Respiratory effort sensation during exercise with induced expiratory-flow limitation in healthy humans

Nine healthy subjects (age 31 +/- 4 yr) exercised with and without expiratory-flow limitation (maximal flow approximately 1 l/s). We monitored flow, end-tidal PCO2, esophageal (Pes) and gastric pressures, changes in end-expiratory lung volume, and perception (sensation) of difficulty in breathing. Subjects cycled at increasing intensity (+25 W/30 s) until symptom limitation. During the flow-limited run, exercise performance was limited in all subjects by maximum sensation. Sensation was equally determined by inspiratory and expiratory pressure changes. In both runs, 90% of the variance in sensation could be explained by the Pes swings (difference between peak inspiratory and peak expiratory Pes). End-tidal PCO2 did not explain any variance in sensation in the control run and added only 3% to the explained variance in the flow-limited run. We conclude that in healthy subjects, during normal as well as expiratory flow-limited exercise, the pleural pressure generation of the expiratory muscles is equally related to the perception of difficulty in breathing as that of the inspiratory muscles.     

The effects of drugs and anaesthetic agents on the urinary bladder and sphincters

The influence of sedative, anaesthetic and neuromuscular blocking drugs on diagnostic urethral pressure profiles and cystometrograms has been investigated. These agents have marked effects on the results obtained; in particular, the urethral pressure profile was raised by opiates and lowered by anaesthetic induction agents. Bladder capacity as measured by the cystometrogram was greatly increased by halothane. These findings indicate that urodynamic studies should be performed only on conscious unsedated patients.     

Acute benign intracranial hypertension with spontaneous recovery (reference to 5 cases)

Infections were a major cause of death in 84% of 38 autopsied renal allograft recipients in a south Indian hospital. Pyogenic bacteria and fungi were the most common etiological agents encountered, being present in 50 and 47% of cases, respectively. Tuberculosis and hepatitis B virus infection were more prevalent and Pneumocystis carinii and cytomegalovirus disease rarer than in comparable series from non-tropical countries. 1 case each of amoebiasis, strongyloidiasis and filariasis were the parasitic infections encountered.     

The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification

Retinoids (vitamin A and its metabolites) are suspected of regulating diverse aspects of growth, differentiation, and patterning during embryogenesis, but many questions remain about the identities and functions of the endogenous active retinoids involved. The pleiotropic effects of retinoids may be explained by the existence of complex signal transduction pathways involving diverse nuclear receptors of the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families, and at least two types of cellular retinoic acid binding proteins (CRABP-I and -II). The different RARs, RXRs, and CRABPs have different expression patterns during vertebrate embryogenesis, suggesting that they each have particular functions. Another level at which fine tuning of retinoid action could occur is the metabolism of vitamin A to active metabolites, which may include all-trans-retinoic acid, all-trans-3,4-didehydroretinoic acid, 9-cis-retinoic acid, and 14-hydroxy-4,14-retroretinol. Formation of the metabolite all-trans-4-oxo-retinoic acid from retinoic acid was considered to be an inactivation pathway during growth and differentiation. We report here that, in contrast, 4-oxo-retinoic acid is a highly active metabolite which can modulate positional specification in early embryos. We also show that this retinoid binds avidly to and activates RAR beta, and that it is available in early embryos. The different activities of 4-oxo-retinoic acid and retinoic acid in modulating positional specification on the one hand, and growth and differentiation on the other, interest us in the possibility that specific retinoid ligands regulate different physiological processes in vivo.     

Histoplasma endocarditis on a stenosed aortic valve presenting as dysphagia and weight loss

A 40-year-old man with aortic stenosis and disseminated histoplasmosis did not respond to treatment with itraconazole. Though there was no haemodynamic deterioration, valvar regurgitation, or embolic phenomena a presumptive diagnosis of infective endocarditis was made. This was confirmed at aortic valve replacement. Antifungal treatment was continued for 18 months after valve replacement and serological tests for Histoplasma became progressively more negative during a three year follow up.     

Hydroxylation of salicylate by the in vitro diaphragm: evidence for hydroxyl radical production during fatigue

There is increasing evidence that oxygen-derived free radicals produced during strenuous work by the diaphragm may contribute to diaphragm fatigue and/or injury. However, the precise identity of these oxygen radicals remains unknown, inasmuch as oxygen free radicals are extremely short lived and their detection in biologic systems is quite difficult. There is recent evidence that the salicylate-trapping method may be a useful means of monitoring tissue production of hydroxyl radical (.OH). This method is predicated on the fact that salicylate's phenolic ring can be attacked by .OH at the 3 or 5 position to yield 2,3- or 2,5-dihydroxybenzoic acid (DHB). These metabolites are stable and can be identified by high-performance liquid chromatography (HPLC) coupled with electrochemical or ultraviolet detection. To test the hypothesis that hydroxylated salicylates are produced during diaphragm fatigue, we exposed in vitro rat diaphragm strips to a physiological saline solution containing 2.0 mM sodium salicylate for approximately 15 min. The solution was then removed, and the strips were fatigued (20 Hz, 200-ms train duration, 1 train/s) via phrenic nerve stimulation for 30 s-10 min. The diaphragm strips were subsequently homogenized, and the homogenate was analyzed by HPLC coupled with ultraviolet detection. Levels of 2,3-DHB were significantly higher in fatigued than in control nonfatigued strips. There was also a significant correlation between the amount of 2,3-DHB in the fatigued muscle and the accumulated tension-time product developed during fatigue. 2,5-DHB was not consistently identified in control or experimental strips.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

In 219 HIV-1-infected men of the Amsterdam cohort we measured CD4+ T cell numbers and in vitro T cell responses to CD3 MoAbs with or without CD28 costimulation and phytohaemagglutinin (PHA). The value of these markers was estimated for disease progression within 4 years. CD28 expression on T cells has been related to T cell responses. CD28 costimulation considerably enhanced T cell reactivity (approximately 8-10-fold) with lower coefficients of variation compared with reactivity to CD3 MoAb alone (median 5 versus 20). T cell reactivity to CD3 plus CD28 MoAb was decreased during HIV-1 infection and was besides CD4+ T cell numbers the only independent predictor for progression to AIDS. Compared with the group with high CD4+ T cell numbers the relative risk (RR) for the group with intermediate levels was 2.28, with low levels 5.20. In the groups with intermediate and low CD3 plus CD28 responses the RR was 2.04 and 4.16, respectively. The combined RR for both was 4.65 and 21.63. The independence of this marker was confirmed when the group with low CD4+ T cell numbers was subdivided into groups with high, intermediate and low T cell responses. The expansion of CD8+CD28- T cells was already apparent in HIV- homosexual men, but CD8+CD28+ T cells specifically decreased in patients with AIDS. CD28 expression on T cells correlated moderately with T cell responses to CD3 plus CD28 MoAb. T cell reactivity to CD3 MoAb in the presence of CD28 MoAb is a stronger prognostic marker than T cell reactivity to CD3 MoAb alone.     

Degeneration of the dendritic arbor as an index of neurotoxicity in identified catecholamine neurons in rat brain slices

The effect of trace element combination, Béres Drop Plus (BDP) on the immune response of rats following single treatment with cytostatic drug (5-fluorouracil, 5-FU) was tested. Animals were treated with 5-FU and SRBC simultaneously, but separately. Rats were pretreated with BDP for 21 days. The body and spleen weight, furthermore the number of spleen cells and antibody producing cells were determined. The antibody titres in blood serum were also measured. The immune system of rats, 5 days following the 5-FU treatment, showed considerable regeneration. Pretreatment of rats with BDP had a beneficial effect on all parameters investigated.