Are hospitals prepared to support newborn survival? – an evaluation of eight first‐referral level hospitals in Kenya*

Objective To assess the availability of resources that support the provision of basic neonatal care in eight first‐referral level (district) hospitals in Kenya. Methods We selected two hospitals each from four of Kenya’s eight provinces with the aim of representing the diversity of this part of the health system in Kenya. We created a checklist of 53 indicator items necessary for providing essential basic care to newborns and assessed their availability at each of the eight hospitals by direct observation, and then compared our observations with the opinions of health workers providing care to newborns on recent availability for some items, using a self‐administered structured questionnaire. Results The hospitals surveyed were often unable to maintain a safe hygienic environment for patients and health care workers; staffing was insufficient and sometimes poorly organised to support the provision of care; some key equipment, laboratory tests, drugs and consumables were not available while patient management guidelines were missing in all sites. Conclusion Hospitals appear relatively poorly prepared to fill their proposed role in ensuring newborn survival. More effective interventions are needed to improve them to meet the special needs of this at‐risk group.     

Regulation of spontaneous activity and oscillatory spike firing in rat midbrain dopamine neurons recorded in vitro

Intracellular recordings were obtained from identified dopamine (DA) neurons in rat midbrain slices maintained in vitro. DA neuron membranes exhibited pronounced instantaneous and time-dependent anomalous rectification that showed evidence of maximal activation at average membrane potentials of -63 and -78 mV, respectively. Action potentials were followed by prominent afterhyperpolarizations (AHP) that consisted of two components. The fast component showed evidence of inactivation at -63 mV independent of the initial membrane potential, whereas the longer-duration, later component increased in amplitude at hyperpolarized potentials. Unlike DA neurons recorded in vivo, there was no evidence of spike frequency adaptation or summation of AHPs with prolonged depolarization-induced spike trains. Spontaneous spike discharge occurred via an endogenous pacemaker potential that was dependent on both TTX-sensitive and cobalt-sensitive processes. Hyperpolarizing prepulses could activate rebound pacemaker discharge, but this rebound activity was progressively blocked with larger-amplitude hyperpolarizing prepulses. DA neurons recorded in the anesthetized animal, freely moving animal, and in vitro preparations have been shown to exist in two states of activity: 1) spontaneously discharging action potentials or 2) hyperpolarized, quiescent, and nonfiring. Furthermore, although it is rare to find DA neurons in the untreated animal in transitional states of activity, quiescent neurons can be activated by stimuli that place a demand on the DA system. The evidence presented here is consistent with the hypothesis that the special combination of membrane properties of DA neurons contribute to the segregation of their activity into active or inactive states.     

A dosage study of the effect of the 21-aminosteroid U74006F on chronic cerebral vasospasm in a primate model

The efficacy of the 21-aminosteroid U74006F was investigated using different dosages in a restricted, randomized, placebo-controlled trial. Forty cynomolgous monkeys were divided into five groups of eight. There were two groups given treatment with placebos, one being saline and the other the vehicle in which U74006F was delivered. There were three U74006F treatment dosage groups: 0.3, 1.0, and 3.0 mg/kg. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and subarachnoid placement of a clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after experimental subarachnoid hemorrhage, angiography was repeated, and the animals were killed. In both saline or vehicle placebo treatment groups, significant vasospasm (VSP) occurred on the clot side in the extradural internal carotid artery (C3), the intradural internal carotid artery, the precommunicating segment of the anterior cerebral artery (A1,) and the MCA (P less than 0.01). After U74006F treatment, significantly less VSP developed in the A1 on the clot side (0.3 mg/kg U74006F treatment group) and the MCA (all U74006F treatment groups, P less than 0.05). When the percentages of change from the baseline for the vessel diameters on the clot side were compared, VSP was attenuated in the A1 (P less than 0.05) and MCA (P less than 0.001) of all U74006F treatment groups as compared with the placebo treatment groups. Only 0.3 mg/kg of U74006F significantly prevented VSP in C3 (P less than 0.01). Although the 0.3 mg/kg dosage appeared to have the most favorable effect, no significant differences were observed among the three dosage groups. Electron microscopy of the MCA on the clot side in the animals treated with U74006F still showed luminal convolutions and morphological changes in the endothelial cells. These changes appeared less prominent in those MCAs with milder VSP. If these results in primates are applicable to humans, U74006F would be useful in reducing VSP after aneurysmal subarachnoid hemorrhage.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.     

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.     

P-glycoprotein,multidrug resistance and tumor progression

P-glycoprotein (Pgp) is a plasma membrane protein that was first characterised in multidrug resistant cell lines. The occurrence of Pgp in clinical tumors has been widely studied. Recent investigations have begun to focus on the relationship between Pgp detection in tumors and treatment outcome. In several types of tumors, detection of Pgp correlates with poor response to chemotherapy and shorter survival. P-glycoprotein overexpression often occurs upon relapse from chemotherapy but may also occur at the time of diagnosis. Studies of experimental rat liver carcinogenesis have shown that Pgp expression increases in late stages of carcinogenesis, suggesting that Pgp may be involved in tumor progression. While some of the Pgp isoforms are known to transport hydrophobic chemotherapeutic drugs out of tumor cells, the biologic effects of Pgp overexpression in tumor cells are not fully understood, because the spectrum of substrates for Pgp-mediated transport has not been determined. In the rat liver carcinoma model, strong expression of Pgp is associated with a highly vascular stroma, suggesting that Pgp in tumor cells may affect the connective tissue stroma. The regulation of Pgp appears to be complex, and little is known about how it is up-regulated during carcinogenesis. Further studies of the role of Pgp in malignancy may contribute to our understanding of molecular mechanisms which underlie tumor progression.