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.     

Marked Q-T prolongation due to encainide therapy

Summary Encainide is a type Ic antiarrhythmie agent. During encainide therapy, mild Q-T interval prolongation can be seen, usually associated with prolongation of the Q-R-S interval. The present case report describes an unusual and marked prolongation of the Q-T interval with no Q-R-S interval prolongation in a patient who was treated with encainide for atrioventricular nodal reentrant tachycardia. The drug metabolite profile in this patient's serum indicated an unusual elevation of the 3-methoxy-O-demethyl encainide metabolite, versus O-demethyl encainide. This elevated metabolite level suggests that 3-methoxy-O-demethyl encainide has a significant effect on prolongation of repolarization. An abnormal metabolism of encainide may be the underlying mechanism by which some patients would manifest an unusual prolongation of Q-T interval during encainide therapy.     

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.     

Abnormality of type IX collagen in a patient with diastrophic dysplasia

There is growing evidence that a spectrum of chondrodysplasias are caused by mutations in the gene coding for type II collagen. The basic molecular defect in diastrophic dysplasia has not been defined, but it appears not to be in collagen type II. Cartilage contains other tissue-specific collagens, types IX, X, and XI, but no mutations have yet been found in their genes in clinical disease. Type IX collagen is hypothesized to play a role in the regulation of type II collagen fibril organization and structure in cartilage extracellular matrix. In this study, we have examined iliac crest growth cartilage from a patient with diastrophic dysplasia. Although collagen fibrils were markedly increased in diameter on transmission electron microscopy, type II collagen appeared to be normal biochemically. Type XI collagen was also normal. However, type IX collagen appeared abnormal on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a pronounced excess of the COL1 domain of the molecule in pepsin extracts. The findings point to an abnormality in structure or metabolism of type IX collagen in diastrophic dysplasia. © 1994 Wiley-Liss, Inc.