The effect of low dose lofepramine in depressed elderly patients in general medical wards.

A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.     

Establishment and characterization of an in vitro model of acquired resistance to cisplatin in a human testicular nonseminomatous germ cell line.

Clinically, human testicular nonseminomatous germ cell tumors exhibit remarkable sensitivity to platinum-based chemotherapy. To define better the mechanistic basis for this unusual sensitivity, the biochemical determinants of platinum-induced cytotoxicity have been investigated in a human testicular tumor cell line (GCT27) established from a previously untreated patient and in an in vitro derived 5.6-fold cisplatin-resistant stable variant (GCT27cisR). Compared to 12 ovarian and 5 cervical human tumor cell lines, the parent GCT27 line was among the most sensitive to the cytotoxic effects of both cisplatin (dosage producing 50% inhibition, 0.2 microM) and carboplatin (dosage producing 50% inhibition, 2.9 microM), thus reflecting clinical data. A 4-day exposure sulforhodamine B-staining assay was used to determine that GCT27cisR was cross-resistant to carboplatin and iproplatin and the classical bifunctional alkylating agents melphalan and chlorambucil. Partial cross-resistance was observed to tetraplatin, methotrexate, and mitomycin C. No cross-resistance was observed to Adriamycin, etoposide, vinblastine, bleomycin, 1-beta-D-arabinofuranosylcytosine, and 5-fluorouracil. Intracellular cisplatin accumulation across the dose range 2.5-100 microM (for 2 h) was 1.6 +/- 0.39-fold (mean +/- SD) greater for the parent line. There was no significant difference in glutathione levels between the two lines. The acquired resistance line was 1.9-fold more resistant than the parent line to the cytotoxic effects of cadmium chloride. There was no significant difference between the two lines, however, in the total amounts of platinum bound to DNA after cisplatin exposure (25, 50, or 100 microM for 2 h). The removal of total platinum adducts from DNA was significantly faster for GCT27cisR compared to the parent line (half-times of removal, 32 and 67 h, respectively). These data suggest that the abnormal sensitivity of the parent testicular tumor cell line to platinum-containing anticancer drugs may be due predominantly to an inherent defect in the ability of these cells to remove platinum from their DNA. This defect is apparently lost in the acquired resistance counterpart. Reduced intracellular accumulation and increased cytoplasmic concentrations of metallothionein may also contribute, in part, to the acquisition of cisplatin resistance in this model.     

Ictal and Interictal Electrographic Seizure Durations in Preterm and Term Neonates

Summary: The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty-eight neonates with 644 electrographic seizures were identified retrospectively. Thirty-five full-term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [>31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of ≤31 weeks EGA. Ictal/ interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two-tailed t tests, chi-square calculations, and one-way analysis of variance (ANOVA) with Duncan's multiple-range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi-square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncan's multiple-range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncan's), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncan's). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE. Inhibitory networks responsible for longer interictal periods are more dominant in OPT infants than in YPT infants, reflecting maturational changes that suppress seizure activity during the latter part of the third trimester before the infant reaches an FT corrected age.     

Gradient of alarm substance in the forced swimming test

Three studies were conducted with rats to study the effects of a proposed alarm substance released during the forced swimming test. In the first study, rats were retested in water previously swum in but which had been subsequently diluted to varying degrees. When water was diluted by more than 25% the proposed alarm substance could no longer be detected. In the second study, rats were retested at various times after initial testing. This study showed that the alarm substance was still active by eight days after it had been initially released. The final study tested animals to see if the alarm substance could be depleted by repeated testing. Testing animals for more than an hour did not result in depletion of the alarm substance. These three studies suggest that the proposed alarm substance secreted by rats during the forced swimming test has considerable biological significance.     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology     

Psychological distress before and immediately after attendance at a male sub-fertility clinic.

Where treatment options are limited, the role of clinical consultation in providing information and support becomes more important. This study examines the immediate impact of medical consultation on male sub-fertility clinic attender's anxiety, depression, self-blame, information appraisal and perceptions of future fertility. Data were collected pre- and immediately post-consultation. Clinical information and consultation details were recorded. Results showed that anxiety levels were high before consultation. Following consultation anxiety and self-blame were both reduced while depression increased. Despite information about poor prognosis being given during consultation, participants remained overly optimistic about their chances of achieving a pregnancy. It appears that the consultation has a distinct psychological impact and possible mechanisms underlying this are discussed.     

Health lifestyles and self-direction in employment among American men: A test of the spillover effect

This paper examines whether American males with a high degree of control over their work situation pursue healthy lifestyles and rate their physical health more positively than those who score low on occupational self-direction. That is, are persons who control their work more likely to also try to control their health through living in a particularly healthy manner? We found that there was no support for a spillover effect from high occupational self-direction to enhanced participation in health lifestyles or more positive self-rated health. The findings suggest health lifestyles have spread throughout occupational work groups in the U.S. and support research that maintains such lifestyles have spread across social strata in America.     

Advanced practice nurses in emergency care settings: A demographic profile.

INTRODUCTION: Very little is known about clinical nurse specialists and nurse practitioners (advance practice nurses [APNs]) who practice in emergency care settings. The Advanced Practice Committee of the ENA sought to determine a profile of these individuals. METHODS: Surveys were distributed to all registrants at 2 ENA conferences and posted on the ENA Web site. This survey asked 17 questions concerning the demographic characteristics of the APN respondents (eg, education, experience, certification, state recognition, and practice area). The survey was completed by 166 APNs. RESULTS: APNs had considerable experience as ED registered nurses before becoming an APN. They obtained their APN education at the master's degree or post-master's degree level. State recognition was required for 89.2% of the APNs. The majority of APNs (61.4%) obtained their certification through the American Nurses Credentialing Center. Nurse practitioners were predominantly family nurse practitioners (43%), and clinical nurse specialists were either critical care clinical nurse specialists (8.9%) or had other certifications (5.9%). APNs provided services in both the main emergency department and the fast track (45.7%) and were relatively new to their role as an APN. DISCUSSION: Consistent with current educational and certification requirements, the vast majority of APNs held a master's degree. Although relatively new to their role as APNs in emergency care, they were nonetheless very experienced as ED registered nurses. The majority of APNs were certified, even though that is not required for practice in all states. Continued research is needed to identify the most effective utilization of APNs, document their contributions to patient care outcomes, and develop strategies to meet their educational and practice needs.     

Burns during pregnancy: a gloomy outcome

The effect of burns on fetal and maternal survival is known to be detrimental. This prospective study describes the performance of pregnant burned patients who were managed and followed up for fetal and maternal outcomes at Ain Shams University's burn unit and Maternity Hospital during the period from October 1995 to September 1996. During the 12-month period, 27 pregnant burned patients were managed. Fetal and maternal mortality correlated with the total body surface area (TBSA) burned, the mortality rate being 63 per cent for both mothers and fetuses in the 25–50 per cent TBSA group. A fetal loss of 56 per cent with no maternal loss were recorded in the 15–25 per cent TBSA group. Experience in dealing with pregnant burned patients proves that early surgical excision and skin grafting, with timely termination of pregnancy are the best lines of treatment. Prevention or minimizing the effects of the burns may be achieved by proper education and guidance of the pregnant woman.