Challenges in HIV post-exposure prophylaxis for occupational injuries in a large teaching hospital in Malawi

We describe the evaluation of the HIV post-exposure prophylaxis (PEP) programme for occupational injuries in Queen Elizabeth Central Hospital, Blantyre, Malawi. An audit was performed 1 year after introduction, by reviewing files of all clients who sought advice regarding PEP. In addition, the incidence of occupational injuries and awareness of the programme were assessed through interviews with nurses. The logistics of the programme were adequate. Of 29 clients who reported occupational injuries,19 started PEP. Only double antiretroviral drug therapy was available; side-effects were common but generally mild. Attendance of scheduled follow-up visits was poor, and few HIV test results after completion of PEP were obtained. Interviews with nurses revealed a high incidence of occupational injuries, but many did not report for advice about PEP; mostly because of unawareness of the programme and a reluctance to be tested for HIV.     

The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase

Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase, a model for the ouabain binding site has recently been presented (Qiu et al. J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific amino acid residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial role. In the present study, a series of ouabain analogues were tested on baculovirus-expressed Na,K-ATPase and an ouabain-sensitive mutant of non-gastric H,K-ATPase (D312E/ S319G/ A778P/ I795L/ F802C). For each analogue, the results obtained by measuring ATPase inhibition and [³H]ouabain replacement agreed rather well. In Na,K-ATPase, strophanthidin had a 7–10 times higher and digoxin a 4–12 times lower affinity than ouabain. The results of the non-gastric H,K-ATPase mutant were rather similar to that of Na,K-ATPase with exception of dihydro-ouabain that showed a much lower affinity with the non-gastric H,K-ATPase mutant. Docking studies showed that all analogues bind to the same pocket in Na,K-ATPase. However, the amino acids to which hydrogen bonds were formed differed and depended on the availability of hydroxyl or keto groups in the ouabain analogues.     

A universal epitope-based influenza vaccine and its efficacy against H5N1

Previous studies have shown that a recombinant vaccine expressing four highly conserved influenza virus epitopes has a potential for a broad spectrum, cross-reactive vaccine; it induced protection against H1, H2 and H3 influenza strains. Here, we report on the evaluation of an epitope-based vaccine in which six conserved epitopes, common to many influenza virus strains are expressed within a recombinant flagellin that serves as both a carrier and adjuvant. In an HLA-A2.1 transgenic mice model, this vaccine induced both humoral and cellular responses and conferred some protection against lethal challenge with the highly pathogenic H5N1 avian influenza strain. Hence, it is expected to protect against future strains as well. The data presented, demonstrate the feasibility of using an array of peptides for vaccination, which might pave the way to an advantageous universal influenza virus vaccine that does not require frequent updates and/or annual immunizations.     

Correlation between BMD and bone scintigraphy in patients with prostate cancer

OBJECTIVE: Bone metastasis is a major cause of morbidity in prostatic cancer. Therefore, detecting and monitoring bone lesions are crucial for treatment of prostatic carcinoma. We aimed to evaluate total body bone mineral density and regional bone mineral density in patients with prostate cancer with and without metastases, and to compare them with bone scintigraphy. METHODS: Fifty-four patients with prostatic carcinoma and 20 healthy subjects were investigated with bone scintigraphy and dual-energy X-ray absorptiometry. The bone scintigraphic findings were classified as normal (score 0: n = 22), abnormal but not typical for metastases (score 1: n = 18), and typical pattern of metastases (score 2: n = 14). RESULTS: The patients with bone metastases prostate cancer had significantly higher total bone mineral density and regional bone mineral density of trunk and pelvis than healthy controls and prostate cancer patients without bone metastases. There was a significant positive correlation between bone scan score and total bone mineral density and regional bone mineral density of trunk and pelvis (r = 0.328, P < 0.05, r = 0.60, P < 0.001, r = 0.480, P < 0.001, respectively). CONCLUSION: Our results show that patients of prostate cancer with bone metastases have increased bone mineral density (BMD) in the pelvis and trunk, possibly because of a predominance of osteoblastic over osteolytic metastases demonstrated by Tc-99m MDP bone scan.     

Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer

PURPOSE: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. PATIENTS AND METHODS: In 44 patients, Tc99m-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V20 (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. RESULTS: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V20 (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 micromol/L before treatment to 86.1 micromol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months, one case of severe renovascular hypertension was observed. CONCLUSION: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored.