Is an osteotome necessary for pterygomaxillary dysjunction or dysjunction through the tuberosity during Le Fort I osteotomy? A systematic review.

Pterygomaxillary dysjunction with an osteotome is commonly used to mobilise the maxilla during Le Fort I osteotomy, despite the risk of serious complications. Different instruments and positions have been tried, including dysjunction through the tuberosity. Down fracture by digital pressure alone has also been advocated, but to our knowledge has not been widely adopted. We have therefore reviewed published papers to see if there is any clinical or anatomical evidence for the use of osteotomes to mobilise the maxilla vertically during a Le Fort I osteotomy for either pterygomaxillary dysjunction or dysjunction through the tuberosity. We found only one paper that analysed the anatomy of the pterygomaxillary fissure and described small bony bridges and syncondroses across the joint. We found no clinical or anatomical evidence for the use of osteotomes in pterygomaxillary separation or separation through the tuberosity. A large clinical trial on down fracture of the maxilla by digital pressure alone showed no serious complications, and we found no strong evidence to justify the use of osteotomes in pterygomaxillary dysjunction or dysjunction through the tuberosity. We have successfully used digital pressure alone in 138 consecutive Le Fort I osteotomies, and we encourage our colleagues to consider adopting this approach.

Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use.

Although there are reports of cases of acute renal failure occurring in cystic fibrosis (CF) patients, usually in association with the use of nephrotoxic antibiotic therapy, there have been no studies of renal function in this patient group. We hypothesized that long-term use of intravenous (IV) nephrotoxic antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal disease in CF patients. In a prospective study, we assessed creatinine clearance as an index of renal function with two techniques (24-hr urine collections and the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease. Using a multiple linear regression model, we evaluated their renal function in terms of their lifetime IV use of aminoglycosides and colistin. Between 31% (Cockroft-Gault formula method) and 42% (24-hr urine collection method) of patients had a creatinine clearance below normal range. Using either method, there was a strong correlation between aminoglycoside use and diminishing renal function (r=- 0.32, P=0.0055), which was potentiated by the coadministration of colistin (r=- 0.42, P <0.0002). However, there was no correlation with colistin when used in combination with other antibiotics alone (r=0.18, P=NS). Repeated IV aminoglycoside use in CF is associated with long-term renal damage. Although this effect is potentiated by colistin, colistin on its own in moderate doses does not appear to be nephrotoxic. IV aminoglycosides should be used cautiously in CF patients, with regular monitoring of renal function.

Bronchoscopic insertion of Gianturco stents for the palliation of malignant lung disease: 10 year experience.

Malignant large airway obstruction is life threatening and may not be amenable to urgent radiotherapy. Palliative airway stenting is difficult and traditionally carried out under general anaesthesia and fluoroscopy. We have shown that self expanding Gianturco metal stents can be placed under local anaesthesia using fibreoptic bronchoscopy and direct vision for the treatment of malignant airway tumours, and report our 10 year experience. All referrals for stenting referred to our unit between 1990 and 1999 were included, looking for histological type, number and site of stents, complications of the procedure, other interventions, and survival. One hundred and sixty two patients (average age 64 years, (range 21-89)) had 307 stents inserted during 167 procedures (144 primary lung tumours, 18 secondary malignancy). There were no operative deaths, but three patients developed a pneumothorax, one requiring intercostal drain insertion. Average survival following stent insertion was less for primary lung cancer than for secondary disease (103 vs. 431 days, P<0.001). There were no excess complications in a subgroup of 64 patients treated locally by oncologists, even when stenting was the primary procedure. This technique is useful in palliating life threatening airway obstruction, particularly for secondary cancer, and can be used in any centre undertaking fibreoptic bronchoscopy.

Intratracheal cocaine induced myocardial infarction: an unusual complication of fibreoptic bronchoscopy.

A 73 year old man developed chest pains 5 minutes after fibreoptic bronchoscopy. The procedure had been performed without sedation following an intratracheal injection of 5 ml 2.5% cocaine solution and xylocaine spray to the pharynx for topical anaesthesia. A 12-lead electrocardiogram showed an evolving anterior myocardial infarction. Cardiac catheterisation revealed coronary artery spasm in the proximal left anterior descending artery at the site of non-significant plaque disease. The risk factors, mechanisms, and treatment of cocaine induced myocardial infarction following intratracheal injections are discussed.

A world-wide internet survey of public knowledge about tuberculosis.

Four simple multiple-choice questions about tuberculosis (TB) were posted on a non-medical internet site for a 2-month period. A total of 564 responses were received. Sixty-two were excluded as individuals had made multiple attempts at the questions. Sixty-five per cent of responses were from North America, 14.5% from Europe and 12% from Australia and New Zealand, with only a small number of responses from Africa, the Indian subcontinent and South America. Of the respondents 49.5% correctly answered that cough is the commonest symptom of TB, 45% knew that TB was transmitted mainly by air-borne droplets, 37.8% knew that TB was caused by a bacterium. Only 19.5% knew that the most important risk factor for developing TB was HIV infection and only 4% answered all questions correctly. This survey suggests that knowledge about tuberculosis is limited in computer-literate individuals throughout the world.

Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis.

Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.

Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection.

We employed laser capture microdissection to remove individual pyramidal neurons from the CA1, CA3, and CA4 regions of formalin-fixed, paraffin-embedded hippocampus from 8 AIDS brains and 2 HIV-1-seronegative normal brains. We amplified HIV-1 gag and nef gene sequences using separate, double round PCR reactions for each of the primer sets. In all 3 hippocampal regions, amplification efficiency was best with sequence length between 284 and 324 bp; HIV-1 nef gene sequences were more common than HIV-1 gag sequences; and rank order for percent positive amplification was CA3 > CA4 > CA1 samples. These results are the first to detect HIV-1 gene sequences in microdissected human tissue. They indicate that brain neurons in vivo contain HIV-1 DNA sequences consistent with latent infection by this virus, and suggest that neurons display a selective vulnerability for HIV infection. Neuronal HIV infection could contribute to neuronal injury and death or act as a potential viral reservoir if reactivated.

Organizational approaches to the HIV/AIDS crisis.

The Centers for Disease Control and Prevention (CDC) has played a major role in controlling the HIV/AIDS epidemic in the United States. After implementation of perinatal zidovudine therapy in 1994, the efforts of the CDC and others produced a dramatic decline in perinatal HIV transmission. However, in recent years, approximately 300 perinatally infected infants have been born annually in the United States. To further reduce this number, the CDC has identified four prevention goals: improve prenatal care, recommend HIV testing, ensure treatment for HIV-infected pregnant women, and ensure follow-up care. To address these goals, the CDC launched a prevention plan consisting of surveillance, research, outreach strategies, grant programs, evaluation efforts, and policy development. Globally, the CDC tailors this plan to meet the needs of developing countries. The CDC provides technical assistance to international organizations to help develop, implement, and evaluate global prevention programs. Specific international sites are targeted for new research and programs to reduce perinatal HIV transmission.

Risk factors for Nipah virus transmission, Port Dickson, Negeri Sembilan, Malaysia: results from a hospital-based case-control study.

A hospital-based case-control study of viral encephalitis was carried out at Port Dickson Hospital, in the state of Negeri Sembilan, Malaysia. Between March and May 1999, 69 clinically diagnosed viral encephalitis cases and 31 controls were interviewed. Job histories on pig farming activities were assessed by a group of epidemiologists and veterinary surgeons. Results show that among clinical cases of viral encephalitis, 52 (75.4%) cases were diagnosed to have Nipah virus infection based on positive serology for antibodies to the cross-reacting Hendra virus antigen. The Nipah virus encephalitis was significantly associated with a history of working in pig farms (p < 0.001, OR = 196.0, 95% CI = 20.4-4741.6), history of contact with animals (p < 0.001, OR = 38.3, 95% CI = 8.2-209.0) and with history of direct contact with pigs (p = 0.002, OR = 34.4, 95% CI = 2.6-1,024.4). The Nipah virus infection was also significantly associated with history of feeding/cleaning pigs (p < 0.001, OR = 102, 95% CI = 11.9-2,271.5). These results provide evidence that involvement in pig farming activities is significantly associated with the risk of getting Nipah virus infection. They are potential risk factors for Nipah virus transmission in the major pig-producing area of Bukit Pelandok, Port Dickson Negeri Sembilan.

K-ras and p53 in pancreatic cancer: association with medical history, histopathology, and environmental exposures in a population-based study.

Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.

Hypermethylation of the p16 (Ink4a) promoter in B6C3F1 mouse primary lung adenocarcinomas and mouse lung cell lines.

Primary lung tumors from B6C3F1 mice and mouse lung cell lines were examined to investigate the role of transcriptional silencing of the p16 (Ink4a) tumor suppressor gene by DNA hypermethylation during mouse lung carcinogenesis. Hypermethylation (>/=50% methylation at two or more of the CpG sites examined) of the p16 (Ink4a) promoter region was detected in DNA from 12 of 17 (70%) of the B6C3F1 primary mouse lung adenocarcinomas examined, whereas hypermethylation was not detected in normal B6C3F1, C57BL/6 and C3H/He mouse lung tissues. Immunohistochemistry performed on the B6C3F1 lung adenocarcinomas revealed heterogeneous expression of the p16 protein within and among the tumors. Laser capture microdissection was employed to collect cells from immunostained sections of four tumors displaying areas of relatively high and low p16 expression. The methylation status of the microdissected samples was assessed by sodium bisulfite genomic sequencing. The pattern of p16 expression correlated inversely with the DNA methylation pattern at promoter CpG sites in nine of 11 (82%) of the microdissected areas displaying variable p16 expression. To provide further evidence that hypermethylation is involved in the loss of p16 (Ink4a) gene expression, three mouse lung tumor cell lines (C10, sp6c and CMT64) displaying complete methylation at seven promoter CpG sites and no p16 (Ink4a) expression were treated with the demethylating agent, 5-aza-2'-deoxycytidine. Re-expression of p16 (Ink4a) and partial demethylation of the p16 (Ink4a) promoter were observed in two cell lines (C10 and sp6c) following treatment. These are the first reported studies to provide strong evidence that DNA methylation is a mechanism for p16 inactivation in mouse lung tumors.

Beta-catenin mutations and protein accumulation in all hepatoblastomas examined from B6C3F1 mice treated with anthraquinone or oxazepam.

The molecular pathogenesis of hepatoblastomas in the B6C3F1 mouse is unclear but may involve alterations in the beta-catenin/Wnt signaling pathway as was recently described for chemically induced hepatocellular neoplasms and human liver cancers. The objective of this study was to characterize the mutation frequency and spectrum of beta-catenin mutations and the intracellular localization of beta-catenin protein accumulation in chemically induced hepatoblastomas. In this study, beta-catenin mutations were identified in all 19 anthraquinone-induced hepatoblastomas and all 8 oxazepam-induced hepatoblastomas examined. Although several hepatoblastomas had multiple deletion and/or point mutations, the pattern of mutations in the hepatoblastomas did not differ from that identified in hepatocellular neoplasms. In a majority of the hepatoblastomas (six of seven) examined by immunohistochemical methods, both nuclear and cytoplasmic localization of beta-catenin protein were detected, whereas in hepatocellular adenomas, carcinomas, and normal liver only membrane staining was observed. Our data suggest that beta-catenin mutations and the subsequent translocation of beta-catenin protein from the cell membrane to the cytoplasm and nucleus may be critical steps in providing hepatocellular proliferative lesions with the growth advantage to progress to hepatoblastoma.

Outcomes of single versus multiple trauma exposure in a screening sample.

Most studies ignore prior trauma exposure when evaluating outcomes of target events. This study explored symptom severity associated with different types of traumatic experiences occurring alone and with multiple exposure. The Stressful Life Events Screening Questionnaire categorized 1,909 sophomore women into groups including no trauma exposure, exposure to a serious non-Criterion A event only, exposure to several unique noninterpersonal and interpersonal events, and exposure to multiple interpersonal events. Women with noninterpersonal trauma did not differ from those without trauma on the Trauma Symptom Inventory. Only interpersonal trauma and non-Criterion A events were associated with elevated symptoms; multiple-exposure participants had significantly higher symptoms than all other groups. Complex trauma histories should be accounted for, even in studies of one target event.

Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia.

An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.

Trauma history as a predictor of psychologic symptoms in women with breast cancer.

PURPOSE: To identify predictors of psychiatric problems in women with early-stage breast cancer. PATIENTS AND METHODS: One hundred sixty women with early-stage breast cancer were recruited from three treatment centers. They filled out self-report questionnaires, including a medical history and demographic survey, the Trauma History Questionnaire, Life Event Questionnaire, Brief Symptom Inventory, Beck Depression Inventory, and Duke-UNC Functional Social Support Questionnaire, and were evaluated using the Structured Clinical Interview for DSM-III-R. RESULTS: Hierarchical regression analyses indicated that four of five variable sets made a significant incremental contribution to outcome prediction, with 35% to 37% of the variance explained. Outcomes were predicted by demographic variables, trauma history variables, precancer psychiatric diagnosis, recent life events, and perceived social support. Cancer treatment variables did not predict outcome. CONCLUSION: The findings highlight the important roles of trauma history and recent life events in adjustment to cancer and have implications for screening and treatment.

Mental status change in older surgical patients. Cognition, depression, and other comorbidity.

The authors studied patients age 60 and over to assess the effect of elective surgery as a precipitating factor for cognitive decline over the postoperative year. They found an association between change in test performance and age, physical disability, and number of depressive symptoms. However, persistent decline in Mini-Mental State Exam scores was associated with identifiable factors related to the initial surgery in only 3/ 251 (1 percent of cases). Depression and new onset of acute illness were confounding factors in the assessment of cognitive decline.

Mycobacterial culture results of smear-positive patients with suspected pulmonary tuberculosis in Liverpool.

The aim of this study was to assess the final mycobacterial culture results of patients with smear-positive sputum or bronchial washings and to investigate the efficiency of local tuberculosis (TB) contact-tracing. Retrospective analysis of mycobacterial cultures and contact-tracing was performed in every patient with smear-positive sputum or bronchoalveolar lavage (BAL) in two Liverpool teaching hospitals (1996-1998). Of these patients 116 with smear-positive sputum or BAL were identified. Mycobacterium tuberculosis (M. tuberculosis) was cultured in 57 (49%), environmental mycobacteria in 37 (32%) and cultures were negative in 22 (19%) of the patients. Contact-tracing information was available in 107 of the 116 (92%) patients. A total number of 1,357 contacts were screened for possible tuberculosis. Of these, 420 (31%) were contacts of patients who cultured environmental organisms or had negative cultures. In this study, 51% of smear-positive patients in Liverpool did not have tuberculosis. Inefficiencies in current contact-tracing procedures have been identified which result from screening contacts of index cases that are subsequently found not to have cultured Mycobacterium tuberculosis. The authors believe that there are clear grounds for using rapid tests to identify and type mycobacteria more quickly than current solid or liquid media methods. It is also suggested that regional variations in the frequency of infection with environmental mycobacteria should be considered when formulating tuberculosis contact-tracing procedures.

Effects of fixation on RNA extraction and amplification from laser capture microdissected tissue.

One of the key end points for understanding the molecular basis of carcinogenesis is the quantitation of gene expression in specific cell populations. Microdissection techniques allow extraction of morphologically distinct cells for molecular analysis. A recent advance in microdissection uses the PixCell laser capture microdissection (LCM) system, which allows for precise removal of pure cell populations from morphologically preserved tissue sections. The objective of this study was to determine the optimal fixation protocol for analyzing RNA from tissue samples using LCM. Optimal fixation must provide acceptable morphology, allow proper laser capture of selected cells, and preserve the integrity of mRNA. We evaluated the effects of both cross-linking and precipitive-type fixatives on frozen and paraffin-embedded mouse liver tissue. For assessment of the quality of the mRNA in LCM samples generated from various fixed tissues, reverse transcription-polymerase chain reaction (RT-PCR)-amplified mouse liver beta2-microglobulin mRNA was detected with ethidium bromide. We also examined mouse glyceraldehyde-3-phosphate-dehydrogenase by using the fluorogenic TaqMan system for real-time quantitative detection of RT-PCR products. Frozen tissues yielded more RT-PCR product than did paraffin-embedded tissues. In both frozen and paraffin-embedded tissues, differences were observed between the fixatives. Precipitive fixatives, such as ethanol and acetone, consistently produced more RT-PCR amplification product than did cross-linking fixatives such as formalin. Optimal fixation protocols for LCM analysis will facilitate the examination of gene expression in specific cell populations, accelerating investigations of the molecular differences responsible for the phenotypic changes observed during carcinogenesis.