Randomized Controlled Clinical Trial of Blood Glucose Awareness Training (BGAT III) in Switzerland and Germany

Although both diabetes and the efficacy of medical management are international issues, psycho-educational interventions might be culturally bound. Blood Glucose Awareness Training (BGAT) is a psycho-educational program for patients with type 1 diabetes mellitus. It is focused on improving recognition and management of extreme blood glucose levels, and is the best documented American psycho-educational program for this purpose. A randomized controlled clinical trial of BGAT's long-term benefits in a non-American setting has been lacking. One hundred and eleven adults with type 1 diabetes mellitus from Switzerland and Germany participated. After a 6 months baseline assessment, subjects were randomly assigned to receive either 2 months of BGAT (n = 56) or a physician-guided self-help control intervention (n = 55). BGAT improved recognition of low (p = 0.008), high (p = .03), and overall blood glucose (p = 0.001), and reduced frequency of severe hypoglycemia (p = 0.04), without compromising metabolic control. BGAT reduced both the external locus of control (p < 0.02) and fear of hypoglycemia (p < 0.02). BGAT was efficacious in reducing adverse clinical events and achieving clinically desirable goals in a European, as well as American setting.     

The high prevalence of bipolar spectrum disorders in young adults with recurrent depression: toward an innovative diagnostic framework

BACKGROUND: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. METHODS: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off > or =8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. RESULTS: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. LIMITATIONS: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi's BSD construct. CONCLUSIONS: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile.     

Cystathionine beta-lyase is important for virulence of Salmonella enterica serovar Typhimurium

The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine beta-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine beta-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine beta-lyase is important for bacterial virulence.     

Approaches to managing volunteer marrow donor registry HLA data. Algorithms for directing donor center-initiated HLA-DR typing of selected donors

The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations     

Immunological and pharmacological analysis of the primary and secondary reagin response to Nippostrongylus brasiliensis in the rat

When systemic anaphylaxis has been induced in rats infected once with the nematode, Nippostrongylus brasiliensis, the gross pathological lesions are found in the small intestine (`early' anaphylaxis). When systemic anaphylaxis is induced in rats infected four times, these lesions appear predominantly in the lungs (`late' anaphylaxis). The reasons for the change in localization of the lesions have been studied.

Reaginic antibodies are involved in both `early' and `late' anaphylaxis but there was no difference in the physicochemical and biological properties of circulating reagins taken after one or after four infections. In particular, no differences in their preference for a distinct tissue structure was detected because, in rats given either `early' or `late' reaginic antibody, passive systemic anaphylaxis resulted in lesions restricted to the small intestine. The amount of `blocking' antibody increased after several successive infections and did not explain the decrease in sensitivity to systemic anaphylaxis which occurred in rats infected twice or three times.

Differences in the degree of anaphylactic sensitization of a given tissue were assessed by measuring titres of local reaginic antibody and concentrations of tissue histamine. Following an initial infection, anaphylactic sensitization is highest along the small intestine; following several successive infections, anaphylactic sensitization is especially high in lung tissue. It is suggested that the changes in the local site and degree of anaphylactic sensitization are due to the increase in immunity of the host which allows the parasite to migrate to the lungs but not to reach the intestine.

     

Pneumocystis carinii f. sp. hominis is not infectious for SCID mice

The infectious power of Pneumocystis carinii f. sp. hominis was explored by inoculating SCID mice intranasally with either P. carinii f. sp. hominis or P. carinii f. sp. muris isolates. Only mice inoculated with mouse parasites developed Pneumocystis pneumonia, as assessed by microscopy and PCR. These results suggest that humans do not contract pneumocystosis from animals.     

Evidence for involvement of a tumor suppressor gene on 1p in malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNST) are rare soft-tissue malignancies. The genetic basis of these tumors is still poorly understood. Cytogenetic analyses predominantly revealed complex karyotypes, precluding the identification of recurrent chromosomal changes. We report loss of 1p material in a near-diploid karyotype with few or no additional structural chromosome changes in two sporadic cases of MPNST, indicating an important role of 1p loss in MPNST development. In one of these two tumors, a distal 1p deletion (1p31.2 approximately pter) was detected suggesting involvement of a tumor suppressor gene located within this distal region of 1p. Further evidence for recurrent 1p loss in MPNST was obtained by interphase fluorescence in situ hybridization, which showed loss of 1p material in 3 out of 13 tumors. These findings together with data from the literature suggest that loss of a tumor suppressor gene located within distal 1p is implicated in the pathogenesis of MPNST.     

Risk and protective factors for suicidal behavior in abused African American women

This study examined risk and protective factors that differentiate low-income, abused African American women (N = 200) who attempted suicide from those who had never made a suicide attempt. Results from multivariate analyses revealed that numerous and/or severe negative life events, a history of child maltreatment, high levels of psychological distress and depression, hopelessness about the future, and alcohol and drug problems were factors associated with attempter status. Protective factors associated with nonattempter status included hopefulness, self-efficacy, coping skills, social support, and effectiveness in obtaining material resources. Culturally competent intervention approaches for abused women should target increasing their protective factors and reducing their risk factors to decrease the likelihood that these women engage in suicidal behavior.     

Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents

1. Intracellular recordings were obtained from neurons in the motor cortex (MCx), in which excitatory postsynaptic potentials (EPSPs) were evoked by microstimulation of the somatosensory cortex (SCx) and the ventrolateral nucleus (VL) of the thalamus. The effects of combined tetanic stimulation of SCx and VL on the amplitudes of these EPSPs were studied. 2. Amplitudes of both corticocortical (CC) and thalamocortical (TC) EPSPs were potentiated after combined tetanic stimulation. This potentiation occurred exclusively in neurons that were located in the superficial layers (II/III) and that received direct input from both the SCx and VL, with both inputs synapsing in close proximity to each other. In all cases, the potentiation lasted until the electrode went out of the cell (21 +/- 25 min, mean +/- SD) the longest being 90 min. We therefore refer to this potentiation as long-term potentiation (LTP). 3. Tetanic stimulation of the thalamus only did not produce LTP in neurons receiving direct input from the VL. 4. LTP was not induced in either CC or TC EPSPs in neurons located in layer V and/or in neurons receiving long-latency CC EPSPs. 5. It is concluded that TC input from the VL to the MCx is potentiated only when coactivated with the CC input from the SCx.     

Visual motion response properties of neurons in dorsolateral pontine nucleus of alert monkey

1. In this study we sought to characterize the visual motion processing that exists in the dorsolateral pontine nucleus (DLPN) and make a comparison with the reported visual responses of the middle temporal (MT) and medial superior temporal (MST) areas of the monkey cerebral cortex. The DLPN is implicated as a component of the visuomotor interface involved with the regulation of smooth-pursuit eye movements, because it is a major terminus for afferents from MT and MST and also the source of efferents to cerebellar regions involved with eye-movement control. 2. Some DLPN cells were preferentially responsive to discrete (spot and bar) visual stimuli, or to large-field, random-dot pattern motion, or to both discrete and large-field visual motion. The results suggest differential input from localized regions of MT and MST. 3. The visual-motion responses of DLPN neurons were direction selective for 86% of the discrete visual responses and 95% of the large-field responses. Direction tuning bandwidths (full-width at 50% maximum response amplitude) averaged 107 degrees and 120 degrees for discrete and large-field visual motion responses, respectively. For the two visual response types, the direction index averaged 0.95 and 1.02, indicating that responses to stimuli moving in preferred directions were, on average, 20 and 50 times greater than responses to discrete or large-field stimulus movement in the opposite directions, respectively. 4. Most of the DLPN visual responses to movements of discrete visual stimuli exhibited increases in amplitude up to preferred retinal image speeds between 20 and 80 degrees/s, with an average preferred speed of 39 degrees/s. At higher speeds, the response amplitude of most units decreased, although a few units exhibited a broad saturation in response amplitude that was maintained up to at least 150 degrees/s before the response decreased. Over the range of speeds up to the preferred speeds, the sensitivity of DLPN neurons to discrete stimulus-related, retinal-image speed averaged 3.0 spikes/s per deg/s. The responses to large-field visual motion were less sensitive to retinal image speed and exhibited an average sensitivity of 1.4 spikes/s per deg/s before the visual response saturated. 5. DLPN and MT were quantitatively comparable with respect to degree of direction selectivity, retinal image speed tuning, and distribution of preferred speeds. Many DLPN receptive fields contained the fovea and were larger than those of MT and more like MST receptive fields in size.(ABSTRACT TRUNCATED AT 400 WORDS)