Occupational outcome after temporal lobectomy for refractory epilepsy.

We evaluated employment after temporal lobectomy for refractory epilepsy in 86 patients (3.5 to 8 years of follow-up). Seventy-three patients qualified for the work force before and after surgery. Unemployment rates declined after surgery (18 patients [25%] unemployed before surgery, eight patients [11%] unemployed after surgery), and underemployment also tended to diminish. Improvement in occupational status related strongly to the degree of postoperative seizure relief. Seizure-free patients fared better (no unemployment, little underemployment) than patients with some seizure-free years and some years with seizures after surgery, whose high underemployment level persisted. Patients with seizures in each year after surgery fared worst (despite reduced seizure frequency), with increased unemployment after surgery. Age at surgery also influenced vocational outcome in patients who were unemployed before surgery. Historical, educational, cognitive, and behavioral measures did not correlate with vocational outcome. Employment gains came slowly; unemployed patients took up to 6 years to obtain work after surgery. Of 13 students at the time of surgery, 11 have graduated and nine are now employed. We conclude that seizures play a large role in limiting employment, and that by alleviating seizures, temporal lobectomy improves employability in people with refractory epilepsy. Surgery thereby provides benefit to individuals with epilepsy by increasing financial independence and to society by reducing unemployment.

Effect of chronic iron overload on procollagen gene expression.

The pathogenesis of hepatic fibrosis and cirrhosis in genetic hemochromatosis may involve a direct effect of excess iron on collagen synthesis in the liver. To investigate this theory, we measured procollagen messenger RNA levels (types I, III and IV) in the livers of rats in which we produced chronic parenchymal iron overload by feeding them dietary carbonyl iron (2.5%, wt/wt) for up to 18 mo. This feeding resulted in predominantly parenchymal iron deposition in a periportal distribution similar to that seen in genetic hemochromatosis. Increased amounts of collagen fibrils were observed in iron-loaded livers on electron microscopy; all iron-loaded livers showed some periportal fibrosis. Although very high hepatic iron concentrations (range = 340 to 1,100 mumol/gm dry wt) were achieved in the carbonyl iron-loaded rats, we saw no consistent difference between steady-state messenger RNA levels for procollagens types I, III and IV in control and iron-loaded livers examined at five different time points up to 18 mo. Messenger RNA levels of the cytokine transforming growth factor-beta 1, which has been implicated as having a role in the production of extracellular matrix proteins, were also measured. No significant differences were observed between iron-loaded and control livers. These results suggest that excess parenchymal iron does not have a direct effect on the expression of the procollagens or transforming growth factor-beta 1 genes in iron-loaded livers and that factors other than, or in addition to, iron are necessary for fibrosis to occur.

Self-reported stress and risk of breast cancer.

BACKGROUND: Many women attribute the development of their breast cancer to psychosocial factors such as stress and depression. Yet investigations of the relationship between breast cancer and stressful life events have had inconsistent outcomes, due in part to studies with small sample sizes and reliance on hospital-based populations. METHODS: As part of a population-based, case-control study of breast cancer etiology, we evaluated the association between stressful life events and the risk of breast cancer among 258 breast cancer patients and 614 randomly selected population-based controls. Information on 11 stressful life events was collected in telephone interviews with women aged 50-79 who were participating in the ongoing study. RESULTS: Breast cancer patients and controls experienced the same number of stressful life events in the five years prior to diagnosis or an equivalent reference date (controls), averaging 2.4 and 2.6 events, respectively. After adjustment for known breast cancer risk factors, there was no association between weighted stressful life event scores and the risk of breast cancer (odds ratio [OR] = 0.90 per unit increase; 95% confidence interval [CI], 0.78-1.05). Only one life event, death of a close friend, was significantly more often reported by controls (OR = 0.72; 95% CI, 0.52-1.00). Other life events were inconsistently and nonsignificantly associated with breast cancer risk. CONCLUSIONS. The results of this retrospective study do not suggest any important associations between stressful life events and breast cancer risk.

Effects of iron loading on free radical scavenging enzymes and lipid peroxidation in rat liver.

A comparison of the antioxidant protective system and presence of lipid peroxidation was made between rats iron-loaded by two different mechanisms. Superoxide dismutase activity, glutathione peroxidase activity, and reduced glutathione concentrations, together with malondialdehyde production, were measured in the livers of rats chronically iron-overloaded by (a) parenteral iron (primarily Kupffer cell iron deposition) and (b) dietary carbonyl iron (mainly parenchymal iron deposition). In carbonyl iron-treated rats, hepatic superoxide dismutase activity was significantly decreased, whereas hepatocyte lipid peroxidation, as measured by malondialdehyde levels, was significantly increased when compared with control rats at or above iron concentrations of 100 and 185 mumol/g dry wt, respectively. However, no significant decrease in superoxide dismutase activity or significant increase in malondialdehyde levels was observed in iron dextran-treated rats. Glutathione peroxidase activities and reduced glutathione concentrations in rats, iron-loaded by either method, were not significantly different from those of control animals. These results suggest that the deposition of iron in the reticuloendothelial cells of the liver does not lead to lipid peroxidation; however, iron deposited in the parenchymal cells of the liver may lead to an altered free radical antioxidant protective system, resulting in lipid peroxidation in these cells at a similar level of iron loading. We conclude that the cellular site of iron deposition as well as the hepatic iron concentration is important in determining iron-induced liver injury.

Assessing breast self-examination.

BACKGROUND: Women practice breast self-examination (BSE) according to their own schedule and skill. This variation in how BSE is performed has complicated the interpretation of studies of BSE efficacy and utilization. METHODS: We compared two methods commonly used to assess BSE competency, self-report of practice and ability to detect lumps in a model, among 81 women participating in a controlled toxicity trial of tamoxifen. Subjects were postmenopausal, were under 65 years of age, and had a history of breast cancer within the past 10 years but were currently free of disease. Women were asked to describe their usual BSE practice and were assigned a score (0-10) based on the number of recommended techniques and positions mentioned. Subjects were then instructed to examine a silicone breast model embedded with lumps (HealthEdCo) and to report any abnormalities. RESULTS: Overall proficiency was low by both measures. No significant correlation (r = 0.16, P = 0.15) was found between the two measures of proficiency. Higher correlations were observed among older women and among those practicing BSE monthly. CONCLUSIONS: This study suggests that the two techniques are not comparably evaluating BSE proficiency. Further, both of these methods are likely to be poor measures of true BSE practice.

Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin 5.

Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.