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Biomedical subjects

R Watson

Publications and source records attributed to R Watson.

At least 289 records · Page 16Linked to original sources

Phase II study of mitoxantrone in epithelial ovarian cancer.

Forty-six patients with advanced epithelial ovarian cancer were treated with mitoxantrone (14 mg/m2) given iv every 3 weeks. All patients had evaluable disease. Forty-one patients had had previous treatment, 38 with cisplatin. Twelve patients achieved partial response (two had had no previous treatment; ten had received previous treatment with cisplatin with or without other agents); two of the responders, both previously treated with cisplatin, achieved complete clinical remissions. Median duration of response was 24 weeks (range, 10-30). Toxicity was acceptable, with minimal subjective toxicity. Hematological toxicity was dose-limiting, but it was possible to increase the dose on one or more courses by 2 mg/m2 in 16 patients. The drug was given as a bolus, and there was no evidence of acute cardiac side effects. These data suggest that mitoxantrone has significant activity in epithelial ovarian cancer and deserves further study.

Adult↗

Nonisotopic M13 probes for detecting the beta-globin gene: application to diagnosis of sickle cell anemia.

M13 DNA probes labeled with biotinylated psoralen and a streptavidin-horseradish peroxidase conjugate provide nonradioactive detection of the sickle cell and normal alleles of the beta-globin locus. The two biotinylated probes contain single-stranded sequences complementary to two different Sau3AI restriction fragments from the 5' region of the beta-globin gene and double-stranded M13 vector sequences. These probes are labeled with biotinylated psoralen photochemically linked to DNA. After hybridization, the presence of biotinylated probe bound to target DNA is detected in 3 h by using a streptavidin-horseradish peroxidase conjugate and the substrate, 3,3',5,5'-tetramethylbenzidine. Digestion of the normal (beta A) allele of the beta-globin gene with MstII (or isoschizomers) yields a 1.14-kb restriction fragment, while digestion of the mutant beta S allele yields a 1.34-kb fragment. These fragments can be resolved by gel electrophoresis and detected by Southern blot hybridization. The nonradioisotopic probe system can detect the beta-globin restriction fragment in as little as 0.5 microgram of human DNA and can distinguish heterozygotes (beta A beta S) from homozygotes (beta A beta A or beta S beta S) in 2.0 micrograms of human DNA.

Alleles↗

Analysis of the autophosphorylation activity of transformation defective mutants of avian erythroblastosis virus.

The v-erb B protein of avian erythroblastosis virus (AEV) possesses an associated protein kinase activity in vitro. Analysis of temperature-sensitive mutants, and nonconditional host range mutants of AEV demonstrated that there was no simple correlation between this autophosphorylation activity and the transformation ability of the various AEV mutants. These data suggest that although this kinase activity may be central to transformation by AEV it is in itself insufficient.

Alpharetrovirus↗

Use of nonisotopic M13 probes for genetic analysis: application to HLA class II loci.

Previously, DNA polymorphisms in the HLA gene cluster have been analyzed using radioactive probes in Southern blot experiments; the restriction fragment length polymorphisms (RFLPs) revealed by this analysis are capable of subdividing HLA serological types. Here, we report the use of DNA probes labeled with biotinylated psoralen to provide nonisotopic detection of HLA class II RFLP patterns. These biotinylated probes contain cDNA sequences encoding the alpha and beta chains of DP, DQ, and DR HLA class II genes as inserts in M13 vectors. The recombinant M13 molecules are partially double-stranded with single-stranded HLA cDNA regions and contain biotinylated psoralen covalently linked to duplex DNA by UV irradiation. Following hybridization, the presence of biotinylated probe bound to target DNA is detected using a streptavidin-horseradish peroxidase conjugate, which converts the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue precipitate in less than 1 hr. The probe and detection system described here can detect single-copy genes in less than 0.5 microgram of total human DNA on Southern blots and generates the same specific RFLP patterns as do probes labeled with 32P by nick-translation. These biotinylated HLA class II probes have been applied to tissue typing for bone marrow transplantation and the study of insulin-dependent diabetes susceptibility, revealing in each case relevant polymorphisms not detected by serologic typing.

Biotin↗

Effects of certain i.v. anaesthetics on liver blood flow and hepatic oxygen consumption in the greyhound.

The effects of increasing concentrations of thiopentone, Althesin and etomidate on liver blood flow and hepatic oxygen consumption were investigated in the anaesthetized greyhound. All three agents studied produced dose-related decreases in general cardiovascular indices such as mean arterial pressure, cardiac output and systemic vascular resistance; all three anaesthetics produced decreases in liver blood flow. During the low rates of infusion with Althesin and etomidate, significant decreases in hepatic arterial blood flow were recorded at a time when the systemic circulation was not significantly affected. Indeed, during the low rates of infusion with each of the three agents, hepatic arterial resistance and mesenteric vascular resistance increased by up to 40% above baseline values. During the high rates of infusion, hepatic arterial and mesenteric vascular resistances either returned to or decreased below control values and the decreases in liver blood flow were a consequence of generalized cardiovascular depression. Despite relatively unchanged hepatic oxygen consumption, all the anaesthetics produced significant decreases in the hepatic oxygen supply.

Alfaxalone Alfadolone Mixture↗

A haemorheological study of lignocaine.

Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations (mean 0.80 microgram ml-1; range 0.31-1.86 micrograms ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s-1). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.

Adult↗

Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals. Report of 82 cases.

The present report describes the clinical and laboratory profile of 82 previously healthy individuals who developed cytomegalovirus (CMV)-induced mononucleosis. Many of these patients posed initial diagnostic problems and were hospitalized with diagnoses such as fever of undetermined origin, active viral hepatitis, acute leukemia, probable systemic lupus erythematosus, autoimmune hemolytic anemia, and severe pancytopenia. These patients underwent a variety of diagnostic biopsies, including liver biopsies (6) and bone marrow aspirations (9). Four patients had exploratory laparotomies, 1 for a ruptured spleen, and another had a splenectomy following an erroneous initial diagnosis of agnogenic myeloid metaplasia. There was no apparent clinical response to a short course of steroid therapy in 3 of 5 cases and acyclovir in another. The vast majority of these patients demonstrated infectious mononucleosis-type reactive blood smears, negative heterophil antibody studies, mildly or moderately elevated aspartate aminotransferase activity, and evidence for subclinical hemolysis on serial specimens. The peak serum bilirubin levels were above 2.0 mg/dl in only 2 of 71 cases tested, both of the latter patients having significant hemolysis (hemoglobin values 8.6-9.3 g/dl). The CMV-IgM test had a high sensitivity for detection of CMV macroglobulins (positive in 81 of 82 cases). In contrast, complement-fixing antibodies to CMV showed diagnostic four-fold titer changes in only 39/82 cases (47.6%). Despite its great sensitivity, the CMV-IgM test is limited by a one-way crossreaction of acute Epstein-Barr virus (EBV)-IM sera and spurious positive reactions in some sera due to the presence of rheumatoid factors. Based on EBV-specific serologic studies, the 82 patients with CMV-IM could be divided into 4 groups: 3 patients without antibodies to EBV; 2) 69 patients with uncomplicated serologic data indicative of long-past EBV infections; (3) 6 patients with unusual antibody profiles, e.g., anti-D responses; and (4) 5 patients, including 1 originally susceptible to EBV, with apparent dual CMV/EBV infections. At the conclusion of our study, final diagnoses and initial hematologic data were correlated in 750 cases in which CMV macroglobulins were searched for. The vast majority of patients with active CMV infections initially demonstrated either markedly or moderately reactive peripheral blood smears. These data support our impression that diagnostic tests for CMV, as well as for EBV, are seldom indicated in symptomatic previously healthy patients whose blood smears during the acute phase (first several weeks) of their illnesses are either nonreactive or minimally reactive.

Adolescent↗

Value of magnetic resonance imaging in the evaluation of patients with complete and high degree block due to intracanal neoplasm.

Magnetic resonance imaging (MRI) of 26 patients with high degree or complete epidural and/or intradural myelographic block, due to primary or secondary neoplasm were analysed. The ratio of false negative MRI was 11.5 per cent. MRI findings were considered to be indicative of lesser block than indicated by myelography in almost 50 per cent of patients. Correlation between the two modalities was highest in cases associated with significant vertebral collapse, malalignment and angulation of the spine and angulation of the spinal cord.

Humans↗

Treatment of acute obstructive renal failure with high-dose methylprednisolone.

High-dose methylprednisolone sodium succinate (Solu-Medrol) therapy was administered to two patients with acute renal failure and anuria secondary to cancer-related urinary tract obstruction. Following the administration of intravenous methylprednisolone, obstruction was relieved, as evidenced by increased urinary flow and improvement of renal function. The salutary effect of methylprednisolone is probably related to the relief of obstruction secondary to a decrease in tumor-associated edema similar to the effect obtained in patients with brain tumors and spinal cord compression by epidural metastases. The temporary improvement in renal function allowed time for more definitive therapy to be instituted under more favorable clinical conditions.

Acute Kidney Injury↗

Intrauterine fetal death due to umbilical cord torsion.

We report a case of intrauterine fetal death due to torsion of the umbilical cord. Umbilical cord torsion has usually been regarded as secondary to fetal death or cord constriction or due to a lack or abnormality of Wharton's jelly. A postmortem examination showed torsion of the umbilical cord at the placental end in a cord without constriction and with normal Wharton's jelly. We therefore suggest that umbilical cord torsion in the absence of predisposing constriction or abnormality of Wharton's jelly can obstruct the umbilical blood vessels and cause intrauterine death.

Adolescent↗

Comparative merits of conventional, computed tomographic, and magnetic resonance imaging in assessing mediastinal involvement in surgically confirmed lung carcinoma.

Thirty-four patients with operable malignant tumors of the lung had computed tomography and magnetic resonance imaging of the chest in addition to regular chest roentgenograms and bronchoscopy. The purpose of the study was to assess the extent of tumor involvement in the hilum and the mediastinum by direct invasion and by regional lymph node metastasis. At thoracotomy, 23 tumors were completely resected and 11 were treated by interstitial implantation of radioisotopes. In addition, a mediastinal lymph node dissection or sampling was performed to correlate nodal involvement with the preoperative studies. The tumor was peripheral in 21 patients and central in 13. Histologically, 18 tumors were adenocarcinomas, 14 epidermoid cancers, and two atypical carcinoids. Preoperatively, 18 tumors were classified as N0 disease, nine as N1, and seven as N2. Pathologically, 11 were N0, eight N1, and 15 N2. Plain chest roentgenograms correlated poorly with the nodal findings at operation. Both magnetic resonance and computed tomographic imaging were highly accurate in assessing the hilum and the presence of mediastinal adenopathy, with a sensitivity rate of 87%. Except for identifying contact with the mediastinum, neither method correlated well with mediastinal invasion when present (sensitivity rate 55% for computed tomography and 64% for magnetic resonance) and neither method could differentiate hyperplastic from metastatic nodes. Hence, no advantage of magnetic resonance over computed tomographic scanning was noted in assessing tumor involvement of the mediastinum by direct invasion or by regional lymph node metastasis.

Adult↗

A controlled trial of health education in the physician's office.

Screening of 6,144 patients in a general practice clinic to assist physician case-finding uncovered 983 (16%) who were uncontrolled hypertensives. Following physician recommendation, 115 patients volunteered for a controlled trial to test the effectiveness of supplementary strategies to the pharmaceutical management of high blood pressure. A study of nonparticipants indicated that about 7% of the practice population was eligible for cardiovascular health education. One group received a health education program, a second was allocated to self-monitor their blood pressure for 6 months, a third group was allocated to both strategies, and the final group, acting as a control, continued to receive their usual care. Physician monitoring of patients continued for the duration of the study and blood pressures decreased in all patients. The study's most important outcome was the joint reduction of blood pressure and medication strength. These were assessed by a "blind" clinician before and after the interventions according to criteria set out in the "stepped-care" approach to management of high blood pressure. People allocated to a health education program conducted in the doctor's common room did twice as well on this measure as those who were not so educated. Daily self-monitoring of blood pressure for 6 months proved to be too much for the majority of those so instructed. It is concluded that the general practice setting remains an important place for health education to prevent cardiac disease and suggestions are made for incorporating this into everyday practice.

Australia↗