A radiation hybrid map of the human genome

We have developed a panel of whole-genome radiation hybrids by fusing irradiated diploid human fibroblasts with recipient hamster cells. This panel of 168 cell lines has been typed with microsatellite markers of known genetic location. Of 711 AFM genetic markers 404 were selected to construct a robust framework map that spans all the autosomes and the X chromosome. To demonstrate the utility of the panel, 374 expressed sequence tags (ESTs) previously assigned to chromosomes 1, 2, 14 and 16 were localized on this map. All of these ESTs could be positioned by pairwise linkage to one of the framework markers with a LOD score of greater than 8. The whole genome radiation hybrid panel described here has been used as the starting material for the Genebridge4 panel that is being made widely available for genome mapping projects.      

Sodium-lithium countertransport and family history of hypertension in childhood

We have studied the relationship between sodium-lithium countertransport, determined in childhood, and family history of hypertension. Countertransport was measured in healthy children and those with secondary hypertension. There was no significant difference in countertransport between these two groups. In the normal children ( n = 52, median age 6.8 years), there was a positive relationship between body mass index and countertransport (r_s= 0.34, p <0.02). A positive relationship between family history of hypertension using a ranked scoring system, and countertransport, not related to age, body mass or blood pressure (n = 34, r_s= 0.63, p<0.001 ) was also found. There was no significant relationship between intraccllular sodium concentration and countertransport. These data confirm that countertransport in normal children is related to body mass index and indicate that a genetic predisposition to primary hypertension marked by sodium-lithium countertransport is identifiable in childhood.     

The Prevalence of Severe Pain,its Etiopathological Characteristics and Treatment Profile of Patients Referred to A Tertiary Cancer Care Pain Clinic

Pain is the most feared symptom in cancer. About 52–77% patients suffer pain despite World Health Organization (WHO) recommendations. Out of total, one-third patients suffer moderate to severe pain. This study was undertaken to determine the prevalence, etiopathogenesis and characteristics of severe pain and treatment response among pain clinic referrals in a busy tertiary care cancer center. This study found a high prevalence (31.5%) of severe pain. A total of 251 patients who had complete pain data were analyzed for etiopathological characteristics and treatment response. Head and neck cancer contributed the highest prevalence among all regions. Oncologists prescribed non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol with or without mild opioids to 14% patients and pain clinic physicians prescribed opioids and overall 63.7% patients had a better response after pain clinic referral, even then, morphine was not prescribed to many deserving patients. Doctors need pain education about opioids to remove any fear of prescribing opioids in presence of severe pain.     

Human malignancy-associated nucleolar antigen as a marker for tumor cells in patients with acute leukemia

Tumor burden in adult patients with acute leukemia is assessed using the percentage of blast cells in the bone marrow or blood. It is clear, however, that not all blast cells are leukemic cells, especially during rapid marrow regeneration. Similarly, some leukemia cell lines have been shown to differentiate in vitro, and the same process also occurs in vivo. Therefore, the leukemic burden may be due to more differentiated cells as well as to blast cells. The purpose of this study was to investigate whether the human malignancy-associated nucleolar antigen (HMNA) could be used as a marker for leukemic cells and to examine its potential as a diagnostic tool. The proportion of HMNA-positive cells in the bone marrow of patients with acute leukemia was determined by indirect immunofluorescence with antibodies to HMNA and was compared with the differential counts routinely made in the clinic laboratory. The percentages of HMNA-positive cells among the nucleated cells in the marrow of 72 patients with clinical evidence of leukemia were significantly higher (range 9%-98%, median 83%) than those observed for nonleukemic individuals (range less than 0.05%-2.5%, median 1%) or for fractions of marrow cells from normal volunteers enriched for normal early progenitor cells (less than or equal to 2%). Patients with leukemia in remission had a lower percentage of HMNA- positive cells (range 0%-83%, median 3%). The percentage of HMNA- positive cells increased as patients approached relapse. Although the percentage of HMNA-positive cells was related to the percentage of blast cells in the bone marrow of the patients with leukemia, some partially differentiated cells were also HMNA-positive in some specimens, and some blastic cells were HMNA-negative in other specimens. These studies indicate the potential usefulness of HMNA as a marker for leukemic cells.     

成人脑死亡判定的循证医学指南更新——美国神经病学会质量标准分会报告

目的就如下问题对美国神经病学会1995年脑死亡判定实践标准进行更新：①符合脑死亡临床判定标准的患者神经功能能恢复吗？②确定患者神经功能永久性停止的恰当观察时间是多长？③有时可能观察到脑死亡患者的复合肢体运动,这是否错误地提示仍然保留脑功能？④何种技术手段判断呼吸停止是相对安全的？⑤是否存在新的辅助检测能准确判断患者脑死亡？方法系统回顾MEDLINE及EMBASE数据库1996年1月-2009年5月收录的文献,其研究仅限于成年人（≥18岁）。结果及建议对成年人,按照美国神经病学会于1995年确定的脑死亡判定实践标准,目前尚无判定为脑死亡患者出现神经功能恢复的报告。脑死亡患者可以存在复合的自发运动及假阳性触发呼吸机。目前还无足够的证据用以确定神经功能不可逆性停止的最短观察时间。通过氧扩散来确定呼吸停止是安全的,但目前还无足够证据确定呼吸停止检测技术的相对安全性。目前还无足够的证据确定新型辅助检测能否准确判断患者全脑功能已经停止。     

Comparitive evaluation of different systems of medicines and the present scenario of chikungunya in Kerala

ObjectiveTo identify the chikungunya outbreaks in both indoor and outdoor patients in some selected hospitals in our locality and the burden and magnitude of the disease, to compare different system of medicines (allopathic, Ayurvedic, homeopathy etc) and to explore the knowledge, attitude and practices of pharmacists and other health care professionals in the treatment of chikungunya.MethodsA six-month study was carried out. Detailed history was taken from the case history, personal interview of doctors and suspected cases. Personal data such as name age, sex, location, date of onset of illness, medical history, general/systemic examination features, drugs used (allopathy, Ayurveda, homeopathy, or traditional) for the treatment, etc. were noted down. A simple questionnaire was prepared and distributed to various doctors practicing various systems of medicines.ResultsA total of 209 suspected cases were identified from July to December, 2009. People in the age group of 20–40 years were more affected. The study revealed that females were more affected than males. The Grade-III (58.73%) population was more prone to chikungunya than Grade-II (38.75%) and Grade-I (2.87%). It showed that fever, pain in muscles, and sleeping disturbances were the intense symptoms of chikungunya. Myocarditis and arthritis were concomitant diseases which worsened chikungunya symptoms. It also indicated the effective medicine for compliance is nonsteroidal antiinflammatory drugs (NSAIDS).ConclusionsFrom our study we found that in some places there is no proper documentation, even though there are proper guidelines framed by the relevant authorities. It can be concluded from the study that all the systems of medicine are equally important for the management of chikungunya. Additional effort in promoting the guidelines at local level and proper documentation helps to achieve the goal of curbing the chikungunya. It is high time to increase our effort and promote these messages at grassroot level which benefits the society/community as a whole.     

Safety and efficacy of liraglutide in patients with type 2 diabetes with elevated liver enzymes: individual patient data meta-analysis of the LEAD programme

BackgroundFatty liver disease has reached epidemic proportions in type 2 diabetes. Glucagon-like peptide-1 (GLP-1) analogues are licensed for treatment of type 2 diabetes, yet little data exist on efficacy and safety in liver injury. We aimed to assess the safety and efficacy of 26 weeks' liraglutide on liver function compared with an active placebo.MethodsIndividual patient data meta-analysis was done with patient level data combined from six 26-week, phase 3, double-blind randomised controlled trials on type 2 diabetes, which comprise the Liraglutide Effect and Action in Diabetes (LEAD) programme. In addition, the LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis.FindingsOf 4442 patients analysed, 2241 (50·8%) had an abnormal alanine aminotransferase (ALT) at baseline (mean 33·8 IU/L [SD 14·9] in female participants; 47·3 [18·3] in male participants). Liraglutide 1·8 mg reduced ALT in these patients compared with placebo (?8·20 vs ?5·01 IU/L, p=0·003), and was dose dependent (no significant differences vs placebo with liraglutide 0·6 or 1·2 mg). This effect was lost after adjustment for liraglutide's effect on reduction of weight (corrected mean ALT difference vs placebo ?1·41 IU/L, p=0·21) and HbA1c (corrected mean ALT difference vs placebo 0·57 IU/L, p=0·63). Adverse effects with 1·8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In the LEAD-2 sub-study, liraglutide 1·8 mg (26 weeks) improved hepatic steatosis (CT-measured liver:spleen attenuation ratio) from baseline (0·10, p=0·001) and showed a trend towards improvement compared with placebo (0.10 vs 0·00, p=0·07).Interpretation26 weeks of liraglutide (1·8 mg) is safe, well tolerated, and improves liver enzymes compared with placebo in patients with type 2 diabetes.FundingWellcome Trust.     

Duration and predictors of emergency surgical operations - basis for medical management of mass casualty incidents

Background

Hospitals have a critically important role in the management of mass causality incidents (MCI), yet there is little information to assist emergency planners. A significantly limiting factor of a hospital''s capability to treat those affected is its surgical capacity. We therefore intended to provide data about the duration and predictors of life saving operations.

Methods

The data of 20,815 predominantly blunt trauma patients recorded in the Trauma Registry of the German-Trauma-Society was retrospectively analyzed to calculate the duration of life-saving operations as well as their predictors. Inclusion criteria were an ISS ≥ 16 and the performance of relevant ICPM-coded procedures within 6 h of admission.

Results

From 1,228 patients fulfilling the inclusion criteria 1,793 operations could be identified as life-saving operations. Acute injuries to the abdomen accounted for 54.1% followed by head injuries (26.3%), pelvic injuries (11.5%), thoracic injuries (5.0%) and major amputations (3.1%). The mean cut to suture time was 130 min (IQR 65-165 min). Logistic regression revealed 8 variables associated with an emergency operation: AIS of abdomen ≥ 3 (OR 4,00), ISS ≥ 35 (OR 2,94), hemoglobin level ≤ 8 mg/dL (OR 1,40), pulse rate on hospital admission < 40 or > 120/min (OR 1,39), blood pressure on hospital admission < 90 mmHg (OR 1,35), prehospital infusion volume ≥ 2000 ml (OR 1,34), GCS ≤ 8 (OR 1,32) and anisocoria (OR 1,28) on-scene.

Conclusions

The mean operation time of 130 min calculated for emergency life-saving surgical operations provides a realistic guideline for the prospective treatment capacity which can be estimated and projected into an actual incident admission capacity. Knowledge of predictive factors for life-saving emergency operations helps to identify those patients that need most urgent operative treatment in case of blunt MCI.     

The Human Phenotype Ontology

Robinson PN, Mundlos S. The Human Phenotype Ontology. A standardized, controlled vocabulary allows phenotypic information to be described in an unambiguous fashion in medical publications and databases. The Human Phenotype Ontology (HPO) is being developed in an effort to provide such a vocabulary. The use of an ontology to capture phenotypic information allows the use of computational algorithms that exploit semantic similarity between related phenotypic abnormalities to define phenotypic similarity metrics, which can be used to perform database searches for clinical diagnostics or as a basis for incorporating the human phenome into large‐scale computational analysis of gene expression patterns and other cellular phenomena associated with human disease. The HPO is freely available at http://www.human‐phenotype‐ontology.org .