The action of psychotropic drugs on DOPA induced behavioural responses in mice.

The "DOPA potentiation" test in mice was investigated for its usefulness in the detection of compounds with antidepressant properties. It was found that the anti-depressant drugs imipramine, amitriptyline, 5-methylamino-acetyl-6-methyl-5,6-dihydro-phenanthridine-HCl (Org OI77) and 1,2,3,4,10,14b-hexahydro-2-methyl-dibenzo[c,f]pyrazino[1,2-a]azepine-HCl (mianserin, Org GB 94) potentiated the behavioural effect of DOPA in groups of mice which had been treated 17 h previously with the monoamine oxidase inhibitor (MAOI) iproniazid. However, the DOPA response was also potentiated by a variety of centrally acting drugs which do not have antidepressant properties (atropine, methysergide, chlordiazepoxide, apomorphine). The peptide hormones ACTH4-10 and desglycinamide lysine vasopressin had equivocal effects while melanocyte stimulating hormone release-inhibiting factor (MIF) had no effect on the DOPA response. The DOPA response was inhibited by the neuroleptics chlorpromazine and haloperidol. There appeared to be no correlation between the effects of the drugs on the behavioural responses elicited by DOPA and the changes found in the brain concentration of noradrenaline, dopamine, serotonin, gamma-aminobutyric acid, tryptophan and tyrosine. It is concluded that the "DOPA potentiation" test cannot be considered as a reliable test in the detection of anti-depressant compounds.     

Digitizing the moving face during dynamic displays of emotion

Humans typically decode facial signals during dynamic interactions in which the face moves. In this study, we digitized real time video signals in order to examine movement asymmetries across the face during emotional and nonemotional expressions. Forty dextral males were tested. For each expression, a 400 ms video segment was analyzed for changes in signal value (pixel intensity) over consecutive frames. The upper and lower face regions were examined separately due to differences in the cortical enervation of facial muscles in the upper (bilateral) vs lower face (contralateral). Results revealed distinctly different movement asymmetries over the lower and upper hemiface. In the upper face, more movement occurred over the right side for most facial expressions, regardless of emotionality. The latter finding questions the assumption that muscles of the upper face are symmetrical and/or bilaterally enervated in a symmetrical manner. In the lower face, negative expressions linked to fight-flight emotions (i.e. fear, anger) were associated with greater left sided movement, whereas happiness tended to be associated with more right sided movement. No consistent pattern of movement asymmetry occurred for nonemotional expressions. Although the valence-related movement asymmetries in the lower face are consistent with neuropsychological models of emotional expressivity, it remains unclear whether they reflect activation or inhibitory hemispheric mechanisms. Taken together, these data suggest that multiple factors may contribute to expressive movement asymmetries of the face.     

Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer.

PURPOSE: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses. CONCLUSIONS: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

Neurological outcome of methylmalonic acidaemia

OBJECTIVE: To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study. PATIENTS: All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups. RESULTS: There was a significant difference between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant difference in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age. CONCLUSIONS: Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group.     

The significance of a high plasma ammonia value.

At a tertiary referral centre, just over 50% of patients with plasma ammonia values over 200 micro mol/l had inborn errors of metabolism. To distinguish artefactual high values from those requiring treatment, the measurement should be repeated immediately if the result is above 200 micro mol/l and at lower concentrations if the patient is encephalopathic.     

Severe influenza B myocarditis and myositis.

OBJECTIVE: To report an influenza B infection with associated myocarditis and severe skeletal myositis. DESIGN: Case report. SETTING: Cardiac intensive care unit in a university-affiliated children's hospital. PATIENT: A 4-yr-old girl. RESULTS: The patient was successfully supported with extracorporeal membrane oxygenation for profound myocardial dysfunction and a combination of plasmapheresis and continuous venovenous hemodialysis for rhabdomyolysis and acute renal failure. CONCLUSIONS: This case provides a reminder that patients presenting with viral illness or myoglobinuria accompanied by renal failure, with or without associated myocarditis, may be demonstrating symptoms of influenza B.     

Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia.

AIMS: To investigate glucose and leucine kinetics in association with metabolic and endocrine investigations in children with ketotic hypoglycaemia (KH) in order to elucidate the underlying pathophysiology. METHODS: Prospective interventional study using stable isotope tracer in nine children (mean age 4.23 years, range 0.9-9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range 0.16-12.3 years; four males). RESULTS: Plasma insulin levels were significantly lower in KH compared to subjects in the non-KH group. Plasma ketone body levels were significantly higher in KH than in non-KH. Basal metabolic rate was significantly higher in subjects with KH (45.48+/-7.41 v 31.81+/-6.72 kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non-KH, 0.84+/-0.05 v 0.8+/-0.04. Leucine oxidation rates were significantly lower in children with KH (12.25+/-6.25 v 31.96+/-8.59 micromol/kg/h). Hepatic glucose production rates were also significantly lower in KH (3.84+/-0.46 v 6.6+/-0.59 mg/kg/min). CONCLUSIONS: KH is caused by a failure to sustain hepatic glucose production rather than by increased glucose oxidation rates. Energy demand is significantly increased, whereas leucine oxidation is reduced.     

Latent demand for the bone-anchored hearing aid: the Lippy Group experience.

OBJECTIVE: The usefulness of the bone-anchored hearing aid (BAHA) for conductive and mixed hearing losses and recently for single-sided deafness has been well documented. Less clear is the number of patients who might benefit from the BAHA and how many would be interested in having the surgery. The purpose of this investigation is to examine these latter issues from the perspective of an otology practice. STUDY DESIGN: Retrospective review. SETTING: Private otology practice. PATIENTS: Approximately 44,000 patient records were reviewed. On the basis of this review, 617 patients were sent a letter describing the BAHA and explaining that they might be candidates. One hundred sixty-two of these patients made an appointment to be evaluated for the BAHA. METHODS: Patients who responded to the BAHA letter underwent an otologic and audiological evaluation to confirm their candidacy. The BAHA surgery and device were described, and interested patients tried the BAHA test band in the office. Patient responses to the BAHA were noted. RESULTS: Approximately 1.4% of the cases reviewed (617/44,000) were considered to be potential BAHA candidates. One hundred forty-six of the 162 patients who scheduled a BAHA evaluation were confirmed to be candidates. After seeing and learning about the BAHA, 92% of the verified candidates wanted to try the BAHA test band. Most patients who tried the test band (92%) liked the BAHA, and nearly a third (30.6%) had BAHA surgery. Patients with conductive or mixed hearing loss who tried the test band were more likely to have BAHA surgery than those with single-sided deafness (45.8% versus 27.3%). The major limiting factor was infrequent or inadequate insurance coverage for the procedure or device. CONCLUSIONS: Although the percentage of patients in an otology practice who could benefit from the BAHA is small, finding and alerting potential BAHA candidates are worthwhile.