Reconsidering the pathogenesis of ocular toxoplasmosis

PURPOSE: To review recent observations regarding the sources of Toxoplasma gondii infection and rates of ocular involvement in cases of infection acquired after birth, and to reconcile them with older observations and widely held beliefs about the pathogenesis of ocular toxoplasmosis. METHOD: A review of pertinent reports from the medical literature. RESULTS: There are several potential sources and routes of infection, including inhalation of spores and ingestion of contaminated drinking water, that were previously unrecognized. Ocular involvement in cases of acquired infection appears to be more common than heretofore believed. A variety of host and parasitic factors may influence rates of ocular infection and the characteristics of ocular disease. CONCLUSIONS: The scars from which recurrent toxoplasmic retinochoroiditis arise may be the result of remote, acquired infections in many cases, rather than the residua of congenital infections, as commonly assumed. A better understanding of the epidemiology of T. gondii infection, as well as the host and parasitic factors that influence disease presentation, is important for developing strategies for prevention and management of ocular toxoplasmosis.     

Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers

Montelukast, a cysteinyl leukotriene receptor antagonist, is being developed for the treatment of asthma and related diseases. This study was designed to evaluate whether montelukast at clinically used dosage levels would interfere with the anticoagulant effect of warfarin. In a two-period, double-blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a 12-day treatment with montelukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration-time curves and peak plasma concentrations of either R- or S-warfarin. However, slight but statistically significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half-life of the less potent R-warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio (INR) for prothrombin time (AUC0-144 and INR maximum). The results of this study suggest that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.     

Effect of toxic thioureas on resistance of rats to growth in the lungs of intravenously and intratracheally seeded tumour cells.

Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.     

Relationship of Body Core Temperature and Warm-up to Knee Range of Motion

This study examined the effects of submaximal, treadmill exercise-induced body core temperature (BCT) increase on selected knee range of motion (ROM). Twenty males, 18-35 years old, were tested (randomized crossover) for ROM, BCT, and heart rate (HR), followed by either Treatment I (20 minutes of rest) or Treatment II (20 minutes of submaximal running). The two treatments were subsequently followed by a two-minute passive stretch. Range of motion was assessed before and after passive stretch treatment intervention. Treatment means differed for BCT and HR (p < 0.001) but not for ROM after exercise intervention. It was concluded that 20 minutes of exercise increased BCT (>1 degrees C) but had no effect on knee ROM. J Orthop Sports Phys Ther 1991;13(3):126-131.     

Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers.

In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, "null cells", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents.     

Workshop: manpower planning to meet needs

Ms. Holland describes the building of a data base which can be updated and used to plan for manpower needs. She includes an analysis of the present work force, of the organizational structure and of the demand situation as well as productivity trends. Her skills inventory can be applied to a large variety of institutions.     

The three systems: a conceptual way of understanding nocturnal enuresis

Childhood nocturnal enuresis has traditionally been regarded as a multifaceted problem with a variety of treatment interventions. This paper proposes a model based on the notion that nocturnal enuresis arises through the ill functioning of one or more of the following three systems - a lack of vasopressin release during sleep; bladder instability; and/or an inability to arouse from sleep to bladder sensations. Clinical signs of each system are outlined and the appropriate treatment intervention for each is discussed. It is argued that addressing nocturnal enuresis in this way will enhance overall treatment effectiveness.     

A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder.

The symptoms of bipolar disorder suggest dysfunction of anterior limbic networks that modulate emotional behavior and that reciprocally interact with dorsal attentional systems. Bipolar patients maintain a constant vulnerability to mood episodes even during euthymia, when symptoms are minimal. Consequently, we predicted that, compared with healthy subjects, bipolar patients would exhibit abnormal activation of regions of the anterior limbic network with corresponding abnormal activation of other cortical areas involved in attentional processing. In all, 10 unmedicated euthymic bipolar patients and 10 group-matched healthy subjects were studied with fMRI while performing the Continuous Performance Task-Identical Pairs version (CPT-IP). fMRI scans were obtained on a 3.0 T Bruker system using an echo planar imaging (EPI) pulse sequence, while subjects performed the CPT-IP and a control condition to contrast group differences in regional brain activation. The euthymic bipolar and healthy subjects performed similarly on the CPT-IP, yet showed significantly different patterns of brain activation. Specifically, bipolar patients exhibited increased activation of limbic, paralimbic, and ventrolateral prefrontal areas, as well as visual associational cortices. Healthy subjects exhibited relatively increased activation in fusiform gyrus and medial prefrontal cortex. In conclusion, these differences suggest that bipolar patients exhibit overactivation of anterior limbic areas with corresponding abnormal activation in visual associational cortical areas, permitting successful performance of an attentional task. Since the differences occurred in euthymia, they may represent trait, rather than state, abnormalities of brain function in bipolar disorder.