Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice.

These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation.     

Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor.

Depression is common in Parkinson's disease (PD) and affects 30 to 50% of all patients. In contrast to the wealth of research on depression in PD, little is known about the occurrence of depression in other movement disorders. The primary objective of the current study was to determine whether the high prevalence of depression symptoms seen in PD is also found in other movement disorders, by directly comparing rates of specific depression symptoms and depression severity across PD, dystonia, and essential tremor (ET). Three hundred and fifty-four patients with PD, 83 patients with dystonia, and 53 patients with ET completed the Beck Depression Inventory (BDI). We found no significant between-groups differences for depression severity, frequency, or endorsement of specific depression symptoms. Forty-eight percent of PD patients, 37.3% of dystonia patients, and 34% of ET patients were found to be at least mildly depressed (BDI score of 10 or higher). The most commonly endorsed symptoms were fatigability, difficulty with work, anhedonia, and sleep disturbance. Clinicians should be aware that depression is a frequent problem in dystonia and ET, in addition to PD, and inquire about depression symptoms in these patients so that they can be appropriately treated.     

Effects of alpha 2-adrenergic blockade on renal hemodynamics in patients with insulin dependent diabetes mellitus.

The role of renal alpha 2-adrenoceptors in the regulation of glomerular filtration and renal perfusion is unknown. We studied the effects of alpha 2-adrenergic blockade on renal hemodynamics in six patients with insulin-dependent diabetes mellitus (IDDM) and in six healthy subjects. At the basal state, glomerular filtration rate (GFR) was higher in IDDM although the difference from control levels was not statistically significant. Volume expansion, achieved by infusion of isotonic sodium chloride solution, during placebo infusion induced a significant drop in GFR in healthy subjects but not in IDDM patients. Infusion of the alpha 2-adrenoceptor antagonist idazoxan did not further modify the effect of volume expansion on GFR. Renal plasma and blood flow as well as filtration fraction were not significantly changed by volume expansion or idazoxan infusion. Plasma renin activity and plasma aldosterone levels decreased during volume expansion in both IDDM and control subjects. In conclusion, volume expansion induced decreased GFR in healthy controls but not in IDDM patients. Since infusion of idazoxan did not affect GFR or other parameters of renal hemodynamics, renal alpha 2-adrenoceptors do not seem to be involved in the regulation of renal function. Hence, enhanced renal alpha 2-adrenoceptor activity is not likely to underlie hyperfiltration as seen in IDDM.     

Disclosure of sexual abuse. The secret is out--what now?

The sexual abuse of a child is a well-kept secret. Disclosure creates difficulties for the child, the family, and sometimes for the professionals working with them. A multidisciplinary, multiagency model is one method to facilitate care and recovery for the child victim. Each agency and service has a different purpose and goal. Cooperative coordination and communication are the keys to case management with reduced psychological trauma for the child and family. Child psychiatric nurses can be effective members of the child abuse health team model. Advocacy roles also can be developed by nurses who work with sexual victimization through the avenues of media, writing, committee membership and research.     

Tuberculosis risk among migrant farm workers on the Delmarva peninsula.

A survey was conducted to ascertain the risk of tuberculosis (TB) among migrant farm workers on the Delmarva peninsula. Relevant histories were obtained from 842 migrants; a total of 709 skin tests were completed, and 239 sputum specimens were examined for acid-fast bacilli (AFB) and culture. No cases of infectious tuberculosis were ascertained by history or AFB examination. One sputum culture was positive for M. tuberculosis and 13 were positive for various species of nontuberculous mycobacteria. Thirty-seven per cent of migrants tested had significant skin test reactions of 10 mm or more. Reaction rates for men were 41 per cent and for women 25 per cent. Age specific rates ranged from 14 per cent in children aged 5-14 to 54 per cent for ages 45-54. Rates for the principal national/ethnic groups were Haitians 55 per cent, Mexicans 36 per cent, US Blacks 29 per cent and US-born Latinos 20 per cent. Based on these results and other information currently available, it is recommended that current Centers for Disease Control (CDC) recommendations for TB prophylaxis continue to be applied for migrant workers, but that mass screening by skin testing in camp populations not be emphasized. Other recommendations focus on: case finding of active disease, improving continuity and follow-up, increasing coordination among involved agencies, and actively supporting improved economic and living conditions for migrant farm workers.     

Energetics and evolution: An emerging research domain

The study of energetics is important to human biology because the availability and utilization of food energy influence health, survival, and reproduction. Over the last decade, human biologists, biological anthropologists, and other evolutionary scientists have increasingly come to recognize the importance of energy dynamics in shaping evolutionary processes. Thus far, different lines of energetics research have been conducted largely in isolation from one another. This thematic collection examines topics of evolutionary energetics from several different perspectives, drawing together research from human paleontology, comparative primate and mammalian biology, human population biology, and mathematical modeling. It represents a starting point for further integrative research on human evolutionary energetics. Am. J. Hum. Biol. 14: 547–550, 2002. © 2002 Wiley‐Liss, Inc.     

Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.

PURPOSE: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up. PATIENTS AND METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. RESULTS: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. CONCLUSION: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.     

Two unusual duplication anomalies of the urinary tract: use of percutaneous urography

We performed suprapubic percutaneous urography in two patients to diagnose unusual duplication anomalies of the urinary tract, since preoperative diagnosis was unclear after routine noninvasive studies. In both patients standard suprapubic puncture technique was employed. The procedure was used to confirm the diagnosis of duplication of the bladder in one case and to establish the site of origin of a ureterocele in the other. The technique employed in suprapubic cystography may be extended to the diagnosis of unusual cystic abnormalities in the pelvis that may be of urinary tract origin.