Prevalence of hospital-acquired infections in a tertiary referral hospital in northern Tanzania.

Hospital-acquired infections (HAI) are a major and largely preventable cause of morbidity and morbidity worldwide. Very few reports on the prevalence of HAI in sub-Saharan Africa have been published and most of those that have appeared in the press have focused on surgical-wound infection. In the present, questionnaire-based, point-prevalence study, in which the doctor on the ward round was used as the primary informant, the prevalences of all HAI among all the inpatients at a tertiary referral hospital in northern Tanzania were estimated. On the day of the study, there were 412 inpatients (in 15 ward areas) and 61 cases of HAI were identified, giving an overall HAI prevalence of 14.8%. The prevalences of HAI were particularly high in the medical intensive-care unit (40%), the surgical (orthopaedic and general surgery) wards (36.7%), and one of the general medical wards (22.2%). Factors associated with a patient having a HAI were hospitalization for >30 days [odds ratio (OR) = 4.07; 95% confidence interval (CI) = 2.07-7.99]; being a patient on the orthopaedic and general surgical ward known as 'Surgical 2' (OR = 2.14; CI = 1.02-4.46); and being referred from another health facility (OR = 1.90; CI = 1.02-3.42). The most commonly identified HAI in the hospital were urinary-tract infections (14 cases), followed by surgical-wound infections (10 cases) and then lower respiratory-tract infections (six cases). Twenty HAI were 'unspecified'. The study was rapid and cheap to carry out. The results not only gave a baseline estimate of HAI in the study setting but also identified key areas for interventions to reduce HAI.

The British quasi-market in health care: a balance sheet of the evidence.

OBJECTIVES: To summarise the findings from a comprehensive review of research on the effects of the three main elements of the quasi-market reforms of the UK National Health Service (NHS) introduced in 1991/92: General practices becoming fundholders by volunteering to purchase elective care for their patients; Health authorities becoming purchasers of emergency, unplanned and elective services, together with a range of alternatives to fundholding operating under their auspices; The conversion of providers of hospital and community health services to NHS trusts separate from their local health authorities. METHODS: Published and unpublished studies which included any data on the impact of the three main planks of the quasi-market changes, produced between 1991 and late 1998, were identified using a combination of electronic databases, library catalogues at the King's Fund, London, bibliographies, reference lists of individual studies, a survey of NHS directors of public health and consultations with subject area experts. Each main element of the quasi-market was assessed in relation to its impact on: efficiency (primarily productivity); equity; quality; choice and responsiveness; and accountability. RESULTS: There was relatively little measurable change that could be related unequivocally to the core mechanisms of the quasi-market. CONCLUSIONS: The incentives were generally too weak and the constraints too strong to generate the consequences predicted by either proponents or critics of the quasi-market. On the other hand, the way in which the NHS operates was changed irrevocably by the reforms.

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. I. An atomic absorption spectrophotometric method.

Suitable analytical methods are required for quantitative determination of trace levels of ingredients in samples obtained for purposes of cleaning validation. We describe below an atomic absorption method for the quantitation of cisplatin, an antineoplastic agent, in aqueous samples. Cisplatin was reacted with diethyldithiocarbamic acid (DDTC), sodium salt, to yield a platinum-DDTC (Pt-DDTC) complex. The Pt-DDTC chelate was extracted into methylene chloride, the extract was mixed with acetonitrile, and the platinum content was then determined using a Zeeman atomic absorption (AA) spectrophotometer. The extraction conditions and AA experimental conditions were set up such that the detection level could be extended to 0.5 ng/ml. Reproducible results were obtained at a quantitative working standard concentration of 5 PPB. The absorbance response was found to be a linear function of cisplatin concentration in the region between 0.5 PPB and 20 PPB, which is about 10% to 400% of the target analyte concentration of 5 PPB. The target analyte concentration was set at 5 PPB such that it was at least 10 times the detection limit of about 0.5 PPB.

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. II. A high-performance liquid chromatographic method.

A high-performance liquid chromatographic (HPLC) method is described for the determination of residual levels of cisplatin from extracts of surfaces with very low surface area; from extracts of surfaces of coupons made of Teflon (polytetrafluoroethylene, PTFE), stainless steel, and glass; and in aqueous solution collected after rinsing equipment and parts. Initially, the method was developed to determine cisplatin at concentrations ranging from 20 to 200 ng/ml by direct injection. Retaining the same method conditions, the scope of the method was expanded by the addition of a sample preconcentration step, allowing analyses at levels ranging from 0.5 ng to 20 ng/ml. Preconcentration is necessary for the determination of cisplatin in rinse waters at a quantifiable concentration of about 2 PPB. Under these conditions, the detection limit is about 0.2 to 0.3 ng/ml. Residual cisplatin on different types of surfaces, including surfaces with very low surface area, can be determined by swabbing each test surface with a derivatizing solution. The cisplatin recovered in the swabbing solution can be analyzed by HPLC using direct injection or preconcentration, depending on the expected level of cisplatin in the sample. Initial methods were developed to quantitate at a cisplatin concentration of about 100 PPB or higher in solution extracted from surfaces. However, when surface areas are limited because of the size of the parts, solution concentration becomes very low as a result of the minimum volume required for extraction. To support the application of swabbing techniques to surface analysis, stainless steel, Teflon, and glass surfaces were spiked with cisplatin at 2.5 to 20 ng/cm2. Satisfactory overall recoveries of 90% +/- 10% were obtained from all surfaces. Cisplatin has no ultraviolet/visible (UV/Vis) spectral-active functional group that can be used to detect low levels of cisplatin. Hence, diethyldithiocarbamate (DDTC) was used as a derivatizing agent to increase sensitivity to UV absorption at 340 nm. Diethyldithiocarbamate forms complexes with the platinum in cisplatin to yield a platinum-DDTC (Pt-DDTC) complex with a high molar-extinction coefficient. The Pt(DDTC)2 complex thus formed was chromatographically separated and the quantitated by comparison of its detector response to that of a similarly derivatized standard preparation. DDTC also has application as a cleaning agent for cisplatin (e.g., for production equipment cleaning, spill cleanup). Destruction of cisplatin can be affected by the reaction of cisplatin with this cleaning agent. Derivatization of cisplatin will convert active cisplatin to platinum-DDTC on surfaces or in solution. Final cleaning can be accomplished using a water-for-injection rinse. After such a cleaning process, the rinse water, when collected and analyzed, showed levels of free cisplatin less than the detection concentration of 0.2 PPB and a total platinum concentration less than 10 PPB as Pt-DDTC complex.

Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular carcinoma cells.

BACKGROUND: Previous studies demonstrated that excess IL-6 production correlated with the metastatic potential of rat hepatocellular carcinoma cells. In the work reported here a retroviral construct containing the gene for murine IL-6 was introduced into otherwise nonmetastatic tumor cells to directly determine the effect of IL-6 overexpression on tumor metastatic potential. METHODS: The clonal cell lines 1682.C.2.9.L0 (L0, poorly metastatic) and 1682.C.2.9.L10 (L10, highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet. Viral supernatant was used to infect the PA317 amphotropic cell line, and retrovirus produced from these cells infected the poorly metastatic L0 hepatocellular carcinoma cell line. Neomycin-resistant cells were selected in G418 and designated L0-IL-6. RESULTS: As determined by bioassay, L0 cells produce 10 +/- 1.2 U/mL IL-6 in culture, whereas L10 cells release 95 +/- 11 U/mL (P < 0.01, Student's t-test). Retroviral-mediated IL-6 gene transfer resulted in the production of 1266 +/- 48 U/mL IL-6 by L0-IL-6 cells under identical culture conditions. When an inoculum of 5 x 10(6) cells is injected subcutaneously, both L0 and L10 cell lines result in primary tumors with equivalent rates of growth; only L10 cells metastasize to the lung, however. A similar inoculation of L0-IL-6 cells produced local tumors in all 24 animals tested. Interestingly, 15 of 24 (62%) animals presented with metastatic nodules in the abdominal cavity, whereas no such tumors were found in animals receiving L10 cells. CONCLUSION: Overexpression of IL-6 increases metastatic potential of tumor cells, with preferential metastases to the abdominal cavity when compared with tumor cells elaborating endogenous IL-6.

Interleukin-6 production by rat hepatocellular carcinoma cells is associated with metastatic potential but not with tumorigenicity.

BACKGROUND: The phenotypic characteristics that allow some tumor cells to metastasize have not been fully identified. The production and/or response of tumor cells to various growth factors have been shown to distinguish cells of differing metastatic potentials. OBJECTIVES: To determine (1) whether rat hepatocellular carcinoma cell lines produce interleukin-6 (IL-6) and (2) whether production of IL-6 correlates with either metastatic potential or tumorigenicity. METHODS: The clonal cell lines 1682.C.2.9.L0 (poorly metastatic) and 1682.C.2.9.L10 (highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet and adapted to growth in vitro. RESULTS: Both cell lines resulted in primary tumors with equal frequency and developed a 40-mm nodule in a similar period time, when an inoculum of 5 X 10(6) cells was injected subcutaneously; however, only L10 cells metastasized to the lung. These cell lines did not demonstrate differential expression of several antigens noted to correlate with metastatic potential, including CD44 variant glycoprotein, p53, transferrin receptor, and E-cadherin. In contrast, L0 cells produced less than 10 U of IL-6 per milliliter in culture (as determined by bioassay using 7TD1 cells), whereas L10 cells released more than 95 U of this cytokine per milliliter under identical culture conditions (P<.01, Student's t test). In addition, serum concentrations of IL-6 were elevated in animals bearing L10-induced primary tumors but not in those with L0-induced tumors of comparable mass. Exogenous addition of IL-6 to both tumor cell lines had no effect on the rate of growth in vitro, supporting the similar the tumorigenic potentials observed in vivo. CONCLUSION: Excess IL-6 production appears to identify cells with metastatic potential and does not appear to be essential to the establishment of a primary tumor.

Electron transport chain activity in normal and activated rat macrophages.

The pivotal role played by the macrophage in specific and nonspecific immunity suggests that the physiological status of the macrophage may effect the overall regulation of the host defense system. Many studies have evaluated macrophages as effector cells by examining expression of surface markers, cytokine release, or tumor killing in the presence of challenge to host defenses. In this report, the physiological parameter of mitochondrial respiration in freshly isolated rat macrophages is shown to be regulated upon activation in vivo. Assay conditions for the reduction of MTT [3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide] in rat macrophages were optimized and used to quantitate electron transport chain activity as a measure of mitochondrial respiration. Corynebacterium parvum administration significantly increased the activity of the mitochondrial electron transport chain in both peritoneal (120% increase, 0.18 +/- .01 vs 0.40 +/- .03, P < 0.01) and liver macrophages (143% increase, 0.12 +/- .02 vs 0.30 +/- .06, P < 0.01) as detected by augmented MTT reduction. It is demonstrated further that MTT reduction is distinct from the respiratory burst activity of macrophages and supports the mitochondrial localization of intracellular MTT reduction in this cell type. These results demonstrate that electron transport chain activity is a physiological indicator of macrophage activation.

Activation of casein kinase II in response to insulin and to epidermal growth factor.

Insulin treatment enhances casein kinase II (CKII) activity in 3T3-L1 mouse adipocytes and H4-IIE rat hepatoma cells, the magnitude of the activation varying from 30% to 150%. Activation of CKII was apparent after 5 min of exposure of 3T3-L1 cells to insulin, was maximal by 10 min, and persisted through 90 min. The insulin-stimulated activity was inhibited by low concentrations of heparin and was stimulated by spermine. Activation of CKII was effected by physiological concentrations of insulin (EC50 = 0.15 nM), suggesting that the effect is a true insulin response and not one mediated through insulin-like growth factor receptors. Epidermal growth factor (100 ng/ml for 10 min) also activated CKII in A431 human carcinoma cells, which is consistent with other observations that insulin and epidermal growth factor may have some common effects. Insulin stimulation of CKII activity was due to an increase in the maximal velocity of the kinase; the apparent Km for peptide substrate was not altered. Enhanced activity did not appear to result from increased synthesis of CKII protein, because cycloheximide did not block the effect and because an immunoblot developed with antiserum to CKII showed no effect of insulin on the cytosolic concentration of CKII. Because insulin-stimulated CKII activity was maintained after chromatography of cell extracts on Sephadex G-25, it is unlikely that the effect is mediated by a low-molecular-weight activator of the kinase. Rather, the results are consistent with the possibility that insulin activates CKII by promoting a covalent modification of the kinase.