Evaluation of antiretroviral therapy results in Blantyre,Malawi

We performed a cross sectional study to evaluate treatment results of the paying antiretroviral therapy clinic of Queen Elizabeth Central Hospital, Blantyre. The only antiretroviral therapy was a fixed drug combination of stavudine, lamivudine and nevirapine.

Methods

Interviews, laboratory tests (CD4 count, viral load, nevirapine plasma levels, transaminases) and data extraction from files. 422 (59 %) of the patients who started antiretroviral therapy since 2000 were lost to follow up. The 176 patients enrolled in the study had good virological and excellent clinical treatment results. The most common side effect was peripheral neuropathy. Nevirapine plasma levels were remarkably high and associated with successful virological treatment results. Two simple adherence questions pertaining to the use of medication in the previous 8 days corresponded well with nevirapine levels. The most important reasons for non-adherence were shortage of drugs in the hospital pharmacy and personal financial constraints.

Conclusions

1. Many patients were lost to follow up.
2. High nevirapine levels contributed to good therapy results in those studied.
3. Simple adherence questions predicted sub-therapeutic nevirapine levels.
4. Antiretroviral drug supply needs to be uninterrupted and free of charge, to prevent avoidable non-adherence.

     

Reproducibility of cervical range of motion in patients with neck pain

Background  

Reproducibility measurements of the range of motion are an important prerequisite for the interpretation of study results. The aim of the study is to assess the intra-rater and inter-rater reproducibility of the measurement of active Range of Motion (ROM) in patients with neck pain using the Cybex Electronic Digital Inclinometer-320 (EDI-320).     

Obstruction of the left hepatic duct: diagnosis and treatment by selective fine-needle cholangiography and percutaneous biliary drainage

Obstruction of the left hepatic duct due to periportal pathologic conditions was identified by fine-needle transhepatic cholangiography in 28 patients. Selective cholangiography of the left duct was performed in 30 instances and subsequent selective left-sided catheter decompression was carried out in 23 cases. Techniques for selective puncture and drainage of the left duct required procedure modifications to accommodate the specific anatomic and pathologic features of the obstructed left duct system. Ultrasonography was indispensable as an aid to delineation of the left duct anatomy for directing needle puncture. Accurate documentation and successful catheter drainage of left duct obstruction are important contributions to the total management of patients with high biliary obstruction.     

Conservative treatment in patients with an acute lumbosacral radicular syndrome: design of a randomised clinical trial [ISRCTN68857256]

Background  

The objective is to present the design of randomised clinical trial (RCT) on the effectiveness of physical therapy added to general practitioners management compared to general practitioners management only in patients with an acute lumbosacral radicular syndrome (also called sciatica).     

Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth

The tumor suppressor gene phosphatase and tensin homologue (PTEN) regulates the phosphatidylinositol-3'-kinase (PI3K) signaling pathway and has been shown to correlate with poor prognosis in high-grade astrocytomas when mutational inactivation or loss of the PTEN gene occurs. PTEN mutation leads to constitutive activation of protein kinase B (PKB)/Akt with phosphorylation at the PKB/Akt sites Thr-308 and Ser-473. Integrin-linked kinase (ILK) has been shown to regulate PKB/Akt activity with the loss of PTEN in prostate cancer. We now demonstrate that ILK activity regulates PKB/Akt activity in glioblastoma cells. The activity of ILK is constitutively elevated in a serum-independent manner in PTEN mutant cells, and transfection of wild-type PTEN under the control of an inducible promoter into mutant PTEN cells inhibits ILK activity. Transfection of ILK antisense (ILKAS) or exposure to a small-molecule ILK inhibitor suppresses the constitutive phosphorylation of PKB/Akt on Ser-473 in PTEN-mutant glioblastoma cell lines. In addition, the delivery of ILKAS to PTEN-negative glioblastoma cells resulted in apoptosis. Rag-2M mice bearing established ( approximately 100 mg) human U87MG glioblastoma tumors, treated QD x 5 for 3 consecutive weeks with ILKAS (i.p. 5 mg/kg), exhibited stable disease with < or =7% increase in tumor volume over the 3-week course of treatment. In contrast, animals treated with an oligonucleotide control or saline exhibited a >100% increase in tumor volume over the same time period. Our initial results indicate that therapeutic strategies targeting ILK may be beneficial in the treatment of glioblastomas.     

Improved outcome of preterm infants when delivered in tertiary care centers

OBJECTIVE: Previous studies that compared outcomes of infants born outside tertiary care centers (outborn) with those born in tertiary care centers (inborn) did not account for admission illness severity and perinatal risks. The objective of this study was to examine whether outborn status is associated with higher mortality and morbidity, after adjustment for perinatal risks and admission illness severity (using the Score for Neonatal Acute Physiology, Version II [SNAP-II]) among preterm infants who were admitted to Neonatal Intensive Care Units (NICUs). METHODS: Logistic regression analysis was used to compare the risk-adjusted outcomes of 3769 singleton infants born at or before 32 weeks' gestation, who were admitted to 17 Canadian NICUs during 1996-1997. RESULTS: Outborn and inborn infants had significantly different gestational ages, perinatal risk factors (maternal hypertension, prenatal care, antenatal corticosteroid therapy, 5-minute Apgar score, delivery type, small for gestational age) and admission SNAP-II. Outborn infants were at higher risk of death (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2, 2.5), grade III or IV intraventricular hemorrhage (adjusted OR 2.2, 95% CI 1.5, 3.2), patent ductus arteriosus (adjusted OR 1.6, 95% CI 1.2, 2.1), respiratory distress syndrome (adjusted OR 4.8, 95% CI 3.6, 6.3), and nosocomial infection (adjusted OR 2.5, 95% CI 1.9, 3.3), even after adjusting for perinatal risks and admission illness severity. CONCLUSIONS: Outborn infants were less mature and more ill than inborn infants at NICU admission. However, even after adjustment for perinatal risks and admission illness severity, inborn infants had better outcomes than outborn infants. Our results support in-utero transfer of high-risk pregnancies to a tertiary level facility.     

The effect of antigen given intravenously on specific antigen-sensitive lymphocytes of peripheral blood in man

In the course of fibrinolytic therapy with the streptococcal antigen streptokinase the effect of antigen intravenously on specific antigen-sensitive lymphocytes in the peripheral blood was studied.

Seven out of ten patients had streptokinase-sensitive lymphocytes in the peripheral blood before the beginning of therapy. Stimulation by streptokinase was temporarily rendered negative in all seven cases during the course of treatment. Some time after the termination of therapy specifically sensitive lymphocytes reappeared in the circulation. Lymphocytes of three patients were stimulated by streptokinase only after the treatment period.

Stimulation of lymphocytes by phytohaemagglutinin or by tuberculin in sensitized individuals, was not disturbed. Thus streptokinase given intravenously involves selectively streptokinase-sensitive cells. It is assumed that after interaction with homologous antigen these lymphocytes are directed to lymphoid tissues where proliferation and differentiation takes place.