Head imaging in suspected non accidental injury in the paediatric population. In the advent of volumetric CT imaging, has the skull X-ray become redundant?

AIM: To assess whether the inclusion of skull radiography, as part of the skeletal survey performed in suspected non-accidental injury (NAI), is still justified when volume computed tomography (CT) of the head has also been performed. MATERIALS AND METHODS: This was a retrospective study which included 94 patients aged between 24 days and 23 months who presented to the Emergency Department between August 2014 to July 2016 and had subsequent investigations for suspected NAI. Patients were identified from the local radiology systems (Carestream PACS and CRIS) using strict inclusion and exclusion criteria. Inclusion criteria were any suspected NAI patient who had both unenhanced volume CT head and skull radiography during the same episode of presentation. Any child with suspected NAI who only had one of either CT or radiographs of the skull (and not both) were excluded. RESULTS: None of the cases reviewed demonstrated additional findings on skull X-rays that were not demonstrated on the CT head. Due to the starkness of this result, the confidence interval is 0-3.9%. In two cases, additional bony findings were demonstrated on the CT head which were not evident on the skull X-rays. CONCLUSION: Skull X-rays could be excluded from the NAI skeletal survey without missing intracranial injuries or skull fractures in cases where a contemporaneous volumetric CT head is also performed.

A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area.

BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50 year olds were randomized to receive 3 doses ∼ 8 weeks apart of saline placebo, or 10 µg, 30 µg, or 100 µg of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5 µg of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1 year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (p = 0.0036 and p = 0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33 days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (p < 0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14 days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF compared to placebo (p = 0.023 and p < 0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10 µg, 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (p = 0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.

SNAREs contribute to the specificity of membrane fusion.

Intracellular membrane fusion is mediated by the formation of a four-helix bundle comprised of SNARE proteins. Every cell expresses a large number of SNARE proteins that are localized to particular membrane compartments, suggesting that the fidelity of vesicle trafficking might in part be determined by specific SNARE pairing. However, the promiscuity of SNARE pairing in vitro suggests that the information for membrane compartment organization is not encoded in the inherent ability of SNAREs to form complexes. Here, we show that exocytosis of norepinephrine from PC12 cells is only inhibited or rescued by specific SNAREs. The data suggest that SNARE pairing does underlie vesicle trafficking fidelity, and that specific SNARE interactions with other proteins may facilitate the correct pairing.

Diagnostic accuracy of C-reactive protein for active pulmonary tuberculosis: a meta-analysis.

SETTING: Systematic screening for active pulmonary tuberculosis (PTB) is recommended for high-risk populations, including people living with the human immunodeficiency virus (PLHIV); however, currently recommended TB screening tools are inadequate for most high-burden settings. OBJECTIVE: To determine whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active PTB. DESIGN: We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (10 mg/l cut-off point) for culture-positive PTB. Pooled diagnostic accuracy estimates were generated using random-effects meta-analysis for out-patients and in-patients, and for pre-specified subgroups based on HIV status and test indication. RESULTS: We identified nine unique studies enrolling 1793 adults from out-patient (five studies, 1121 patients) and in-patient settings (five studies, 672 patients), 72% of whom had confirmed HIV infection. Among out-patients, CRP had high sensitivity (93%, 95%CI 88-98) and moderate specificity (60%, 95%CI 40-75) for active PTB. Specificity was lowest among in-patients (21%, 95%CI 6-52) and highest among out-patients undergoing TB screening (range 58-81%). There was no difference in summary estimates by HIV status. CONCLUSION: CRP, which is available as a simple, inexpensive and point-of-care test, can be used to screen PLHIV presenting for routine HIV/AIDS (acquired immune-deficiency syndrome) care for active TB.

The placebo effect in irritable bowel syndrome trials: a meta-analysis.

BACKGROUND: Despite the apparent high placebo response rate in randomized placebo-controlled trials (RCT) of patients with irritable bowel syndrome (IBS), little is known about the variability and predictors of this response. OBJECTIVES: To describe the magnitude of response in placebo arms of IBS clinical trials and to identify which factors predict the variability of the placebo response. METHODS: We performed a meta-analysis of published, English language, RCT with 20 or more IBS patients who were treated for at least 2 weeks. This analysis is limited to studies that assessed global response (improvement in overall symptoms). The variables considered as potential placebo modifiers were study design, study duration, use of a run-in phase, Jadad score, entry criteria, number of office visits, number of office visits/study duration, use of diagnostic testing, gender, age and type of medication studied. FINDINGS: Forty-five placebo-controlled RCTs met the inclusion criteria. The placebo response ranged from 16.0 to 71.4% with a population-weighted average of 40.2%, 95% CI (35.9-44.4). Significant associations with lower placebo response rates were fulfillment of the Rome criteria for study entry (P=0.049) and an increased number of office visits (P=0.026). CONCLUSIONS: Placebo effects in IBS clinical trials measuring a global outcome are highly variable. Entry criteria and number of office visits are significant predictors of the placebo response. More stringent entry criteria and an increased number of office visits appear to independently decrease the placebo response.

An unusual localization of mucormycosis diagnosed by fine needle aspiration cytology: a case report.

Mucormycosis is an uncommon fungal infection, occurring mainly in patients with acidosis, chronic illnesses and malignancies. The most frequent site of involvement in patients of hematological malignancies is the respiratory tract. Isolated subcutaneous localization of mucormycosis in such patients is extremely rare. We report a case of a young patient of non-Hodgkin's lymphoma on chemotherapy who presented with a subcutaneous swelling on the anterior aspect of right thigh. Fine needle aspiration cytology (FNAC) smears from the swelling revealed numerous characteristic broad, irregularly contoured and pleomorphic hyphae of mucormycosis. This fungus seldom grows in culture and confirmation of the diagnosis depends on cytological or histological examination of infected tissues. Our case report documents a rare site of isolated mucormycosis infection and emphasizes the role of FNAC as a simple, rapid, accurate, and useful method of diagnosing fungal infections.

Cloning and expression of Vitreoscilla hemoglobin gene in Burkholderia sp. strain DNT for enhancement of 2,4-dinitrotoluene degradation.

The gene (vgb) encoding the hemoglobin (VHb) of Vitreoscilla sp. was cloned into a broad host range vector and stably transformed into Burkholderia (formerly Pseudomonas) sp. strain DNT, which is able to degrade and metabolize 2,4-dinitrotoluene (DNT). Vgb was stably maintained and expressed in functional form in this recombinant strain (YV1). When growth of YV1, in both tryptic soy broth and minimal salts broth containing DNT and yeast extract, was compared with that of the untransformed strain, YV1 grew significantly better on a cell mass basis (A(600)) and reached slightly higher maximum viable cell numbers. YV1 also had roughly twice the respiration as strain DNT on a cell mass basis, and in DNT-containing medium, YV1 degraded DNT faster than the untransformed strain. YV1 cells pregrown in medium containing DNT plus succinate showed the fastest degradation: 100% of the initial 200 ppm DNT was removed from the medium within 3 days.

Prognostic significance of DNA aneuploidy and p21 ras oncoprotein expression in colorectal cancer and their role in the determination of treatment modalities.

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21 ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21 raspositive and p21 ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21 ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.

Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system.

BACKGROUND: This study attempts to understand the correlation (if any) between surgical stress of renal transplantation and serum levels of pro-oxidant/antioxidants. METHODS: Twenty-four ESRD patients having undergone transplant surgery followed from day-1 to day-10 postsurgery were investigated for serum levels of MDA, SOD, Vit. C and E. The drug regimen received was immunosuppressant, H2 blockers and antihypertensives as per the situation. RESULTS: The typical observations indicated elevated serum levels of MDA from preoperative stage reaching peak value 24 hrs after surgery followed by a steady fall and achieving minima on the 10th day. As regards antioxidants enzyme SOD, Vit. C, Vit. E were low from pretransplant day reaching minima 24 hours postoperatively and returning to normal from 7th day. CONCLUSIONS: The present investigation has amply shown a typical imbalance between pro-oxidant/antioxidants from pretransplant day up to 24 hrs and there after returning to normal level from 7th day suggestive to desired recovery and surgical stress not a limiting factor in way of health progress renal transplant. Dietary intake of Vit. C and E in mega doses can be a good therapeutic measure.

Obstructive symptoms associated with the Lap-Band in the first 24 hours.

BACKGROUND: The Lap-Band is a gastric restrictive procedure for the treatment of morbid obesity. We review the etiology of obstructive complications that present in the first postoperative 24 h. METHODS: Fifty-six Lap-Band procedures were performed by one surgeon between January and September 2002. RESULTS: Six patients presented with obstruction within 24 h of surgery: gastric slippage in three patients, gastric edema in one patient, and esophageal hypomotility in two patients. CONCLUSIONS: Placing the band in an esophagogastric position as per Belachew and Weiner reduced our incidence of gastric slippage to none. Endoscopy with placement of a nasogastric feeding tube can relieve obstruction caused by esophageal hypomotility. Gastric edema with no clinical signs of obstruction will resolve with time. Clinicians must be aware of the unique complications that come with the advent of this new procedure.

Effects of the GABAB receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APA) on food intake in rats.

It has previously been demonstrated that central administration of the GABAB agonist baclofen increases food intake in non-deprived or satiated animals by action at the central GABAB receptors. It has also been shown that systemic administration of baclofen increases food intake in non-deprived rats. Although baclofen crosses the blood brain barrier from systemic circulation to enter the brain, it is conceivable that it may increase food intake by a peripheral mode of action. This possibility was examined in the present study. The effects of intraperitoneal (i.p.) administration of the GABAB receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APA) were investigated on food intake in non-deprived rats. 3-APA is a potent GABAB agonist that does not penetrate the blood brain barrier. The results show that while baclofen (1-4 mg/kg) increases food intake in a dose-related manner, 3-APA (0.5-2 mg/kg) has no effects on food consumption. The results indicate that a peripheral GABAB mechanism is not involved in the hyperphagia elicited by systemic administration of baclofen and suggests that the drug increases food intake by a central mode of action.

The effects of the benzodiazepine receptor ligand 3-(methoxycarbonyl) amino-beta-carboline on food and water intake in rats.

The effects of the benzodiazepine receptor ligand 3-(methoxycarbonyl) amino-beta-carboline (beta-CMC) were investigated on food intake in rats that had been fasted for 22 h, and on water intake in rats that had been deprived of water for 16 h. beta-CMC (2-8 mg/kg i.p.) produced a dose-related inhibition of food intake. Significant hyperphagia (p < 0.01) was observed with the 8 mg/kg dose. By contrast, the 8 mg/kg dose did not affect water intake in thirsty rats. The data suggests that beta-CMC has properties on food intake similar to those of a benzodiazepine receptor inverse agonist.

Interpreting epithelial cell abnormalities detected during cervical smear screening--a cytohistologic approach.

PURPOSE: To determine the underlying pathology and clinical significance of epithelial cell abnormalities (ECA) identified during cervical Papanicolaou (Pap) smear screening. MATERIAL AND METHODS: A total of 19,215 Pap smears stained by Papanicolaou stain were screened during a 36-month period. They were classified according to The Bethesda System (TBS) for cervical cytology screening and the results of ECA were compared with histology. The chi square test was applied to determine the significance and validity of high-grade lesions on cytology diagnosis. RESULT: 360 cases of ECA were identified. Mean age at presentation was 50.58 years. Cytohistologic correlation of ECA was possible in n = 249 (69.17%) of cases. Out of these, 18 cases were negative, six were inflammatory, three were benign, and 222 cases showed pathology ranging from mild dysplasia to invasive carcinoma. The chi square test showed a highly significant predictive value (p < 0.001) for high-grade lesions detected on Pap smears. CONCLUSION: Pap smear results of high-grade squamous intraepithelial lesions (HSIL) or invasive malignancy are highly reliable and the patient may be considered directly for therapeutic intervention. Of cytologically detected ASCUS cases 38.89% were diagnosed as CIN (1-3) on histology. Thus the management of these patients needs to be re-evaluated. Atypical glandular cells of undetermined significance (AGUS) detected in postmenopausal women signify an underlying pathology. These patients should be further investigated and followed to biopsy if necessary.

Radiology case of the month. Incidental discovery on mammography done for a palpable breast mass. Granular cell tumor.

A 32-two-year-old woman complains of a palpable lump in her left breast. Her past medical and family history is non-contributory. There was no palpable lump on clinical breast examination. A mammogram was performed.

Role of mitotic counts in the grading and prognosis of the breast cancer.

100 Cases of invasive breast cancer were studied for Tumor type, Tumor site, Nodal Status, Mitotic counts, Nuclear pleomorphism, Tubule formation and Nottingham modification of Bloom Richardson Grading. The follow up of the 82 patients treated with surgery and adjuvant treatment was available. Mitotic activity index (MAI) counted with strict criteria of elston CW, emerged as one of the most significant prognostic parameter followed by overall grade in predicting Tumor free survival (TFS) for the patients. Mitotic count also correlated well with overall Grade and lymph node status in predicting the TFS. This parameter is very useful where advanced studies like flowcytometry and immunohistochemical studies of the cell proliferation marker are not available.

Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique.

The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome.

OBJECTIVE: Comparison of the differences between availability of animal-derived surfactant preparations used to treat premature infants is incomplete. The objective of this study was to assess the short-term treatment efficacy of the two most commonly used surfactant preparations in the United States, beractant (100 mg kg(-1) initial and subsequent doses) and poractant alfa (200 mg kg(-1) initial and 100 mg kg(-1) subsequent doses), in very premature, mechanically ventilated infants <30 weeks gestation with respiratory distress syndrome (RDS). STUDY DESIGN: Inborn infants at two institutions, open label, 1:1, randomized controlled trial. Level of respiratory support for first 72 h of life. Morbidities of prematurity observed during the neonatal intensive care unit hospitalization. RESULT: We studied 52 infants 24 0/7 to 29 6/7 weeks gestation; 25 received poractant alfa (27.1±1.6 weeks, birth weight of 930±231 g) and 27 received beractant (26.7±1.7 weeks, P=0.343 and birth weight 900±271 g, P=0.668). Respiratory support for the first 72 h of life was lower in the poractant alfa than beractant group for mean airway pressure (MAP, P=0.003) and respiratory index (MAP × FiO(2), P=0.032). Infants in the poractant alfa group had a greater number of infants extubated at 48 (13/25 vs 6/27, P=0.027) and 72 h (15/25 vs 8/27, P=0.029) than the beractant group. Although the study was not powered to detect morbidities of prematurity, the prevalence of PDA and air leaks was less in the infants treated with poractant alfa than in those treated with beractant. Rates of bronchopulmonary dysplasia (8/23 vs 11/22, P=0.303) or death (2/25 [corrected] vs 5/27, P=0.272) were similar in the infants treated with poractant alfa and beractant, respectively. CONCLUSION: This study suggests significant short-term benefits to the use of the larger initial dose of poractant alfa than beractant in very premature infants with RDS. Further studies involving a larger number of preterm infants are needed to assess long-term effects.

Development and Validation of a Simple Isocratic HPLC Method for Simultaneous Estimation of Phytosterols in Cissus quadrangularis.

Cissus quadrangularis L. is a promising remedy prescribed in the ancient Ayurvedic literature for bone fracture healing properties. As this activity has been extensively investigated and well established, a range of formulations containing C. quadrangularis has been marketed. This work reports the development and validation of a reliable RP-HPLC method for the analysis of phytosterols in the various extracts of the plant. The proposed method utilizes a Cosmosil C(8) column (250 ΄ 4.6 mm) with a compatible Phenomenex C(8) guard column with isocratic elution of acetonitrile and water (95:5 v/v) at 25°. An effluent flow rate of 2 ml/min and UV detection at 202 nm was used for the analysis of phytosterols. The described method was linear in the range of 1-500 µg/ml, with excellent correlation coefficients. The precision, robustness and ruggedness values were also within the prescribed limits (less than 2%). The recovery values were within the range, which indicates that the accuracy of the analysis was good and that the interference of the matrix with the recovery of phytosterols was low. The phytosterols were found to be stable in a stock solution for 48 h (% RSD was below 2%) and no interfering extra peaks were observed under controlled stress conditions. The proposed method is simple, specific, precise, accurate, and reproducible and thus can be used for routine analysis of C. quadrangularis phytosterols in quality control laboratories.

Safety and immunogenicity of a recombinant nonglycosylated erythrocyte binding antigen 175 Region II malaria vaccine in healthy adults living in an area where malaria is not endemic.

Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 µg) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.