KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.     

Comparison of MRI with CT for the radiotherapy planning of prostate cancer: a feasibility study

This feasibility study was performed to evaluate the suitability of MRI in defining appropriate pelvic radiotherapy treatment volumes, and to compare MRI sequences with CT for prostate cancer radiotherapy. Five patients with localized prostate cancer, imaged with four MRI sequences (spin echo (SE) T1, turbo SE (TSE) T2, high resolution TSE (HR) T2, and FLASH 3D (F3D)), compared with their corresponding CT planning scans. Segmentation ability of the following pelvic structures: prostatic apex (PA), prostate, rectum, bladder and seminal vesicles (SV), were evaluated by three independent observers. They used a five point grading scale based on the anatomical definition of the organ boundary, tissue contrast and multiplanar display. Results were averaged for the group and for each sequence. There was no significant interobserver variation in the assessed scores (p > 0.1). The average scores (+/- 1 SD) for all pelvic structures assessed by each imaging sequence were CT 1.3 +/- 0.6; SE T1 2.4 +/- 0.9; TSE T2 2.4 +/- 0.7; HR T2 2.2 +/- 0.7 and F3D 3.4 +/- 0.6. Compared with CT, the average MR score for each assessed pelvic structure was higher with a trend for all transaxial MR sequences to provide improved segmentation of the PA and rectum. The F3D sequence scored highest as it provided multiplanar views and avoided the problem of partial volume averaging. MRI, compared with CT, appears to provide improved definition of pelvic treatment volumes but further work is required to confirm this and to address the issues of MRI associated distortion and dosimetry before MRI can be used routinely for pelvic radiotherapy planning.     

Aggressive preoperative use of intraaortic balloon pump in elderly patients undergoing coronary artery bypass grafting

BACKGROUND: The use of the intraaortic balloon pump (IABP) in patients undergoing coronary artery bypass grafting has been traditionally associated with a high complication rate and adverse outcomes. However, recent reports show that many of these catastrophic outcomes can be avoided by preoperatively placing the IABP in high-risk patients. To further validate these reports, we defined a set of liberal criteria for preoperative IABP insertion and applied them to a series of elderly patients (70 years or older) undergoing isolated coronary artery bypass grafting. METHODS: Two hundred six consecutive patients who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass were retrospectively reviewed. A rapid recovery protocol emphasizing reduced cardiopulmonary bypass time, an anesthetic protocol for early extubation, perioperative administration of corticosteroids and thyroid hormone, and aggressive diuresis was applied to all patients. Patients who required an urgent operation because of failed percutaneous transluminal coronary angioplasty, a critical left main stenosis (70% or greater), pronounced left ventricular dysfunction (left ventricular ejection fraction 40% or less), or unstable angina refractory to medical therapy or who required an emergency reoperation received preoperative IABP support. RESULTS: The 30-day mortality rate for the entire group was 4.4%. There were 97 patients (47%) who received a preoperative IABP (group II) in comparison with 109 patients (53%) who did not fulfill the preoperative insertion criteria (group I). Patients in group II had a lower left ventricular ejection fraction (mean, 46% versus 59%, p<0.001) and a higher incidence of congestive heart failure (35% versus 17%, p<0.01) and acute myocardial infarction (37% versus 17%, p<0.01) than patients in group I. The average postoperative hospital length of stay for patients in group II was slightly longer than for those in group I (9.0+/-10.5 versus 6.0+/-3.7 days, p<0.01). However, there were no statistically significant differences in complication or mortality rates between the two groups. Only 2 patients (2.2%) had complications related to IABP insertion. Lower extremity ischemia occurred in both patients, and both were treated successfully with thromboembolectomy. CONCLUSIONS: Liberal preoperative insertion of the IABP can be performed safely in high-risk elderly patients undergoing coronary artery bypass grafting, with results comparable to those in lower risk patients.     

Reduced postoperative atrial fibrillation using multidrug prophylaxis

BACKGROUND: Atrial fibrillation (AFIB) is the most common complication following coronary artery bypass grafting (CABG). Despite three decades of recognition, efforts to reduce the high incidence reported (15%-30%) have been largely unsuccessful. Reasons for postoperative AFIB are likely multifactorial. As a result, we defined a multidrug prophylaxis based on agents known to be individually effective. This method was applied prospectively to a series of consecutive CABG patients with the goal of reducing the incidence of new-onset postoperative AFIB. METHODS: Isolated CABG with cardiopulmonary bypass was performed on 517 consecutive patients. A rapid recovery protocol emphasizing AFIB multidrug prophylaxis was applied to all patients. All patients received 10 microg of triiodothyronine intraoperatively when the clamp on the aorta was released. Immediately following CABG, parenteral magnesium was administered to assure a serum magnesium > 2.2 mEq/dL. Thyroxine 200 microg was administered parenterally to all patients on postoperative days 1 and 2. Metoprolol (25 mg to 100 mg/day) was begun on all patients after extubation provided: heart rate > 85 beats/min and systolic blood pressure > 130 mmHg. Parenteral procainamide (12 mg/kg) loading dose, followed by a maintenance dose (2 mg/min), was used for patients who developed premature atrial contractions (> 1/min), nonsustained supraventricular tachycardia, or any episodes of atrial fibrillation. All patients also received postoperative digitalization, steroids, and aggressive diuresis. RESULTS: The 30-day operative mortality was 3.7%. The overall incidence of new-onset postoperative AFIB was 10.3% (53 patients). There was no major difference in operative mortality (7.5% vs 3.2%, p = 0.23), Parsonnet risk score, or intraoperative variables between AFIB patients and the non-AFIB patients. Patients presenting with a preoperative acute myocardial infarction (p < 0.05), left main stenosis > or = 70% (p < 0.01), and advanced age > or = 70 years (p < 0.05) were at increased risk of developing AFIB. The length of stay for patients with AFIB was 9.9 +/- 9.6 days versus 5.9 +/- 5.2 days (p < 0.001). CONCLUSION: Application of a multidrug prophylaxis can reduce postoperative AFIB to a low incidence. Identification of associated clinical features can help predict patients at risk for postoperative AFIB. Additional strategies to target postoperative AFIB may include treatment at the earliest recognition of atrial rhythm instability.     

Women and men managers in pharmacy: gender issues

This paper examines the backgrounds, behaviours, and attitudes of a representative sample of male and female pharmacy managers in Ontario, Canada. It shows that the female managers are younger than their male colleagues, and spend significantly more time on childcare activities. There were no differences between the male and female managers in terms of work commitment and job responsibilities, but the female managers spent more time in direct patient contact, an activity that the qualitative analysis indicated was important to them. Female managers were also more supportive of strategies that would encourage additional patient counseling. For faculty in health administration programs, the results suggest that the importance that females place on the psycho-social aspects of their jobs as managers needs to be recognized and supported in the development and delivery of courses of study.     

Steric hindrance is not required for n-alkanol cutoff in soluble proteins.

A loss of potency as one ascends a homologous series of compounds (cutoff effect) is often used to map the dimensions of binding sites on a protein target. The implicit assumption of steric hindrance is rarely confirmed with direct binding measurements, yet other mechanisms for cutoff exist. We studied the binding and effect of a series of n-alkanols up to hexadecanol (C16) on two model proteins, BSA and myoglobin (MGB), using hydrogen-tritium exchange and light scattering. BSA binds the n-alkanols specifically and, at 1 mM total concentration, is stabilized with increasing potency up to decanol (C10), where a loss in stabilizing potency occurs. Cutoff in stabilizing potency is concentration-dependent and occurs at progressively longer n-alkanols at progressively lower total n-alkanol concentrations. Light scattering measurements of n-alkanol/BSA solutions show a smooth decline in binding stoichiometry with increasing chain length until C14-16, where it levels off at approximately 2:1 (alkanol:BSA). MGB does not bind the n-alkanols specifically and is destabilized by them with increasing potency until C10, where a loss in destabilizing potency occurs. Like BSA, MGB demonstrates a concentration-dependent cutoff point for the n-alkanols. Derivation of the number of methylenes bound at K(D) and the free energy contribution per bound methylene showed that no discontinuity existed to explain cutoff, rendering steric hindrance unlikely. The data also allow an energetic explanation for the variance of the cutoff point in various reductionist systems. Finally, these results render cutoff an untenable approach for mapping binding site sterics in the absence of complementary binding measurements, and a poor discriminator of target relevance to general anesthesia.     

Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

Effects of potassium citrate/citric acid intake in a mouse model of polycystic kidney disease

The kidney function in a model of autosomal dominant polycystic kidney disease (PKD), the Han:SPRD rat, is dramatically improved by chronic ingestion of a solution of potassium citrate and citric acid (KCitr). This study investigated whether this treatment would also be beneficial in the pcy/pcy mouse, a model of autosomal recessive PKD. Starting at 1 month of age, male CD-1 pcy/pcy and normal CD-1 mice were provided with a solution of 55 mM K(3) citrate/67 mM citric acid or tap water to drink. The pcy/pcy mice on the KCitr solution failed to grow normally and showed elevated plasma urea levels when compared to water-drinking littermates. Growth of normal CD-1 mice was not affected by KCitr intake. The pcy/pcy mice were then provided with a more dilute solution of KCitr to drink: this resulted in greater kidney wet and dry weights and a higher kidney weight/body weight ratio, but no beneficial effects. We conclude that pcy/pcy mice cannot tolerate a high level of KCitr intake and that a lower level is of no benefit. Whether KCitr therapy would be helpful in patients with PKD is still an open question.