofilament antibody as a myenteric plexus marker, and imaged using indirect immunofluorescence techniques. High titer sera (> or = 1:50) from 19 out of 41 scleroderma patients stained myenteric neurons, whereas none of 22 normals or 5 patients with idiopathic GI dysmotility were positive. Although 6 out of 20 SLE and 6 out of 10 mixed connective tissue disease patients' sera stained myenteric plexus neurons, when positive sera were absorbed with calf thymus extract to remove antinuclear antibody, 15 scleroderma sera, 0 SLE, and 2 mixed connective tissue disease patients retained positive staining of myenteric neurons. Western blotting using actin and neuronal intermediate filament preparations failed to show immunoreactivity with scleroderma sera containing antimyenteric neuronal antibodies. Paraneoplastic sera associated with GI dysmotility stained myenteric neurons in a different pattern than seen with scleroderma sera. A positive correlation between the presence of Raynaud's phenomenon and antimyenteric neuronal antibodies was observed in scleroderma patients. Our results indicate that IgG antibodies reacting with myenteric neurons are present in many patients with scleroderma. Although the neuronal antigen has not yet been identified, the presence of myenteric neuronal antibodies in patients with GI dysmotility and scleroderma suggests a neuropathic process.

Incidence and predictors of atrial flutter in the general population.

OBJECTIVES: The goal of our study was to determine the incidence and predictors of atrial flutter in the general population. BACKGROUND: Although atrial flutter can now be cured, there are no reports on its epidemiology in unselected patients. METHODS: The Marshfield Epidemiological Study Area (MESA), a database that captures nearly all medical care among its 58,820 residents was used to ascertain all new cases of atrial flutter diagnosed from July 1, 1991 to June 30, 1995. To identify predisposing risk factors, we employed an age- and gender-matched case-control study design using eight additional variables. RESULTS: A total of 181 new cases of atrial flutter were diagnosed for an overall incidence of 88/100,000 person-years. Incidence rates ranged from 5/100,000 in those <50 years old to 587/100,000 in subjects older than 80. Atrial flutter was 2.5 times more common in men (p < 0.001). The risk of developing atrial flutter increased 3.5 times (p < 0.001) in subjects with heart failure and 1.9 times (p < 0.001) for subjects with chronic obstructive pulmonary disease. Among those with atrial flutter 16% were attributable to heart failure and 12% to chronic obstructive lung disease. Three subjects (1.7%) without identifiable predisposing risks were labeled as having "lone atrial flutter." CONCLUSIONS: This study, the first population-based investigation of atrial flutter, suggests this curable condition is much more common than previously appreciated. If our findings were applicable to the entire U.S. population, we estimate 200,000 new cases of atrial flutter in this country annually. At highest risk of developing atrial flutter are men, the elderly and individuals with preexisting heart failure or chronic obstructive lung disease.

Trends in nonfatal coronary heart disease in the United States, 1980 through 1989.

BACKGROUND: Although coronary heart disease mortality has been decreasing, little is known about trends in morbidity from coronary heart disease. We evaluated trends in nonfatal coronary heart disease in the United States during 1980 through 1989. METHODS: We analyzed data from the National Health Interview Survey, an ongoing survey of representative samples of the civilian, noninstitutionalized population of the United States. Survey respondents were determined to have coronary heart disease if they reported ever having a myocardial infarction or heart attack, angina pectoris, or coronary heart disease. Incidence was defined as initial onset of a coronary heart disease condition during the year preceding the interview date. RESULTS: About 6 million people were estimated to be living with coronary heart disease. The age-standardized prevalence was relatively constant at about 25 per 1000. Among white men, however, prevalence increased significantly over the 10-year period. Among 75- to 84-year-old men, prevalence increased from 100 per 1000 in 1980 to 179 per 1000 in 1989. Among men and women 45 to 54 years old, prevalence decreased. Overall, the incidence rate of nonfatal coronary heart disease was relatively flat (at about 3 per 1000 per year after 1983). Among white women, the incidence rate increased from 1.4 to 2.8 per 1000, and by the end of the decade it nearly equaled the incidence rate among white men. CONCLUSIONS: Overall, the burden of nonfatal coronary heart disease remained fairly constant during the 1980s. The trends, however, were not uniform in all population groups. The apparent increasing incidence among women deserves continued monitoring. An encouraging trend is the decreasing prevalence in the younger age groups.

Coronary artery disease in diabetic patients with lower-extremity arterial disease: disease characteristics and survival. A report from the Coronary Artery Surgery Study (CASS) registry.

OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.

The role of public health surveillance: information for effective action in public health.

Public health surveillance can provide the quantitative information needed for setting priorities and establishing rational health policy. Although there are many examples of the effective use of such information, the full potential for surveillance has not yet been realized. To a large degree, failure to achieve this potential has resulted from limited perspectives regarding the role and conduct of surveillance. Both practitioners (those who conduct surveillance) and users (those who apply surveillance data in a real-world setting) have fallen victim to such myopia. Public health surveillance must be advocated as an essential part of the global health agenda if we are to achieve international goals for improving health status. As we improve our appreciation of the variety of uses for public health surveillance data, we need to understand more fully the determinants of the decision-making process. Effective dissemination of information and effective communication are as important as data collection and analysis. No longer do we have--or should we have--the luxury of collecting information for its own sake. The information collected must have a demonstrated utility. Developing and training personnel to have expertise in public health surveillance will necessarily incur opportunity costs. Bridging gaps in data methodology and coverage will force us to weigh alternatives and to compromise. We hope that the International Symposium on Public Health Surveillance will accomplish several goals. First, we wish to foster international understanding of the definition, role, and importance of surveillance in reducing morbidity and mortality, in improving quality of life, and in setting effective health priorities. Second, we hope that this symposium will serve as a springboard for identifying issues and topics that can be addressed in greater depth at future international meetings. Finally, we see the symposium as an essential step in developing a firm commitment on the part of countries, donor agencies, and multilateral organizations to develop the essential capacity for public health surveillance throughout the world. Each country should have the capacity to measure and monitor changes in health status, risk factors, and health-service access and utilization among its people. All countries should have the means to detect emerging health problems and implement measures for their control, to evaluate the impact of health policies and programs, and to communicate health information in a meaningful fashion to policymakers and the public. If we are successful in these endeavors, the long-term effects on the public's health will be well worth the struggle required to achieve them.(ABSTRACT TRUNCATED AT 400 WORDS)

Myenteric plexus neurons have developmentally acquired differences in the medium molecular weight subunit of neurofilament protein.

We have previously shown that neurofilaments in enteric neurons are immunologically distinct from those found in the central nervous system. In particular, one monoclonal antibody to the medium molecular weight neurofilament subunit, called NN18, stained the perikarya of enteric neurons very weakly, if at all, although other medium molecular weight neurofilament subunit antibodies clearly showed the presence of significant amounts of medium molecular weight neurofilament subunit. We have since located the epitope for NN18 in a peptide sequence at the carboxy terminal tail of medium molecular weight neurofilament subunit and have now looked for further neurofilament antibodies that stain the same region. We found two monoclonal antibodies, RMO1 and RMO59, that recognize the same peptide. These antibodies also show much reduced staining in myenteric neurons compared to those in the central nervous system, suggesting that this region of the medium molecular weight neurofilament subunit is specifically modified in certain cells. In the developing enteric nervous system, we found that all the antibodies show strong staining of enteric neurons in the neonatal rat, but that with NN18, RMO1, and RMO59, the staining intensity decreases during further development, and by postnatal day 21 all three demonstrate decreased or absent staining identical to the adult. These results indicate that myenteric neurons, in contrast to the brain, have a developmentally regulated modification in a specific region of the medium molecular weight neurofilament subunit, which may reflect adaptation to structural stress by myenteric neurons.

Frequency of uncomplicated angina pectoris in type A compared with type B persons (the Framingham Study).

The impact of type A behavior on coronary artery disease was examined in 570 men and 719 women based on 20 years of follow-up in the Framingham Study. A comparison of type A and B persons showed similar levels of systolic blood pressure, total and high density lipoprotein cholesterol and body mass index. Behavioral status also was unrelated to diabetes, cigarette smoking and alcohol intake. Despite similar cardiovascular risk profiles, type A behavior was associated with more than a 2-fold excess risk of angina pectoris, uncomplicated by other symptoms of coronary artery disease (p less than 0.05 for men and p less than 0.01 for women). Type A behavior, however, was not related to an increased risk of myocardial infarction and fatal coronary events. Among the victims of uncomplicated angina, the risk of subsequent coronary morbidity and mortality in both type A and type B men and women increased by more than 4-fold (p less than 0.001). Although the risk was reduced among type A persons, it was not statistically significant. It is concluded that uncomplicated angina pectoris occurs with greater frequency in type A persons than in those who are type B, without explanation by concomitant risk factors. In addition, the prognosis for myocardial infarction and coronary artery disease mortality in angina patients classified as type A is as serious as the prognosis for those who are type B.

Coronary artery disease and coronary artery bypass grafting in diabetic patients aged > or = 65 years (report from the Coronary Artery Surgery Study [CASS] Registry).

A cohort of 317 diabetic patients, aged > or = 65 years, with angiographically proven coronary artery disease, was analyzed and followed for a mean of 12.8 years. Compared with 1,843 age-matched nondiabetic patients, diabetic patients were more likely to (1) have a higher number of coronary occlusions, (2) not be current smokers, (3) have higher systolic but lower diastolic blood pressures, (4) have evidence of peripheral vascular disease, and (5) be women. They did not differ significantly with respect to total cholesterol, family history of coronary artery disease, history of hypertension, or left ventricular hypertrophy. In the total elderly cohort, diabetes was found to be an independent predictor of mortality, conferring a 57.0% increased risk of death. Survival analysis showed that diabetic subjects consistently had higher mortality than nondiabetics. However, the relative survival benefit of coronary artery bypass graft surgery versus medical therapy was comparable in diabetic and nondiabetic patients. Surgical therapy conferred a reduction in mortality of 44%.

Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial.

INTRODUCTION: Motilin-receptor agonists are prokinetics; whether they relieve the symptoms of functional dyspepsia is unknown. We aimed to test the efficacy of the motilin agonist ABT-229 in functional dyspepsia patients with and without delayed gastric emptying. METHODS: Patients were randomized with postprandial symptoms and documented functional dyspepsia by endoscopy (n=589 in intention-to-treat analysis). Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated 13C octanoic acid breath test. Patients were then further randomized within each strata, to receive one of four doses of ABT-229 (1.25, 2. 5, 5 or 10 mg b.d. before breakfast and dinner) or placebo for 4 weeks, following a 2-week baseline. The primary outcome was the assessment of change in symptom severity over the 2 weeks from baseline to final visit, based on a self-report questionnaire measuring severity on visual analogue scales. RESULTS: Baseline characteristics across the treatment arms were very similar. No significant differences in the upper abdominal discomfort severity score (maximum 800 mm) were observed for any active treatment arm vs. placebo (mean change from baseline -139, -141, -145, -160 and -134 mm for placebo, 1.25, 2.5, 5, and 10 mg, respectively, at 4 weeks by intention-to-treat). More patients on placebo reported a good or excellent global response than patients on 1.25 or 5 mg of active therapy (both P < 0.05). The results were very similar in those with and without delayed gastric emptying. Helicobacter pylori status did not predict response. Excluding patients with any baseline heartburn (total remaining n=240), ABT-229 10 mg was inferior to placebo in relief of upper abdominal discomfort. CONCLUSIONS: ABT-229 was of no value for relief of symptoms in functional dyspepsia, compared with placebo.

Epidemiologic research in an integrated regional medical care system: the Marshfield Epidemiologic Study Area.

To capitalize on Marshfield Clinic's advantages for population-based health research, we developed the Marshfield Epidemiologic Study Area (MESA). Marshfield Clinic is an integrated system consisting of a large multispecialty clinic and 23 affiliated clinics. Clinic physicians provide virtually all of the medical care, both inpatient and outpatient, for residents of the area. MESA consists of 14 ZIP codes in which over 95% of the 50,000 residents and most significant health events are captured in Marshfield Clinic databases, including all deaths, 94% of hospital discharges, and 92% of medical outpatient visits. MESA exemplifies the research potential of integrated medical care systems and the efforts required to realize that potential. Because it is representative of a defined population and provides an unselected sample of patients, MESA is well suited for epidemiologic research and research elucidating the clinical spectrum and natural history of diseases and the effectiveness of treatment.

Cervical cancer screening among women with and without hysterectomies.

OBJECTIVE: To compare the rate of Papanicolaou testing in a population-based sample of women with medical documentation of 1) total hysterectomy for benign conditions, 2) total hysterectomy for malignant conditions, and 3) hysterectomy with cervix intact to rates among women who had not had a hysterectomy. METHODS: The Marshfield Epidemiologic Study Area was used to identify a retrospective cohort of women with hysterectomies age-matched to women without hysterectomies. This study compares the Papanicolaou test rate per year (outcome) by hysterectomy status (exposure) for women with total hysterectomy for benign reasons (n=197), total hysterectomy for malignancy (n=75), supracervical hysterectomy (n=43), and no hysterectomy (n=315). RESULTS: Compared with women who did not have a hysterectomy (nonexposed), women with a hysterectomy (exposed) for benign reasons had significantly fewer Papanicolaou tests; on average, one less test every 3 years (mean difference=-0.34 tests/year, P < .001). Contrary to this, women with a malignancy-related hysterectomy had significantly more tests than their nonexposed counterparts (mean difference=0.87 tests/year, P < .001); nearly one additional test per year. Finally, women with supracervical hysterectomies had the same rate of testing as their nonexposed counterparts (mean difference=-0.03 tests/year, P=.62); on average, one test every 2.5 years. CONCLUSION: This study demonstrates that Papanicolaou testing rates vary by type and reason for hysterectomy. Women with hysterectomies for benign reasons may be receiving from two to three times as many tests as needed. Notably, women with intact cervices following hysterectomy have similar testing rates (one every 2.5 years) as women without hysterectomies. This has direct implications for leaving a woman's cervix intact given normal cytology at the time of hysterectomy.

Endothelin-1 expression in myenteric neurons cultured from rat small intestine.

Endothelin is a potent vasoactive peptide. More recently, endothelin-1 (ET-1) has been found in neural tissues such as spinal cord, brain and peripheral ganglion cells. Inagaki (Gastroenterology 101 (1991) 47) reported evidence of ET-1-like immunoreactivity in enteric neurons, but there are no reports of ET-1 peptide or mRNA expression specifically in myenteric neurons. Using a primary culture of myenteric neurons, we set out to evaluate ET-1 peptide and mRNA expression. Myenteric neurons were cultured using a dissection and enzyme dispersion technique. ET-1 reactivity was localized to neurons and ET-1 levels from cells and media were assayed by radioimmunoassay under a variety of media conditions or with depolarizing buffer or veratridine (75 microM). Prepro ET-1 mRNA expression was determined by Northern analysis of total RNA utilizing a rat ET-1 cDNA. ET-1 immunoreactivity was observed almost exclusively in myenteric neurons. Cells contained 0.78 pg/micrograms protein and did not vary with variations in media conditions. Basal release/secretion into media occurred but was not enhanced by depolarizing media or veratridine. High levels of ET-1 mRNA expression were identified. These results of high level constitutive expression of ET-1 linked with previous reports of ET-1 modulation of cholinergic intestinal smooth muscle contraction suggest a neuromodulatory role.

Differential increase in neuropeptide Y-like levels and myenteric neuronal staining in diabetic rat intestine.

Neuropeptide Y is a regulatory peptide found in adrenergic and non-adrenergic neurons. Diabetes, which may cause autonomic neuropathy, induces an increase in hypothalamic neuropeptide Y (NPY) levels; thereby we measured the effects of chronic diabetes on neuropeptide Y in the intestine. Rats were injected with streptozotocin (65 mg/kg) and maintained for up to 20 weeks. Another group of rats was injected with 6-hydroxydopamine (50 mg/kg) x 2 to induce sympathectomy. Ileum and colon were harvested and both whole and microdissected intestine were (1) stained with antibodies to neuropeptide Y, vasoactive intestine polypeptide, and neurofilaments or (2) extracted for neuropeptide Y radioimmunoassay. Neuropeptide Y levels were similar under all conditions in the colon, but there was a trend toward an increase in the diabetic whole ileum. NPY levels were significantly increased in the dissected myenteric plexus ileal layer in diabetics. We noted an increase in the number of neuropeptide Y and vasoactive intestine polypeptide immunoreactive myenteric neurons in diabetics and after 6-hydroxydopamine-induced sympathectomy. Diabetes, and to a lesser extent sympathectomy, induced an increase in ileal neuropeptide Y levels and neuropeptide Y-staining myenteric but not submucosal neurons. Altered tissue levels of neuropeptide Y may account for certain of the gastrointestinal disturbances commonly seen in diabetes.

Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force.

The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non-invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non-caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal-evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.

Risk factors for regret after tubal sterilization: 5 years of follow-up in a prospective study.

The Collaborative Review of Sterilization is a prospective, multicenter study that interviewed 7,590 women before they underwent tubal sterilization and then conducted yearly follow-up interviews that included questions on sterilization regret. These women contributed 26,641 observations (for up to 5 years after the procedure, 1978 to 1988) to an analysis of the presterilization characteristics most consistently associated with poststerilization regret. Young age at the time of sterilization was the strongest predictor of regret, regardless of parity or marital status; among women 20 to 24 years of age at sterilization, an average of 4.3% reported regret over the follow-up period. The rate of regret was significantly lower for women 30 to 34 years of age (2.4%).

Psychosocial factors in the epidemiology of coronary heart disease in women.

Although the study of coronary heart disease has provided a fruitful area of research for the psychosocial risk factors for disease, the amount of information among women is limited. Many of the psychological concepts tested in women have been developed from studies of men. The assumption that these psychological constructs (such as type A behavior) are pertinent to the psychology of women must be questioned. When women are included in studies of any disease, the questions asked of them must be applicable to their environment, behaviors, and psychological milieu. Because of the limited amount of data on women, it is difficult to draw conclusions regarding the relationships of psychosocial variables and the development of CHD. Several studies have indicated, however, that the change from a positive to an inverse relationship of SES to CHD in men has not been observed in women. Across various time periods and in different populations low SES is related to the occurrence of CHD in women. The reason for this is not known, and this is clearly an area for future investigations. Several measures of low social support have been found to be related to increase risk of CHD mortality and morbidity in women. A problem with this research is that each study demonstrated a different measure of social support to be the detrimental factor. This may be due to true differences between populations or may be a result of bias introduced from studying different age groups and different populations. It seems to be fairly clear that type A behavior, as measured in Framingham, is not related to definite CHD in women. The fact, however, that type A is related to anginal pain should not be minimized. These men and women are suffering from chest pain and are at increased risk to develop subsequent acute coronary events. For the most part, other personality variables, such as emotional lability, anxiety, depression, and neuroticism, have not been shown to be related to coronary disease in women. This may also be due to a true lack of effect or may be the result of not being able to separate the various manifestations of CHD and perhaps to limited sample sizes of women, which leads to a lack of power to detect at true effect. In the field of coronary heart disease epidemiology, as more studies include women and ask questions that are meaningful to them, a clearer understanding of the possible psychosocial etiology of disease will be possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Community intervention and trends in dietary fat consumption among black and white adults.

OBJECTIVE: This study assessed whether a state public health department could effectively implement an affordable nutrition intervention program at the community level. DESIGN: Cross-sectional data were collected via telephone surveys of 9,839 adults, aged 18 years or older, in 1987, 1989, and 1991 in two South Carolina communities. Nutrition education programs began in 1988 in one community. The other community served as a comparison site. We assessed and compared changes in community levels of dietary fat and weekly meat consumption, salt use, and nutrition promotion awareness with analysis of covariance regression techniques that included race, sex, and age as covariates. RESULTS: We observed favorable changes in most eating behaviors and levels of awareness in both communities. The intervention community experienced greater absolute changes that the comparison community in use of animal fats (-8.9% vs -4.0%; P = .02) and liquid or soft vegetable fats (+8.4% vs +3.6%; P = .04), and in awareness of restaurant nutrition information (+33.0% vs +19.4%; P = .0001). Although the primary type of dietary fat used differed between black and white respondents, we observed significant change among both groups. CONCLUSIONS: These results suggest that community-wide nutrition education programs may have augmented regional or national changes in dietary behavior among white and black adults in the intervention community.

Psychosocial risk factors for coronary heart disease in women.

The area of psychosocial risk factors for heart disease has not been as thoroughly studied in women as it has been in men. Findings from various studies are often conflicting or nonconclusive. This article summarizes the salient findings from various studies of social, behavioral, and psychological risk factors in women and delineates potential avenues for future research.

Systemic lupus erythematosus presenting initially with acute pancreatitis and a review of the literature.

A patient with systemic lupus erythematosus is reported whose initial clinical presentation was that of acute pancreatitis, confirmed by pancreatic isoamylase elevation and pancreatic enlargement on computerized tomography. A lack of a correlation with steroid therapy and a need to document pancreatitis in a multisystem disease like lupus with radiographic evidence as well as pancreatic isoamylase elevations is emphasized.

Presence of gonadotropin-releasing hormone (GnRH) receptor mRNA in rat myenteric plexus cells.

Idiopathic neuromuscular disease of the gastrointestinal tract (functional bowel disease) is thought to result from the malfunction of neurons within the enteric nervous system. Gonadotropin-releasing hormone (GnRH) analogs have recently been shown to organize the disordered motility patterns typical in these patients and to produce significant, long-term symptomatic improvement. To determine whether GnRH analogs might bind to an endogenous enteric nervous system GnRH receptor, reverse transcription-polymerase chain reaction (RT-PCR) was performed using cultured neonatal rat enteric neuron RNA and rat GnRH receptor primers. A PCR product of the predicted size was cloned and nucleotide sequence analysis demonstrated that the myenteric plexus PCR product encoded a portion of the GnRH receptor sequence previously identified in rat pituitary. These results suggest that cells in the myenteric plexus express GnRH receptors that may bind exogenously administered GnRH analogs. The expression of GnRH receptors in enteric neurons would provide an explanation for the effectiveness of GnRH analogs in treatment of idiopathic neuromuscular disease of the gastrointestinal tract.