[Ernst L. Wynder, M.D., Dr. Sc. h.c. (mult.), Dr. med. h.c.--1922-1999. A memorial].
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Germany↗
Biomedical subjects
I Hoffman
Publications and source records attributed to I Hoffman.
Prevalence of hepatitis C infection in Malawi and lack of association with sexually transmitted diseases.
To investigate the role of sexual transmission for Hepatitis C virus (HCV) we studied its prevalence in sub-Saharan Africa where sexually transmitted diseases (STDs) are prevalent. Overall, HCV prevalence was 3.9% and similar in 206 STD patients, 127 dermatology patients, and 100 blood donors. No association with HIV or syphilis was observed. Despite high prevalence of STDs, sexual transmission does not appear to significantly contribute to HCV transmission in Malawi.
Cohort Studies↗
Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen.
We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls, n = 14) in Malawi. We have previously shown that the presence of urethritis is associated with an eightfold increase in virus load in the seminal plasma compartment (M. S. Cohen et al., Lancet 349:1868-1873, 1997). The purpose of this study was to determine whether genital tract inflammation and its treatment caused genetic instability in cell-free HIV-1 populations. In a cross-sectional analysis at study entry, three-fourths of the STD and control subjects had multiple V3 populations in their blood while 60% of the STD subjects and 79% of the control subjects had multiple V3 populations in their semen. Overall, one-fourth of all of the subjects showed discordance between results with blood and semen specimens when samples were compared for the presence and absence of subpopulations. When differences in the relative levels of abundance of bands were also taken into account, two-fifths of all of the subjects showed discordance between the compartments. Among the subset of subjects in whom multiple virus populations could be detected, half showed discordance between the compartments. There were no differences between STD and control cohorts for these comparisons of the compartments in this cross-sectional analysis at study entry. Longitudinal analysis of the viral populations from two separate clinic visits over 1 to 4 weeks showed that the complexity of each V3 population as measured by Shannon entropy was different in blood and semen at the two time points, indicating that the blood and semen constitute different compartments for HIV-1. The seminal plasma compartment was more dynamic than the blood plasma compartment for the STD subjects who were treated for urethritis, with changes being noted in the presence or absence of V3-HTA bands in the semen of 29% of these subjects but in the blood of only 9% of these subjects. However, the changes were generally small. Overall, our results suggest that 40% of male subjects show discordance between seminal and blood viral populations and that the complexity of each V3 population was different between the two compartments. Both of these results point to the partial independence of the seminal compartment as a viral niche within the body.
Base Sequence↗
Carvedilol in class IV heart failure.
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Adrenergic beta-Antagonists↗
Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica.
Individuals presenting consecutively with genital ulcers in Kingston, Jamaica, underwent serological testing for human immunodeficiency virus (HIV) infection, chlamydial infection, and syphilis. Ulcer material was analyzed by multiplex polymerase chain reaction (M-PCR) analysis. DNA from herpes simplex virus (HSV), Haemophilus ducreyi, and Treponema pallidum was detected in 158 (52.0%), 72 (23.7%), and 31 (10.2%) of 304 ulcer specimens. Of the 304 subjects, 67 (22%) were HIV-seropositive and 64 (21%) were T. pallidum-seroreactive. Granuloma inguinale was clinically diagnosed in nine (13.4%) of 67 ulcers negative by M-PCR analysis and in 12 (5.1%) of 237 ulcers positive by M-PCR analysis (P = .03). Lymphogranuloma venereum was clinically diagnosed in eight patients. Compared with M-PCR analysis, the sensitivity and specificity of a clinical diagnosis of syphilis, herpes, and chancroid were 67.7%, 53.8%, and 75% and 91.2%, 83.6%, and 75.4%, respectively. Reactive syphilis serology was 74% sensitive and 85% specific compared with M-PCR analysis. Reported contact with a prostitute in the preceding 3 months was associated with chancroid (P = .009), reactive syphilis serology (P = .011), and HIV infection (P = .007). The relatively poor accuracy of clinical and locally available laboratory diagnoses pleads for syndromic management of genital ulcers in Jamaica. Prevention efforts should be intensified.
Adult↗
Trichomonas vaginalis as a cause of urethritis in Malawian men.
BACKGROUND AND OBJECTIVES: Trichomonas vaginalis is one of the most common sexually transmitted infections. In Malawi, rates of trichomoniasis in women are high. The prevalence of T. vaginalis infection in men is expected to be high but has not previously been documented. GOALS: We sought to determine the prevalence of trichomoniasis in Malawian men with and without urethritis, to evaluate a polymerase chain reaction detection assay for T. vaginalis in urethral swabs and to examine the effect of T. vaginalis infection on excretion of human immunodeficiency virus (HIV) in semen. STUDY DESIGN: Men presenting at the Sexually Transmitted Diseases (STD) and Dermatology Clinics in Malawi were enrolled in a cross-sectional study. We compared a polymerase chain reaction-based test for T. vaginalis detection with wet-mount microscopy and culture of urethral swabs. HIV serology was determined by enzyme-linked immunosorbent assay (ELISA), and HIV-1 RNA concentrations in semen were measured by quantitative nucleic acid sequence-based analysis. RESULTS: T. vaginalis was detected in 51 of 293 men. The estimated prevalence among symptomatic men was 20.8% and among asymptomatic men, 12.2%. Polymerase chain reaction performed with a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97) compared to wet-mount microscopy and culture. There was no difference in the rate of HIV seropositivity in men with and without T. vaginalis infection. However, in men with symptomatic urethritis, the median HIV RNA concentration in seminal plasma from men with T. vaginalis was significantly higher that in seminal plasma from HIV-positive men without trichomonas.
Animals↗
Specificity of dysuria and discharge complaints and presence of urethritis in male patients attending an STD clinic in Malawi.
OBJECTIVE: This study evaluated the specificity of discharge and dysuria for laboratory confirmed urethritis in symptomatic men presenting to an urban STD clinic in Malawi for treatment and returning for follow up evaluation. METHODS: Clinical treatment trial where consecutive consenting men with urethritis were enrolled and administered a questionnaire, examined, tested, and given one of five urethritis treatments with an efficacy range of 33-95%. Men returning for follow up were questioned, examined, and tested. RESULTS: The presence of both discharge and dysuria were highly specific for laboratory confirmed urethritis (over 90%). Compared with men who had complaints of both discharge and dysuria, men with complaints of dysuria alone were more likely to have reported prior treatment, 72% v 48% (p = 0.003), and less likely to have had gonorrhoea, 64% v 83% (p = 0.04). Men with complaints of discharge or dysuria without evidence of discharge were rare but half of them had documented urethritis. Among men who returned for follow up, 72% had no symptoms of either discharge or dysuria. However, among the 238 men with no symptoms at follow up, laboratory documented gonorrhoea occurred in 9% and non-gonococcal urethritis in 21%. DISCUSSION: In this population of men discharge or dysuria were specific symptoms for urethritis. The symptom of dysuria should be added as an entry criterion for evaluation for urethritis in the World Health Organisation's treatment recommendations. The high prevalence of asymptomatic infection at follow up in a population of men who received suboptimal antimicrobial therapy suggests that the most effective therapy available should be given at the first visit.
Adolescent↗
Sexually transmitted diseases are common in women attending Jamaican family planning clinics and appropriate detection tools are lacking.
OBJECTIVES: To assess sexually transmitted diseases (STD) among women attending Jamaican family planning clinics and to evaluate decision models as alternatives to STD laboratory diagnosis. METHODS: Women attending two family planning clinics in Kingston were interviewed and tested for syphilis seroreactivity using toluidine red unheated serum test and Treponema pallidum haemagglutination, for gonorrhoea using culture, for chlamydial infection using enzyme linked immunoassay, and for trichomoniasis using culture. Urine was tested with leucocyte esterase dipstick (LED). The women were treated based upon a clinical algorithm. Computer simulations explored the use of risk inclusive decision models for detection of cervical infection and/or trichomoniasis. RESULTS: Among 767 women, 206 (26.9%) had at least one STD. The prevalence of gonorrhoea was 2.7%; chlamydial infection 12.2%; gonococcal and/or chlamydial cervical infection 14.1%; trichomoniasis 11.5%; syphilis seroreactivity 5.9%. The clinical algorithm was 3.7% sensitive and 96.7% specific in detecting cervical infection. Detection of cervical infection and/or trichomoniasis was 63.5% sensitive and 60.6% specific using LED and 57.7% sensitive and 46.2% specific using the risk inclusive algorithm employed in Jamaican STD clinics. Either cervical friability or LED (+) or family planning clinic attender less than 25 years old with more than one sexual partner in the past year was 72.5% sensitive and 53.3% specific. The positive predictive values of the STD clinic algorithm, LED, and two developed decision models ranged from 25.0% to 33.4% to detect cervical infection and/or trichomoniasis in these women. CONCLUSION: STDs were quite prevalent in these mainly asymptomatic family planning clinic attenders. None of the evaluated decision models can be considered a good alternative to case detection using laboratory diagnosis. Appropriate detection tools are needed. In the meantime, available STD control strategies should be maximised, such as promotion of condom use; adequate treatment of symptomatic STD patients and partners; and education of women and men.
Adult↗
Indicators and the measurement of STD case management in developing countries. STD PI6&7 Working Group.
The paper reviews methodologies for measuring quality of sexually transmitted disease (STD) case management through facility based assessments. These include observations and interviews of providers, as promoted by the World Health Organization's Global Programme on AIDS, and some of the viable alternatives including patient exit interviews, mystery patients, record review and patient encounter forms with supervisory visits. The paper concludes that the alternative approaches are feasible in resource poor settings and that they provide crucial data for evaluation and continued program development.
Case Management↗
Development of an antimicrobial susceptibility surveillance system for Neisseria gonorrhoeae in Malawi: comparison of methods.
Susceptibility of Neisseria gonorrhoeae to gentamicin, the primary treatment for gonorrhea in Malawi since 1993, was determined by using agar dilution MICs, E-test MICs, disc diffusion, and clinical cure rate. Agar dilution MICs were slightly higher in 1996 than in 1993 isolates, with a concomitant drop in the clinical cure rate. E-test MICs were substantially lower than agar dilution determinations, with only 77.4% within 1 log2 concentration.
Anti-Bacterial Agents↗
S-phase induction by adenovirus E1A requires activation of cdc25a tyrosine phosphatase.
Adenovirus E1A proteins can induce quiescent cells to enter S-phase and also affect the expression of cellular genes including various cell cycle regulators. Here we show that human cdc25A, a tyrosine phosphatase involved in regulation of the G1/S-phase transition of the cell cycle, is a target of the adenovirus E1A protein in virus-infected human fibroblasts. Expression of E1A in quiescent fibroblasts leads to a rapid increase in cdc25A phosphatase activity and also increases both cdc25A and cyclin E gene expression. Inhibition of cdc25A function by antibody injection prevents virus-induced entry into S-phase. These results indicate that induction of high levels of cdc25A and its potential positive regulator cyclin E mediates the ability of E1A to induce S-phase in the presence of antiproliferative signals.
Adenovirus E1A Proteins↗
Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest.
Alpha interferon is a potent growth inhibitor of Daudi Burkitt's lymphoma cells. We show here that alpha-interferon signaling interacted simultaneously with several components of the basic cell cycle machinery, causing cells to enter into a state that had many features characteristic of the G0 state. Within a few hours after alpha-interferon treatment, cyclin D3 mRNA and protein levels dropped to undetectable levels and, in parallel, the activities of cyclin A- and cyclin E-associated kinases were significantly reduced. The latter resulted from the rapid alpha-interferon-mediated elimination of cdc25A, a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk2 in cyclin-cdk complexes. This regulation represents a novel mechanism through which an external inhibitory cytokine interacts with the cell cycle machinery. At later time points after alpha-interferon treatment, the levels of the 55-kDa slowly migrating hyperphosphorylated form of cyclin E and of cyclin A were also reduced. The antiproliferative effects were reversible, and cultures from which alpha interferon was removed reentered S phase after a lag that typically corresponded to approximately two doubling times. During this lag period, the expression of cyclin D3 and cyclin A, as well as of the cdc25A phosphatase, continued to be switched off, in spite of the removal of alpha interferon from the cell surface. In contrast, c-myc, which represents another downstream target gene that is subjected to negative regulation by alpha interferon, was relieved from suppression much earlier, concomitant with the decay in early signaling of the cytokine. The delayed pattern of cyclin reexpression provides evidence that alpha-interferon signaling imposes a G0-like state on this system.
Burkitt Lymphoma↗
Improvement of myocardial perfusion by short-term fluvastatin therapy in coronary artery disease.
Patients with hypercholesterolemia have impaired coronary and peripheral endothelial function. In patients with coronary artery disease, intracoronary acetylcholine infusion or mental stress causes paradoxical vasoconstriction, whereas lowering cholesterol restores endothelial function. The impact of lipid lowering by fluvastatin on myocardial perfusion in hypercholesterolemic patients with perfusion abnormalities was assessed by thallium-201 single photon-emission computed tomography (SPECT). A total of 22 patients were treated with fluvastatin (40 mg once daily) for 6 weeks, followed by 40 mg twice daily if low density lipoprotein cholesterol (LDL-C) levels were decreased by < or = 30%. During the 12-week treatment period, myocardial perfusion was measured by quantitative SPECT after standardized stress testing at baseline and after 12 weeks. Preliminary results for 17 male patients (mean age, 59.3 +/- 6.7 years) are presented here. LDL-C decreased from 191 +/- 26 to 146 +/- 28 mg/dL (p < 0.001). In ischemic segments myocardial perfusion increased by 30% (280 +/- 100 to 365 +/- 110 counts per matrix; p < 0.001). In normal segments perfusion increased by only 5% (451 +/- 74 to 473 +/- 69 counts per matrix; p < 0.005). The change in perfusion rate between ischemic and normal segments was significant (p < 0.005). In conclusion, LDL-C lowering with short-term fluvastatin therapy improved myocardial perfusion, especially in areas of ischemia. This suggests that improvement is due to functional restoration of coronary endothelium by fluvastatin, before anatomic regression of stenosis can occur following long-term treatment.
Adult↗
Chromosomal localization of the murine cadherin-11.
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Animals↗
Prevalence of genital infections in medical inpatients in Blantyre, Malawi.
The limited information on the prevalence of sexually transmitted diseases (STDs) in Malawi suggests that they are common. In studies in Lilongwe in 1989 and Blantyre in 1990, the prevalence of STDs was 4.4% in unselected outpatients and 42% in antenatal clinic patients respectively. Malawi is one of the countries worst affected by the HIV pandemic, with an estimated national HIV seroprevalence of 10% in the age group over 15 years and of 32% in pregnant women who attended antenatal clinics in Blantyre in 1993. Heterosexual intercourse is the main mode of HIV transmission in sub-Saharan Africa, accounting for up to 80% of cases of HIV infection. Concomitant genital ulcer disease facilitates sexual transmission of HIV. Non-ulcerative STDs may also play a role in facilitating sexual transmission of HIV but the evidence is less clear. The identification and treatment of people with STDs therefore presents an opportunity for decreasing HIV transmission. Queen Elizabeth Central Hospital (QECH) is the District Hospital for Blantyre, Malawi's largest city (about 500,000 population) and the tertiary referral hospital for Malawi's Southern Region. There are two general medical wards, one male and one female, to which about 11,000 patients were admitted in 1993. Bed occupancy can run at up to 150-200% and resources are limited. The top ten causes of admission are malaria, gastroenteritis, anaemia, pneumonia, dysentery, tuberculosis, AIDS, meningitis, hypertension and ascites. The leading causes of death are AIDS and tuberculosis.
Adolescent↗
Comparison of molecular and microscopic techniques for detection of Treponema pallidum in genital ulcers.
We compared the ability of direct immunofluorescent staining (DFA) and the PCR to detect Treponema pallidum in specimens from patients with genital ulcer disease. Touch preparations from 156 patients with genital lesions were fixed in acetone and stained with a fluorescein-labeled monoclonal antibody specific for the 37-kDa antigen of T. pallidum. After microscopic examination, the smear was removed from the slide with a swab. DNA was extracted with phenol-chloroform and precipitated with isopropanol. Ten microliters of the extracted DNA was amplified by PCR using primers for the gene encoding the 47-kDa protein of T. pallidum and hybridized to an internal probe. Twenty-two of 156 specimens were positive for T. pallidum by DFA and PCR, while 127 were negative by both methods, yielding a concordance of 95.5% (kappa = 0.84). Four specimens were positive by PCR and negative by DFA, while three specimens were negative by PCR and positive by DFA. The DFA-negative, PCR-positive specimens may have resulted from the presence of large numbers of leukocytes on the slides, obscuring visualization of treponemes. The DFA-positive, PCR-negative results were not due to inhibition of the PCR since purified T. pallidum DNA was amplified when added to aliquots of these specimens. Negative results in these specimens were most likely due to inefficient recovery of their DNA. These data suggest that DFA and PCR are equivalent methods for detection of T. pallidum on touch preparations of genital lesions. Further refinements of the PCR assay are necessary for it to significantly improve the detection of T. pallidum in genital lesions.
Antigens, Bacterial↗
Practice guidelines and reminders to reduce duration of hospital stay for patients with chest pain. An interventional trial.
OBJECTIVE: The acceptability, safety, and efficacy of practice guidelines have rarely been evaluated. Moreover, despite the recent development of guidelines and decision aids for patients admitted to coronary care and intermediate care units, few have been tested in clinical practice. DESIGN: A prospective, controlled clinical trial with an alternate-month design. SETTING: A large teaching community hospital. PATIENTS: Patients admitted to coronary care and intermediate care units with chest pain who were considered at low risk for complications according to a practice guideline (n = 375). INTERVENTION: Physicians caring for patients with chest pain who were at low risk for complications received concurrent, personalized written and verbal reminders regarding a guideline that recommended a 2-day hospital stay. RESULTS: Use of the practice guideline recommendation with concurrent reminders was associated with a 50% to 69% increase in guideline compliance (P < 0.001) and a decrease in length of stay from 3.54 +/- 4.1 to 2.63 +/- 3.0 days (0.91-day reduction, 95% CI, 0.18 to 1.63; P = 0.02) for all patients with chest pain considered at low risk for complications. The intervention was associated with a total (direct and indirect) cost reduction of $1397 per patient (CI, $176 to $2618; P = 0.03). No significant difference was found in the hospital complication rate between patients admitted to the hospital during control and intervention periods, and no significant difference was noted in complications, patient health status, or patient satisfaction when measured 1 month after hospital discharge. CONCLUSION: These results suggest that implementation of this practice guideline through concurrent reminders reduced hospital costs for patients with chest pain considered at low risk for complications. Further study of the guideline is warranted.
Aged↗
Temperature acceleration in cold oral stimulation.
This study measured the temperature acceleration of a cold probe as it contacts human tissue. Both the effects of touching a cold probe to the oral cavity were investigated. The results indicated a rapid warming pattern. This warming is effected first by temperature changes resulting from the probe being moved from ice into room temperature and second by the contact to oral mucosa. In fact, in some cases, the probe had reached minimal cold sensation levels by the time it reached the oral cavity. Results also indicated that 6 sec after the probe is lifted from the ice, the temperature closely approximates temperatures perceived as warm or at least neutral, but not cold.
Body Temperature↗