Infrequent syncope in a heavy vehicle driver

We present a case study of a truck driver with sinus node dysfunction diagnosed with the help of an implantable loop recorder more than 18 months after implantation. This case emphasizes that cardiogenic syncope may be very infrequent and its diagnosis can be elusive despite extensive testing.     

Enumerating leptospires using the coulter counter

The currently accepted gold standard for enumeration of leptospires is tabulation of organisms using a Petroff-Hausser counting chamber and dark-field microscopy, a technically demanding, time-consuming technique. Quantification of leptospires with a Coulter counter produced reliable and reproducible counts, comparable to the counting chamber. This experiment demonstrates that the faster, less technically demanding Coulter counter may be an alternative to determine numbers of leptospires.     

Sex differences in the effect of diabetes duration on coronary heart disease mortality

BACKGROUND: It is not known whether the coronary heart disease (CHD) mortality risk associated with recent (RDM; <10 years) or long-standing diabetes mellitus (LDM; > or =10 years) varies by sex. METHODS: The relationship between diabetes duration and CHD mortality was evaluated among 10 871 adults (aged 35-74 years at baseline) using the 1971-1992 National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. RESULTS: The CHD mortality rates per 1000 person-years in men with no myocardial infarction (MI) or diabetes, MI only, RDM only, LDM only, MI and RDM, and MI and LDM were 5.5 (95% confidence interval, 4.8-6.2), 15.2 (11.6-20.0), 13.2 (7.9-22.1), 11.4 (6.4-20.3), 36.0 (16.7-77.7), and 35.4 (14.0-89.7), respectively. The corresponding rates in women were 2.9 (2.5-3.3), 7.3 (5.0-10.8), 5.2 (3.5-7.7), 10.7 (7.5-15.5), 9.3 (4.3-19.9), and 21.6 (6.1-76.0), respectively. Compared with MI, the multivariate hazard ratios and their 95% confidence intervals (adjusted for age, race, smoking, hypertension, total cholesterol level, and body mass index) for fatal CHD in men with RDM, LDM, MI and RDM, and MI and LDM were 0.7 (0.3-1.3), 0.8 (0.4-1.4), 3.2 (1.4-7.4), and 2.4 (0.8-6.7), respectively. The corresponding ratios in women were 0.9 (0.6-1.3), 1.8 (1.1-3.2), 1.3 (0.5-3.5), and 1.6 (0.2-10.9), respectively. CONCLUSIONS: In men, RDM and LDM were associated with as high a risk for CHD death as MI. In women, although RDM had a CHD mortality risk similar to MI, LDM had an even greater risk. Because women with LDM are at very high risk for CHD mortality, current guidelines may need to be further refined to match intensity of treatment to risk in these women.     

Inhibition of the development of collagen-induced arthritis in rhesus monkeys by a small molecular weight antagonist of CCR5

OBJECTIVE: Collagen-induced arthritis (CIA) in the rhesus monkey is a nonhuman primate model of rheumatoid arthritis (RA). The close phylogenetic relationship between humans and the rhesus monkey makes this model useful for the preclinical safety and efficacy testing of new therapies that are inactive in animals more distinctly related to humans. In this study, we tested the therapeutic potential of a novel, small molecular weight antagonist of CCR5, SCH-X, in this model. METHODS: CIA was induced in 10 rhesus monkeys. The animals were allocated to receive SCH-X or saline as the control (n = 5 in each group). Treatment was initiated on the day of CIA induction and continued for 45 days. Monkeys were monitored before and 63 days after CIA induction for macroscopic signs of clinical arthritis, such as soft-tissue swelling and body weight. Furthermore, markers of inflammation and joint degradation were monitored to follow the disease course. RESULTS: Only 2 of 5 animals in the SCH-X-treated group displayed prominent soft-tissue swelling, compared with all 5 saline-treated monkeys. In addition to the suppression of joint inflammation, treatment with SCH-X resulted in a reduction in joint destruction, as demonstrated by lower rates of urinary excretion of collagen crosslinks, with confirmation by histology. Whereas in all saline-treated monkeys, marked erosion of joint cartilage was observed, this was absent in 4 of the 5 SCH-X-treated monkeys. CONCLUSION: The systemic effects of treatment with SCH-X were a suppressed acute-phase reaction (reduction in C-reactive protein level) in the 3 treated monkeys with CIA that remained asymptomatic, and an altered antibody response toward type II collagen. The results suggest that the CCR5 antagonist SCH-X might have a strong clinical potential for treatment during periods of active inflammation, as seen in RA.     

Multiple signaling defects in the absence of RIP140 impair both cumulus expansion and follicle rupture

The nuclear receptor corepressor RIP140 is essential in the ovary for ovulation, but is not required for follicle growth and luteinization. To identify genes that may be subject to regulation by RIP140 or play a role in ovulation, we compared ovarian gene expression profiles in untreated immature wild-type and RIP140 null mice and after treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin. Many genes involved in signaling, extracellular matrix formation, cell-cell attachment, and adhesion were aberrantly regulated in the absence of RIP140, varying according to the hormone status of the mice. Notable among these was the reduced expression of a number of genes that encode components of signaling pathways and matrix proteins required for cumulus expansion, a key remodeling process necessary for ovulation. Histological analysis confirmed that cumulus expansion in RIP140 null mice is reduced, oocyte detachment from the mural cell wall is impaired, and follicles fail to rupture in response to LH. Although the expression of many genes involved in cumulus cell expansion was reduced, there was a subset of genes involved in extracellular matrix formation and cell-cell interactions that was up-regulated and may interfere with ovarian tissue remodeling. We propose that widespread gene dysregulation in ovarian tissues in the absence of RIP140 leads to the anovulatory phenotype. This helps to define an important role for RIP140 in the regulation of multiple processes leading to ovulation.     

Electroconvulsive therapy in general hospital psychiatry: A focus on new indications and technologies

This paper documents the recent dramatic shift towards the delivery of psychiatric services in the general hospital setting and outlines the increasing number of special indications for electroconvulsive therapy (ECT). These include: delusional depressions; depressions which are not responsive to antidepressants; affective illness in geriatric populations, depression, mania or schizophrenia in patients who cannot tolerate medication side effects, and drug-refractory Parkinson's disease.Such technological advances as nondominant unilateral placement of electrodes, brief pulse electrical stimulation, and simultaneous ictal monitoring of EEG and EKG have increased the safety while reducing the side effects of the procedure. In that comparative studies show ECT to have safety and efficacy superior to antidepressant agents in the treatment of severe depressive illness, the author encourages physicians to consider this treatment which is becoming increasingly available through our general hospital services.     

Comparison of the antiviral effects of 5-methoxy-methyldeoxyuridine-5′-monophosphate with adenine arabinoside-5′-monophosphate

Methoxymethyldeoxyuridine-5′-monophosphate (MMUdR-MP) and arabinofuranosylade-nine-5′-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1^r (mutant resistant to MMUdR). MMUdR in combination with Ara-AMP showed additive activity; whereas the MMUdR-MP and Ara-AMP combination was antagonistic against herpes viruses. MMUdR in combination with Ara-A was synergistic in reducing the log virus yield. Cytotoxicity (microscopic lesions) was observed on exposure to MMUdR-MP and Ara-AMP at 450 and 90 μM, respectively. Rapidly proliferating RK-13 cells exposed to Ara-AMP (64 μM) were killed. In the same system, the cells surviving after incubation with MMUdR-MP (650 μM), multiplied at an almost normal rate.