Lessons from a cyclist. Doctors should do more to promote physical activity.
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Bicycling↗
Biomedical subjects
R Davis
Publications and source records attributed to R Davis.
Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study.
PURPOSE: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. METHODS AND MATERIALS: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. RESULTS: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. CONCLUSIONS: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.
Adolescent↗
Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.
OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.
Acquired Immunodeficiency Syndrome↗
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↗
Skills training or occupational therapy for persistent schizophrenia.
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Allied Health Personnel↗
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↗
Do HMOs purposely stall in paying claims?
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Health Maintenance Organizations↗
Fat-soluble vitamin deficiencies.
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Adult↗
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↗