The molecular genetics of the incision step in the DNA excision repair process

This review describes the evolution of research into the genetic basis of how different organisms use the process of excision repair to recognize and remove lesions from their cellular DNA. One particular aspect of excision repair, DNA incision, and how it is controlled at the genetic level in bacteriophage, bacteria, S. cerevisae, D. melanogaster, rodent cells and humans is examined. In phage T4, DNA is incised by a DNA glycosylase-AP endonuclease that is coded for by the denV gene. In E. coli, the products of three genes, uvrA, uvrB and uvrC, are required to form the UVRABC excinuclease that cleaves DNA and releases a fragment 12-13 nucleotides long containing the site of damage. In S. cerevisiae, genes complementing five mutants of the RAD3 epistasis group, rad1, rad2, rad3, rad4 and rad10 have been cloned and analyzed. Rodent cells sensitive to a variety of mutagenic agents and deficient in excision repair are being used in molecular studies to identify and clone human repair genes (e.g. ERCC1) capable of complementing mammalian repair defects. Most studies of the human system, however, have been done with cells isolated from patients suffering from the repair defective, cancer-prone disorder, xeroderma pigmentosum, and these cells are now beginning to be characterized at the molecular level. Studies such as these that provide a greater understanding of the genetic basis of DNA repair should also offer new insights into other cellular processes, including genetic recombination, differentiation, mutagenesis, carcinogenesis and aging.     

Users' subjective evaluation of electronic vision enhancement systems

The aims of this study were (1) to elicit the users' responses to four electronic head-mounted devices (Jordy, Flipperport, Maxport and NuVision) and (2) to correlate users' opinion with performance. Ten patients with early onset macular disease (EOMD) and 10 with age-related macular disease (AMD) used these electronic vision enhancement systems (EVESs) for a variety of visual tasks. A questionnaire designed in-house and a modified VF-14 were used to evaluate the responses. Following initial experience of the devices in the laboratory, every patient took home two of the four devices for 1 week each. Responses were re-evaluated after this period of home loan. No single EVES stood out as the strong preference for all aspects evaluated. In the laboratory-based appraisal, Flipperport typically received the best overall ratings and highest score for image quality and ability to magnify, but after home loan there was no significant difference between devices. Comfort of device, although important, was not predictive of rating once magnification had been taken into account. For actual performance, a threshold effect was seen whereby ratings increased as reading speed improved up to 60 words per minute. Newly diagnosed patients responded most positively to EVESs, but otherwise users' opinion could not be predicted by age, gender, diagnosis or previous CCTV experience. User feedback is essential in our quest to understand the benefits and shortcoming of EVESs. Such information should help guide both prescribing and future development of low vision devices.     

National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003).

BACKGROUND: We evaluated historical trends in the Staphylococcus aureus infection rate, economic burden, and mortality in US hospitals from 1998 through 2003. METHODS: The Nationwide Inpatient Sample was used to assess trends over time of S. aureus infection during 1998-2003. Historical trends were determined for 5 strata of hospital stays, including all inpatient stays, surgical procedure stays, invasive cardiovascular surgical stays, invasive orthopedic surgical stays, and invasive neurosurgical stays. RESULTS: During the 6-year study period from 1998 through 2003, the rate of S. aureus infection increased significantly for all inpatient stays (from 0.74% to 1.0%; annual percentage change (APC), 7.1%; P=.004), surgical stays (from 0.90% to 1.3%; APC, 7.9%; P=.001), and invasive orthopedic surgical stays (from 1.2% to 1.8%; APC, 9.3%; P<.001). For invasive neurosurgical stays, the rate of S. aureus infection did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (from 1.4% to 1.8%; P=.034). The total economic burden of S. aureus infection for hospitals also increased significantly for all stay types, with the annual percentage increase ranging from 9.2% to 17.9% (P<.05 for all). In 2003, the total economic burden of S. aureus infection was estimated to be $14.5 billion for all inpatient stays and $12.3 billion for surgical patient stays. However, there were significant decreases in the risk of S. aureus-related in-hospital mortality from 1998 to 2003 for all inpatient stays (from 7.1% to 5.6%; APC, -4.6%; P=.001) and for surgical stays (from 7.1% to 5.5%; APC, -4.6%; P=.002). CONCLUSIONS: The inpatient S. aureus infection rate and economic burden of S. aureus infections for US hospitals increased substantially from 1998 to 2003, whereas the in-hospital mortality rate decreased.     

Systemic lupus erythematosus induced by isoniazid.

The case is described of a 73 year old man who presented with a lupus-like syndrome related to treatment with isoniazid and had IgG antinuclear antibodies against the nucleo-histone complex (H2A-H2B)-DNA. After a short course of treatment with prednisone and discontinuation of isoniazid the patient's lupus symptoms resolved and a gradual decrease in antibodies to (H2A-H2B)-DNA occurred. This case suggests that isoniazid is capable of inducing an autoantibody specificity associated with drug related lupus.     

Assisting adolescents toward mental health

The developmental stage of adolescence may be so turbulent as to require psychiatric intervention. The adaptive difficulties experienced by Offer's tumultuous group of adolescents were once considered normal problems for that age group. Now they are considered to be a precursor to more serious psychosocial problems and require entry into the mental health care system. The adolescent psychiatric patient may experience adaptive difficulties, such as delinquency, substance abuse, and sexual acting out, or a diagnosed psychiatric disorder. The level of care an adolescent requires depends upon the type and severity of his dysfunction. Early detection and prevention is largely accomplished through education. Assessment and crisis intervention require the structure of an acute care inpatient setting. Long-term treatment may be necessary to provide a corrective emotional experience for the severely dysfunctional adolescent. Research endeavors should be directed toward further exploration of the relationship between adaptive difficulties and adult psychiatric disorder. Outcome studies would be helpful in evaluating the success of psychiatric nursing intervention at multiple levels of complexity.     

Modulation of bone loss during calcium insufficiency by controlled dynamic loading

Summary Changes in the midshaft cross-sectional area of the ulna were measured in egg-laying turkeys on a diet insufficient in calcium. Left: right comparisons were used to assess the bone loss over a six-week period due to 1) calcium insufficiency, 2) calcium insufficiency plus disuse, and 3) calcium insufficiency and disuse interrupted by a short daily period of intermittent loading applied from an external device. Calcium insufficiency alone in the intact ulna resulted in a 15% reduction in cross-sectional area. In the functionally deprived bones this loss was increased to 32%. In bones where the disuse was interrupted by a single short daily period of loading, the degree of bone loss was significantly modified (P<0.006) to 25%. No significant difference in the modulating effect of loading was achieved by varying the peak strain from 0.0015 to 0.003, the strain rate from 0.01 to 0.05, or the duration of the single loading period from 100 sec per day to 25 minutes. All the loading regimes employed had been demonstrated to be osteogenic in mature male birds on a diet sufficient in calcium.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

Management of fibroadenoma of the breast.

Fibroadenoma is a common cause of discrete breast lumps in young women. There is agreement that fibroadenomas can be diagnosed preoperatively with a high degree of confidence and that some of the lesions thus diagnosed will resolve, possibly obviating the need for excision. There is, however, wide disagreement over the proportion of fibroadenomas that resolve spontaneously and therefore the benefit that accrues from an expectant policy. The aim of this study was to audit the management of fibroadenomas on one unit and clarify their natural history over a 5-year period. A cohort of 70 women with 87 fibroadenomas diagnosed using a triple assessment of clinical examination, cytology and imaging (sonomammography) have been followed for a minimum of 5 years. In all, 53 of the 'fibroadenomas' have been excised. In four cases the histology revealed benign disease other than fibroadenoma; there were no neoplasms. The sensitivity of cytology and sonomammography for the diagnosis of fibroadenoma were 84% and 98% respectively. Thirty-four fibroadenomas have not been excised. Of 25 fibroadenomas that have been reassessed after at least 5 years of follow-up, 13 (52%) have reduced in size, 4 (16%) are unchanged in size and 8 (32%) have grown. No patient has developed a carcinoma at the site of the presumed fibroadenoma. This study confirms that an expectant management policy of fibroadenomas has not resulted in misdiagnosis of carcinomas. Further, since a significant proportion of fibroadenomas remain static or reduce in size over a 5-year period many women can avoid excision.     

An analysis of ultrafiltration during acute peritoneal dialysis in rats

Transport into and from the peritoneal cavity is effected through separate membranes. Peritoneal function is the sum of the contributions of these membranes. The peritoneal dialysis membranes are defined as intestinal viscera and mesentery, parietal lining membrane, and liver and diaphragm. The present study was undertaken to determine which of these membranes participate in ultrafiltration during peritoneal dialysis. Studies were performed in rats using a hypertonic (1200 mOsm/L) dialysate solution containing 5.6% glucose, 2.8% amino acid, and electrolytes. Both intact and eviscerated rats were studied. The experiments were repeated in animals whose diaphragms were fibrotic and densely adherent to liver. Preparation of the diaphragm did not impact upon ultrafiltration. Ultrafiltration in controls (54 vs. 56 ml with and without a fibrotic diaphragm respectively) and in eviscerated groups (44 vs. 45 ml with and without a fibrotic diaphragm respectively) were not significantly different. However, controls had significantly more ultrafiltration than did eviscerated animals (p less than 0.01). The parietal viscera accounted for 56-59% of the ultrafiltration. This study demonstrates that both the intestinal viscera and parietal walls participate in ultrafiltration.