Investigation of central visual fields in patients with age-related macular changes

The effect of early macular pigmentary and drusen changes on the central visual field was investigated in elderly patients with normal visual acuities. Visual field measurements were taken with the Humphrey Field Analyser using its 24-2 and 10-2 full threshold programs. No significant differences were found between two patients groups, one with and one without the macular changes. We conclude that fine pigmentary changes and hard drusen do not cause changes in visual functioning and can be accepted as normal age-related changes.     

A double-blind comparison of valproate and lithium in the treatment of acute mania.

OBJECTIVE: This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs. METHOD: Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA). RESULTS: At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response. CONCLUSIONS: Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.     

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

Cognitive-behavioral treatment of late-life generalized anxiety disorder

This study addressed the efficacy of cognitive-behavioral therapy (CBT), relative to minimal contact control (MCC), in a sample of 85 older adults (age 60 years and over) with generalized anxiety disorder (GAD). All participants completed measures of primary outcome (worry and anxiety), coexistent symptoms (depressive symptoms and specific fears), and quality of life. Results of both completer and intent-to-treat analyses revealed significant improvement in worry, anxiety, depression, and quality of life following CBT relative to MCC. Forty-five percent of patients in CBT were classified as responders, relative to 8% in MCC. Most gains for patients in CBT were maintained or enhanced over 1-year follow-up. However, posttreatment scores for patients in CBT failed to indicate return to normative functioning.     

Postnatal development of GABA-mediated synaptic inhibition in rat hippocampus

Developmental alterations in GABAergic synaptic transmission were examined physiologically and biochemically in hippocampus of rats from 3 days of age to adulthood. Neither antidromic nor orthodromic stimulation could elicit identifiable inhibitory postsynaptic potentials in CA1 neurons in slices from rats 5 or 6 days of age. In contrast, at this age these stimuli result in large inhibitory postsynaptic potentials in CA3 pyramidal cells. In the latter cells orthodromic stimulation produced a brief monosynaptic excitatory postsynaptic potential which was followed by a large prolonged biphasic hyperpolarization. These signals were strikingly similar to those recorded in 1-month-old rats. In addition, large recurrent inhibitory postsynaptic potentials were produced by antidromic stimulation. By postnatal day 9 similar inhibitory postsynaptic potentials could be elicited in a majority of neurons of the CA1 subfield. As in mature pyramidal cells, application of GABA antagonists, such as bicuculline, selectively eliminated the antidromic inhibitory postsynaptic potential and the first component of the biphasic inhibitory postsynaptic potential generated by stimulation of stratum radiatum. In the CA3 subfield, this blockade of GABA receptors resulted in prolonged afterdischarges in slices from immature but not month-old rats. Measurements of the equilibrium potential and the conductance of antidromic inhibitory postsynaptic potentials in CA3 neurons were very similar when made during the first postnatal week and at 1 month of age. While on days 10-11 the equilibrium potential was very similar to measurements made at these other ages, the conductance was 3-4 times greater. The activity of glutamate decarboxylase, the synthetic enzyme for GABA, was very low at 3 days in hippocampus, and increased until 30 days of age at which time adult values were obtained. By comparison, hippocampal GABA levels were high early in postnatal life. Glutamate decarboxylase activities in microdissected CA3 and CA1 subfields were similar in immature hippocampus. These results demonstrate dramatic differences in the ontogenesis of functional GABAergic inhibitory synaptic transmission in the CA1 and CA3 subfields of rat hippocampus. The late development of GABA-mediated synaptic inhibition in the CA1 subfield could play a role in the susceptibility of immature hippocampus to seizures. However, the large GABA-mediated inhibitory postsynaptic potentials present in the CA3 subfield at the same age have a critical role in dampening neuronal excitability.(ABSTRACT TRUNCATED AT 400 WORDS)     

A bioinformatics pipeline for high-throughput microbial multilocus sequence typing (MLST) analyses

Multilocus sequence typing (MLST) analysis for semi-routine applications is hindered by the downstream, manually intensive steps of processing the raw sequence data files. This report describes the development of an MLST pipeline that automates DNA sequence editing and analysis in order to significantly reduce the time required for processing data. Validation using a pneumococcal dataset revealed complete agreement between the results generated by manual and automated workflows. The MLST pipeline was developed for both double-strand and single-strand sequencing.     

Chronic pneumonia despite adaptive immune response to Mycobacterium bovis BCG in MyD88-deficient mice

To assess the role of Toll-like receptor (TLR) signalling in host response to mycobacterial infection, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with the vaccine strain Mycobacterium bovis (BCG), and the immune response and bacterial burden were investigated. Macrophages and dendritic cells from MyD88-deficient mice stimulated in vitro with BCG mycobacterial antigens produced very low levels of proinflammatory cytokines, while the expression of costimulatory molecules such as CD40 and CD86 was preserved. Upon systemic infection with BCG (2 x 10(6) CFU i.v.) MyD88-deficient mice developed confluent chronic pneumonia with two log higher CFU than wild-type mice. Interestingly, the infection was controlled in liver and spleen and there was efficient systemic T-cell priming with high IFNgamma production by CD4+ splenic T cells in MyD88-deficient mice. Lung infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon specific restimulation, and a reduced capacity to produce nitric oxide and IL-10. In summary, despite the dramatic reduction of the innate immune response, MyD88-deficient mice were able to mount an efficient T-cell response to mycobacterial antigens, which was however insufficient to control infection in the lung, resulting in chronic pneumonia in MyD88-deficient mice.     

Audit of intensive care unit admissions from the operating room

An audit of 265 intensive care unit (ICU) admissions from the operating room was performed for the year 1991. In a quality assurance exercise we identified 34 unanticipated ICU admissions (UIAs) by a retrospective peer review of the medical charts. Of these UIAs, 16 were deemed predictable and seven preventable. Five of the seven potentially preventable UIAs were judged to have had inappropriate intravenous fluid management. This has prompted changes in our education programme. In an assessment of our resource management, we evaluated prospectively collected data on the Apache II scores on the day of admission, the incidence of ICU-specific interventions, length of stay in ICU, and outcomes. ICU-specific interventions were not initially required in 36% of admissions and these patients had a low risk (1.1%) of eventually requiring ICU-specific interventions. In comparison with patients requiring ICU-specific interventions, they had lower Apache II scores (10.2 vs 13.1), shorter ICU stays (medians of one vs two days), lower ICU mortality (0 vs 8.2%), P < 0.05, but hospital mortality was not different (7.4 vs 15.3%). This audit has prompted re-organisation of our intensive care services, so that patients not requiring ICU-specific interventions will be managed in an intermediate care area with nurse.patient ratios of 1:3 or 4, in comparison with 1:1 or 2 ratios in the intensive care area.     

Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study

Rationale: Serotonergic (5-HT) mechanisms may be involved in impulse control (including anti-social behavior) across psychiatric syndromes. Age of onset may differentiate alcoholics on psychopathological characteristics associated with impulse control, especially mood disturbance, hostility, and a broad range of antisocial behaviors. Thus, there may be a predictable relationship between markers of 5-HT function and age of onset-related characteristics. Objective: We tested the hypothesis that there would be a predictable relationship between the ratio of plasma tryptophan to large neutral amino acids (i.e. TRYP/LNAA ratio), a marker of 5-HT function, age of onset and related psychopathological characteristics associated with impulse control. Methods: Fifty-eight male and female DSM-IV diagnosed alcoholics attending an outpatient treatment center completing a comprehensive psychopathological assessment, and from whom blood samples were obtained. Results: Plasma TRYP/LNAA ratio was positively correlated with symptoms of dysphoria, and negatively associated with harm avoidance on Cloninger’s Temperament and Character Inventory. Low tryptophan availability was associated with antisocial-type personality characteristics. Interestingly, the few (nine) subjects who had both early onset alcoholism and antisocial personality disorder had a higher plasma tryptophan but similar TRYP/LNAA ratio to the others. Conclusions: These data suggest that a low plasma TRYP/LNAA ratio is associated with susceptibility to anxiety, antisocial-type personality characteristics, and an early age of onset for alcoholism. In contrast, a high plasma TRYP/LNAA ratio is associated with a later onset of alcoholism and dysphoria. Received: 26 May 1998/Final version: 24 November 1998