Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of Tanzania: Implications for prevention and treatment

Background  

Variability in stages of the HIV-1 epidemic and hence HIV-1 prevalence exists in different areas in sub-Saharan Africa. The purpose of this study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk factors that may help to develop preventive strategies in rural Kilimanjaro, Tanzania.     

Gastrointestinal malacoplakia in children

Four children, whose ages ranged from 1 to 13 years, with malacoplakia of the gastrointestinal tract were treated at King Faisal Specialist Hospital between 1979 and 1983. All patients had either a preceding or a coexisting chronic illness. In one patient, malacoplakia was an incidental finding, while the remaining three patients presented with bloody diarrhea, abdominal pain, recurrent fever, and severe malnutrition. Colonoscopy in two patients revealed markedly inflamed and friable mucosa with focal ulceration alternating with patches of normal mucosa and pseudopolyposis. They were treated with antibiotics and cholinergic agonists. Three patients responded favorably, while one patient continued to have extensive active disease. Although the response to therapy is unpredictable, patients may respond if the treatment is continued on a long-term basis.     

Effects of atrial natriuretic peptide and sodium nitroprusside on epidermal growth factor-stimulated wound repair in rabbit corneal epithelial cells

PURPOSE: Treatment of rabbit corneal epithelial cells (RCEC) with epidermal growth factor (EGF) stimulates cell proliferation and wound repair in a cell culture model system. Studies have also shown that atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP), a nitric oxide-generating agent, inhibit proliferation of a variety of cell types. The aim of the present work was to examine whether ANP or SNP has any effect on EGF-stimulated proliferation of RCEC involved in wound repair. METHODS: The SV-40 immortalized RCEC were cultured in 24-well plates until they became confluent. Wounds of uniform size (8 mm diameter) were created and the cells allowed to grow in the presence and absence of EGF and/or other agents. At prescribed time intervals, the cells were stained by Giemsa and the wound areas digitized and quantified by Sigma Image Scan System. The cGMP contents in RCEC, treated with or without ANP or SNP, were measured by radioimmunoassay. RESULTS: Addition of EGF (1-100 ng/ml) to RCEC stimulated cell proliferation which significantly reduced the time required for wound closure. Addition of ANP (1 nM to 10 microM) or SNP (10 microM to 1 mM), in the presence of EGF, dose-dependently inhibited the growth factor-stimulated wound closure in RCEC. When added alone to the cells, ANP or SNP increased cGMP accumulation in a dose-dependent manner. Addition of ANP (1 microM) or SNP (1 mM) to primary corneal epithelial cells, in the presence and absence of EGF, also inhibited the wound closure with a corresponding increase in cGMP contents. Treatment of the cells with ODQ (10 nM to 10 microM), a soluble guanylate cyclase inhibitor, dose-dependently decreased the SNP-induced accumulation of cGMP, and reversed the inhibitory effect of SNP on EGF-stimulated wound closure. Addition of membrane-permeable cGMP analog, 8-bromo-cGMP, to RCEC inhibited the EGF-stimulated wound closure in a dose-dependent manner. Treatment of RCEC with mitomycin C (5 microM) exerted a marked inhibitory effect on wound closure in the presence and absence of EGF, and also abrogated the inhibitory effect of 8-bromo-cGMP on wound closure in the EGF-treated and untreated cells. CONCLUSIONS: The results demonstrate that ANP and SNP inhibit the EGF-stimulated wound repair in RCEC. The effect of these agents is mediated via activation of guanylate cyclases that generate cGMP. Cyclic GMP appears to exert its inhibitory effect at the level of cell proliferation and not cell migration. The data suggest an important role for cGMP-dependent protein kinase in proliferation of RCEC stimulated by EGF.     

Significance of beta-blockers in the perioperative period

Beta-blockers have emerged as one of the key therapeutic agents that can decrease cardiac morbidity and mortality. Advances in cardiac beta-adrenergic receptor physiology and pharmacology have provided new insights into the beneficial effects of beta-blockers in cardiovascular medicine. Although significant advances have been made, many specific questions still remain to be answered. We will review some of these developments and the current role of beta-blockers in peri-operative medicine.     

Co-delivery of an antisense oligonucleotide and 5-fluorouracil using sustained release poly (lactide-co-glycolide) microsphere formulations for potential combination therapy in cancer

Antisense oligonucleotides (AODNs) can selectively inhibit oncogene expression by Watson-Crick hybridisation to target mRNA and are being increasingly considered for use in combination with conventional drugs for potential anticancer therapy. Combination therapy of AODNs and cytotoxic agents using biodegradable polymeric delivery systems potentially offers several advantages including site-specific or organ-directed targeting, protection from digesting enzymes, and improved pharmacokinetics/pharmacodynamics resulting from sustained delivery of the entrapped drugs. Using a model AODN targeting the epidermal growth factor receptor (that is over-expressed in several cancers including breast and brain cancer) and the commonly used cytotoxic agent, 5-fluorouracil (5-FU), we have examined the use of poly (lactide-co-glycolide) (P(LA-GA)) microsphere formulations for co-delivery of these agents. Both agents were either co-entrapped in a single microsphere formulation or individually entrapped in two separate microsphere formulations and release profiles determined in vitro. Using a double emulsion method for preparing the P(LA-GA) microspheres suitable entrapment and sustained release over 35 days was observed in both types of formulation. Release of AODN and 5-FU from all formulations appeared to be biphasic. However, the release rates of the two agents were significantly slower when co-entrapped as a single microsphere formulation compared to those obtained with the separate formulations. Electrophoretic mobility shift assays suggested that this might be, in part, due to an interaction of 5-FU with the oligodeoxynucleotide (ODN). Further, our data suggest that by mixing individual formulations of 5-FU and ODNs at different mass ratios allowed greater flexibility in achieving the desired release profile as well as avoiding potential drug-drug interactions. Thus, co-administration of individual P(LA-GA) microsphere formulations of AODNs and 5-FU, at appropriate mass ratios, appears worthy of further investigation for the potential co-delivery of these anti-cancer agents in vivo.     

Non-ahr gene susceptibility Loci for porphyria and liver injury induced by the interaction of 'dioxin' with iron overload in mice

Among the actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in mice is the induction of hepatic porphyria. This is similar to the most common disease of this type in humans, sporadic porphyria cutanea tarda (PCT). Evidence is consistent with the actions of dioxin being mediated through binding to the aryl hydrocarbon receptor (AHR) with different Ahr alleles in mouse strains apparently accounting for differential downstream gene expression and susceptibility. However, studies of dioxin-induced porphyria and liver injury indicate that the mechanisms must involve interactions with other genes, perhaps associated with iron metabolism. We performed a quantitative trait locus (QTL) analysis of an F(2) cross between susceptible C57BL/6J (Ahr(b1) allele) and the highly resistant DBA/2 (Ahr(d) allele) strains after treatment with dioxin and iron. For porphyria we found QTLs on chromosomes 11 and 14 in addition to the Ahr gene (chromosome 12). Studies with C57BL/6.D2 Ahr(d) mice confirmed that the Ahr(d) allele alone did not completely negate the response. SWR mice are syngenic for the Ahr(d) allele with the DBA/2 strain but are susceptible to porphyria after elevation of hepatic iron. Analysis of SWRxD2 F(2) mice treated with iron and dioxin showed a QTL on chromosome 11, as well as finding other loci on chromosomes 1 (and possibly 9), for both porphyria and liver injury. These findings show for the first time the location of genes, other than Ahr, that modulate the mechanism of hepatic porphyria and injury caused by dioxin in mice. Orthologous loci may contribute to the pathogenesis of human sporadic PCT.     

Management of allergic fungal sinusitis with intracranial spread

Allergic fungal sinusitis (AFS) is a form of paranasal nasal disease if not managed early often involves bone destruction and extension into the orbit and anterior skull base. We present our study of patients with AFS with intracranial, exdradural extension. This study includes our experience of 26 patients with the histological and immunological diagnosis of AFS based on findings of branching septate fungi interspersed with eosinophilic mucin and Charcot-Leyden crystals without fungal invasion of soft tissue, with intracranial extension. All had erosion of bone, which was observed on computerized tomography (CT) scans, extending intracranially and eight had disease that additionally involved the lamina papyracea. The average age of patients in this study was 25 years (range 9–46). There were 20 male and 6 female patients. All patients were immunocompetent. Skin test against aspergillin showed all patients had Type 1 hypersensitivity. All patients underwent transnasal and/or transmaxillary endoscopic approaches for debridement and eight underwent orbital decompression. No patient underwent craniotomy for removal of intracranial extradural disease. No patient had a cerebrospinal fluid leak. Postoperatively, all 26 were treated with a course of corticosteroids. The follow-up period ranged from 2 to 5 years. We conclude AFS is a unique form of fungal disease that might mimic anterior skull base and paranasal sinus tumors. Most cases can be successfully managed with transnasal and/or transmaxillary endoscopic techniques.     

Neuroendocrine carcinoma of the ethmoid sinus

The paranasal sinuses are a rare site for neuroendocrine carcinoma (NEC). In contrast to the other regions, NEC of the sinuses has been reported to be recurrent and locally destructive. We report a case of NEC of the ethmoid sinuses. The patient was a 16-year-old Indian boy and was treated with radiation therapy to 6500 rad. He has been disease free for the past 5 years. All the cases reported to date were also reviewed.Adapted from a presentation at the annual meeting of the American Academy of Otolaryngology Head and Neck Surgery, Inc., Washington, D.C., 13–17 September 1992