Epidemiology of human parvovirus B19 in children with sickle cell disease

Human parvovirus (HPV) B19 causes significant morbidity and mortality in children with sickle cell disease (SCD), but little data are published about the epidemiology of HPV B19 infection and its associated complications in this patient population. In this study, prevalence and incidence rates of HPV B19 were determined in 633 patients with SCD followed at The Children's Hospital of Philadelphia between November 1996 and December 2001. Thirty percent (30%) were HPV B19 immunoglobulin G (IgG) positive at first testing, and the 70% without evidence of past HPV B19 infection were tested annually. One hundred ten patients developed evidence of HPV B19 infection for an incidence rate of 11.3 per 100 patient years. Sixty-eight episodes of HPV B19-induced transient red cell aplasia occurred with the following clinical events: fever (89.7%), pain (61.8%), acute splenic sequestration (19.1%), and acute chest syndrome (11.8%). Pain, fever, and acute splenic sequestration were more frequent events with acute HPV B19 infections compared with acute events in uninfected patients. The results of this epidemiologic study, the largest and most comprehensive to date, justify the development of HPV B19 prevention strategies to diminish the frequent and often severe complications associated with HPV B19 infections in patients with SCD.     

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

The goal of this work was to develop an in silico model that allows predicting segmental-dependent permeability throughout the small intestine (SI). In vivo permeability of 11 model drugs in 3 SI segments (jejunum, mid-SI, ileum) was studied in rats, creating a data set that reflects the conditions throughout the SI. Then, a predictive model was developed, combining physicochemical drug properties influencing the underlying mechanism of passive permeability: Log p, polar surface area, M_W, H-bond count, and Log f_u, with microenvironmental SI conditions. Excellent correlation was evident between the predicted and experimental data (R² = 0.914), with similar predictability in each SI segment. Log p and Log f_u were identified as the major determinants of permeability, with similar contribution. Total H-bond count was also a significant determinant, followed by polar surface area and M_W. Leaving out any of the model parameters decreased its predictability. The model was validated against 5 external drugs, with excellent predictability. Notably, the model was able to predict the segmental-dependent permeability of all drugs showing this trend experimentally. Model predictability was better in the high-permeability versus low-permeability range. Overall, our approach of constructing a straightforward in silico model allowed reliable predictions of segmental-dependent intestinal permeability, providing new insights into relative effects of drug-related factors and gastrointestinal environment on permeability.     

Influence of Diabetes Mellitus and Glycaemic Control on the Characteristics and Outcome of Common Infections

The aim of the present study was to elucidate the effect of diabetes and metabolic control on the presentation, sources, pathogens and outcome of common infections. Of 515 patients admitted to three departments of internal medicine because of a suspected acute infection, 132 (26 %) had diabetes mellitus. Osteomyelitis was diagnosed in 3 % of the diabetic patients and in 1 % of patients without diabetes, and infection of the extremities in 7 % and 0 %, respectively (p = 0.003). Klebsiella sp. caused 24 % of urinary tract infections in diabetic patients, versus 13 % in patients without diabetes (p = 0.1). The percentage of Staphylococcus aureus infections in diabetic patients was 10 % versus 5 % in non-diabetic patients (p = 0.06). The gross mortality rate in the diabetic patients was 10 %, and in patients without diabetes, 12 %. In patients without fatal underlying disorders, mortality in the diabetic patients was 10 % (2 % in patients with glycosylated haemoglobin (GHb) lower than median, and 17 % in patients with GHb higher than median) and in the non-diabetic patients 4 % (p = 0.04). Five factors were independently and significantly related to mortality in diabetic patients: acute respiratory distress (very large odds-ratio [OR]), coma (OR 3.8, 95 % confidence interval [CI] 1.0–14.3), GHb above the median (OR 3.3, 95 % CI 1.8–6.2), the interaction between GHb and absence of a severe underlying disorder (OR 12.0, 95 % CI 2.9–50.7) and duration of diabetes (OR of 1.072 for 1-year increment, and 1.42 for a 5-year increment). Choice of empiric antibiotic treatment in diabetic patients with suspected bacterial infection should take into account the preponderance of Klebsiella sp. and Staphylococcus aureus infections. The present results favour an association between poor glycaemic control and a fatal outcome of infectious diseases in diabetic patients.     

Clinical parameters predicting tonsillar malignancy

European Archives of Oto-Rhino-Laryngology - Tonsillectomy is indicated in unilateral tonsillar enlargement (UTE) to rule out malignancy, which eventually is found in about 1.4% of the patients....     

Effect of cyclophosphamide and levan treatment on bone marrow and peripheral blood cells in B16-F10 melanoma-bearing mice

Immunotherapeutic agents have often been found to provoke opposite effects on tumor growth--inhibitory or stimulatory--depending on dose, timing or route of administration. The reason for these opposite effects is not yet known. Levan (polyfructose), an immunomodulatory polysaccharide, has been found to exert opposite effects on the growth of the F10 variant of B16 melanoma. Low doses inhibit and high doses enhance the growth of this tumor. Cyclophosphamide (CY) augments the inhibitory effect of the polysaccharide. In order to elucidate the mechanism of these opposite effects, we tried to determine the changes induced by levan at inhibitory and stimulatory doses, alone or in conjunction with CY, on the lymphatic and hematopoietic systems of B16-F10 melanoma-bearing mice. In a previous study we reported the effect of these treatments on the morphology of spleen and lymph nodes (Leibovici, Kopel, Siegal & Gal-Mor (1986). Int. J. Immunopharmac., 8, 391). In the present study, we examined the effect of the treatments on bone marrow and peripheral blood composition. The growth of the tumor itself, as well as the various treatments, induced very marked changes in both bone marrow and blood. Tumor inoculation produced a sharp leukopenia and anemia followed by a restoration of both white and red blood cells. In the bone marrow, the tumor caused a gradual decrease in lymphocyte number. CY accentuated the severe leukopenia caused by the tumor. Lymphocyte depletion was prolonged, while restoration of granulocytes was achieved by day 7. A similar pattern of changes was observed in the bone marrow. With levan, opposite effects were observed in blood and bone marrow with the two doses in relation to the number of the cells of the lymphoid and myeloid lines: while 0.1 mg (tumor inhibitory) doses caused a more active restoration of lymphocytes as compared to 10 mg (tumor stimulatory) doses, an opposite effect was seen on the myeloid series--the high dose induced a more pronounced granulocytosis than the low dose. In the combined treatment, the low levan dose accelerated lymphocyte restoration in bone marrow compared to CY, while the high dose delayed the recovery of these cells. The results of the present study in conjunction with our previous study may explain the basis of the intriguing tumor inhibitory-stimulatory effects of some immunomodulators. Moderate increases in myeloid cell series appear to favor tumor inhibition and high increases favor tumor stimulation. In addition, the results of this study suggest that a regulatory relation might exist between the proliferation of the lymphoid and myeloid cell series.     

Enhancement of theophylline clearance by intravenous albuterol

Co-administration of intravenous albuterol and theophylline resulted in increased theophylline clearance in a child with severe asthma. This required a threefold increase in theophylline dosage to maintain therapeutic serum theophylline concentrations. The possible effect of intravenous albuterol on theophylline metabolism was further supported by a 50 percent decrease in theophylline clearance upon discontinuation of albuterol and a second increase in its clearance when albuterol was readministered. To the best of our knowledge, this is the first documentation of enhanced theophylline clearance by albuterol.     

Shyness and social phobia in Israeli Jewish vs Arab students

Background

Social anxiety disorder (SAD) has been repeatedly shown to be very prevalent in the Western society with prevalence rates of 10% or above. However, very few studies have been performed in the Middle East and in Arab countries.

Methods

A total of 300 Israeli students participated in our study and were administered the Liebowitz Social Anxiety Scale (LSAS), the Cheek and Buss Shyness Questionnaire (CBSQ), and a sociodemographic questionnaire.

Results

A total of 153 Jewish and 147 Arab students participated in the survey. Social anxiety disorder was found in 12.33% of the sample, according to the LSAS cutoff score of more than 60. The 2 subsamples had similar LSAS and CBSQ scores and similar SAD-positive rates (LSAS >60). Females had higher scores on the LSAS, as were those without a spouse and those who had been in psychological treatment. Based on a regression analysis, the significant predictors of the LSAS score were the CBSQ score and female sex. A very high correlation was found between the LSAS and the CBSQ scores.

Conclusions

Although our sample is not representative of the whole Israeli population, we conclude that SAD and shyness were similarly prevalent in Jewish and Arab students in Israel. Social anxiety disorder scores were higher among females, those without a spouse, and those who received psychological treatment. Further studies on the clinical and cultural characteristics of SAD in Israeli subcultures would add to the growing body of knowledge on SAD in various cultures.     

Comparison of budesonide and beclomethasone dipropionate for treatment of asthma.

Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 micrograms twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 micrograms twice daily.     

A simple technique for decompression of distended gallbladder during laparoscopic cholecystectomy

During laparoscopic cholecystectomy, distended gallbladder can create exposure difficulties, that precludes adequate visualization, thus rendering laparoscopic dissection impossible and even unsafe. To overcome this problems, we devised a simple technique for the decompression of distended gallbladders.