Diadenosine pentaphosphate increases levels of intracellular calcium in astrocytes by a mechanism involving release from caffeine/ryanodine- and IP3-sensitive stores

Diadenosine polyphosphates (ApnAs, n = 2 to 6 phosphate groups) activate P2-type cell-surface adenine nucleotide purinoreceptors, increase the influx of calcium into neural cells, and modulate the binding of ryanodine to ryanodine receptor-regulated intracellular calcium release channels. In this study, we tested the hypothesis, using single cell fluorescence techniques and cultured human fetal astrocytes, that p1, P5-di(adenosine-5') pentaphosphate (Ap5A)-induced increases in levels of intracellular calcium ([Ca2+]i) resulted from release of calcium from intracellular pools. Basal [Ca2+]i were 141+/-12 nM and Ap5A increased [Ca2+]i to 980+/-150 nM. The effect of Ap5A on [Ca2+]i was mediated in part through activation of purinoceptors and influx of extracellular calcium because the purinoceptor antagonist pyridoxal-phosphate-6-azophenel-2', 4'-disuphonic acid blocked by 52%, and chelation of extracellular calcium with EGTA prevented, almost completely, Ap5A-induced increases in [Ca2+]i. Implicating calcium release from IP3- and ryanodine-regulated pools of intracellular calcium were findings that Ap5A-induced increases in [Ca2+]i were blocked, at least in part, by thapsigargin, ryanodine, caffeine, and xestospongin, and Ap5A increased by 2-fold the production of IP3. Release of calcium from IP3- and ryanodine-regulated intracellular pools may be an important signaling event in neural cells that are exposed to Ap5A.     

One-year audit of admissions to the Intensive Care Unit of the Queen Elizabeth Central Hospital,Blantyre

The intensive care unit at Queen Elizabeth Central Hospital (QECH) has 4 beds and offers level 2 care. A retrospective audit of all admissions to the unit during 2002 was carried out. There were a total of 339 admissions giving a bed occupancy rate of 82 %. Surgical patients made up 81 % of admissions. 45% of all admissions were ventilated. Overall mortality was 38%. Ventilated patients had a mortality of 71% compared with 10% for non-ventilated. Data are also presented for mortality within the surgical and paediatric surgical admissions.     

Car surfing: an underreported mechanism of serious injury in children and adolescents

BACKGROUND: Car surfing, in which participants stand on top of a moving vehicle as though it were a surfboard, has been reported as a cause of traumatic injury in only 5 cases in the literature. Over the last 8 years, however, the authors have treated 26 children, primarily adolescents, for injuries resulting from car surfing. This report describes the injuries and outcomes of this potentially underreported mechanism of injury. METHODS: Medical records of 26 patients treated for car surfing injuries between 1991 and 1999 were reviewed. Demographics, hospital course, and type and severity of injuries were analyzed. RESULTS: Eighteen boys (69%) and 8 girls (31%) with an average age of 15.7+/-3.4 years (range, 6 to 22) have presented with injuries related to car surfing. All patients had fallen from the hood, roof, or trunk of a moving motor vehicle, the majority falling from the hood (n = 13; 50%). Injury severity was evaluated using the Injury Severity Scores (ISS; 12.4+/-6.5), Revised Trauma Score (RTS; 7.5+/- 1.1) and Glasgow Coma Score (GCS; 13.5+/-3.2). Injury severity was equivalent between boys and girls (P>.05). Central nervous system injuries predominated, with closed head injuries occurring in 22 (85%) and loss of consciousness in 10 (39%). Skull fractures occurred in 11 (42%) and intracranial bleeding in 9 (35%). Long-term cognitive rehabilitation was necessary in 22 (85%) patients. Three patients (12%) had spinal column fractures, with 2 (8%) suffering permanent paralysis. Two extremity (8%) and 3 (11.7%) pelvic fractures occurred. Most patients (73%) suffered significant skin and soft tissue injuries. Two patients (8%) presented with solid visceral injuries, and 1 child died. CONCLUSIONS: Car surfing is an extremely high-risk behavior in children and adolescents that leads to significant morbidity, long-term disability, and is potentially fatal. The incidence of car surfing may be greater than has been reported previously; therefore, prevention programs aimed at discouraging this high-risk behavior in children and adolescents should be considered.     

The clinical significance of vacuum mixing bone cement

This controlled study compared the strength and porosity of 48 polymethylmethacrylate cement-implant constructs prepared with open bowl versus vacuum mix technique. Forty-eight blast finished stainless steel rods of 13 mm diameter were implanted with centralizers into 17-mm inner diameter tubes that had been retrograde filled with polymethylmethacrylate cement. The eight cement preparations used were open bowl and vacuum mixed Simplex, Osteobond, Zimmer Dough Type, or Palacos R. Six replications of each condition were performed. The tubes were maintained at 37 degrees C. Each tube was cut transversely into five segments. The center three segments were used for data analysis: pushout strength, cycles to failure, and interface porosity analysis. Rod pushout data showed there was no significant difference between open bowl and vacuum mixed samples when all cement brands were combined. Mean sheer force for Palacos R vacuum mixed samples was greater than open bowl (634+/-47 versus 423+/-171), whereas the force for the Zimmer Dough Type cement open bowl was greater than that of the vacuum mixed samples (901+/-71 versus 705 +/-82). Cycles to failure data did not show significant differences when open bowl and vacuum mixed samples were compared when cements were analyzed individually or combined. Image analysis of cement-implant interfaces showed that vacuum mixing reduced void area significantly compared with open bowl mixing in the Palacos R and Osteobond preparations. Vacuum mixing does not appear to reduce cement prosthesis interface porosity or improve its mechanical properties in all cements.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.      

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.      

蛋白C抑制剂对人精子顶体反应和顶体素活性的影响

本研究应用提纯的尿PCI 进行对精子顶体反应和顶体酶的抑制试验。当洗涤后的精子与PCI 一起在体外孵育,其活动率和顶体反应未见降低;但当精子提取物或猪纯顶体素与PCI一起孵育时,其酰胺酶活性明显受到抑制且与PCI 剂量反应时间相关。这种抑制效应可能是通过形成PCI-顶体素复合物而起作用的,尽管这种复合物对SDS不稳定。精液中PCI 的高浓度(220±41.0mg/l)可能通过抑制由于精于变性或受损时释放出的顶体素或其它蛋白酶活性,从而保护生殖道上皮或精子本身不受酶的降解。     

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.     

Management of renal complications in patients with advanced multiple myeloma

Although the kidney is frequently involved in malignant monoclonal gammopathy, the clinical outcome of the patients varies considerably. We retrospectively assessed the clinical course in seventeen patients with acute and chronic renal failure suffering from multiple myeloma, and analyzed their case history focusing on the therapeutic management, the possible clinical improvement as well as the patients' outcome. Treatment included chemotherapy (n = 17), forced diuresis (n = 3), hemodialysis (n = 11, 7 chronic, 4 intermittent) and plasmapheresis (n = 3). Renal function improved in five patients, and was stabilized compensated in four. Seven patients developed end-stage renal disease, one refused further treatment and was lost for follow up. In addition to renal failure, the most frequent complications included local bone destruction (all), anemia (n = 12), low platelet count (n = 11), and bacterial infections (n = 9). One year survival rate after admission to the nephrology department was 76 percent. Chemotherapy in combination with renal replacement therapy may improve the clinical course even in MM patients with serum creatinine levels above 3.0 mg/dL or end-stage renal disease.