Unmet needs of high-risk mothers reduce success of antiretroviral treatment in HIV-infected infants.

In the era of effective prevention of mother-to-child transmission of HIV, the same psychosocioeconomic factors that predispose to mother-to-child transmission also substantially increase the likelihood of antiretroviral therapy failure in infected infants. For HIV-infected infants to benefit from early infant diagnosis and treatment initiation, into which much funding and effort is now invested, it is vital that these unmet needs of high-risk mothers are urgently attended to. From an ongoing study of early infant diagnosis and treatment following in utero transmission in KwaZulu-Natal, South Africa, we describe four cases to highlight these challenges facing transmitting mothers that contribute to treatment failure in their infants.

Modulation of the rhythmic patterns of expression of phosphoprotein phosphatases in human leukaemia cells.

Temporal variations in the expression of phosphoprotein phosphatase 1 (PP1), phosphoprotein phosphatase 2A (PP2A) and protein tyrosine phosphatase 1B (PTP1B) were monitored in the human acute, promyelocytic leukaemia cell line, HL60. Granulocytic differentiation was induced using all-trans retinoic acid (ATRA) and monocytic differentiation by phorbol-12-myristate-13-acetate (PMA). Expression of the enzyme proteins in cell extracts was determined by SDS-PAGE and Western immunoblotting using specific antibodies. For PP1, a single immunospecific band of molecular mass 38 kDa was detected corresponding to the catalytic subunit; induction of differentiation with either ATRA or PMA showed differences in the patterns of expression and, in the case of the latter, the mean value. Two immunospecific bands, of mass 34 and 37 kDa, possibly corresponding to dephosphorylated and phosphorylated forms, respectively, were detected for PP2A, as well as a minor band of mass 46 kDa; dynamic variations in the expression of all 3 forms were observed and there were differences between the control and treated cells. The catalytic domain of PTP1B was detected as a 46 kDa band. A 42 kDa form of the protein was also seen, which may represent a change in phosphorylation state, or be the result of proteolytic cleavage; usually the 46 kDa band was the major form, but on occasion there was a change to predominance of the 42 kDa band.

Correlation of kinin generating activity with Helicobacter pylori-associated gastric infection.

The kallikrein-kinin system involves a biologically complex set of interactive proteases that signal the first-line onset of inflammation and associated cellular processes. The basic enzymatic cleavage of kininogen substrate by the serine protease tissue kallikrein to liberate kinins is regulated by a number of factors. These may include the recently discovered bacterial involvement in the causation of gastritis. The gram-negative Helicobacter pylori organism, colonises the human gastric epithelium and initiates ulcerogenesis and may induce, in the longer term, tumour formation. The aim of this study was to investigate the role of kinins in H. pylori-induced gastric dyspepsia. During endoscopic examination, lavage aspirates of 23 patients were collected, and the tissue kallikrein content measured by a kinin-generating assay and an enzyme-linked immunosorbent assay. Gastric antral and pyloric biopsy tissue was histologically examined for degrees of inflammation and H. pylori infection, and then immunolabelled for tissue kallikrein and kinin receptors. Results show that labelled tissue kallikrein in the fundic glands and parietal cells of the diseased antrum was elevated with increasing severity of gastritis. Further, kinin-generating potential of the lavage fluid appeared to be greater with increasing evidence of infection. Tissue kallikrein immunosorbent assay levels were significantly raised in patients showing mild to moderate H. pylori infection. One outcome of this study may be the inclusion of kinin antagonists in management of gastric dyspepsia.

Kinin receptor status in normal and inflammed gastric mucosa.

No documented studies have been reported on the presence of B1 and B2 kinin receptors in the mammalian gastric mucosa. This first study aimed to immunolocalise sites of B1 and B2 kinin receptors in the human pyloric gastric mucosa and to evaluate its role in gastritis. Biopsies were obtained from patients with dyspepsia during endoscopic examination of the patient. The diagnosis and grading of the gastritis was performed on histological examination. Sections were immunostained for both B1 and B2 receptors using rabbit anti-human B1 and B2 kinin receptor antibodies. Control tissue was obtained from partial gastrectomy specimens, following surgical excision of the antrum for duodenal ulcers. The control antrum tissue showed strong immunoreactivity for kinin B2 receptors with positivity noted along the luminal border, at the base of the mucous and stem cells. The B1 receptor was not immunolocalised. Biopsies of all five patients with gastritis showed a decrease in immunolabelling of the B2 receptor and an induction of the B1 receptor especially in regenerating cells. In gastritis there is destruction of the normal mucosal glandular architecture with subsequent regeneration of the epithelial cells. The pyloric glands are infiltrated by acute inflammatory cells that cause crypt abscesses with loss of the epithelial cell membranes. This may explain the reduction in the immunolocalisation of the B2 kinin receptors and the induction of the B1 receptors in active gastritis. Follow up studies after treatment of the inflammation with a combination of B1/B2 kinin receptor antagonists are indicated.

The evaluation of tissue kallikrein in Helicobacter pylori-associated gastric ulcer disease.

Helicobacter pylori (Hp) associated ulcer disease is a common form of gastric disorder involving mucosal damage and invasion of the mucosa by polymorphic inflammatory cells with concomitant changes in the epithelial cell structure. The bacteria are thought to adhere by specific junction zones to the epithelial cell surface resulting in the degeneration of the mucosal layer. Our study was undertaken to examine the relative status of tissue kallikrein (TK) in antral and fundic biopsies, endoscopically obtained from 10 patients suspected of having gastric disorders. For histological evidence of inflammation the tissue was stained with hematoxylin and eosin and classified as mild, active, chronic and chronic active gastritis. Hp infection was determined by Giemsa staining. For localisation of TK, slide-mounted tissue sections were subjected to PAP and immunofluorescent staining using a goat anti-human TK IgG antibody. The results revealed that in the antral control tissue, removed during partial antractomy, TK was immunovisualised along the luminal border of the deep pyloric glands. The surface epithelia and superficial glands showed no labelling. The fundic control tissue revealed an absence of TK in the superficial and surface epithelial glands, but was positive in the parietal cells. The fundic biopsy specimens showed similar immunoreactivity in these areas. By contrast, in the inflammed pyloric mucosa, there was a shift of TK localisation to the basal part of the glandular cells and there was also expression of TK in the superficial glands that showed histological evidence of regeneration. In the fundic biopsies there was no change observed in the sites of TK localisation (similar to control tissue). It was observed, that even though 8 of the 10 subjects exhibited Hp infection, the inflamed mucosa showed no discernable difference in the staining patterns between the infected and non-infected tissue sections. Our findings suggest an important role for a B1/B2 kinin antagonist in patients with gastritis.

Pirenzepine and cimetidine for duodenal ulcers. A comparative randomised double-blind controlled study.

A double-blind controlled trial was undertaken to compare the relative effectiveness of pirenzepine (Gastrozepin; Boehringer Ingelheim) and cimetidine (Tagamet; SK & F) in healing endoscopically proven duodenal ulcers. Thirty patients with duodenal ulcers were treated with pirenzepine 50 mg twice daily and 30 patients with cimetidine 400 mg twice daily. Endoscopy was repeated after 4 weeks. Ulcers healed completely in 15 patients on pirenzepine and 21 patients on cimetidine (chi-square test 3.05; P less than 0.1); this difference was not significant. Treatment resulted in endoscopic improvement in 25 patients on pirenzepine and in 26 patients on cimetidine; this difference was also not statistically significant (chi-square test 1.18; P less than 0.5). No adverse effects were seen with cimetidine. Mild and reversible side-effects were seen in 4 patients on pirenzepine. The efficacy of pirenzepine appears similar to that of cimetidine in the healing of duodenal ulcers.

Brainstem encephalitis or the Miller Fisher syndrome--a variant of acute idiopathic polyneuropathy. Case reports.

A syndrome comprising ophthalmoplegia, ataxia and areflexia was described by Miller Fisher in 1956. While some consider it to be a benign variety of acute idiopathic (Guillain-Barré) polyneuropathy, there are reports of the need for ventilatory support and of the benefits of plasmapheresis. Two further cases are described. The first patient was seen in 1972 and was well 10 years later. The second patient gave cause for concern and might have benefitted from plasmapheresis, but nevertheless he recovered spontaneously. Miller Fisher believed that the pathological process was located in the peripheral nerve, but others have produced evidence that the cranial nerve nuclei and central connections within the brainstem are involved.

Bicitropeptide powder and placebo in the treatment of duodenal ulcers. A double-blind endoscopically controlled clinical trial.

In a double-blind study comprising 50 patients with endoscopically proven uncomplicated duodenal ulcers a powder formulation of bicitropeptide (BCP-Compound) was found to be superior to placebo. On endoscopic examination 19 patients (76%) treated with bicitropeptide powder had healed, while 3 (12%) showed some degree of healing, a total success rate of 88%. Only 5 patients (20%) on placebo had healed completely while 3 (12%) showed some degree of healing (chi 2 = 17,9667; P less than 0,0005). Blood and urine bismuth levels were measured before and after 6 and 12 weeks of therapy, and showed an increase after the first 6 weeks. By 12 weeks the levels had decreased, although they were still higher than the initial values. The blood levels were, however, significantly lower than postulated toxic levels.

Etiology of colonic strictures in South African black and Indian patients.

The etiology of colonic strictures in 263 South African black and Indian patients is presented. Nonmalignant lesions accounted for strictures in two-thirds of the patients and included amebiasis (27), tuberculosis (24), nonspecific colitis (30), ulcerative colitis/Crohn's colitis (11) and other lesions (36). Malignant lesions caused strictures in approximately a third of the black and Indian patients, which is higher than in other reported series in blacks. Accurate clinical diagnosis is difficult and early histologic confirmation is mandatory in order to institute rational management. Strictures of the right colon in the black population are more likely to be benign, except in younger patients. Left-sided colonic strictures have an equal chance of being benign or malignant, and early histologic confirmation is essential. The coexistence of an underlying malignant lesion in association with an inflammatory lesion in an endemic area should always be considered, particularly if it fails to respond to empirical therapy within a short period of time.

Treatment of duodenal ulcers with cimetidine.

A total of 55 patients were treated with the histamine H2-receptor antagonist cimetidine (Tagamet: SKF) in an endoscopically controlled double-blind trial. Cimetide (200 or 300 mg every 6 hours) was administered to 36 patients, and placebo to 19 patients. Only patients who had been confirmed by endoscopy as having uncomplicated duodenal ulcers were admitted to the trial. Drug or placebo was administered in a randomized double-blind fashion for 6 weeks. Patients underwent clinical examination at weekly intervals. Haematological assessment was made weekly for 7 weeks, and biochemical variables were measured once a week or once every 2 weeks for 6 weeks. Endoscopy was repeated at 6 weeks unless the patient had to be excluded from the trial because of incessant pain after 14 days. No antacid or other treatment was allowed. Seventy-eight per cent of the patients became free of symptoms when treated with cimetidine, and 47% when treated with placebo (chi2 = 5,2235; P less than 0,025 in favour of cimetidine). Endoscopic evidence of healing revealed an improvement of 69,5% in those treated with cimetidine and one of 42% in those treated with placebo (chi2 = 3,8731; P less than 0,05 in favour of cimetidine). No haematological or biochemical changes were noted. It is concluded that the histamine H2-receptor antagonists have a definite place in the treatment of duodenal ulceration.

Prazosin alone and combined with a thiazide diuretic in the treatment of hypertension.

We conducted an uncontrolled study of the efficacy of prazosin in the treatment of hypertension in 45 patients. In 25 patients only prazosin was used and in 20 patients prazosin was combined with a thiazide diuretic. Control of blood pressure was obtained in 22 of the 25 patients (88%) on prazosin alone, and in all the patients on the combined treatment. Adverse effects occurred in 15 of 25 patients (60%) on prazosin alone, and in 13 of the 20 patients (65%) on combined treatment. However, in 18 patients (40%) adverse effects disappeared or were tolerated with continued therapy. In 10 patients (22%) therapy was stopped because of the adverse effects. The median dose of prazosin was 5,73 mg twice a day. Prazosin is a useful alternative to hydralazine in the treatment of hypertension.

Prazosin combined with thiazide diuretic and beta-blocker in the treatment of hypertension.

In a study of 10 patients suffering from hypertension the results showed that combination treatment with prazosin, cyclopenthiazide and a beta-blocker produced a significant fall in blood pressure. Side-effects such as palpitations, headache, syncope and drowsiness which may occur with prazosin alone were obviated by combining prazosin with a beta-blocker.

Basal serum gastrin levels in normal subjects and in various gastro-intestinal conditions.

A total of 1 035 routine serum gastrin investigations was undertaken with a commercially available kit. Levels in 49 normal subjects were similar to those found in 200 patients with duodenal ulcertaion, in 42 patients with gastric ulcers, in 9 patients with carcinoma of the stomach, in 55 patients with chronic alcohol-induced pancreatitis, and in 27 with iron deficiency anaemia. Significantly raised levels of serum gastrin were found in 32 patients with megaloblastic anaemias, where the rise in serum gastrin concentration correlated with a fall in maximal acid output, and in 14 patients with complete vagotomies. It is suggested that a level of less than 2 mEq/h of acid after insulin and a raised serum gastrin level are useful criteria of completeness of vagotomy.

Probable chloroquine-resistant Plasmodium falciparum malaria from Mozambique A case report.

A female patient with Plasmodium falciparum malaria apparently resistant to chloroquine is descirbed. She had recently returned from Mozambique, which may prove to be a new endemic are with resistant strains. The infection was successfully treated with quinine.

Orthostatic hypotension due to Shy-Drager syndrome.

A case of orthostatic hypotension is presented, as well as postmortem neuropathological findings. The features of this case are consistent with those of the Shy-Drager syndrome, which comprises primary orthostatic hypotension and neurological manifestations caused by degenerative disease of the central nervous system.