Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study

A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident.     

Reconstruction of intraoral mucosal defects with revascularized jejunal segments

The intraoral mucosa subserves a multitude of structural and functional roles. This paper details the importance of this within the context of reconstruction. The various methods are reviewed historically. Also, both the experimental and clinical basis for using revascularized jejunum as mucosal reconstruction are presented. © 1994 Wiley-Liss, Inc.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Comprehensive mutational scanning of the p53 coding region by two- dimensional gene scanning

A comprehensive mutational scanning test for the p53 coding region based on multiplex PCR and two-dimensional DNA electrophoresis was designed and evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11) was amplified as a single 8646-bp fragment by long- distance PCR in step one. This fragment served as a template for the subsequent co-amplification of the individual exons in two multiplex groups in step two. The multiplex products were then separated, first on the basis of size in non-denaturant polyacrylamide gels and then on the basis of sequence by denaturing gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting behavior and 2-D gel distribution were designed using a recently developed computer program. The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li- Fraumeni syndrome patients with previously identified germline mutations. All mutations were correctly detected. This assay provides an accurate, cost-effective and non-radioactive method for simultaneous mutational scanning of all p53 coding exons.      

Risk factors for wound infection after cholecystectomy.

BACKGROUND AND PURPOSE: Surgical site infection (SSI) after cholecystectomy is a common problem. The aim of this study was to identify the possible risk factors for the development of SSI. METHODS: 545 consecutive patients who received open (125) or laparoscopic (420) cholecystectomy due to gallbladder disease during the years 1998 to 2000 were included in the study. Potential risk factors including clinical features, biochemical data, and operative types were analyzed by univariate and multivariate analysis. RESULTS: The overall incidence of SSI was 4.4% (24/545). The wound complication rate was significantly lower in the laparoscopic group than in the open group (1.4% vs 14.4%, respectively). Factors associated with SSI found by univariate analysis (p < 0.05) included age, gender, acute cholecystitis, white blood cell count, serum albumin, blood glucose and bilirubin level, type of surgery, operative time and positive bile culture. Stepwise logistic regression analysis showed that abnormal blood glucose [odds ratio (OR), 4.7; 95% confidence interval (CI), 1.6 to 13.5], positive bile culture (OR, 3.5; 95% CI, 1.2 to 10.4), and open cholecystectomy (OR, 4.3; 95% CI, 1.3 to 13.6) were the most significant predictors of SSI. CONCLUSION: Poor control of diabetes mellitus before surgery, positive bile culture and open cholecystectomy significantly increased the rate of SSI. These findings indicate that better control of diabetes mellitus, and appropriate selection of surgical procedure and antibiotic regimen in the management of high-risk patients may reduce the incidence of postoperative SSI.     

Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?

HYPOTHESIS: Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection. DESIGN: A case-controlled study. SETTING: A referral center. PATIENTS: Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study. INTERVENTION: Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value. MAIN OUTCOME MEASURE: The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity. RESULTS: From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively). CONCLUSIONS: Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.     

Preformulation study of a poorly water-soluble drug, alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol: selection of the base for dosage form design

The physicochemical properties of the base and hydrochloride salt of the poorly water-soluble drug alpha-pentyl-3-(2-quinolinylmethoxy) benzenemethanol (REV 5901) were investigated in order to select an appropriate form of the drug for dosage form development. The pH-solubility profiles of both the base and the salt at 37 degrees C were identical and were in agreement with a pKa value of 3.67 determined by the UV spectral method. The solubility of the drug (approximately 0.002 mg/mL at pH 6) increased gradually with a decrease in pH and reached a value of 0.95 mg/mL at pH 1; at pH values less than 1, the solubility decreased due to the common-ion effect. The pHmax, i.e., the pH of maximum solubility of the drug was, therefore, 1.0. The role of the pHmax in the selection of a salt or base form of a compound was investigated. Due to the conversion of the salt to the base at the surface of the dissolving solid at pH values greater than pHmax, the dissolution rates of both the base and the salt were identical. In the solid state, the salt existed in anhydrous and monohydrate forms; the anhydrous salt converted to the hydrate at greater than 40% relative humidity, and the hydrate lost water at 40-60 degrees C. The thermal properties of the salt were indicative of its potential instability, which was confirmed by accelerated stability studies. The base existed in a stable crystalline solid form, and also in an oily liquid form which converted to crystals on standing.(ABSTRACT TRUNCATED AT 250 WORDS)