Treatment of Anaerobic Bacterial Infections with Clindamycin-2-Phosphate

Thirty-five patients with a variety of serious infections caused by anaerobic bacteria responded to clindamycin. Cure was achieved in 27 of the 32 patients with pleuropulmonary and intra-abdominal infections. Mean serum concentrations of clindamycin for the 8 h after intramuscular administration of clindamycin in these patients were at least 2.5 times the minimal inhibitory concentration of clindamycin for more than 90% of anaerobes. This experience suggests that clindamycin is an excellent and relatively safe antibiotic for treatment of infection caused by anaerobes when combined with surgery (when indicated) or other antibiotics active against aerobic gram-negative bacilli, if present.     

Positive inotropic effect of carbachol and inositol phosphate levels in mammalian atria after pretreatment with pertussis toxin

The m-cholinoceptor agonist carbachol elicits a negative inotropic effect in mammalian atria. Pretreatment with pertussis toxin converts the negative to a positive inotropic effect. In this study we investigated the time course of the effects of carbachol on force of contraction and phosphoinositide products in electrically driven left auricles from guinea pig hearts after pretreatment with pertussis toxin (180 micrograms/kg i.v.; 24 hr). Inositol phosphates and phosphatidylinositols were labeled with [3H]inositol and separated with high-performance liquid chromatography and thin-layer chromatography, respectively. All experiments were performed in the presence of LiCl (10 mmol/l). The positive inotropic effect of carbachol (10 mumol/l) began within 2 min and was maximal within 15 min. Inositol 1,4,5-trisphosphate rose within 1 min followed by an increase in inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4-bisphosphate and inositol 1-phosphate beginning within 2 min. It is concluded that the carbachol-induced positive inotropic effect is associated with an increase in the presumed second messengers inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Since the increase in inositol 1,4,5-trisphosphate precedes the increase in force of contraction, it may initiate the positive inotropic effect. The increase in inositol 1,3,4,5-tetrakisphosphate may be involved in maintaining the positive inotropic effect of carbachol.     

Motor imagery in hypnosis: accuracy and duration of motor imagery in waking and hypnotic states

This study assessed response times and accuracy of motor imagery in waking and hypnotic states and to related responses to hypnotic experiences. The Vividness of Motor Imagery Questionnaire (VMIQ) was administered to 47 participants. A mental walking task was then performed in the waking state. In hypnosis, the same task was included within an imaginary journey after a hypnotic induction. An interaction effect showed for condition (waking vs. hypnotic) and distances. The further the participants had to walk in imagination, the longer they took. For all combinations, participants took significantly longer in hypnosis (p < .001) and were significantly less accurate in hypnosis in reproducing the difference between the different distances (p < .001). Results appear to show a relationship between motor imagery and hypnotic responding and support a state-trait conception of imagery.     

Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.     

Effects of vanadate on the c-AMP system of the heart

Summary 300 M vanadate (NH₄VO₃) caused an about 65% increase in force of contraction in isolated electrically driven cat papillary muscles. The positive inotropic effect (PIE) was accompanied by only a small (about 20%) but significant increase in c-AMP levels. 0.3 M isoprenaline (ISO) produced a much greater increase in c-AMP levels (about 80%) while the PIE of ISO was as great as the PIE observed with 300 M NH₄VO₃. In cat right ventricular adenylate cyclase preparations NH₄VO₃ and ISO stimulated adenylate cyclase activity by nearly the same extent. Propranolol (1 M and 5 M) prevented the ISO-induced adenylate cyclase stimulation but not the stimulation due to NH₄VO₃. Phosphodiesterase activity was not affected by NH₄VO₃ (up to 1000 M). It is concluded that the small vanadate-induced increase in c-AMP levels, which is due to adenylate cyclase stimulation, inintact papillary muscles maycontribute to its PIE, but other mechanisms may be at least equally important.

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Über die Wirkung von Vanadat auf das c-AMP-System des Herzens

Zusammenfassung 300 M Vanadat (NH₄VO₃) steigerte an isolierten, elektrisch gereizten Katzenpapillarmuskeln die Kontraktionskraft um ca. 65%. Der positiv inotrope Effekt (PIE) ging einher mit einem nur geringen (ca. 20%), aber signifikanten Anstieg des c-AMP-Gehaltes. 0.3 M Isoprenalin (ISO) verursachte einen sehr viel größeren Anstieg des myokardialen c-AMP-Gehaltes (ca. 80%), während der PIE von ISO gleich groß war wie der PIE von NH₄VO₃. In einer Adenylatcyclasepräparation von rechten Ventrikeln des Katzenherzens stimulierten NH₄VO₃ und ISO die Adenylatcyclaseaktivität in nahezu gleichem Ausmaß. Propranolol (1 M und 5 M) verhinderte die Aktivierung der Adenylatcyclase durch ISO, aber nicht die Aktivierung durch NH₄VO₃. Die Phosphodiesteraseaktivität wurde durch NH₄VO₃ (bis zu einer Konzentration von 1000 M) nicht beeinflußt. Aus den Ergebnissen wird geschlossen, daß der geringe vanadatinduzierte c-AMP-Anstieg, der über eine Stimulation der Adenylatcyclase zustande kommt, zwar am Zustandekommen des PIE beteiligt sein mag, daß aber andere Mechanismen von mindestens ebenso großer physiologischer Bedeutung sind.

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The data have been presented at the Symposium Cardiac Effects of Vanadate, Munich, October 26–27, 1979.

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This work was supported by the Deutsche Forschungsgemeinschaft.     

Expanding the disablement process model among older Mexican Americans

BACKGROUND: Very few studies have examined how disability develops among older Mexican Americans. To determine how disability develops, we explored the Disablement Process model, which posits that impairment, measured by muscle strength, leads to functional limitations, which lead to disability, which ultimately is associated with health-related quality of life (HRQOL). METHODS: A structural equation model approach was used (AMOS 4) with data collected on 622 Mexican Americans aged 71 or older residing in the Southwest. RESULTS: Our results show preliminary support for the Disablement Process model. Impairment is significantly associated with functional limitation (beta =.36, z value = 7.2), which is significantly associated with disability (beta = -.53, z value = 16.1). Finally, disability is significantly related to both physical and mental components of HRQOL (beta = -.69, z value = 23.4; beta = -.26, z value = 6.5, respectively). CONCLUSIONS: Muscle strength as a measure of impairment and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) score as a measure of HRQOL are important factors in understanding disability in older Mexican Americans.     

Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets

Several recent studies have demonstrated that T-helper cell-dependent events during the initial priming period are required for the generation of CD8(+) T cell-mediated protective immunity. The underlying mechanisms of this phenomenon have not yet been determined, mostly because of difficulties in studying memory T cells or their precursor populations at early stages during immune responses. We identified IL-7 receptor (CD127) surface expression as a marker for long-living memory T cells, most importantly allowing the distinction between memory and effector T cells early after in vivo priming. The combination of surface staining for CD127 and CD62L further separates between two functionally distinct memory cell subsets, which are similar (if not identical) to cell subsets recently described as central memory T cells (CD127(high) and CD62L(high)) and peripheral effector memory T cells (CD127(high) and CD62L(low)). Using this new tool of memory T cell analysis, we demonstrate that CD8(+) T cell priming in the absence of T cell help or CD40L specifically alters the generation of the effector memory T cell subset, which appears to be crucial for immediate memory responses and long-term maintenance of effective protective immunity. Our data reveal a unique strategy to obtain information about the quality of long-term protective immunity early during an immune response, a finding that may be applied in a variety of clinical settings, including the rapid monitoring of vaccination success.     

G-CSF and cyclosporin induce an increase of normal cells in hypoplastic paroxysmal nocturnal hemoglobinuria

 Four paroxysmal nocturnal hemoglobinuria (PNH) patients with severe thrombocytopenia, hemolytic anemia and neutropenia were treated using a combination of filgrastim (G-CSF) and cyclosporin. In all patients a trilineage response of hematopoiesis was achieved. In addition, the proportion of glycosyl-phosphatidylinositol (GPI)-deficient granulocytes decreased. All patients mobilized CD34⁺ hematopoietic progenitors into peripheral blood after starting treatment with G-CSF. The majority of early progenitors (CD34⁺CD38^–) after mobilization into peripheral blood was found to be unaffected by the GPI-anchoring defect. No patient developed leukemia while under therapy. We conclude from these data that the combination of G-CSF and cyclosporin represents an efficient option for the treatment of hypoplastic PNH. Received: 27 November 1996 / Accepted: 27 February 1997