Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine.

BACKGROUND: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory. METHODS: We studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.

Lower extremity blood flow in healthy men: effect of smoking, cholesterol, and physical activity--a Doppler study.

Tobacco smoking is one of the principal risk factors of peripheral arterial disease (PAD); cholesterol level has a lesser impact. The effect of leisure-time physical activity (LTPA) has not been studied in depth. The aim of this study was to determine the relative effects of smoking, total cholesterol, and leisure-time physical activity on blood flow parameters in the lower extremities of healthy middle-aged men with no prior symptoms or diagnosis of PAD. The authors examined 130 men, aged 40-65 years, free of known arterial disease and hypertension. The men had either a total cholesterol concentration of < 5.7 or > 7.0 mmol/L, and were either smokers or nonsmokers. LTPA was addressed by a questionnaire. Ankle-brachial index (ABI) was calculated and Doppler examination of the femoral artery was performed before and after an exercise test. Tobacco smoking related significantly to abnormal ABI and Doppler results (odds ratio [OR] 2.42) while the total cholesterol level did not. LTPA had a favorable effect (OR 0.51). Abnormal ABI response was greatest in smokers with high total cholesterol (p < 0.01). Tobacco smoking is a significant risk factor for abnormal ABI response and blood flow abnormalities in healthy men. Regular physical activity has a measurable protective effect. An abnormal ABI suggests early atherosclerosis and indicates risk factor assessment and physician intervention.

[Changes in myocardial infarction incidence and mortality in Iceland.].

INTRODUCTION: According to public health reports ischaemic heart disease was an uncommon cause of death in Iceland at the beginning of the last century. This death rate increased steadily until the ninety-eighties whereafter it leveled off and started to decline. The objective of the present study is to assess in detail the changes in myocardial infarction attack, incidence and death rate as well as case fatality. MATERIAL AND METHODS: Crude death rate from ischaemic heart disease is available from the Statistical Bureau of Iceland from 1911 to 1996 and age and sex standardized death rate from 1951. In this paper, however, the material is mainly from the MONICA Project, a multinational study of myocardial infarction under the auspices of the World Health Organization. The study, in which Iceland has participated since 1981, registers all myocardial infarctions in people aged 25-74 years in the whole country. The registration is performed according to standardized criteria and external quality control was applied throughout by WHO designated quality control centers. The registration now covers the period 1981-1998. RESULTS: The crude death rate in ischaemic heart disease in both sexes combined increased steadily until about 1980 when it accounted for about 30% of deaths. Age and sex specific death rate from these diseases increased from 1951 to about 1970, leveled off for the next 10 years and has since decreased. The MONICA data show a decline of death rate from myocardial infarction of 57% in men aged 25-74 during 1981-1998 and a 51% decline in women. Incidence rate has declined by 40% and 34% in men and women respectively and attack rate by 49% and 44%. Incidence, death rate and case fatality in myocardial infarction in Iceland compares favorably with other European countries. CONCLUSIONS: Myocardial infarction incidence and death rates have been declining in Iceland during the last two decades. Case fatality is now among the lowest compared to other countries. Preventive measures are most likely to further reduce incidence and death rates in myocardial infarction in Iceland.

[Thyrotoxicosis and coexistent diseases in atrial fibrillation.].

OBJECTIVE: To evaluate the prevalence of thyrotoxicosis and coexistent diseases in patients with atrial fibrillation admitted to a general medicine ward. MATERIAL AND METHODS: All patients with the discharge diagnosis of atrial fibrillation were studied. The study design was retrospective for the years 1993-1994 and prospective from April 1995 through December 1997. Information on thyroid function tests was obtained from medical records in the retrospective part, but TSH, T4 and T3 were measured for patients admitted during the prospective part. Coexistent diseases were recorded. RESULTS: Atrial fibrillation was diagnosed in 167 patients (58 in the retrospective part and 109 in the prospective part). Males were predominant (59.3%) and the average age was 73.7 years (span 26-100). Adequate information on thyroid function tests was available for 135 patients (58.6% of the retrospective part and 92.7% of the prospective part). 24 (17.8%) had abnormal thyroid function tests, predominantly women (71%). Ten had an isolated elevation of TSH, seven an isolated depression of TSH, two hypothyroidism and five other abnormalities. Hypertension was the most common coexistent disease (76 of 167 patients (45.5%). Ischemic heart disease was found in 44 (26.3%) and valvular heart disease in 27 (16.2%). No known coexistent disease was found in 32 (19.2%). CONCLUSIONS: 1) Thyrotoxicosis is rare in patients with atrial fibrillation who are admitted to a general medicine ward. Routine measurement of thyroid function tests in this patient population is therefore not warrented. 2) Unspecific abnormalities of thyroid function tests are common and are most likely due to diseases outside the thyroid gland or medications. 3) Hypertension, ischemic heart disease and heart valve disease are the most common coexistent diseases in this group of patients.

Effects of leisure-time physical activity and ventilatory function on risk for stroke in men: the Reykjavík Study.

BACKGROUND: Stroke is a major cause of illness, death, and health expenditures. Leisure-time physical activity may reduce the risk for stroke. OBJECTIVE: To examine the association of leisure-time physical activity and pulmonary function with risk for stroke. DESIGN: Prospective cohort study. SETTING: Reykjavík, Iceland. PARTICIPANTS: 4484 men 45 to 80 years of age followed for a mean (+/-SD) of 10.6 +/- 3.6 years. MEASUREMENTS: Patients underwent physical examination, blood sampling, and spirometry and completed a questionnaire about health and exercise. Computerized hospital records were used to identify strokes, and the Icelandic National Registry was used to identify deaths. RESULTS: New stroke developed in 249 men (5.6%) (hemorrhagic stroke in 44 [18%] and ischemic stroke in 205 [82%]). In a multivariable hazard analysis that controlled for known risk factors for cerebrovascular disease, leisure-time physical activity maintained after 40 years of age was associated with a reduced risk for stroke (relative risk, 0.69 [CI, 0.47 to 1.01] for total stroke and 0.62 [CI, 0.40 to 0.97] for ischemic stroke). Risk for stroke increased with diminished ventilatory function (FVC or FEV1) (relative risk, 1.9 [CI, 1.06 to 3.25] for the lowest compared with the highest quintile). CONCLUSION: Middle-aged men who participate in leisure-time physical activity and have good pulmonary function seem to have a lower risk for stroke than men who are not active or have diminished pulmonary function.

Fatalities from myocardial infarction in Nordic countries and Lithuania. The MONICA Investigators.

AIM: To investigate fatalities from myocardial infarction at 28 days and one-year among patients aged 35-64 years in the Nordic and Lithuanian centres participating in the World Health Organization MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) Project. METHODS AND RESULTS: Altogether 9100 myocardial infarction events registered according to the protocol of the MONICA Project were included in the study. For these events, one-year follow-up was carried out using routine mortality statistics. Fatalities were expressed as age-standardized means per year for a 3-year period from the mid-1980s. The myocardial infarction fatalities at 28 days (including out-of-hospital deaths) in the eight participating populations varied among men, between 36.5% (95% confidence interval 32.6-40.4%) in Iceland and 54.6% (51.2-57.9%) in Kaunas, Lithuania, Among women, it varied from 32.4% (26.4-38.4%) in Iceland to 57.5% (51.8-63.2%) in Glostrup, Denmark. More than half of this mortality occurred suddenly and the patient did not reach hospital alive. Fatalities for the period from day 28 to one year varied among men, from 5.3% (2.9-7.6%) in Iceland to 10.9% (8.0-13.8%) in North Karelia, Finland, and among women from 3.5% (0.4-6.5%) in Kuopio, Finland, to 13.5% (7.2-19.7%) in Glostrup, Denmark. CONCLUSIONS: Approximately half of the myocardial infarction patients died within one year after the onset of the attack and half of those who died, died out-of-hospital. While the myocardial infarction fatalities differed considerably between the participating populations, differences of this magnitude are unlikely to be totally explained by differences in the registration procedures. Further comparisons of acute coronary care and secondary prevention measures are warranted.

[Acute myocardial infarction in Iceland 1982-1983. Prognosis and risk factors in the pre-thrombolytic era.].

This nationwide study describes the short- and longterm outcome of acute myocardial infarction in Iceland 1982-83 prior to the routine use of aspirin and thrombolytic therapy. The material consists of 486 cases of acute myocardial infarction, 390 men and 96 women aged 25-64 years. Death prior to hospitalization occured in 124 cases but hospital treatment was given to 287 men and 75 women. Evidence of a previous myocardial infarction was found in 22%. An anterior myocardial infarction was present in 29% and an inferior myocardial infarction was present in 31%. The 28 day mortality was 12.4% but the long-term mortality over a mean of 7.1 year was 35.9%. The principal determinants of the risk of death in both sexes were ST-segmentelevation on admission ECG with a relative risk of 1.78, the use of digitalis and diuretics prior to the onset of an acute myocardial infarction with a relative risk of 1.89 and 1.72. Those treated with inotrophics in hospital had a relative risk of 2.81 but patients treated with anticoagulants in hospital had an improved prognosis with a relative risk of 0.45 but nitrates and b-blockers did not affect the outcome.

Long-term prognosis of different forms of coronary heart disease: the Reykjavik Study.

BACKGROUND: While coronary heart disease (CHD) is a serious and often fatal disease the prognosis is variable and major effort has been invested in risk stratification. The purpose of this study was to examine the relation between long-term prognosis and risk factors in different clinical categories of CHD. METHODS: A general population sample of 9141 men, aged 34-79 at entry into the study was divided into six groups with respect to manifestations of CHD at entry: I. Symptomatic infarction. II. Silent or unrecognized infarction. III. Angina pectoris with ischaemic changes on ECG. IV. Angina without ischaemic changes. V. Angina by Rose questionnaire but not confirmed by a physician. VI. No manifestations of CHD. RESULTS: The risk factor profile varied considerably between the different categories and by life-table analysis marked differences in survival were demonstrated between the groups. The risk factors maintained their detrimental effects on prognosis in the presence of CHD. Thus, age, serum total cholesterol, impaired glucose tolerance and smoking were found by Cox's regression to be statistically significant independent risk factors of CHD mortality among men having manifestations of CHD (groups I-V). Furthermore, the composite risk score, a measure of the overall risk factor exposures had marked effect on the prognosis of the various CHD groups. When the comprehensive risk factor score for both CHD mortality and all-cause mortality was accounted for marked differences persisted in the long-term prognosis. Compared to those without CHD the infarct groups had about a 7.6- and 3.7-fold risk of dying from CHD and all causes respectively. Those with angina had from 2.5- to 3.2-fold risk of CHD mortality and 1.7- to 2.2-fold risk of all-cause mortality depending on the subgroup of angina, again compared to those without manifestations of CHD. CONCLUSION: Different categories of CHD had different risk factor profiles and the long-term prognosis resulted from a complex interplay between those factors and the diagnostic category of CHD. The risk factors maintained their detrimental effects on prognosis in the presence of CHD and after accounting for the comprehensive risk factor score marked differences persisted in the long-term prognosis, being worst for those having suffered a myocardial infarction, either symptomatic or silent.

Anorectal function of children with neurological problems. I: Spina bifida.

Anorectal function was assessed with anorectal manometry in 45 children with spina bifida (21 girls and 24 boys, mean age 11 1/2 years). 24 enuretic children served as controls. The pressure in the first and second centimeters of the anal canal was lower among index children than controls and also lower among those with high spinal lesions compared with those with low lesions. Rectal activity (rectal sensation and trace appearance) during rectal distension appeared to be reduced among index children; sensation was particularly poor among those with high spinal lesions. Manometry may be useful in children with spina bifida as it provides a clearer understanding of sphincter function and leads to a more rational approach to the management of bowel problems.

Anorectal function of children with neurological problems. II: cerebral palsy.

In response to the frequent complaint of difficulties with defecation experienced by children with cerebral palsy, 34 children (13 girls and 21 boys, mean age 10 years) with cerebral palsy were investigated by questionnaire and anorectal manometry. 24 enuretic children served as controls for the anorectal manometry. Constipation affected 26 of 29, defecation distress eight and faecal incontinence 16 of the index children, but incontinence was mild in most cases. Index children had a low resting pressure in the first centimetre of the anal canal, slow anal rhythmical activity and a pressure increase in the first centimetre during maximum rectal distension. These findings suggest anal sphincter and/or pelvic floor muscle incoordination, but no evidence of abnormal rectal function. The authors conclude that surgical intervention was not indicated for the index children, but that medical treatment could be improved.

The prevalence of hypertrophic cardiomyopathy in men: an echocardiographic population screening study with a review of death records.

The purpose of this study was to estimate the prevalence of hypertrophic cardiomyopathy (HCM) in 3607 men from the Reykjavik study of 1979-81. Of these, 452 men had an abnormal (group A) and 3155 a normal electrocardiogram. An echocardiographic control group of 128 men was selected from cohorts with a normal electrocardiogram (group B). Until 1987, 189 deaths had occurred, 59 from group A and 130 from cohorts with a normal ECG including 4 from group B. To identify subjects with HCM, survivors of groups A and B were examined by echocardiography and by review of all autopsy data and death certificates. HCM was found in 14 subjects from group A but none in group B. Two additional cases were found at autopsy in cohorts with a normal ECG. The prevalence of HCM in men with an abnormal and normal ECG was 3.6% and 0.8%, respectively. The overall prevalence was calculated to be 1.1% with a 95% confidence interval of 0.3-3.2%. Men with HCM reported more symptoms than others in groups A and B (P < 0.05-0.001). 25% were without symptoms. Asymptomatic ventricular arrhythmias were detected by Holter monitoring in 45% of men with HCM. The total annual mortality was 1.6% compared with 0.5% in the group with a normal ECG (P < 0.001).

Predictive value of apolipoproteins in a prospective survey of coronary artery disease in men.

Some studies have suggested that measurements of apolipoproteins may be valuable in the clinical assessment of susceptibility to coronary artery disease, over and above the lipoprotein lipids. Only a few of these studies have been prospective in nature and further knowledge is therefore needed to clarify the issue. The independent prognostic value of apolipoproteins (apo-B, apo-AI and apo[a]) with regard to coronary artery disease was estimated from a prospective survey among 1,332 randomly selected Icelandic men, aged 45 to 72 years, participating in a health survey from 1979 to 1981. The group was followed for 8.6 years, and during that period 104 men had fatal or nonfatal myocardial infarction. The Cox's proportional hazards model was used to estimate the significance of independent variables. The results of multivariate analysis showed that apo(a) was a significant independent risk factor (odds ratio 1.22 for 1 SD), but apo-AI was a stronger negative risk factor (odds ratio 0.70 for 1 SD). Apo-B was a highly significant risk factor in a univariate analysis, but not in a multivariate analysis when serum cholesterol was included. Previous population surveys in Iceland have confirmed the importance of cigarette smoking, cholesterol, triglycerides and blood pressure as risk factors for coronary artery disease. The present results illustrate additional importance of apo-AI and apo(a) concentrations in predicting coronary artery disease among Icelandic men, whereas apo-B did not contribute anything further to the prediction than serum total cholesterol.

Perianal appearances associated with constipation.

The perianal appearances were studied prospectively of 136 constipated children (mean age 3.9 years, 67 boys, 69 girls). Anal dilatation, fissures, tags, warts, perianal oedema, redness, blueness, and veins were recorded. It was noted whether dilatation occurred immediately or at 30 and 60 seconds with the buttocks minimally separated, and on subsequent firm lateral traction of the buttocks. The degree of faecal loading was assessed in all children. Anal dilatation was found in 24 (18%) and first appeared on lateral traction in eight (6%). In three quarters of the children with dilatation faecal loading or perianal signs were present. Fissures were found in 35 (26%) children and tags in seven (5%). Perianal redness was more likely to be associated with fissures, and blueness with dilatation. We conclude that there are no pathognomonic perianal signs in childhood constipation and that the technique of anal examination should be standardised.

Fecal isolation of Pseudomonas aeruginosa from patients with cystic fibrosis.

Fecal isolation of Pseudomonas aeruginosa was observed in 8 of 10 patients with cystic fibrosis who at the time of sampling also exhibited colonization of the respiratory tract. In contrast, P. aeruginosa cells were isolated at low frequency (9.1%) from the stools of 44 patients with cystic fibrosis with no previous history of chronic colonization. The results of this study suggest that the gastrointestinal tract is not a significant chronic reservoir of P. aeruginosa prior to pulmonary colonization.

Carbachol depolarizes and accelerates pacemaker activity in the sinoatrial node of chicks treated with pertussis toxin.

Carbachol hyperpolarized the membrane of sinoatrial (SA) node cells from saline-treated chicks in a concentration-dependent fashion (10(-8)-10(-4) M). The rate of spontaneous impulse generation diminished in the presence of carbachol; complete inhibition (arrest) occurred at 10(-6) M. The hyperpolarization and negative chronotropic effect of carbachol (10(-8)-10(-6) M) were prevented by pretreatment of chicks with islet activating protein. Treatment with islet activating protein, which inactivates the guanine nucleotide binding proteins Gi and Go unmasked "stimulant" effects at high (greater than or equal to 10(-5) M) concentrations of carbachol. The stimulant effects included membrane depolarization and an acceleration of spontaneous impulse generation detected at 10(-5) and 10(-4) M carbachol, respectively. Because the depolarization and acceleration produced by carbachol occurred in the presence of propranolol, they are independent of endogenous catecholamines. As with the inhibition of the SA node, the stimulation by carbachol was mediated by muscarinic receptors and prevented by atropine. We speculate that the depolarization of SA node cells by carbachol, as in left atrium, may be mediated by products of phosphoinositide metabolism because phosphoinositide hydrolysis is activated at the same concentrations (greater than or equal to 10(-5) M). The ionic mechanism for the carbachol-induced depolarization and acceleration in SA node cells is not known. By analogy with results in left atrial cells from islet activating protein-treated animals, the mechanism would involve an increased intracellular Na+ activity and stimulation of Na-Ca exchange.

The clinical spectrum of tricuspid regurgitation detected by pulsed Doppler echocardiography.

The clinical diagnosis of tricuspid regurgitation (TR) is often difficult. Two-dimensional pulsed Doppler echocardiography offers a sensitive and specific method for detecting and semi-quantitating tricuspid regurgitation. The clinical, radiographic, radionuclide, echocardiographic, and when available, the right cardiac catheterization findings were evaluated in 36 patients with a diagnosis of tricuspid regurgitation by pulsed Doppler. Ten healthy subjects served as controls. The underlying cardiac cause was rheumatic heart disease in 7 (20%), ischemic heart disease in 12 (33%), dilated cardiomyopathy in 5 (14%), hypertensive heart disease in 2 (5%), aortic valve stenosis and/or regurgitation in 3 (8%), mitral valve prolapse with mitral regurgitation in 1 (3%), and congenital heart disease in 6 (17%). Seven patients (19%) had a temporary or permanent transvenous right ventricular pacing wire. A systolic murmur was heard in 29 patients (81%) with 16 (46%) having an elevated jugular venous pressure. Tricuspid regurgitation was clinically suspected in only 2 patients (6%). Isolated tricuspid regurgitation was uncommon, seen in 6 patients (17%), and usually secondary to congenital heart disease, ischemic heart disease, with the use of a transvenous pacing wire and following mitral valve replacement. Right cardiac catheterization was performed in 10 patients, of which 7 demonstrated elevated right atrial and pulmonary artery pressure. Pulsed Doppler echocardiography offers a practical and accurate method of detecting and evaluating the severity of tricuspid regurgitation. Tricuspid regurgitation is generally a functional disorder, and frequently occurs in association with left sided valvular heart disease, cardiomyopathy or congenital heart disease.