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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 91 records · Page 5Linked to original sources

Sequencing of cognitive-behavioral treatments for bulimia nervosa.

OBJECTIVE: This study investigated the efficacy of a stepped-care trial of brief group psychoeducation (PE) followed by individual cognitive-behavioral therapy (CBT) in the treatment of bulimia nervosa. METHOD: Fifty-six subjects first completed PE and were then randomly assigned to either a 16-week trial of CBT (PE + CBT) or to no further treatment follow-up (PE-alone). RESULTS: Compared to PE-alone, PE + CBT produced significantly greater reductions in the specific eating symptoms of binging and purging and significantly higher remission rates that were maintained over a 16-week follow-up. However, there were no differential treatment effects on measures of nonspecific psychopathology. Among PE + CBT subjects, remission in specific eating symptoms was associated with greatest improvements in non-specific psychopathology. The outcome of nonremitted PE + CBT subjects and PE-alone subjects was no different at posttreatment or follow-up. DISCUSSION: These results provide limited support for offering individual CBT to subjects once they have completed an initial trial of group PE.

Adolescent↗

Cost-effective adenosine dosing for the treatment of PSVT.

We reviewed our experience with adenosine for the conversion of paroxysmal supraventricular tachycardia (PSVT) to determine whether the recommended dosing strategy of 6 mg, followed by 12 mg, is cost-effective in actual practice. We observed a 65% conversion rate to sinus rhythm with the initial dosage of 6 mg adenosine (95% CI, 54% to 75%), and, based on subsequent cost analysis, conclude that the current strategy should not be replaced by a 12-mg-first strategy. If the packaging of adenosine was changed so that 12 mg cost less than twice 6 mg, this analysis should be revisited.

Adenosine↗

Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors.

Chemotherapy for malignant brain tumors has a limited efficacy largely due to restricted blood-brain barrier permeability for chemotherapeutic drugs. Intraarterial chemotherapy (IAC) has the advantage of increased uptake during the first passage of the drugs through tumor capillaries. Initial IAC trials had less than satisfactory results due to unacceptable toxicities. Between 1987 and 1996, 173 patients with primary and metastatic brain tumors were treated with intraarterial (intracarotid and/or intravertebral) cisplatin and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients received either cisplatin at 40 mg/m2 and VP-16 at 20 mg/m2 or cisplatin at 60 mg/m2 and VP-16 at 40 mg/m2. Nausea and vomiting were the most common toxicities (42 patients, 14% of cycles). Arterial puncture was associated with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incidence of failure to canulate the carotid or vertebral arteries (3 patients). Neurologic toxicities included headache (1.4% of cycles, 5 patients), focal seizures (1.4% of cycles, 5 patients), transient confusion and urinary retention/incontinence (1.9% of cycles, 8 patients), and blurred vision (0.9% of cycles, 4 patients). We have not seen visual loss, strokes, major vessel dissection or thrombosis, or myelosuppression. Toxicity incidence was higher in patients with metastatic brain tumors than in those with primary brain tumors (34% versus 17%, p < 0.001). It was also higher in patients who had brain radiation therapy (RT) prior to IAC than in those who had RT concomitant with IAC (31% versus 19%, p = 0.05). No significant difference in toxicity incidence was noticed between patients who received RT concomitant with IAC and those who received RT after IAC (19% and 23% respectively, p = 0.08). Intracarotid chemotherapy given prior to RT resulted in 23 months of median survival for patients with glioblastoma multiforme. Intraarterial chemotherapy with cisplatin and VP-16 is a relatively safe treatment modality, especially in patients with primary brain tumors who have not received brain radiotherapy.

Adolescent↗

Perception of cognitive function in older adults following coronary artery bypass surgery.

This study examined the effects of coronary artery bypass grafting (CABG) on objective and subjective measures of neurocognitive functioning. Participants were 170 older patients (127 men and 43 women; mean age = 61 years) undergoing CABG. Measures of neurocognitive function, depression, anxiety, and perceived cognitive abilities were administered immediately prior to and 6 weeks following surgery. Although objective measures of impaired cognitive performance following CABG were not related to perceived cognitive difficulties, the presence of anxiety and depression was related to the perception of cognitive functioning. Patients who reported high levels of anxiety and depression 6 weeks after surgery perceived themselves as having poorer cognitive function. Interventions designed to reduce emotional distress could improve patient's perceived cognitive abilities following CABG.

Aged↗

Paraplegia: prolonged standing using closed-loop functional electrical stimulation and Andrews ankle-foot orthosis.

One T10 paraplegic male (CS) implanted in 1991 with a Nucleus FES-22 stimulator has been able to achieve closed-loop standing for 1 h. The knee angles are monitored by electrogoniometers, resulting in the quadriceps stimulation time being less than 10%. Stance stability is achieved by the Andrews anterior ankle-foot orthosis (AFO). The use of accelerometers for trunk inclination and vertical acceleration during controlled stand-to-sit, diminishes slamming onto the seat. CS does one-handed tasks with objects of 2.2 kg. In another T10 paraplegic male (FR), surface stimulation was applied over 1.5 years to both femoral nerves at the groin for conditioning and prolonged standing. With quadricep conditioning, 55 Nm at 45 degrees of knee flexion is produced. With the AFO and knee monitoring, FR can stand uninterrupted for up to 70 min and perform one-handed tasks. In August 1998, he was implanted with the multifunctional Praxis FES 24-A stimulator for restoration of limb movements, bladder and bowel function, and pressure sore prevention.

Acceleration↗

Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.

Africa↗

Experimental reproduction of viral chorioretinitis in kangaroos.

OBJECTIVE: To investigate whether preparations containing Wallal and/or Warrego viruses could cause disease when inoculated subcutaneously into captive kangaroos. DESIGN AND PROCEDURE: Four groups of two kangaroos, seronegative to both Wallal and Warrego virus, were each inoculated with wild Wallal virus, cultured Wallal virus, wild Warrego virus, or wild Warrego virus followed by wild Wallal virus after 3 weeks. A single uninoculated animal served as a control. Animals were monitored weekly under anaesthesia, examined ophthalmoscopically (including fundic photography), and samples collected for haematological and serum biochemical analysis, virus isolation, PCR and serological examination for antibodies against Wallal and Warrego viruses. Animals inoculated with cultured Wallal virus were killed at week 10, and remaining kangaroos were reinoculated with cultured Wallal virus at week 12. RESULTS: Virus was isolated from the blood of two kangaroos 2 weeks after inoculation with Wallal virus preparations, and from a third kangaroo 2 weeks after reinoculation. By 3 weeks after inoculation, all kangaroos given Wallal virus preparations had seroconverted to Wallal virus and one had seroconverted to Warrego virus. Fundic changes were detected in the three viraemic kangaroos 4 or more weeks after inoculation, and lesions were present in the eye and brain typical of those seen in field cases of chorioretinitis. No other kangaroos had lesions. Wallal virus was identified by PCR and immunohistochemical analysis in the retina of one affected animal and orbivirus-like particles were seen by electron microscopy in the remains of retinal cells. CONCLUSION: The condition of chorioretinitis was reproduced in three of eight kangaroos by inoculation with preparations containing Wallal virus.

Animals↗

Effect of lamivudine on human T-cell leukemia virus type 1 (HTLV-1) DNA copy number, T-cell phenotype, and anti-tax cytotoxic T-cell frequency in patients with HTLV-1-associated myelopathy.

Patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) typically have a high HTLV-1 proviral load in peripheral blood mononuclear cells and abundant, activated HTLV-1-specific cytotoxic T lymphocytes (CTLs). No effective treatment for HAM/TSP has been described so far. We report a 10-fold reduction in viral DNA for five patients with HAM/TSP during treatment with the reverse transcriptase inhibitor lamivudine. In one patient with recent-onset HAM/TSP, the reduction in viral DNA was associated with a fall in the frequency of CTLs specific to two peptides in the immunodominant viral antigen Tax. The half-life of peripheral blood mononuclear cell populations was estimated from changes in viral DNA copy number, CTL frequency, reduction in CD25 expression, and the loss of dicentric chromosomes following radiation-induced damage. Each of these four different techniques indicated a cellular half-life of approximately 3 days consistent with continuous lymphocyte replication and destruction. These results indicate that viral replication through reverse transcription significantly contributes to the maintenance of HTLV-1 viral DNA load. The relative contribution of proliferation versus replication may vary between infected people.

Adult↗

MAPK activation determines renal epithelial cell survival during oxidative injury.

Ischemia/reperfusion (I/R) injury induces both functional and morphological changes in the kidney. Necrosis, predominantly of the proximal tubule (PT), is the hallmark of this model of renal injury, whereas cells of the distal nephron survive, apparently intact. We examined whether differences in cellular outcome of the various regions of the nephron may be due to segmental variation in the activation of the mitogen-activated protein kinases (MAPKs) in response to I/R injury. Whereas c-Jun N-terminal kinase (JNK) is activated in both the cortex and inner stripe of the outer medulla, the extracellular regulated kinase (ERK) pathway is activated only in the inner stripe in which thick ascending limb (TAL) cells predominate. These studies are consistent with the notion that ERK activation is essential for survival. To test this hypothesis directly, we studied an in vitro system in which manipulation of these pathways and their effects on cellular survival could be examined. Oxidant injury was induced in mouse PT and TAL cells in culture by the catabolism of hypoxanthine by xanthine oxidase. PT cells were found to be more sensitive than TAL cells to oxidative stress as assessed by cell counting, light microscopy, propidium iodide uptake, and fluorescence-activated cell sorting (FACS) analysis. Immunoprecipitation/kinase analysis revealed that JNK activation occurred in both cell types, whereas ERK activation occurred only in TAL cells. We then examined the effect of PD-098059, a MAP kinase kinase (MEK)-1 inhibitor of the ERK pathway, on PT and TAL survival. In TAL cells, ERK inhibition reduced cell survival nearly fourfold (P < 0.001) after oxidant exposure. In PT cells, activation of the ERK pathway by insulin-like growth factor I (IGF-I) increased survival by threefold (P < 0.001), and this IGF-I-enhanced cell survival was inhibited by PD-098059. These results indicate that cell survival in the kidney after ischemia may be dependent on ERK activation, suggesting that this pathway may be a target for therapeutic treatment in I/R injury.

Animals↗

Extensive lipomatous metaplasia in bilateral macronodular adrenocortical hyperplasia.

OBJECTIVE: We describe a case of macronodular hyperplasia with marked adrenal enlargement in which mature adipose tissue was a significant component. To our knowledge, this condition has not been reported previously. METHODS: A 42-year-old woman with newly diagnosed Cushing's syndrome underwent endoscopic bilateral adrenalectomy to remove bilateral adrenal masses. RESULTS: Both adrenal glands displayed features of macronodular hyperplasia with marked adrenal enlargement, and abundant mature adipose tissue was identified in some nodules of both glands. CONCLUSIONS: Lipomatous metaplasia is histologically demonstrated in a case of macronodular hyperplasia with marked adrenal enlargement. This distinctive change may be secondary to metaplastic transformation of either stromal cells or adrenocortical cells. The presence of lipomatous metaplasia would appear to indicate adrenocortical process, since, to our knowledge, it has never before been described in the adrenal nodule.

Adipose Tissue↗

Protein-protein interactions in the assembly of Shigella flexneri invasion plasmid antigens IpaB and IpaC into protein complexes.

Shigella flexneri is a facultative intracellular bacterial pathogen that invades human colonic epithelial cells by a process called pathogen-induced phagocytosis. Pathogen entry requires three virulence plasmid-encoded proteins called invasion plasmid antigens (Ipa) B, C and D which are secreted upon bacterial contact with a host cell. Following their secretion, IpaB and IpaC are found within a complex of proteins that may also contain IpaA and IpaD. Previous work has shown that exogenously added recombinant IpaC is sufficient for promoting the uptake of S. flexneri in gentamicin-protection assays. It is shown here that purified recombinant Ipa proteins can also be used to investigate the formation of Ipa protein complexes in vitro. The protein-protein contacts involved in the formation of Ipa complexes appear to include previously undescribed IpaC-IpaC interactions in addition to a strong association between IpaB and IpaC. IpaD does not appear to interact with either IpaB or IpaC in vitro although it is possible that recombinant IpaD forms homodimers that are stabilized by disulfide bridges involving this protein's single cysteine residue. This investigation represents the first characterization of the biochemistry of Ipa complex assembly.

Anisotropy↗

Flux enhancement for membrane filtration of bacterial suspensions using high-frequency backpulsing.

A promising method for reducing membrane fouling during crossflow microfiltration of biological suspensions is backpulsing. Very short backpulses (0.1-1.0 s) have been used to increase the net flux for washed bacterial suspensions and whole bacterial fermentation broths. The net fluxes under optimum backpulsing conditions for the washed bacteria are approximately 10-fold higher than those obtained during normal crossflow microfiltration operation, whereas only a 2-fold improvement in the net flux is achieved for the fermentation broths. A theory is presented that is based on external fouling during forward filtration and nonuniform cleaning of the membrane during reverse filtration. The model contains an adjustable parameter which is a measure of the cleaning efficiency during backpulsing; the cleaning efficiency found by fitting the model to the experiments increases with increasing frequency and duration of the backpulses. The theory predicts an optimum backpulsing frequency, as was observed experimentally. An economic analysis shows that crossflow microfiltration with backpulsing has lower costs than centrifugation, rotary vacuum filtration, and crossflow microfiltration without backpulsing.

Biotechnology↗

Ambulation by traumatic T4-12 paraplegics using functional neuromuscular stimulation

The review describes and discusses the status of the major approaches to functional neuromuscular stimulation (FNS) for the purpose of ambulation by traumatic complete thoracic-level paraplegics, namely, hybrid body bracing with FNS, percutaneous FNS, fully implanted FNS, and transcutaneous FNS. For each approach, the review discusses the system for which the most published user data are available and, where relevant, where the largest user population exists. The review covers methodologies and system descriptions. The Analysis sections of the review discuss ambulation performance, patient-training aspects, and, when available, multi-user medical, physiological, and psychological evaluation data. A comparative tabulation is given in the Synthesis section of the review.

Journal Article↗

Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production.

The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic effects of inflammatory cytokines represents a potential hinderance to the use of such cells for transplantation therapy of insulin-dependent diabetes mellitus (IDDM). In the current study, we show that IL-1beta induces destruction of INS-1 insulinoma cells, while having no effect on a second insulinoma cell line RIN1046-38 and its engineered derivatives, and that this difference is correlated with a higher level of expression of manganese superoxide dismutase (MnSOD) in the latter cells. Stable overexpression of MnSOD in INS-1 cells provides complete protection against IL-1beta-mediated cytotoxicity, and also results in markedly reduced killing when such cells are exposed to conditioned media from activated human or rat PBMC. Further, overexpression of MnSOD in either RIN- or INS-1-derived lines results in a sharp reduction in IL-1beta-induced nitric oxide (NO) production, a finding that correlates with reduced levels of the inducible form of nitric oxide synthase (iNOS). Treatment of INS-1 cells with L-NMMA, an inhibitor of iNOS, provides the same degree of protection against IL-1beta or supernatants from LPS-activated rat PBMC as MnSOD overexpression, supporting the idea that MnSOD protects INS-1 cells by interfering with the normal IL-1beta-mediated increase in iNOS. Because NO and its derivatives have been implicated as critical mediators of beta-cell destruction in IDDM, we conclude that well regulated insulinoma cell lines engineered for MnSOD overexpression may be an attractive alternative to isolated islets as vehicles for insulin replacement in autoimmune diabetes.

Animals↗

Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.

Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.

ADAM Proteins↗