Aids and cancer in Africa: the evolving epidemic in Zimbabwe

BACKGROUND: Zimbabwe is severely affected by the AIDS epidemic, and many cancers in African populations are related to infectious agents. OBJECTIVE: To study the current pattern, and short-term changes in incidence, of cancers related to infectious agents (and especially to HIV), with respect to the evolving epidemic of AIDS. METHODS: Analysis of data on the African population of Harare, Zimbabwe, from the Zimbabwe Cancer Registry, for the period 1990-1995. Comparison with data on prevalence of HIV seropositivity, and notifications of AIDS. RESULTS: Comparing results from 1993-1995 with those for 1990-1992 shows a continuing increase in the incidence of Kaposi's sarcoma with a doubling of the rates in both men and women. A dramatic increase in the incidence of squamous cell tumours of the conjunctiva was also observed, as well as a significant increase in the incidence of non-Hodgkin's lymphoma in women. There was no apparent increase in risk for Hodgkin's disease, myeloma, liver cancer, or cancer of the cervix. CONCLUSIONS: The AIDS epidemic has had a dramatic effect on the profile of cancer. The changes in incidence involve several cancers previously linked to AIDS in North America and Europe.     

Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay

Purpose

We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections.

Subjects and methods

Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients’ data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment.

Results

A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N = 319). All-cause 30-day mortality rates were 20.1% (N = 64) and 11.8% (N = 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio = 1.88, 95% confidence interval [CI], 1.29-2.72, P = .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio = 1.58, 95% CI, 0.99-2.54, P = .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P = .002). This association was consistent after adjusting for other variables (P = .006).

Conclusion

Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.     

毛茛甙的抗诱变作用及代谢转化

研究表明,毛茛甙可显著抑制MMC和MMS等诱变剂对沙门氏菌TA_(100)和TA_(102)回复突变作用;对MMC诱发的小鼠PEC徽核抑制率达56.5%。代谢研究表明:毛茛甙抑制DNA生物合成的作用可被肝微粒体酶和胞浆液分别降低46和12%;RP-HPLC测定显示,体外毛茛甙可被肝微粒代谢转化。     

Microwave hyperthermia radiosensitized iridium-192 for recurrent brain malignancy

Twenty-one patients whose solitary detectable biopsy proven recurrent brain malignancies produced Central Nervous System (CNS) symptoms warranting further intervention received 60-minute 43 degrees C (180 degree-minute) interstitial 2450 MHz microwave hyperthermia fractions. All received brain teletherapy prior to recurrence. The first 15 received no brachytherapy and served as a toxicity pilot. All 15 enjoyed neurologic improvement, 12 symptomatic improvement, and 12 objective response as mass reduction and/or tumor necrosis. The next 6 patients were selected with more favorable Karnofsky performance status, no known active malignancy elsewhere, and received afterloading Ir-192 interstitial implantation juxtaposed to radiosensitizing hyperthermia. Volume dose varied from 1000 to 2245 rad, and dose rate from 40 to 100 rad/hr. Dose selected varied as a function of pre-recurrence teletherapy dose, general condition, histologic type, and volume. Neurosurgical debulking, if technically indicated through no additional aperture or trauma, was permitted if consistent with preservation of neurological function. Six enjoyed neurologic improvement, symptom reduction, and objective tumor response; three remain alive, and one experienced transient improvement. Complications, histologic subtypes, autopsy findings, stereotactic approach, thermal monitoring methods and CT follow-up of objective response are presented along with computer dosimetry and isotherm chart. Our microtraumatic universal catheter technique for CT guided stereotactic biopsy, aspiration, decompression, thermal sensory loop, thermalization antennae, and brachytherapy without multiple trauma nor changing catheters is stressed. The rationale for combined modes peculiar to the CNS will be outlined.2+ Proposal for incorporating controlled-release ARA-C chemotherapy polymer micro-rods into the interstitial format will be offered. The preceeding is an FDA-approved controlled clinical trial.(ABSTRACT TRUNCATED AT 250 WORDS)     

A projection of the impact of lipid-lowering therapy on high-risk employee disability and medical costs

OBJECTIVE: The objective of this study was to examine the impact of introducing rosuvastatin calcium on direct and indirect costs among patients at high risk for coronary heart disease. METHODS: An economic simulation model was developed to project the number of cardiovascular events and associated direct and indirect costs under varying treatment scenarios. RESULTS: In an average-sized commercial health plan with 210,000 covered lives and 9,336 high-risk patients, an uptake of rosuvastatin by 11% of high-risk patients would result in eight fewer cardiovascular events, a net savings of 0.85 million dollars in direct medical costs and a net savings of 36,404 dollars in productivity loss over a period of 5 years. The overall reduction in total costs is equivalent to 1735 dollars per rosuvastatin-treated patient. CONCLUSIONS: At current statin prices, the use of rosuvastatin could lead to fewer cardiovascular events and lower direct and indirect costs.     

Nanoparticle translocation across mouse alveolar epithelial cell monolayers: Species-specific mechanisms

Studies of polystyrene nanoparticle (PNP) trafficking across mouse alveolar epithelial cell monolayers (MAECM) show apical-to-basolateral flux of 20 and 120 nm amidine-modified PNP is ~ 65 times faster than that of 20 and 100 nm carboxylate-modified PNP, respectively. Calcium chelation with EGTA has little effect on amidine-modified PNP flux, but increases carboxylate-modified PNP flux ~ 50-fold. PNP flux is unaffected by methyl-β-cyclodextrin, while ~ 70% decrease in amidine- (but not carboxylate-) modified PNP flux occurs across chlorpromazine- or dynasore-treated MAECM. Confocal microscopy reveals intracellular amidine- and carboxylate-modified PNP and association of amidine- (but not carboxylate-) modified PNP with clathrin heavy chain. These data indicate (1) amidine-modified PNP translocate across MAECM primarily via clathrin-mediated endocytosis and (2) physicochemical properties (e.g., surface charge) determine PNP interactions with mouse alveolar epithelium. Uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and (based on comparison with our prior results) specific epithelial cell type.From the Clinical EditorIn this study of polystyrene nanoparticle trafficking across mouse alveolar epithelial cell monolayers, the authors determined that uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and the specific type of epithelial cells.     

Studies on the mechanisms of active ion fluxes across alveolar epithelial cell monolayers

Summary To investigate the cell physiologic and biological properties of the alveolar epithelium, we studied rat alveolar epithelial cell monolayers grown on permeable supports in primary culture. Type II alveolar epithelial cells were disaggregated using elastase, and partially purified on a discontinuous metrizamide gradient. These isolated cells were plated onto tissue culture-treated Nuclepore membrane filters at 1.5×10⁶ cells/cm² and maintained in a humidified incubator (5% CO₂ in air, 37° C). After 2 days in culture, the bathing media on both sides of the cell monolayers were changed to fresh culture medium, thus removing nonadherent cells (mostly leukocytes). These monolayers exhibit a high transmonolayer resistance (>2000 -cm²) and actively transport ions. Radionuclide flux studies indicate that Na⁺ is the predominant ionic species absorbed actively under baseline conditions, accounting for about 80% of the total active ion transport. Cl^– seems to be passively transported across the epithelium. However, when the epithelium is exposed to a beta-agonist (terbutaline), active absorption of Na⁺ is increased and active absorption of Cl^– occurs. Although it is clear that both active Na⁺ and Cl^– transport are dependent on Na⁺/K⁺-ATPase activity, and that Na⁺ enters cells predominantly through channels, the specific mechanisms by which Cl^– enters and exits the alveolar epithelial cells remain unclear. The stimulated reabsorption of Na⁺ and Cl^– may be important in helping to remove excess fluid from alveolar air spaces in the lung.