Gustin from human parotid saliva is carbonic anhydrase VI

It has been found that yeast mutants deficient in cytosolic superoxide dismutase CuZnSOD are hypersensitive to ferrous iron. In contrast mutants that are deficient in catalases and cytochrome c peroxidase do not differ from the standard strain in this respect. These findings suggest that iron toxicity may depend on the redox status of the cell. They also shed light on the role of superoxide dismutases in preventing the toxic effects of oxygen.     

Use of advance directives: facilitating health care decisions by adults with mental retardation and their families

As increasing numbers of adults with mental retardation survive into adulthood and old age, they may face decisions about their health care and end-of-life treatment. Advance directives may serve as a tool for communicating one's preferences about future medical treatment. Information about the types, extent of use, and ethical context of advanced directives is provided and four critical issues regarding use of advanced directives by adults with mental retardation and their families are examined: assessment of decision-making capacity, standards for surrogate decision-making, family involvement in advanced directives planning, and constraints on the use of advanced directives. Implications for professionals are discussed, including ways to facilitate advance care planning.     

Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine

BACKGROUND: We compared our results with bullous vs diffuse emphysema by performing a bilateral thoracoscopic stapled volume reduction technique in 15 patients (age 45-80, 10 males, five females). METHODS: Eight patients demonstrated bullous emphysema and seven patients diffuse emphysema. Lung reduction was performed with a bilateral thoracoscopic stapled technique utilizing bovine pericardium in the supine position. RESULTS: Comparison of the bullous versus diffuse groups revealed no significant differences in means for the following variables: length of air leak (7.5 vs 3.3 days); length of stay (8.1 vs 6.5 days); pre-op FEV1, (23% vs 22%); pre-op dyspnea index (3.4 vs 3.6). At 3 months the bullous subset had a highly significant improvement (p < 0.007) in FEV1 (88%) compared with the diffuse subset FEV1 (59%). CONCLUSIONS: These early results suggest that patients with bullous emphysema are at no greater risk and demonstrate a significantly greater improvement in FEV1 than patients with diffuse emphysema.     

Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy

Endogenous opioid peptides appear to be involved in acute behavioral effects induced by single doses of ethanol. However, its role in repeated ethanol exposure has not been studied. In the present study ethanol was given to rats at the doses of 2 and 4 g/kg by a stomach gauge for 15 days, and its effects on spontaneous motility, open-field activity, and active avoidance behavior recorded on the 3rd, the 6th and the 15th days. Then the effect of naloxone (0.5 and 2 mg/kg by intraperitoneal route) was tested against a challenge ethanol dose, administrated by oral route, on the 16th day. Control animals received tap water and saline instead of ethanol or naloxone, respectively. Both doses of ethanol induced a decrease in spontaneous motility that was antagonized by naloxone. Open-field ambulations were increased by the high dose of ethanol, low-dose lacking effect; naloxone did not modify these ethanol effects. The low dose of ethanol shortened latency time in shuttlebox, the high dose causing escape and freezing responses; none of these effects were modified by naloxone. Therefore, endogenous opioid peptides appear to play a limited role in the chronic effects of ethanol in rats; particularly its effects in tests inducing an increase in the level of anxiety were resistant to naloxone.     

Biliary reflux can be a contributory cause of esophagitis

In recent years duodenogastric reflux has been recognised as a possible cause of oesophagitis. Alone or in combination, bile salts, trypsin, pepsin, and hydrochloric acid have all been shown to cause oesophagitis. Duodenal content in the oesophagus can be measured by means of a new fibre-optic sensor, Bilitech 2000, a device measuring the occurrence of bilirubin and yielding 24-hour readings from the distal oesophagus. Studies in which the device has been used have shown oesophageal bilirubin to be increased in patients with oesophagitis, especially in the subgroup with such complications as oesophageal stricture or ulceration, or Barrett's oesophagus. The evidence suggests that unsatisfactory response to proton pump inhibitors in reflux patients might be due to an increase in duodenal reflux, and should be treated surgically with fundoplication or biliary diversion. This may also be true of oesophagitis patients with complications, though this remains to be shown in clinical studies.     

A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.     

Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyprolline excretion (HypE) levels (Le., group 1, HypE < 5.0 mumol/l of glomerular filtrate [GF]; group 2, HypE of 5.0-9.9 mumol/l of GF; group 3, HypE > 10 mumol/l of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.     

Diagnosis and pathophysiology of paradoxical embolism

A review of the experience with 134 consecutive patients with germinal cell testicular neoplasia indicates that definitively accurate staging of the malignancy at presentation is the single most important prognostic factor. Nearly two-thirds of the patients with all types of germinal malignancies survived or died of other causes and the highest survival rates were seen among patients with earlier stages of seminoma. In recent years patients with all types of germinal malignancies of the testis have been treated by radical retroperitoneal lymphadenectomy with enhancement of survivals. Patients with seminoma and non-seminomatous tumors exhibited increased survival rates with node dissection. In 66 consecutive lymphadenectomies the complication rate was less than 14 per cent, with only 1 death related to the operation. Retroperitoneal lymphadenectomy not only affords therapeutic advantage but also provides an opportunity for accurate surgical staging of disease and allows for rational decision relative to additional treatment, radiation therapy or chemotherapy.