Departments of medicine and international health

There is an emerging role in international health for departments of medicine that care to accept the challenge. Supervised medical rotations in the developing world and the care of culturally distinct immigrant populations provide unique opportunities to expand the scope of medical education while emphasizing a sensitive and humanistic approach to health care. The restraints imposed by diminished laboratory support and limited availability of drugs can foster reliance on diagnostic skills and the essential elements of therapy. Medical schools may elect to become involved in international health, but they must do so without becoming exploitative. Rotations of students, residents, and faculty in both directions should lead to productive interaction at both the clinical and research levels, for all participants.     

Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response

Background: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance.Aim: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated.Methods: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg⁻¹ day⁻¹) in a single dose at bed time (n=13) or in three divided gifts with meals (n=14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between.Results: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean±SEM) was 40.1±2.4 in the single dose group vs 40.8±2.8 in the multiple dose group (p=NS) and was positively correlated with biochemical improvement (AP: r=0.47, p=0.02; GGT: r=0.58, p=0.002; ASAT: r=0.67, p=0.002; ALAT: r=0.52, p=0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens.Conclusion: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.     

Trends in Alcohol-Related Mortality among New Mexico's American Indians, Hispanics, and Non-Hispanic Whites

Reduction of alcohol-related mortality is a national goal for health promotion and disease prevention. We conducted this analysis to determine whether trends in New Mexico's Hispanics, non-Hispanic Whites, and American Indians were consistent with national trends in alcohol-related mortality, and whether differences in drinking patterns could account for racial and ethnic differences in rates. Age-adjusted, race-specific, and ethnic-specific alcohol-related mortality rates and 95% confidence intervals were calculated for 5-year periods for 1958–1991 using New Mexico vital statistics data. We estimated the prevalence of acute and chronic at-risk drinking behaviors and abstinence from data collected by the Behavioral Risk Factor Surveillance System (BRFSS) for the period 1986–1992. We found that alcohol-related mortality rates varied substantially by race, ethnicity, sex, age, and calendar period. American Indians had the highest rates for both sexes. Rates increased sharply from the period 1958–1962 until the late 1970s and the early 1980s, and then began to decrease rapidly. However, during the most recent decade, the rates have followed contrasting trends in the three ethnic and racial groups. Although rates have continued to decline among non-Hispanic Whites, rates for Hispanics and American Indians have not declined, and still remain substantially higher than rates during the 1958–1962 period. Differences in at-risk drinking behaviors reported to the BRFSS do not explain the contrast in race-specific and ethnic-specific mortality rates. Although progress has been made in reducing national per capita alcohol consumption and alcohol-related mortality, certain high-risk racial and ethnic groups may not be sharing in the progress.     

Definitive management of rectal cancer by contact (endocavitary) irradiation

In a retrospective review, 62 patients treated for rectal cancer by contact (endocavitary) irradiation at The Cleveland Clinic Foundation were analyzed. This treatment modality delivers high dose, low penetration irradiation to a rectal cancer by direct contact of a 50 KV x-ray source through a special proctoscope. Cancers selected for this treatment include small (3 cm or less), mobile tumors without presacral lymphadenopathy that are within reach of digital examination and are well- or moderately well-differentiated adenocarcinomas. Between 1973 and 1984, 62 patients (37 males, 25 females) were treated—46 by contact irradiation alone and 16 by contact irradiation after excisional biopsy. The median tumor dose was 12,000 rads administered in four fractions at monthly intervals. Mean follow-up was 31 months. Fiftysix patients (90 percent) were disease-free at the time of review or death (ten died from unrelated causes). Eleven patients (18 percent) developed local recurrence but eight of these without distant metastases were rendered disease-free by other treatment—six by surgical resection and two by further radiotherapy. Mean time since secondary treatment is 20 months. Three patients are alive with incurable disease and three have died from cancer—in three of these six patients there was no evidence of local disease. Ulcerated tumors developed local recurrence in five of 17 cases (29 percent) while polypoid tumors recurred locally in six cases (14 percent). Morbidity from the treatment was minor in nature. It is suggested that contact (endocavitary) irradiation is effective treatment for carefully selected cases of rectal cancer Read at the meeting of the American Society of Colon and Rectal Surgeons, Washington, D.C., April 5 to 10, 1987.     

Pathophysiology and management of unstable angina

Significant progress has been made in recent years in unraveling the dynamic mechanisms involved in the production of unstable angina. This knowledge, and advances in medical and interventional therapy allow the formulation of treatment strategies aimed at specific pathogenic mechanisms and promise to reduce mortality and morbidity. This review covers the diagnosis, pathogenesis, risk stratification, and therapy of unstable angina.     

Adverse effects of direct current cardioversion on cardiac pacemakers and electrodes Is external cardioversion contraindicated in patients with permanent pacing systems?

Use of pacing in sick sinus syndrome and recent developments in pacemaker therapy for intermittent atrial fibrillation raise the question of whether external electrical cardioversion should be used for termination of atrial fibrillation. This paper analyzes three cases of pacemaker and/or electrode dysfunction appearing after direct current (DC) cardioversion for termination of atrial fibrillation. Despite similar conditions during cardioversion in all cases, different dysfunctions reflecting damage to the pulse generator and/or a rise of the stimulation threshold in both, atrial and ventricular leads, have been observed. The possible mechanisms for these effects are discussed and recommendations for the management of cardioversion in patients with permanent pacemaker systems are given.     

High levels of complement-activation capacity in sera from patients with cystic fibrosis correlate with high levels of IgG3 antibodies to Pseudomonas aeruginosa antigens and poor lung function

Heat-stable opsonins from sera of cystic fibrosis (CF) patients were investigated for their ability to activate complement. Complement activation by Pseudomonas aeruginosa after opsonization with patient serum was examined in a complement-consumption assay. Absorption of patients' sera with formalin-treated and boiled bacteria removed specific antibodies and the complement activation decreased. We found a positive correlation between serum complement-activation ability and IgG3 antibody levels to lipopolysaccharide (LPS), alginate, and a crude mixture of P. aeruginosa antigens (sonicate) in a group of patients with high levels of anti-Pseudomonas precipitins. In the same group of patients a significant negative correlation was found between complement activation and lung function. Eighteen patients have been followed longitudinally with serum samples covering the pre-infection, the early, and the late stages of chronic infection. Patients with poor lung function showed significantly higher levels of complement-activation capacity. We conclude that patients with high levels of specific IgG3 antibodies are able to induce a high level of complement activation and then develop more aggressive pulmonary tissue damage, probably secondary to local immune complex formation. Pediatr Pulmonol. 1995; 20:71–77 . © 1995 Wiley-Liss, Inc.     

HDL-cholesterol reductions associated with adult growth hormone replacement

OBJECTIVE: To study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk. PATIENTS: Thirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 +/- 11.8 year; mean +/- SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start. MEASUREMENTS: Fasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)-cholesterol, HDL-subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF-1. LDL-cholesterol was calculated using the Friedewald formula. RESULTS: Compared to placebo, 6 months treatment with hGH therapy resulted in increased IGF-1 (37.6 +/- 4.1 vs. 14.0 +/- 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL-cholesterol concentration from baseline to 6 months (0.97 +/- 0.08 to 0.76 +/- 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo -26 (-340 to 82), median and range, active -4 (-586 to 212) mg/l). There was no change in total cholesterol, LDL-cholesterol, triglycerides or proportion of HDL subfractions. CONCLUSIONS: Treatment with hGH can reduce serum HDL-cholesterol concentrations. Further investigation of this is required.     

Ventricular dysplasia. Nosology and sudden death

The arrhythmia generating dysplasia of the right ventricle is a congenital anomaly suggesting a hereditary substratum. It usually manifests itself as follows: a young patient, with recurrent episodes of ventricular tachycardiac. There is no "pathognomonic sign" of dysplasia. The latter may only be determined by anatomical examination of the heart, macroscopically as well as microscopically. The most difficult differential diagnosis concerns minor or localized forms of dilated idiopathic myocardiopathy or sequelae of myocarditis with ventricular tachycardia originating in the right ventricle. It seems, currently, more appropriate to talk about "arrhythmia generating syndrome of the right ventricle" rather than arrhythmia generating dysplasia of the right ventricle, in these particular cases. The arrhythmia generating syndrome of the right ventricle could cause a sudden death in these young patients, especially during a violent physical exercise or practise of sports. The current nosological classification is based on an experience acquired by comparing a few isolated cases. The search for late potentials by summation-mean measurements and nuclear magnetic resonance could provide a new diagnostic approach.     

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

BACKGROUND: We previously demonstrated that short-cycle structured intermittent therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum levels of lipids. Adherence to such a regimen may be problematic for certain patients. METHODS: Eight patients with a history of receiving combination ART that maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily SIT regimen of didanosine, lamivudine, and efavirenz. RESULTS: For 7 patients, suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks. Four patients with adequate samples had no evidence for an increase in plasma viremia for up to 72 weeks, by use of an assay with a limit of detection of <1 copy/mL. The lack of rebound viremia may be the result of the persistence of efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7 patients. There was no significant change in CD4(+) T cell counts or serum hepatic transaminase or lipid levels. CONCLUSION: A once-daily short-cycle SIT regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell counts. Such a regimen may have importance in resource-limited settings where the monetary cost of continuous ART is prohibitive.