Reduced vancomycin susceptibility and increased macrophage survival in Staphylococcus aureus strains sequentially isolated from a bacteraemic patient during a short course of antibiotic therapy.

PURPOSE: The purpose of the present study was to determine the relatedness of Staphylococcus aureus strains successively isolated over a 7-day period from a single bacteraemic patient undergoing antibiotic treatment with vancomycin. METHODS: The S. aureus strains had been isolated and sequenced previously. Antibiotic susceptibility testing, population analysis profiling, and lysostaphin sensitivity and phagocytic killing assays were used to characterize these clonal isolates. RESULTS: The seven isolates (MEH1-MEH7) were determined to belong to a common multilocus sequence type (MLST) and spa type. Within the third and fifth day of vancomycin treatment, mutations were observed in the vraS and rpsU genes, respectively. Population analysis profiles revealed that the initial isolate (MEH1) was vancomycin-susceptible S. aureus (VSSA), while those isolated on day 7 were mostly heteroresistant vancomycin-intermediate S. aureus (hVISA). Supporting these findings, MEH7 was also observed to be slower in growth, to have an increase in cell wall width and to have reduced sensitivity to lysostaphin, all characteristics of VISA and hVISA strains. In addition, MEH7, although phagocytosed at numbers comparable to the initial isolate, MEH1, survived in higher numbers in RAW 264.7 macrophages. Macrophages infected with MEH7 also released more TNF-α and IFN-1ß. CONCLUSION: We report an increasing resistance to vancomycin coupled with daptomycin that occurred within approximately 3 days of receiving vancomycin and steadily increased until the infection was cleared with an alternative antibiotic therapy. This study reiterates the need for rapid, efficient and accurate detection of hVISA and VISA infections, especially in high-bacterial load, metastatic infections like bacteraemia.

Draft Genome Sequences of Two Staphylococcus aureus Strains Isolated in Succession from a Case of Bacteremia.

Staphylococcus aureus strains MEH1 and MEH7 were successively isolated from the blood of a patient with recurrent bacteremia. The submitted draft genomes of strains MEH1 and MEH7 are 2,914,972 and 2,911,704 bp, respectively.

Sex-related effects of hypothyroidism on cellular proliferation in the hypophyseal mammotroph population of the rat

Changes in the morphology and number ofprolactin-immunoreactive cells have beendescribed in hypothyroidism. However, noanalyses of the changes that occur in the proliferationof these cells have been undertaken.In order to determine the proliferation rate ofrat hypophyseal prolactin cells in hypothyroidismand whether the observed changes arerelated to increases in TRH, a doubleimmunohistochemical study for PCNA andprolactin was carried out in thyroidectomisedrats and in rats treated with TRH. TRH treatment,but not thyroidectomy, increased thepercentage of prolactin-producing cells inboth sexes (p<0.01). However, whereas thecellular proliferation of prolactin-producingcells was significantly increased in males(p<0.01) in both experimental designs, infemale rats the proliferation of prolactin-producingcells was increased after treatmentwith TRH, but not in thyroidectomised rats(p<0.01). Our results demonstrate —mainlyin male rats— that modifications in thehypophyseal-thyroid axis elicit changes inprolactin-producing cells that are related tothe proliferation rate of these cells. Theseresults suggest that sex-related effects of bothTRH and thyroid hormones could be involvedin the physiological regulation of the proliferationof pituitary prolactin-producing cells,because the responses to treatment with TRHwere different from the changes observed inthyroidectomised rats (AU)

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Apoptosis is involved in the antiproliferativeeffect of corticosterone innon-tumoral ACTH pituitary cells

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Nitric oxide attenuates signal transduction: possible role in dissociating caveolin-1 scaffold.

Caveolae harbor different serpentine receptors, intracellular components of signaling cascades, and certain enzymes, including endothelial nitric oxide synthase (eNOS). The regulation of eNOS activity by Ca(2+)/calmodulin and caveolin has been described. We have previously demonstrated that nitric oxide (NO) can modulate signaling initiated via receptors localized to caveolae. In the present study, we show that NO donors induced an increase in the monomeric form of this scaffolding protein in cultured endothelial cells, the effect mimicked by 8-bromo cGMP. Proximity imaging of endothelial cells transfected with the thermotolerant green fluorescent protein-caveolin-1 construct demonstrated that sodium nitroprusside resulted in the increased fluorescence ratio of 410:470 nm, consistent with the distancing of fluorescently tagged caveolin-1. Pulse labeling of endothelial cells with cholera toxin B subunit indicated that sodium nitroprusside reversibly decreased its binding. Signaling via G protein-coupled receptors resident to caveolae was inhibited by pretreatment with NO donor. The data demonstrate that NO modulation of cell signaling is accomplished in part by regulating the state of caveolin-1 oligomerization. NO-induced attenuation of signaling involves reversible dissociation of caveolin scaffold, thus providing both spatial and temporal modulation of signal transduction.

Methods to improve diagnostic accuracy in a community mental health setting.

OBJECTIVE: This study determined the extent to which adding structured procedures improved diagnostic accuracy for outpatients with severe mental illness in a community mental health setting. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research nurse reviewed medical records and amended the SCID diagnoses accordingly. A research psychiatrist or psychologist reviewed the diagnostic data and interviewed each patient to verify or further modify the previous findings. Diagnostic outcomes at each step of the procedure were compared to determine whether adding additional data improved diagnostic accuracy. The additional time required for each element of the diagnostic procedure was also assessed. RESULTS: Kappa comparisons of the different diagnostic levels showed that adding additional data significantly improved accuracy. Diagnoses rendered by combining the SCID and review of the medical record were the most accurate, followed by the SCID alone, and then diagnoses made by psychiatrists during routine care. In addition, the SCID alone identified five times as many current and past secondary diagnoses as were documented routinely in patients' charts. CONCLUSIONS: Combining structured interviewing with a review of the medical record appears to produce more accurate primary diagnoses and to identify more secondary diagnoses than routine clinical methods. The patients' knowledge of their diagnoses was limited, suggesting a need for patient education in this setting. Whether use of structured interviewing in routine practice improves patient outcomes deserves further study.

Cognitive-behavioral therapy for anxiety disorders: why and how it works.

Cognitive-behavioral therapy (CBT) has been found to be effective in the treatment of anxiety disorders such as obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). There is a gap, however, between reports of controlled clinical trials and actual clinical use of the methods of CBT in general medical and psychiatric settings. While psychiatric medications are commonly the first line of treatment, pharmacotherapy may not completely eradicate symptomatology or may have a delayed effectiveness, during which time patients continue to suffer. Cognitive and behavioral interventions can complement, if not replace, pharmacotherapy for relief of symptoms of OCD and PTSD. This article explains how CBT works in the treatment of OCD and PTSD. Basic instructions for implementing these treatment methods are provided.

The nature of help-seeking during psychiatric emergency service visits by a patient and an accompanying adult.

Utilization rates for urban psychiatric emergency services remain high, and the decision to seek care in this setting is poorly understood. Three hundred individuals accompanying patients to a psychiatric emergency service were interviewed about their help seeking and choice of treatment setting. Twenty-three of the interviewees (7.7 percent) were caregivers accompanying patients with severe and persistent mental illness. They were significantly more likely than other interviewees to know the difference between psychiatric emergency services and services offered by other outpatient providers. More than half reported that the patient they accompanied was intermittently noncompliant, which required visiting either a walk-in service during a moment when the patient was cooperative or a facility equipped to provide involuntary treatment.

Depressive effect of isoflurane on motor evoked potentials in the Nubian goat.

PURPOSE: To determine the effect of isoflurane on motor evoked potentials (MEP) in a new animal model designed to verify the applicability of MEPs in brachial plexus surgery, and to compare the results with previous reports in other animals. METHODS: In seven goats, anesthesia was induced with 3 mg x kg(-1) ketamine i.v. and maintained with nitrous oxide 40% in oxygen and 2 microg x kg(-1) x hr(-1) fentanyl i.v.. The MEP were performed with two subcutaneous needle electrodes placed over the occiput (cathode) and the nasion (anode), with their plugs connected to the power output of a Digitimer D 180 electrical stimulator, connected to the trigger input of an electromyograph (model 8400, Cadwell Laboratories, Inc., Kennwick, Washington). Activation of the Digitimer caused central stimulation of the motor cortex, evoking baseline compound muscle action potentials (CMAPs) which were recorded from the left triceps muscle. Subsequently, isoflurane 2% was administered together with repeated central stimulation at 30 sec intervals. RESULTS: Onset of I- (indirect) waves increased from median 15,8 msec to median 26,8 msec P = 0,018 (latency increase ranged from: 9 to 11.5 msec), while peak-to-peak amplitudes decreased and subsequently disappeared. D- (direct) waves showed no latency increase, and finally disappeared as well. After disappearance of CMAPs, isoflurane administration was stopped and MEP repeated. The CMAPs reappeared (range: 210-360 sec) and regained initial peak-to-peak amplitudes and latencies. CONCLUSION: These animal studies suggest that isoflurane should not be used during the recording of MEPs.

Structured diagnostic assessment and depot fluphenazine treatment of multiple suicide attempters in the emergency department.

The aim of this study was to compare the efficacy of two doses of monthly intramuscular (i.m.) injections of fluphenazine decanoate in reducing self-harm behaviours in outpatients with histories of multiple suicide attempts. Fifty-eight patients who presented to a psychiatric emergency service after an attempted suicide and who had histories of multiple suicide attempts, were randomized to receive monthly i.m. injections of fluphenazine decanoate. Thirty patients received monthly 12.5 mg ('low' dose), and 28 patients received monthly 1.5 mg ('ultra low' dose) under double-blind conditions. DSM-III-R diagnoses were obtained on all patients using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P) and SCID for DSM-III-R Personality Disorders (SCID-II). Outcomes were assessed by the Parasuicide History Inventory and the Abnormal Involuntary Movement Scale, collected monthly for 6 months. Patients had an average of six current Axis I and 2.6 Axis II diagnoses, with borderline personality (85%) and alcohol dependence (58%) occurring most frequently in the sample. Both the low dose and ultra-low dose groups showed a marked reduction in self-harm behaviours. For 'serious' self-harm behaviours, there was a trend for a greater effect of the low dose over the ultra-low dose group, however, the differences did not reach statistical significance. A survival analysis indicated that the presence of 'acute' stressors at baseline and female sex were risk factors for continuing (post-randomization) 'serious' self-harm behaviours, while younger age and the absence of concurrent general medical conditions were risk factors for all self-harm behaviours.

Polymorphism in apoprotein-CIII gene and coronary heart disease.

BACKGROUND: The aim of this study was to look into the association, if any, of apoprotein-CIII variant allele with hypertriglyceridemia, hypercholesterolemia and coronary heart disease (CHD). PATIENTS AND METHODS: The prevalence of a C to G substitution in the 3' untranslated region of apoprotein-CIII was studied in a sample of 92 angiographed Saudi subjects, consisting of 65 males and 27 females. The subjects were genotyped by amplification followed by digestion of the gene fragment containing the polymorphic site with Sac I restriction enzyme. RESULTS: The variant allele of apoprotein-CIII was found to be associated neither with hypertriglyceridemia nor with hypercholesterolemia. However, a significant association of this allele (P<0.01) was found with coronary heart disease, independent of other risk factors such as smoking, diabetes and hypertension. An estimation of odds ratio using logistic regression with various risk factors in the model showed that the individuals with this rare allele were 3.4 times more at risk of developing coronary heart disease. This estimate of risk held even after analyzing a subset of individuals above 45 years of age. CONCLUSION: While the association between apoprotein-CIII variant allele and dyslipidemia could not be established in this study, the relationship between this marker and CHD was highlighted in the studied subjects.

Is there a role for continuation phase cognitive therapy for depressed outpatients?

Two pilot studies evaluated the rate of relapse or recurrence (i.e., major depressive disorder) after cognitive therapy (CT). Two sequential cohorts included outpatients who responded to acute phase CT (A-CT) and who agreed to monthly, treatment-free follow-up. In Study 1, the Kaplan-Meier technique estimated relapse and recurrence rates of 40% at 6 months, 45% at 8 months, 50% at 12 months, 67% at 18 months, and 74% at 24 months. In Study 2, responders to A-CT received 8 months (10 sessions) of continuation phase CT (C-CT). In Study 2, relapse or recurrence was 20% at 6 and 8 months, 27% at 12 months, and 36% at 18 and 24 months after A-CT. An exploratory log-rank test showed that relapse or recurrence-free survival was greater in Study 2 than in Study 1. If replicated, this result suggests that C-CT can reduce depressive relapse or recurrence. Alternative explanations are presented.

Effects of amiodarone on ouabain binding to microsomal Na+, K(+)-ATPase in guinea-pig heart preparations.

1. The influence of amiodarone on [3H]ouabain (OUA) binding to myocardial Na+, K(+)-ATPase was studied at various KCl concentrations in guinea pig heart microsomal preparations to test the hypothesis that the drug acts on the same receptor sites as cardiac glycosides. 2. First, a series of assays for OUA binding to Na+, K(+)-ATPase were performed in the range of 64-800 nM at 2.5, 5.0 and 10.0 mM K+ concentration. The drug exhibited increasing binding tendency with increasing concentrations and elevation in K+ levels. 3. Competitive binding assays were then performed at 256, 512 and 800 nM OUA in the presence of 50, 100 and 200 microM amiodarone at 5.0 mM KCl, respectively. At each OUA concentration, a concentration-dependent left-to-right shift was observed in the binding affinity with increasing amiodarone concentration. similar assays at 2.5 and 10.0 mM K+ showed the same trends. These effects were significant for 200 mM amiodarone at all K+ levels and OUA concentrations. 4. Furthermore, different OUA concentrations were also shown to displace amiodarone in a concentration-dependent fashion. 5. These results indicate that amiodarone competes with OUA for specific binding sites on myocardial microsomal Na+, K(+)-ATPase. They lead to the conclusion that myocardial Na+, K(+)-ATPase is a possible receptor for some of the cardiac actions of amiodarone, such as its proarrhythmic effects.

The Inventory of Depressive Symptomatology (IDS): psychometric properties.

The psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for the total sample and from 0.76 to 0.82 for those with current depression. Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.

Insulin withholding for weight control in women with diabetes.

OBJECTIVE: To provide a description of the clinical characteristics that distinguish individuals who withhold insulin for weight control from those who do not. Some individuals with insulin-dependent diabetes mellitus (IDDM) control their weight by withholding insulin and purging excessive calories. This process places patients at risk for developing severe hyperglycemia, diabetic ketoacidosis, and increases the risk of long-term complications of diabetes. RESEARCH DESIGN AND METHODS: Forty-two women with IDDM, ages 16-40, were interviewed and divided into two groups: insulin withholders (IWs) and non-insulin withholders (non-IWs). These groups were compared on physiological, behavioral, psychological, and psychiatric variables. RESULTS: Compared with non-IWs, patients who withheld insulin to control their weight exhibited poorer glycemic control, reported more negative attitudes toward diabetes, were more likely to have pathological scores on the Eating Disorder Inventory 2, and were more likely to report current or past symptoms of anorexia or bulimia nervosa. IWs were also more likely to report lying to physicians about their degree of compliance with their diabetes regimens. CONCLUSIONS: The results of this study indicated that IWs exhibit more symptoms associated with the spectrum of eating disorders than non-IWs. This study showed that insulin withholding for weight control not only exists, but is associated with some maladaptive symptoms and behaviors that need to be addressed by diabetes treatment teams.

Treatment of diabetic impotence with a vacuum device: efficacy and effects on psychological status.

Twelve patients with erectile impotence related to diabetic neuropathy were treated with a vacuum device, Pos-T-Vac. Efficacy of the device and psychological evaluation (Dyadic Adjustment Scale for marital satisfaction and Hamilton Rating Scale for depression) were performed before and 3 months after treatment. Vacuum therapy was successful in 75% of the patients. Patients with successful impotence treatment and normal baseline marital satisfaction scores showed a modest increase in the scores of marital satisfaction (from 114 +/- 3 points, baseline, to 121 +/- 3 points, posttreatment; p less than 0.05). Vacuum therapy for the treatment of erectile dysfunction due to diabetic autonomic neuropathy appears to be safe and effective.