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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 721 records · Page 40Linked to original sources

Osteogenesis imperfecta: from phenotype to genotype and back again.

The presumption that identification of the collagen gene mutations in OI would completely explain the phenotype is unjustified. Full understanding of this fragile bone syndrome will depend on the intelligent interpretation of both the biochemical abnormalities and the clinical features. Between these extremes there is a whole unexplored area of cell biology. To make further progress it seems that we shall have to pay as much attention to the phenotype as to the genotype.

Collagen↗

Is transthoracic impedance arrhythmia specific? Experimental studies.

Transthoracic impedance (TTI) is a major determinant of current flow in defibrillation, and it is therefore important to understand the factors that determine TTI. Our purpose was to evaluate the effect of atrial and ventricular arrhythmias on TTI. In anesthetized, closed-chest dogs we measured TTI by means of a technique previously validated by us, which did not require administration of actual shocks. Measurements were made at baseline (sinus rhythm) and during rapid atrial pacing (atrial fibrillation), rapid ventricular pacing, and electrically induced ventricular fibrillation (VF) with respiration discontinued. TTI was unchanged by rapid atrial or ventricular pacing. When VF was induced and respiration was discontinued, TTI fell immediately from 51.6 +/- 4.3 ohms to 45.6 +/- 4.7 ohms (p < 0.01) and did not change thereafter. The drop in TTI was probably due to respiratory arrest and decreased chest size with full exhalation; when VF was induced but respiration was continued TTI did not change, whereas discontinuing respiration caused TTI to fall even if VF was not induced. We conclude that TTI is not altered by arrhythmias.

Animals↗

Acute myelomonocytic leukemia in a calf.

In a 2-month-old crossbred calf with paraplegia, results of neurologic evaluation were suggestive of a spinal cord lesion caudal to L3. The calf bled from the blood sampling site for an extended period after venipuncture. Leukocytosis, anemia, and thrombocytopenia were observed. The leukocytes were predominantly atypical blast cells. Postmortem examination revealed petechial hemorrhages throughout the internal organs. Bone marrow was pale tan, with no red marrow seen. Atypical leukocytes were diffusely distributed throughout the body, with penetration of the spinal cord and spinal roots, particularly in the lumbar region. Atypical leukocytes stained positively for alpha-naphthyl acetate esterase and chloracetate esterase, and stained with Sudan black B. Atypical leukocytes expressed class-1 and class-2 major histocompatability antigens, but did not express specific T-, B-, or null-cell surface antigens. The final diagnosis was myelomonocytic leukemia. Differential diagnosis of leukemia in calves should include myelogenous leukemia, and requires use of various techniques to make a definitive diagnosis.

Animals↗

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.

BACKGROUND: A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. METHODS: Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. RESULTS: Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. CONCLUSIONS: The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Adolescent↗

Mouse mammary-tumor virus activates Fgf-3/Int-2 less frequently in tumors from virgin than from parous mice.

Tumorigenesis by mouse mammary-tumor virus (MMTV) involves proviral disruption and transcriptional activation of a number of cellular oncogenes, generically termed Int. The frequencies with which different Int genes are activated in different mouse strains can be quite variable, and previous surveys have suggested that insertions at Int-2/Fgf-3 occur primarily in strains that develop pregnancy-dependent mammary tumors. To address this issue, we have determined the relative contributions of 5 known Int genes (Wnt-1, Wnt-3, Fgf-3, Fgf-4 and Int-3) in mammary tumors from virgin BR6 and multiparous BR6, BALB/cfBR6 and RIII mice. Whereas Fgf-3 was implicated in 66%, 80% and 92% of the tumors from the respective parous animals, only 20% of the tumors from virgin mice expressed Fgf-3. This reduced involvement of Fgf-3 was compensated by proviral insertions in Fgf-4, Int-3 and Wnt-3, but the frequency of Wnt-1 activation was relatively constant. These data strengthen the link between Fgf-3 and a pregnancy-dependent phenotype and suggest that, in the strains analyzed, the frequency of Int-gene activation was influenced more by the hormonal status than by the genetic background.

Animals↗

A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease.

BACKGROUND: Because of their susceptibility to pneumococcal sepsis, children with sickle cell disease and fever are usually hospitalized for antibiotic therapy. Outpatient treatment may be a safe and less expensive alternative for selected patients. METHODS: After evaluation in the emergency room, children ranging from 6 months to 12 years of age who had sickle hemoglobinopathies and temperatures exceeding 38.5 degrees C were randomly assigned to treatment as either inpatients or outpatients. We excluded from randomization children at higher risk of sepsis (as defined by specific criteria, including temperature above 40 degrees C, white-cell count below 5000 per cubic millimeter or above 30,000 per cubic millimeter, and the presence of pulmonary infiltrates) or with complications of sickle cell disease (such as a hemoglobin level below 5 g per deciliter, dehydration, or severe pain); these children were treated as inpatients. All patients received an initial intravenous dose of ceftriaxone (50 mg per kilogram of body weight). Those treated as outpatients returned 24 hours later for a second dose of ceftriaxone, whereas the in patients were treated as directed by their physicians. RESULTS: None of the 86 patients (with a total of 98 febrile episodes) in the randomized groups had sepsis, as compared with 6 of the 70 patients (7 of 86 episodes) excluded because of higher risk (P = 0.004). Among the 44 children (50 episodes) assigned to outpatient treatment, there were 11 hospitalizations (22 percent of episodes) within two weeks after treatment (95 percent confidence interval, 12 to 36 percent), whereas after inpatient care only a single patient (2 percent of episodes) was rehospitalized. When the randomized groups were compared, outpatient treatment saved a mean of $1,195 per febrile episode. The median hospital stay was 3 days (range, 1 to 6) for the children randomly assigned to inpatient care and 4 days (range, 1 to 18) for the higher-risk children treated as inpatients (P < 0.001). CONCLUSIONS: With the use of conservative eligibility criteria, at least half the febrile episodes in children with sickle cell disease can be treated safely on an outpatient basis, with substantial reductions in cost.

Ambulatory Care↗

Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study.

Eight subjects with late-life depression, eight subjects with probable Alzheimer disease, and eight healthy age-matched controls were studied using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the resting state with their eyes open and ears unoccluded. The depressed subjects showed widespread reductions in the regional cerebral metabolic rate for glucose in most major neocortical, subcortical, and paralimbic regions that were significantly different from control values (P < 0.01). The metabolic decrements in the depressed group were comparable in magnitude to those seen in the Alzheimer disease group. These data demonstrate widespread nonfocal decline in glucose metabolism in late-life depression that is comparable to the hypometabolism seen in Alzheimer disease. These findings have pathophysiological implications in major depressive disorder in the elderly.

Aged↗

Three-dimensional structure of myosin subfragment-1: a molecular motor.

Directed movement is a characteristic of many living organisms and occurs as a result of the transformation of chemical energy into mechanical energy. Myosin is one of three families of molecular motors that are responsible for cellular motility. The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described. This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility.

Actins↗