Prenatal diagnosis of classic hemophilia.

Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.     

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.     

Estimation of theophylline clearance during intravenous aminophylline infusions

The utility of predicting theophylline clearance (CL) from two serum concentrations obtained during continuous intravenous aminophylline infusion was examined in 16 stable, adult patients. Blood for theophylline measurement was obtained 0, 6, and 12 h after starting infusions and, thereafter, at 12-h intervals. EMIT was used to assay samples in multiple runs as they were obtained. Later, each sample was reassayed by EMIT within a single run. Bayesian least-squares regression and the algebraic method of Chiou were used to predict CL using the 0,6 and 0,12 h concentrations. "Actual" CL was measured by nonlinear least-squares regression of all concentrations obtained during prolonged infusions. Prediction bias and precision were assessed by calculating mean percent error (PCE) and mean absolute percent error (APCE), respectively. A three-way repeated-measures ANOVA was used to examine the effect of the method of CL prediction, assay procedure, and time interval between samples on PCE and APCE. Bayesian predictions were less biased and slightly more precise than Chiou predictions. The assay procedure had no effect on bias but precision was improved using a single-assay run. Predictions were less biased and more precise with 0,12 h versus 0,6 h data. Serum samples for theophylline measurement should be obtained after initiating constant intravenous aminophylline and again 8-12 h later in stable, adult patients. Prediction of CL with either of the concentration-based methods studied will then allow safe and rapid adjustment of dosage to achieve therapeutic serum concentrations.     

An objective comparison of four stress tests in the assessment of "at risk" femoro-distal grafts

Femoro-distal vein grafts for limb salvage have a 30% failure rate at 6 months. Graft surveillance may enable the "at risk" grafts to be recognised and corrected, but there remains the need for a simple test to identify these patients. The ankle pressure response to exercise and reactive hyperaemia has been investigated prospectively in 40 "at risk" femoro-distal non-reversed grafts (median age 73 years, range 51-87 years, M/F = 33:7), defined as those with a resting ankle brachial index less than 0.9 or a drop of greater than 0.2 following a stress test. Four different stress tests have been assessed; active ankle plantar-dorsiflexion for 2 minutes (I), occlusive calf cuff 50 mmHg above systolic pressure for 2 minutes (II), treadmill exercise test for 1 minute, slope = 10%, at 3 km/hr (III) and 4 km/hr (IV). Ankle brachial indices (ABI's) were recorded before and immediately following each test and expressed as mean % drop +/- standard error of mean. Test I was only tolerated by 45% of patients whereas 55% and 50% could complete tests III and IV respectively. By contrast, 85% of patients could tolerate occlusive cuff hyperaemia (test II). Test I produced a significantly lower mean percentage drop in ABI when compared with each of the others (p less than 0.02, Mann U Whitney). There was an excellent correlation between test II and both the 3 km/hr (r = 0.77, p less than 0.001) and 4 km/hr (r = 0.84, p less than 0.001) exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

The radiologic morphology of asymptomatic temporomandibular joints

A high frequency of remodeling changes was demonstrated radiographically in a series of 200 female patients with asymptomatic temporomandibular joints. Fewer than 10% of joints were completely radiologically "normal". Generally, there was an increasing incidence of changes with increasing age and for edentulous patients, but these relationships were by no means direct or mutually exclusive.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal.

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

A low cost, high precision subminiature microdrive for extracellular unit recording in behaving animals

A new design for an inexpensive and reliable subminiature microdrive for unit recording in the freely moving animal is presented. The 'Scribe' microdrive is (a) of a small size and low weight, (b) allows for precise advancement of the electrodes, (c) permits stable unit recordings over time, (d) is simple to install, and (e) is economical to construct. These advantages are a result of its simple, single screw-based drive system and the ready availability of component parts. The Scribe microdrive is a small diameter device suitable for multi-site, multi-electrode applications.     

Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region

The present study investigated the effects of naturally fluctuating endogenous levels of oestrogen on the induction and maintenance of long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus. Using an anaesthetized in vivo preparation, the results showed that the induction of LTP was augmented during the pro-oestrous stage of the oestrous cycle. In contrast to LTP, however, the induction of paired-pulse LTD was severely attenuated during pro-oestrous, but was clearly manifested by rats during met/dioestrous and oestrous stages of the cycle. These findings are discussed with reference to: (i) the modulatory effects of oestrogen on N-methyl-D-aspartate (NMDA) receptor function and gamma-aminobutyric acid (GABA) neurotransmission in the hippocampus; and (ii) the functional implications that such cyclical changes in synaptic plasticity have for learning and memory processes supported by the hippocampus.