Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.      

Prevalence of poor self-rated health and associated risk factors among older adults in Cali,Colombia

Introduction:

Self-rated health (SRH) has beeen considered an important marker of quality of life and an independent predictor of mortality in older adults.

Objective:

To determine the prevalence of poor SRH and identify risk factors associated with poor SRH among older adults residing in the Commune 18 of the city of Cali, Colombia, in 2009.

Methods:

A population-based cross-sectional study with a single-stage cluster sampling design. Sample included 314 persons aged 60 and older. The dependent variable, SRH was dichotomized into good (excellent, very good, good) and poor (fair, poor). Independent variables were sociodemographic, biological, mental, functional and geriatric syndromes. Logistic regression was used for multivariate statistical modeling.

Results:

Overall, 40.1% reported poor SRH (women 42.9%, men 35.0%). Factors independently associated with poor SRH were diabetes mellitus, depression, fear of falling and frailty syndrome (frail and pre-frail vs. non-frail). Widowed men reported poorer health than married men while other marital status (single/separated/divorced) was associated with better self-rated health in women.

Conclusion:

Potential modifiable factors such as depression and frailty syndrome are important determinants for poor SRH in Colombian older adults.

     

Initiation of a pharmacovigilance programme at a tertiary care hospital in South India

Objective India is a country with the availability of a large number of pharmaceutical preparations as branded generics. At the time of this study there was no established pharmacovigilance system at the national level except a co‐ordinating centre at the national capital. The study site was a tertiary care teaching hospital with a bed capacity of 500 and with an average of 200 outpatient visits and 50 inpatient admissions per day. The hospital did not have any system of monitoring and documenting adverse drug reactions. The objective of the study was to introduce an adverse drug reaction (ADR) monitoring programme at a tertiary care teaching hospital and assess ADR‐related issues in both inpatient and outpatient departments. Method All departments willing to report ADRs were included in the study, which was carried out for one year. Physicians and nurses filled in the notification forms when they encountered suspected ADR cases. These cases were then assessed by a panel of four judges. According to Naranjo's algorithm, the ADRs were assessed and classified based on World Health Organization (WHO) classification. Key findings A total of 288 suspected cases were reported and 264 ADRs were confirmed by the panel. According to Naranjo's probability scale, 83 cases were categorized as ‘probable’, 181 cases were classified as ‘possible’, and none were classified as ‘unlikely’ or ‘definite’. The most common classes of drugs involved were antibiotics (25%), psychotropics (20%), analgesic and cardiovascular agents (14% each). Generalised itch and rash, tremors, urticarial drug reaction, oral ulcer, gastritis and akathesia and extrapyramidal symptoms were found to be the most common ADRs observed; 2.1% of the patients in the studied departments had ADRs. Conclusion The ADR reporting system was initiated at the hospital and was well received by the physicians. Appreciable participation of physicians was noted during the study in reporting ADRs. The study also gave an insight into the awareness of physicians about ADR‐related issues. The number of ADRs reported was reasonably comparable with the findings of other authors from India.     

Histological investigation of skin biopsies in otosclerosis and osteogenesis imperfecta

Summary The hypothesis that homeostatic control mechanisms control mucociliary function in ciliated mucous membrane was tested. Nasal mucociliary transport rates were recorded in chickens in vivo at successive intervals during exposure to SO₂ or after inoculation with Newcastle disease virus (NDV), or both. Either agent alone caused deceleration of the turbinate clearance. However, when SO₂ exposure was limited to one nasal fossa and turbinate mucociliary rates were determined in the unexposed and infected side, the two acted antagonistically and yielded approximately normal rates. Exposure of the nasal mucosae to SO₂ caused decreased rates of sinus clearance, while NDV infection of nasal membranes induced increased rates of sinus clearance. Exposure of nasal mucosae to both agents acted antagonistically to effect rates of sinus clearance in normal ranges. These data support the idea of homeostasis.Research support from NIH grant no. 5 RO1 ES-00741     

An evaluation of resident training in breast procedures

BACKGROUND: The purpose of this study was to determine if senior residents are participating in advanced level breast cases. METHODS: A retrospective review of 1,583 breast procedures on 1,213 patients over 2 years was performed. Each case was evaluated for the type of case: (1) junior level (PGY 1 and 2)--core needle biopsy, fine needle aspirate, excisional biopsy, needle localized biopsy, lumpectomy, partial mastectomy, and simple mastectomy; and (2) senior level--stereotactic breast biopsy, sentinel lymph node biopsy, axillary dissection, and modified radical mastectomy. All cases were reviewed for level of resident involved. RESULTS: Overall, seniors performed 31% of the cases, junior residents performed 42%, and 27% were unattended by any resident. Senior level breast cases were specifically examined to compare whether a senior or junior was present. Overall, 891 defined senior cases were performed. A senior level resident attended 34% of these, leaving 66% covered by junior residents or uncovered altogether. CONCLUSIONS: It is clear when evaluating breast procedures that senior residents are less involved than junior residents. Furthermore, the fact that many of the reported cases (28%) and, more significantly, senior level cases (26%) have no resident involved leads us to conclude that senior level residents are not taking advantage of the opportunity to gain experience in performing advanced level breast procedures in our surgical program.     

Senior surgical residents can accurately interpret trauma radiographs

Surgical residents routinely interpret radiographic studies during the evaluation of trauma patients, which directs further evaluation and invasive procedures. Official interpretations--"post-reading"--of radiographs by radiologists may be delayed by hours or even days. Trauma surgeons frequently act on their impressions before "official" readings are available. It has been demonstrated that surgical residents can accurately perform and interpret trauma ultrasound examinations. The purpose of this study was to evaluate the ability of senior surgery residents to interpret basic trauma radiographs. Interpretations of trauma radiographs (cervical spine, chest, pelvis, and CT of the brain) were recorded prospectively by the senior surgery resident present during trauma evaluations. These interpretations were compared with the findings of the radiologist as obtained from the official radiology report. Differing results were divided into clinically significant and clinically nonsignificant findings using defined criteria. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were determined. Interpretations of trauma radiographs by senior residents achieved an accuracy of 100 per cent for cervical spine radiographs, 95.9 per cent for chest radiographs, 98.0 per cent for pelvis radiographs, and 97.9 per cent for CT of the head. In aggregate senior residents interpreted trauma radiographs with 97.9 per cent accuracy. Differences that were considered clinically significant according to preset criteria occurred in 2.1 per cent of observations. We conclude that senior general surgical residents can accurately interpret trauma radiology, including CT of the brain. These results suggest that institutional policies for post-reading of trauma radiology should be reassessed.     

What is normal intra-abdominal pressure?

The causes and effects of increased intra-abdominal pressure and abdominal compartment syndrome have been well documented. However, there have been no large series to determine normal intra-abdominal pressure in hospitalized patients. The purpose of this study was to determine normal intra-abdominal pressure in randomly selected hospitalized patients and to identify factors that predict variation in normal intra-abdominal pressure. A total of 77 patients were prospectively enrolled between September 1998 and July 1999. Data obtained included patient demographics (i.e., age, gender, height, weight, and body mass index), reason for hospitalization and bladder catheterization, previous and current surgical status, comorbidities, and intra-abdominal pressures. Intra-abdominal pressure readings were obtained through an indwelling transurethral bladder (Foley) catheter. Data were analyzed by analysis of variance and multiple regression analysis. There were 36 females and 41 males with a mean age of 67.7 years. Average weight, height, and body mass index were 79.6 kg, 1.70 m, and 27.6 kg/m2, respectively. Mean intraabdominal pressure was 6.5 mm Hg (range 0.2-16.2 mm Hg). Body mass index was positively related to intra-abdominal pressure (P < 0.0004). Gender, age, and medical and surgical histories did not significantly affect intra-abdominal pressure. However, using multiple regression analysis, a relationship between intra-abdominal pressure, body mass index, and abdominal surgery was discovered. Intra-abdominal pressure is related to a patient's body mass index and influenced by recent abdominal surgery. Thus, the normal intra-abdominal pressure can be estimated in hospitalized patients by using the derived equation. Knowledge of the expected intra-abdominal pressure can then by used in recognizing when an abnormally high intra-abdominal pressure or abdominal compartment syndrome exists.     

Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.