Treatment of depression among impoverished primary care patients from ethnic minority groups

OBJECTIVE: The aim of this study was to determine whether supplementing traditional cognitive-behavioral therapy for depression with clinical case management would reduce the rate of dropout from care and improve outcomes for ethnically diverse, impoverished medical outpatients. METHODS: The study was a randomized trial that compared cognitive-behavioral group psychotherapy alone (N=103) with the same therapy supplemented by clinical case management (N=96). RESULTS: The patients who received supplemental case management had lower dropout rates than those who received cognitive-behavioral group therapy alone. Supplemental case management was associated with greater improvement in symptoms and functioning than cognitive-behavioral therapy alone for patients whose first language was Spanish (N=77) but was less effective for those whose first language was English (N=122). CONCLUSIONS: Supplemental case management improves retention in traditional mental health outpatient care and can improve outcomes for Spanish-speaking patients.     

Genetic mapping and characterization of the bleeding disorder in the fawn-hooded hypertensive rat

Release of platelet dense granule contents occurs in response to vascular injury, playing an important role in platelet aggregation and primary hemostasis. Abnormalities of the platelet dense granules results in a bleeding disorder of variable severity termed "storage pool defect" (SPD). We have examined the fawn-hooded hypertensive (FHH) rat as a model of SPD in order to genetically map the locus (Bd) responsible for prolonged bleeding. Platelet function assays of the FHH rat confirmed the presence of a platelet dense granule SPD. However electron microscopy and lysosomal enzyme assays indicated differences between the FHH rat and other rodent models of SPD. Genetic mapping through the use of congenic FHH rats localized the Bd locus to an approximately 1 cM region on rat chromosome 1. Through the use of comparative mapping between species and analysis of the initial draft of the rat genome assembly, six known and thirty-four putative genes were identified in the Bd locus. None of these genes have been previously implicated in platelet function. Therefore positional cloning of the gene responsible for the bleeding disorder in the FHH rat will lead to new insights in platelet physiology, with implications for diagnosis and management of hemostatic and thrombotic disorders.     

Pyruvate protection against beta-amyloid-induced neuronal death: role of mitochondrial redox state

The mechanism by which beta-amyloid protein (A beta) causes degeneration in cultured neurons is not completely understood, but several lines of evidence suggest that A beta-mediated neuronal death is associated with an enhanced production of reactive oxygen species (ROS) and oxidative damage. In the present study, we address whether supplementation of glucose-containing culture media with energy substrates, pyruvate plus malate (P/M), protects rat primary neurons from A beta-induced degeneration and death. We found that P/M addition attenuated cell death evoked by beta-amyloid peptides (A beta(25-35) and A beta(1-40)) after 24 hr treatment and that this effect was blocked by alpha-ciano-3-hydroxycinnamate (CIN), suggesting that it requires mitochondrial pyruvate uptake. P/M supply to control and A beta-treated neuronal cultures increases cellular reducing power, as indicated by the ability to reduce the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The early increases in ROS levels, measured by dichlorofluorescein (DCF) fluorescence, and caspase-3 activity that follow exposure to A beta were notably reduced in the presence of P/M. These results place activation of caspase-3 most likely downstream of oxidative damage to the mitochondria and indicate that mitochondrial NAD(P) redox status plays a central role in the neuroprotective effect of pyruvate. Inhibition of respiratory chain complexes and mitochondrial uncoupling did not block the early increase in ROS levels, suggesting that A beta could initiate oxidative stress by activating a source of ROS that is not accesible to the antioxidant defenses fueled by mitochondrial substrates.     

Systemic co-treatment with alpha-melanocyte stimulating hormone delays hearing loss caused by local cisplatin administration in guinea pigs

It has previously been demonstrated that ototoxicity induced by systemic administration of cisplatin is reduced by concomitant administration of melanocortins, like alpha-melanocyte stimulating hormone (alpha-MSH). However, these experiments were hampered by large interanimal variability. Therefore, we re-investigated the effects of systemically administered alpha-MSH during local (intracochlear) administration of cisplatin. Guinea pigs, implanted with a round-window electrode, allowing daily monitoring of the compound action potentials (CAPs), and a mini-osmotic pump, pumping either 0.5 microl/h physiological saline or cisplatin solution (15 microg/ml), were co-treated daily with a subcutaneous bolus injection of either alpha-MSH (75 microg/kg) or physiological saline for 1 week or until the electrocochleogram showed a persistent decrease in CAP amplitude (40 dB threshold shift at 8 kHz). Next, the animals were sacrificed and the cochleas were processed for histology. After 2-3 days, cisplatin alone caused a threshold shift at all frequencies (2-16 kHz). Co-administration with alpha-MSH consistently delayed the criterion threshold shift by 1 day. When the 40 dB criterion had been reached, similar outer hair cell losses in both the cisplatin/alpha-MSH- and cisplatin/saline-treated groups were observed. This experiment confirms that direct administration of cisplatin into the cochlea results in considerably less interanimal variability than systemic administration and that co-treatment with alpha-MSH delays cisplatin ototoxicity. Since cisplatin was delivered directly to the cochlea, the ameliorating effect of alpha-MSH probably involves a cochlear target.     

Peritoneal Regeneration after Implant of a Composite Prosthesis in the Abdominal Wall

Prosthetic materials currently used to repair abdominal wall defects occasionally must be placed in direct contact with the visceral peritoneum. The prosthesis–peritoneum interface is the site of several possible problems, including the formation of adhesions and erosion of the intestinal loops, which may lead to the formation of fistulas. This investigation was designed to compare the behavior of two prosthetic biomaterials in composite form at the level of the peritoneum. Defects (7 × 5 cm) were created in the abdominal wall of 18 white New Zealand rabbits weighing approximately 2500 g. The defects (involving aponeurotic and muscular planes and the parietal peritoneum) were repaired with polypropylene (PL) + ePTFE (Preclude dura substitute) or Parietex composite (PC) prostheses. The prostheses were secured to the edges of the defect by continuous PL sutures interrupted at the corners of the implant. Three study groups were established according to the type of implant: group I (n= 6) (controls)—PL; group II (n= 6)—PL + ePTFE; and group III (n= 6)—PC. The animals were sacrificed 14 days after implant, and the prostheses were examined by light microscopy and scanning electron microscopy (SEM). The formation of adhesions at the prosthesis–visceral peritoneum interface were quantified according to a protocol previously described by us. The biomechanical resistance of the implant was evaluated using strips comprising prosthetic material and anchorage tissue. The Mann-Whitney U-test was used to compare data corresponding to each group. There was no postimplant mortality. No infection or rejection of the prosthesis was observed in any of the animals. Firm adhesions were detected in the PL implants, whereas in the PL + ePTFE and PC implants the adhesions were loose. The mean prosthetic surface areas covered by adhesions were 7.67, 0.10 and 0.19 cm² for groups I, II, and III, respectively, showing a significant difference between values corresponding to groups I and II and to groups I and III (p < 0.05). Comparison of values recorded for groups II and III yielded no significant difference (p > 0.05). In groups II and III, the neoperitoneum was homogeneous and composed of organized and vascularized connective tissue covered by a mesoendothelium that was interrupted by accumulations of fibroblasts and white blood cells. In contrast, a disorganized neoperitoneum of rough texture was observed in the group I specimens. At times, areas of hemorrhage and necrosis corresponding to the sites of adhesion formation could be observed. Resistance to traction of composite implants (mean ± SD: 15.72 ± 1.32 and 15.89 ± 2.73) was similar to that of the PL implants (15.03 ± 2.92) (Mann-Whitney U-test, p < 0.05). It may be concluded that (1) composite prostheses show optimum behavior in terms of adhesion formation at the prosthesis–visceral peritoneum interface; (2) the neoperitoneum formed after the implant of a composite prosthesis almost physically and functionally replaces the normal peritoneum; (3) a significantly greater degree of peritoneal regeneration is achieved after implant of a PC prosthesis; and (4) there was no significant difference regarding biomechanical resistance between PL prostheses and PL + ePTFE and Parietex composites.     

Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT

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Meningitis due to mixed infection with penicillin-resistant and penicillin-susceptible strains of Streptococcus pneumoniae

Streptococcus pneumoniae is the major cause of bacterial meningitis. We report a case of meningitis due to a mixed infection with two distinct strains of S. pneumoniae: one penicillin-resistant strain of serotype 9V and one penicillin-susceptible strain of serotype 7. The two strains exhibited different pulsed-field gel electrophoresis profiles.