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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 289 records · Page 16Linked to original sources

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Acquired Immunodeficiency Syndrome↗

Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors.

Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood-brain barrier permeability. The advantage of regional intra-arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high-grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra-arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.

Adult↗

The myoD gene family: nodal point during specification of the muscle cell lineage.

The myoD gene converts many differentiated cell types into muscle. MyoD is a member of the basic-helix-loop-helix family of proteins; this 68-amino acid domain in MyoD is necessary and sufficient for myogenesis. MyoD binds cooperatively to muscle-specific enhancers and activates transcription. The helix-loop-helix motif is responsible for dimerization, and, depending on its dimerization partner, MyoD activity can be controlled. MyoD senses and integrates many facets of cell state. MyoD is expressed only in skeletal muscle and its precursors; in nonmuscle cells myoD is repressed by specific genes. MyoD activates its own transcription; this may stabilize commitment to myogenesis.

Animals↗

Synovial sarcoma: a clinicopathological review.

We have reviewed 20 cases of synovial sarcoma. The main clinical and pathological features of these cases are outlined. Typically these tumours arise in the leg in young adults with a long history before presentation and diagnosis. Clinical and radiological findings are unhelpful in making an early diagnosis. The five year survival rate in this series was 43%. The best guide to prognosis was assessment of mitotic activity. A high index of suspicion is required if the diagnosis is not to be missed. Adequate wide excision of the tumour is the mainstay of treatment.

Adolescent↗

Simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder.

Simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon. Twenty-two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between January 1970 and July 1986. The overall five-year survival was 40 percent, with patients presenting with prostate cancer doing better (50%) than those with bladder cancer (32%). Retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and, when indicated, radiation therapy added postoperatively for the bladder cancer. Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated for their bladder cancer. Treatment was usually radical cystoprostatectomy with or without postoperative radiation. None died of prostate cancer. Patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer.

Adenocarcinoma↗

Efficacy of a brief group psychoeducational intervention for bulimia nervosa.

This study compared a brief group treatment that was designed to be purely educational (ED) with a longer course of individual cognitive-behavioural (CB) therapy intended to represent more standard clinical care. Participants were 65 women who sought treatment at Toronto General Hospital, met DSM-III criteria for bulimia nervosa at a normal weight and reported vomiting at least twice weekly. Results indicated that the CB treatment, as expected, was generally more effective than the ED intervention, but on several important outcome indices both treatments appeared to be equally effective for the healthiest 25-45% of the sample. The more intensive individual CB treatment was associated with greater improvement in patients who were more severely symptomatic. However, the ED intervention proved significantly more cost-effective and it was suggested that a sequential treatment program might achieve the superior benefits associated with the longer individual CB treatment at a reduced cost.

Adolescent↗

The quick fix?

Explore the source record for details and available documents.

Humans↗

Renal transplantation from elderly living donors.

A worldwide shortage of cadaveric donors has led to the increased utilization of elderly living donors, with controversial results. In an attempt to assess the effect of donor age on graft survival and subsequent renal function, we analyzed our clinical results in 276 consecutive recipients of living related renal transplants spanning both the cyclosporine and the azathioprine eras, of whom a total of 44 recipients received kidneys from donors over 55 years old. All recipients were otherwise similar in age, race, haplotype mismatch, number of retransplants, and number of pretransplant transfusions, apart from an increased number of diabetics among the CsA-treated recipients of elderly kidneys (38% vs. 14%). The cumulative patient and graft survival rates at 1 and 5 years were independent of donor age whether CsA or AZA was utilized. Nor was the incidence of rejection or infection significantly different in the older donor group when compared with the younger cohort. Short-term and intermediate-term renal function, as assessed by serum creatinine, was however poorer but stable in the older donor group when compared with the younger one. The mean serum creatinine levels at 1 year in the CsA- and AZA-treated recipients of kidneys from older donors were 2.4 and 2.0 mg/dl, respectively, compared with 1.6 and 1.4 mg/dl, respectively, when the donor age was less than 55 years (P less than 0.001). Since renal function at the end of the first posttransplant year is considered a determinant of long-term graft survival, this is a cause for concern, but in view of the universal shortage of organs and the negligible morbidity to donors, renal transplantation from elderly living donors remains an acceptable practice.

Age Factors↗

Diabetes mellitus after renal transplantation in the cyclosporine era--an analysis of risk factors.

Despite mounting experimental evidence that cyclosporine inhibits pancreatic islet cell function, clinical data on posttransplant diabetes mellitus (PTDM) in renal allograft recipients in the cyclosporine era are scarce. Between June 1983 and December 1988, 39 of 337 (11.6%) cyclosporine-treated adult renal transplant recipient whose grafts survived longer than 1 year developed PTDM. Of these, 43.6% and 74.4% were diagnosed by 3 and 12 months posttransplant, respectively, and 51.3% were insulin-dependent. Incidence of PTDM was highest in blacks (19.8%) and Hispanics (21.3%) and in those with HLA-A 30 and Bw 42 antigens. Older recipients and those that received cadaveric kidneys were more likely to develop diabetes than those who received living related allografts (14% vs. 5.3%, P less than 0.05). The rate of PTDM appeared to be independent of the type of induction, immunosuppressant therapy, incidence of rejection, total steroid and cyclosporine dose, percentage of body weight gain in the first posttransplant year, and serum creatinine concentration. Actuarial 5-year, decaying from 100% at 1 year, patient and graft survival rates were 87% and 70%, respectively, in the PTDM group compared with 93% and 90%, respectively, in controls. Causes of graft failure among the diabetics included chronic rejection (6), patient death (3), noncompliance with immunosuppressants (2), and sepsis (1). The incidence of infectious complications was significantly higher in the PTDM group compared with the control group (53% vs. 16%, P less than 0.05), with all 5 deaths among the diabetics being sepsis-related.

Communicable Diseases↗

Muscle-specific transcriptional activation by MyoD.

We focus on the mechanism by which MyoD activates transcription. Previous experiments showed that when the 13-amino-acid basic region of E12 replaced the corresponding basic region of MyoD, the resulting MyoD-E12Basic chimeric protein could bind specifically to muscle-specific enhancers in vitro and form dimers with E12, but could not activate a cotransfected reporter gene or convert 10T1/2 cells to muscle. Here we show that back mutation of this chimeric protein (with the corresponding residues in MyoD) re-establishes activation, and we identify a specific alanine involved in increasing DNA binding and a specific threonine required for activation. Using a reporter gene containing MyoD-binding sites located downstream from the transcription start site, we show that MyoD-E12Basic can bind in vivo and thereby inhibit expression of the reporter. In vivo binding is also supported by the fact that the addition of the "constitutive" VP16 activation domain to MyoD-E12Basic restores full trans-activation potential. The normal MyoD-activation domain maps within the amino-terminal 53 residues and can be functionally replaced by the activation domain of VP16. The activity of the MyoD-activation domain is dramatically elevated when deletions are made almost anywhere in the rest of the MyoD molecule, suggesting that the activation domain in MyoD is usually masked. Surprisingly, MyoD-E12Basic can activate transcription in CV1 and B78 cells (but not in 10T1/2 or 3T3 cells), suggesting that the activation function of the basic domain requires a specific factor present in CV1 and B78 cells. We propose that to function, the masked MyoD-activation domain requires the participation of a second factor that recognizes the basic region. We refer to such a factor as a recognition factor.

Amino Acid Sequence↗

What scientists funded by the tobacco industry believe about the hazards of cigarette smoking.

Despite overwhelming evidence documenting the hazards of cigarette smoking, the tobacco industry denies that smoking has been proven to cause disease. The industry professes a desire to clear up the smoking and health "question" and often points to its support of the Council for Tobacco Research (CTR) as evidence of its interest in investigating the health dangers of smoking. This paper presents results of a survey of CTR-funded scientists regarding their beliefs about the health dangers posed by smoking cigarettes. The vast majority of scientists funded by the CTR believe that cigarette smoking is an addiction that causes a wide range of serious, often fatal, diseases. This result suggests that the tobacco industry is unwilling to accept even the opinions of scientists it has deemed worthy of funding. Scientists should consider the ethical implications of accepting funds from the CTR and other tobacco industry-supported institutions.

Advertising↗

Retrospective analysis of posttransplantation diabetes mellitus in black renal allograft recipients.

OBJECTIVE: To study the incidence, outcome, and possible etiopathogenic factors involved in posttransplantation diabetes mellitus in cyclosporine-treated black renal allograft recipients. RESEARCH DESIGN AND METHODS: One hundred thirty-eight nondiabetic black renal transplant recipients whose grafts survived greater than 1 yr were studied retrospectively. RESULTS: Twenty-eight (20.3%) patients developed posttransplantation diabetes mellitus, 46 and 75% were diagnosed by 6- and 12-mo posttransplantation, respectively, and 46% were insulin dependent. Diabetes was more frequently encountered in older recipients and recipients of cadaveric kidneys but was independent of sex, number of transplants, incidence of acute rejection, percentage of body weight gain, steroid or cyclosporine dose, and use of beta-blockers and/or diuretics. Renal function was similar in the diabetic group compared with the control group. Actuarial 5-yr graft survival was 82% in the diabetic cohort compared with 78% in the control group, with chronic rejection accounting for all graft losses within the diabetic group. CONCLUSIONS: Twenty percent of black cyclosporine-treated renal allograft recipients developed diabetes mellitus in the posttransplantation period. However, its presence did not appear to influence intermediate-term graft or patient survival.

Adult↗

The stability of thiamine and thiamine tetrahydrofurfuryl disulfide added to table wines.

Both thiamine hydrochloride and thiamine tetrahydrofurfuryl disulfide were added separately to table wines at concentrations equivalent to 0.3 and 1.5 microgram of free thiamine per kJ of caloric energy. The resultant mean increments in thiamine activity, measured by Lactobacillus fermenti microbiological assay after 21 months of storage, were in the range 55 to 103% of the added vitamin, indicative of high bioavailability of thiamine from this source.

Biological Assay↗

Delayed cementation and bond strength of dual-cure cements.

The purpose of this study was to determine whether the shear bond strength to enamel of three dual-cure resin cements is affected by delaying the time between cement mix and application. Etched, silanated Dicor cylinders were bonded to etched enamel with each cement at various time intervals: Immediately after mix, just prior to chemical set and at an intermediate time. Shear bond values were determined using the Instron. No significant differences were found among any of the cements at any of the times. The clinical implication is that as long as these cements remain fluid, there will not be a significant change in the bond strength of Dicor to enamel.

Acrylic Resins↗