Bacterial meningitis in the newborn: a Kuwaiti experience

Forty-five neonates with bacterial meningitis admitted to a regional hospital in Kuwait over a 5-year period are reported. The attack rate was 6.7/10,000 live births. Listeria monocytogenes was the most common bacteria isolated (31 per cent), followed by Streptococcus agalactiae (15 per cent), and Escherichia coli (11 per cent). Gram negative pathogens constituted 38 per cent of the total. Ten patients died (22 per cent) and 10 (28 per cent of the survivors) developed severe neurological sequelae.     

Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.

Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.     

Ethnic differences in response to non-selective beta-blockade among racial groups in Malaysia

OBJECTIVE: To determine whether racial differences in response to blockade of beta receptors occur among racial groups in Malaysia that are the Malays, Indians and Chinese. SUBJECTS, MATERIALS AND METHOD: 35 healthy male volunteers representing the 3 main racial groups in Malaysia (12 Malays, 12 Chinese and 11 Indians) were studied in a randomized, placebo-controlled, crossover and single-blind design. Propranolol 80 mg 12-hourly was given orally for 48 hours. Six hours after the last dose subjects attended an exercise session where resting and exercise heart rate, blood pressure, plasma potassium and glucose levels, resting FEV1 and plasma propranolol concentrations were recorded. RESULTS: No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values. CONCLUSION: We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.     

Nephronophthisis: a variant

The case report describes a young boy with renal, retinal, hepatic and cerebellar involvement in a rare syndrome. He had polyuria, deranged renal functions and cystic lesions in kidneys, which led to the diagnosis of nephronophthisis (NPH). Extra-renal involvement with night blindness, truncal ataxia, mental retardation and hepatosplenomegaly. Thus, every patient with NPH should be carefully examined for extra-renal involvement.     

Detection of Infectious bursal disease virus by ELISA using an antipeptide antibody raised against VP3 region

Antigenic determinant analysis was carried out on VP3, one of major immunogenic proteins of Infectious bursal disease virus (IBDV) using computer algorithms. Altogether 17 peptides were synthesized for predicted putative regions and were tested for their reactivity with IBDV-positive polyclonal sera as well as with antisera to other common avian viruses to confirm specificity and to rule out cross reactivity. Of 17 peptides tested, three were selected and synthesized in multiple antigenic peptide (MAP) format. The immunization of rabbits with the three MAPs resulted in high humoral immune response. The purified antipeptide antibodies were screened against native IBDV antigen and the respective titers were determined. Out of the three antisera to MAPs that raised against the MAP3, spanning the amino acids (aa) 974-995 region on the VP3 protein had a very high titer (2048) and reacted specifically with IBDV. Thus, the antiserum to MAP3 detected native virus in enzyme-linked immunosorbent assay (ELISA), revealing the presence of a potential antigenic determinant on the C-terminus of the protein. This study proved that an antipeptide antibody could be used as a safe and specific tool for the diagnosis of IBD in chickens.     

A unique fracture pattern of the proximal phalanx in children: fractures through the phalangeal neck with an attached dorsal bony flange

This paper describes a unique fracture pattern of the proximal phalanx in children that has not been specifically studied in the literature. Volarly, the fracture line passes through the phalangeal neck and then the fracture line passes dorsally to include a dorsal flange of the metaphysis. Fractures were classified into three types: type I fractures were undisplaced with no finger deformity; type II fractures were mildly displaced in the antero-posterior plane without lateral angulation or scissoring; while type III fractures were severely displaced or had associated lateral angulation or scissoring deformity. Over a 6-year-period, nine cases were seen by the authors. The mechanism of injury was by entrapping the digit in a closing door in all cases. The mean age of patients was 5 years. Types I and II fractures were seen in five children and all were treated by splinting with an excellent outcome. Two children with type III fractures were treated with closed reduction and either splinting (one case) or k-wire (one case), and both had a poor initial outcome. The remaining two children with type III fractures were treated with open reduction and internal fixation with an excellent outcome. Differences between these fractures and the classic phalangeal neck fractures are discussed.     

Dependence of human forearm skin postocclusive reactive hyperemia on occlusion time

INTRODUCTION: Human postocclusive forearm skin reactive hyperemia is not only a potential means of identifying early signs of cardiovascular diseases, it can also be used in the assessment of local microvascular response to topically applied compounds on skin. The method is not fully characterized. In this study, we investigated the influence of occlusion time on postocclusive forearm skin reactive hyperemia using laser Doppler fluximetry (LDF). METHODS: Twenty healthy male volunteers were studied on three separate days (at least 24 h apart) via a randomized design. Volunteers were studied in a supine position while fasted. Laser Doppler probes were placed on the volar surface of the antebrachium. In preliminary studies, 3 min of upper arm blood flow occlusion at suprasystolic pressure was found to be the upper limit of tolerability. Subsequently, volunteers were randomized to receive 1, 2, or 3 min occlusion on 3 different days. Skin blood flux was measured before, during, and after occlusion using LDF. The primary outcome calculated was maximal change in skin blood flux before and after occlusion, expressed in arbitrary units (AU). RESULTS: Skin blood flux changes (mean+/-S.E.M.) after 1, 2, and 3 min occlusion period were 15.39+/-1.27 AU, 24.84+/-1.62 AU, and 32.14+/-1.73 AU, respectively. Using repeated-measures analysis of variance (ANOVA), significant difference (P<.05) in skin blood flux changes were revealed between these three occlusion durations, where 3 min occlusion produced significantly greater in skin blood flux occlusion change compared to 1 and 2 min occlusion. DISCUSSION: Three minutes of occlusion produces the greater postocclusive reactive hyperemia. It is recommended that studies using postocclusive forearm skin reactive hyperemia should occlude the forearm for at least 3 min.     

Paroxysmal "funny turns" in an elderly woman--a 95-year-old with an insulinoma

A 95-year-old woman was admitted to hospital with a fractured neck of femur following a fall. There was no past history of note other than numerous episodes of "funny turns" preceding falls some of which resulted in fractures. During her admission she had a "funny turn". Immediate investigations revealed hypoglycaemia and subsequent biochemical abnormalities, most likely due to a benign endocrine tumour--an insulinoma.     

Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats

Background: The present study was conducted to elucidate the protective role of Withania somnifera against bromobenzene induced nephrotoxicity and mitochondrial dysfunction in rats. Methods: In this study, Wistar albino rats of either sex were divided into six groups consisting of six animals each. The first one was control, those in group II received bromobenzene (10?mmol/kg, intragastric intubation) once, but group III and IV animals received W. somnifera (250 and 500?mg/kg, orally), respectively for 8 days followed by bromobenzene once on the 8th day and silymarin (100?mg/kg, orally) was given for 8 days to group V animals and then bromobenzene on the last day. Group VI animals received only W. somnifera (500?mg/kg) for 8 days. Results: The levels of renal lipid peroxidation, lysosomal enzymes and glycoprotein were increased significantly (p?<?0.05) in the bromobenzene alone treated rats and antioxidant status and mitochondrial enzymes were found to be decreased, when compared to the control group. The levels of kidney functional markers (urea, uric acid and creatinine) were also found to be abnormal in serum of bromobenzene alone treated rats. On the other hand, administration of W. somnifera (250 and 500?mg/kg) along with bromobenzene offered a significant dose-dependent protection to the biochemical alterations as observed in the bromobenzene alone treated rats, which was also evidenced by histopathology. Conclusion: Thus, the oral administration of W. somnifera significantly protected against the bromobenzene induced nephrotoxicity and renal mitochondrial dysfunction in rats.     

Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo

The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions ( P ≤ 0.02), in soft agar colony number and size ( P ≤ 0.05), and in anoikis resistance ( P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining ( P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination. ( Cancer Sci 2009; 100: 434–440).