Delawir Kahn

FAILURE OF REPEATED INJECTION SCLEROTHERAPY TO IMPROVE LONG-TERM SURVIVAL AFTER OESOPHAGEAL VARICEAL BLEEDING: A Five-year Prospective Controlled Clinical Trial

The role of sclerotherapy in long-term management after oesophageal variceal bleeding was assessed by comparing repeated sclerotherapy by means of a rigid oesophagoscope in 37 patients with control medical management in 38 patients. Varices were eradicated in 21 of the 22 patients analysed (95%) in the sclerotherapy group, but recurred in 13 of the 21 patients (average 21.5 months). Varices persisted in 13 of 14 surviving controls. The sclerotherapy patients had fewer recurrent bleeds than control patients (43 versus 73); the majority occurred before variceal eradication and were mild. However, there was no difference in survival in the two groups. The commonest cause of death was liver failure (37 patients). 32 complications occurred in 24 patients during 258 injections. Repeated sclerotherapy failed to improve survival in this trial, although varices were eradicated and recurrent variceal bleeds were prevented with adequate follow-up.

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients

BACKGROUND A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Negative-pressure wound therapy II: negative-pressure wound therapy and increased perfusion. Just an illusion?

Background: A recent study demonstrated that negative-pressure wound therapy increases underlying tissue pressure. This finding is incongruous with studies using laser Doppler that show that perfusion is immediately increased on initiation of suction. This study investigated perfusion in negative-pressure wound therapy using two alternative modalities. Methods: Radioisotope perfusion imaging was used to determine perfusion beneath circumferential negative-pressure wound therapy dressings on 20 healthy hands (n = 20). Ten hands received suction pressures of −400 mmHg and 10 received −125 mmHg, with the contralateral hand used as a control without any suction. Transcutaneous partial pressure of oxygen was used to determine perfusion beneath noncircumferential negative-pressure wound therapy dressings on 12 healthy legs (n = 12), with each volunteer being sequentially randomized to receive suction pressures of −400 and −125 mmHg, respectively. Results: Tissues undergoing circumferential negative-pressure wound therapy demonstrated a mean reduction in perfusion of 40 ± 11.5 percent (p < 0.0005) and 17 ± 8.9 percent (p < 0.0005) at suction pressures of −400 mmHg and −125 mmHg, respectively. Perfusion reduction at −400 mmHg was significantly greater than at −125 mmHg (p < 0.015). In the noncircumferential negative-pressure wound therapy group, there was a mean reduction in transcutaneous partial pressure of oxygen of 7.35 ± 7.4 mmHg (p < 0.0005) and 5.10 ± 7.4 mmHg (p < 0.0005) at suction pressures of −400 mmHg and −125 mmHg, respectively. There was a tendency for greater reductions in the −400 mmHg group, but this was not significantly different from the −125 mmHg group (p = 0.07). Conclusions: These findings demonstrate that perfusion beneath negative-pressure wound therapy decreases for increasing suction pressure. Thus, it is suggested that negative-pressure wound therapy should be used with caution on tissues with compromised vascularity, particularly when used circumferentially.

Renal Transplantation between HIV-Positive Donors and Recipients

Investigators in South Africa undertook four renal transplantations involving HIV-positive donors and HIV-positive recipients with end-stage renal disease. At 12 months after transplantation, all recipients had good renal function and had not needed dialysis since the procedure.

HIV-Positive–to–HIV-Positive Kidney Transplantation — Results at 3 to 5 Years

BACKGROUND The outcome of kidney transplantation in human immunodeficiency virus (HIV)-positive patients who receive organs from HIV-negative donors has been reported to be similar to the outcome in HIV-negative recipients. We report the outcomes at 3 to 5 years in HIV-positive patients who received kidneys from HIV-positive deceased donors. METHODS We conducted a prospective, nonrandomized study of kidney transplantation in HIV-infected patients who had a CD4 T-cell count of 200 per cubic millimeter or higher and an undetectable plasma HIV RNA level. All the patients were receiving antiretroviral therapy (ART). The patients received kidneys from deceased donors who tested positive for HIV with the use of fourth-generation enzyme-linked immunosorbent assay at the time of referral. All the donors either had received no ART previously or had received only first-line ART. RESULTS From September 2008 through February 2014, a total of 27 HIV-positive patients underwent kidney transplantation. Survivors were followed for a median of 2.4 years. The rate of survival among the patients was 84% at 1 year, 84% at 3 years, and 74% at 5 years. The corresponding rates of graft survival were 93%, 84%, and 84%. (If a patient died with a functioning graft, the calculation was performed as if the graft had survived.) Rejection rates were 8% at 1 year and 22% at 3 years. HIV infection remained well controlled, with undetectable virus in blood after the transplantation. CONCLUSIONS Kidney transplantation from an HIV-positive donor appears to be an additional treatment option for HIV-infected patients requiring renal-replacement therapy. (Funded by Sanofi South Africa and the Roche Organ Transplantation Research Foundation.).

The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of Human Immunodeficiency Virus type 1 in an inhibition assay

BackgroundDespite the continuous shedding of HIV infected blood into the oral cavity and the detectable presence of the AIDS virus at a high frequency, human saliva is reported to inhibit oral transmission of HIV through kissing, dental treatment, biting, and aerosolization. The purpose of this study was to purify salivary MUC5B and MUC7 mucins from crude saliva and determine their anti-HIV-1 activities.MethodsFollowing Sepharose CL-4B column chromatography and caesium chloride isopycnic density-gradient ultra-centrifugation, the purity and identity of the mucins was determined by SDS-PAGE and Western blotting analysis respectively. Subsequently an HIV-1 inhibition assay was carried out to determine the anti-HIV-1 activity of the crude saliva and purified salivary mucins by incubating them with subtype D HIV-1 prior to infection of the CD4+ CEM SS cells.ResultsWestern blotting analysis confirmed that the mucin in the void volume is MUC5B and the mucin in the included volume is MUC7. The HIV inhibition assay revealed that both the crude saliva and salivary MUC5B and MUC7 mucins inhibited HIV-1 activity by 100%.ConclusionAlthough the mechanism of action is not clear the carbohydrate moieties of the salivary mucins may trap or aggregate the virus and prevent host cell entry.

Inhibition of Human Immunodeficiency Virus Type 1 Activity by Purified Human Breast Milk Mucin (MUC1) in an Inhibition Assay

It has been reported that breast-feeding is responsible for approximately 40% of the HIV transmissions from HIV-positive mothers to children. Human breast milk, however, is known to contain numerous biologically active components which protect breast-fed infants against bacteria, viruses, and toxins. The purpose of this study was to purify and characterize breast milk mucin and to determine its anti-HIV-1 activity in an HIV inhibition assay. Sepharose CL-4B column chromatography and caesium chloride isopycnic density gradient purification were used to isolate and purify the mucin. Following Western blotting and amino acid analysis, an HIV-1 inhibition assay was carried out to determine the anti-HIV-1 activity of crude breast milk and purified milk mucin (MUC1) by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells). SDS-PAGE analysis of the mucin, together with its amino acid composition and Western blotting, suggested that this purified mucin from human breast milk was MUC1. The HIV inhibition assay revealed that while the purified milk mucin (MUC1) inhibited the HIV-1 activity by approximately 97%, there was no inhibition of the HIV-1 activity by crude breast milk. Although the reason for this is not clear, it is likely that because the MUC1 in crude milk is enclosed by fat globules, there may not be any physical contact between the mucin and the virus in the crude breast milk. Thus, there is a need to free the mucin from the fat globules for it to be effective against the virus.

Antiviral Activity of Purified Human Breast Milk Mucin

Human breast milk is known to contain numerous biologically active components which protect breast fed infants against microbes, viruses, and toxins. The purpose of this study was to purify and characterize the breast milk mucin and determine its anti-poxvirus activity. In this study human milk mucin, free of contaminant protein and of sufficient quantity for further analysis, was isolated and purified by Sepharose CL-4B gel filtration and cesiumchloride density-gradient centrifugation. Based on the criteria of size and appearance of the bands and their electrophoretic mobility on sodium dodecyl sulfate polyacrylamide-gel electrophoresis, Western blotting together with the amino acid analysis, it is very likely that the human breast milk mucin is MUC1. It was shown that this breast milk mucin inhibits poxvirus activity by 100% using an inhibition assay with a viral concentration of 2.4 million plaque-forming units/ml. As the milk mucin seems to aggregate poxviruses prior to their entry into host cells, it is possible that this mucin may also inhibit other enveloped viruses such as HIV from entry into host cells.

Long-term injection sclerotherapy treatment for esophageal varices. A 10-year prospective evaluation.

Long-term injection sclerotherapy after proved variceal bleeding was assessed in 245 patients. The majority had alcoholic cirrhosis and the patients were equally distributed between modified Pugh-Childs risk grades A, B, and C. Esophageal varices were eradicated in 88% of the 140 patients who survived long enough for analysis, and remained eradicated for a mean of 19.4 months. The incidence of recurrent variceal bleeding after the first hospital admission was 0.02 bleeding episodes per patient month of follow-up study and was markedly reduced after eradication of varices. The overall cumulative survival rates at 1, 5, and 10 years were 54%, 39%, and 29%, respectively. The prognosis was influenced by the risk grade and the number of variceal bleeds before entering the study and to a lesser extent by the etiology of the cirrhosis. Fifty-two per cent of the patients died during the 10-year period. Liver failure was the major cause of death. Complications were mostly of a minor nature but they became cumulative with time. Minor complications included mucosal slough and injection-site leak, although the latter had an associated mortality risk. Significant esophageal stenosis and esophageal rupture were rare. As a result of this study a more radical surgical policy is proposed for sclerotherapy failures. These are defined as patients in whom varices are difficult to eradicate or who continue to have major variceal bleeds. Such patients should be subjected to either a portosystemic shunt or a devascularization and transection procedure.

Fragmentation pattern of mucins in normal and diseased gastric mucosae : A glycoprotein fractionates with gastric mucins purified from mucosal scrapings of cancer and peptic ulcer patients

Background/Aims: Gastric cancer, a fatal malignancy, is prevalent in the Western Cape region of South Africa. The aim of this study was a biochemical characterisation of gastric mucins in this disease, compared with gastric ulceration and controls from transplant donors. Methods: Mucins were extracted in a denaturing medium (to prevent endogenous proteolysis) and purified by caesium chloride density gradient ultracentrifugation. Analysis of mucin was by gel filtration, SDS-PAGE and Western blotting methods. Results: All samples of mucin when analysed by gel filtration were found to contain polymeric glycoprotein together with varying amounts of lower-molecular-weight glycoprotein. SDS-PAGE and Western blot analysis showed that diseased stomachs had glycopeptides of a wider range in size and antigenicity with a greater number of smaller fragments immunoreactive to monoclonal antibodies 2–12M1 and 9–13M1. We identified by SDS-PAGE a glycoprotein which co-fractionates in a caesium chloride density gradient with mucins isolated from gastrectomy specimens resected for carcinoma and peptic ulceration and which was absent from mucins of the transplant donor control group. This neuraminidase-sensitive glycoprotein resisted dissociation from mucin during purification in a 3.5 M CsCl density gradient but was partially separable by Sepharose 2B gel chromatography and heat treatment (100°C, 2.0 min) in SDS. Chemical analysis of the glycoprotein by HPLC favours it being an N-linked glycoprotein. Its non-ideal electrophoretic properties make its exact size estimation difficult and we ascribe to it a broad size range of Mr ∼55–65 kD. Conclusion: We conclude that mucins from diseased stomachs were more degraded than those from donors and that the diseased mucosa reproducibly secretes a Mr ∼55–65 kD glycoprotein, the role of which needs to be established.