Neurogenic bladder in acquired immune deficiency syndrome (AIDS).

This is the first report of incidence of neurogenic bladder in patients with acquired immune deficiency syndrome (AIDS) and emphasizes that it is a significant cause of various voiding dysfunctions in these patients. Neurologic disease occurs in about one third of patients with AIDS. Both central and peripheral nervous systems may be involved. Urodynamic evaluation is necessary for assessment and management of neurogenic voiding disorders in this group of patients.     

Diminution in Kerosene-Mediated Induction of Drug Metabolizing Enzymes by Asbestos in Rat Lungs

Abstract: In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal coexposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.     

Gastric carcinoma--a study of 100 cases in northern Pakistan.

We describe 100 consecutive patients with histologically proven gastric carcinoma who were admitted to various hospitals in Northern Pakistan. Twenty-six per cent of patients were under 40 years of age. In a majority of patients the tumour was of a morphological type associated with poor prognosis. In most cases the disease was already at an advanced stage at the time of diagnosis, and most patients died within one year.     

Effect of dietary fish oil supplementation on the antigen-induced late-phase response in the skin.

We have studied the effect of dietary fish oil supplementation (3.2 gm/day of eicosapentaenoic acid and 2.2 gm/day of docosahexaenoic acid) for 10 weeks on the antigen-induced, cutaneous late-phase response (LPR) in 16 atopic individuals. All subjects developed an LPR to intradermal allergen injection. The mean +/- SEM area of induration at 6 hours was 1840 +/- 472 mm2. A biopsy was performed at the LPR site at 6 hours. Subjects were then randomized to receive fish oil or placebo olive oil in a double-blind, parallel fashion, for 10 weeks. After the diet, there were no significant differences between fish oil and placebo treatment in the size of the immediate wheal-and-flare response or the extent of induration at 4 and 6 hours, as compared with prediet values in each group. Histologically, at 6 hours, there was a significant infiltrate into the allergen site compared with that of the control diluent site of total inflammatory cells (p less than 0.002) as well as of eosinophils (p less than 0.001). However, there were no significant differences when pre- and postdiet values were compared. Hence, we conclude that dietary fish oil supplementation does not inhibit the cutaneous LPR clinically or histologically.     

Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial

A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.     

The physiological regulation of toll-like receptor expression and function in humans

Eleven mammalian toll-like receptors (TLRs 1–11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14⁺ monocytes following activation with specific TLR ligands was greater ( P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34°C). Strenuous exercise resulted in a decrease ( P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14⁺ monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14⁺ monocytes following activation with specific TLR ligands was decreased ( P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.     

The effect of dimethyl sulfoxide (DMSO) on the growth of dermatophytes.

Dimethyl sulfoxide(DMSO) is frequently used as a solvent for antifungal drugs in various studies to determine their MICs. Reports on comparative evaluation of methods for the susceptibility testing of antifungal drugs have shown there is poor agreement among methods. Besides other factors which could cause variability in the results, one important factor might be the effect of DMSO on the growth of fungi. The effect of DMSO on the growth of some species of Candida has been reported in the literature. The present study aimed at determination of the effect of different concentrations of DMSO (0.125 to 10%) on the growth of dermatophytes by agar diffusion method. There was no growth of fungi in 10% DMSO, between 1.25 and 5% there was a rather linear dose-related inhibitory effect on the growth, significantly different from the controls, and below 1% there was a variable effect among the species. DMSO down to 0.25% significantly inhibited the growth of most strains of M. canis. The lower concentrations of DMSO, which apparently do not affect the growth of fungi, may potentiate the effect of antifungal drugs.     

Gangliosides of cultured astroglia

Cultured astrocytes prepared from newborn rat brain and 13-day-old chick embryonic brain were analyzed qualitatively and quantitatively for ganglioside content. All preparations contained approximately the same total level: 2.4-3.4 micrograms N-acetylneuraminic acid (NeuAc)/mg protein. In contrast, the value for primary cultures of neurons from chick embryonic brain was 5.9. The non-hexosamine-containing species, GM3 and GD3, comprised 75-85% of the total in astroglial cultures, the remainder consisting mainly of structural types other than the gangliotetraose series; choleragenoid assay revealed the latter to be virtually absent or to comprise at most a few percent. Deficiency of gangliotetraose synthesizing ability was indicated by the very low level of UDP-GalNac:GM3 N-acetylgalactosaminyltransferase detected in the cells. Treatment of cultured astrocytes with astroglial growth factor 2 or dibutyryl cyclic AMP caused little if any change in quantity or pattern of gangliosides. The large majority of cells stained in a manner characteristic of astrocytes: positive for glial fibrillary acidic protein, negative for galactosyl ceramides. Staining with cholera toxin and anti-GM1 antibody was essentially negative, as was that with tetanus toxin, A2B5 monoclonal antibody, and antibody to GD3. All evidence thus points to cultured astrocytes of rat and chick brain containing appreciable gangliosides, most of which are GM3 and GD3 with the majority of the remainder comprising structures other than the gangliotetraose type.