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Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 37 records · Page 2Linked to original sources

The effects of collagen synthesis inhibitory drugs on somitogenesis and myogenin expression in cultured chick and mouse embryos.

The role of fibrillar collagen on myogenic differentiation has previously been studied in tissue culture cell lines but has not been studied in situ. We treated cultured chick and mouse embryos with collagen synthesis inhibitors to determine the role of fibrillar collagen on somitogenesis and on myogenic differentiation in vivo. Stage 12 chick embryos and 8.7 dpc mouse embryos were cultured in control medium or a range of concentrations of the collagen synthesis inhibitors ethyl-3,4-dihydroxybenzoate (EDHB) or cis-hydroxy-proline (CHP). Chick embryos were cultured for 24 h and mouse embryos were cultured for 30 h. Both collagen synthesis inhibitors produced a range of somite abnormalities including formation of fewer and irregular somites in both chick and mouse at high drug concentrations, as well as formation of double somites in EDHB-treated chick embryos. Examination of EDHB-treated mouse embryos by scanning electron microscopy demonstrated a dosage-dependent loss of fibrillar collagen and associated extracellular matrix. Expression of myogenin in EDHB-treated mouse embryos, examined by whole-mount in situ hybridization, was suppressed at higher dosage levels. This study suggests that inhibition of fibrillar collagen production and/or loss of fibrillar collagen in the developing avian and mammalian embryo results in abnormal somite formation and perturbed myogenic differentiation.

Animals↗

CT for the evaluation of flank pain.

Unenhanced helical CT allows rapid and accurate determination of whether a stone is present anywhere in the urinary tract. There is a learning curve for both radiologist and urologist, but a number of signs are highly predictive of stone. Helical CT scans should always be accompanied by a "scoutogram" to convey an idea of what the stone might look like. The scan requires no contrast medium and takes only 5 to 10 minutes of imaging time, making it cost effective. It behooves both urologists and radiologists to familiarize themselves with the techniques for reading these scans.

Costs and Cost Analysis↗

Screening for high utilizing somatizing patients using a prediction rule derived from the management information system of an HMO: a preliminary study.

BACKGROUND: Somatization is a common, costly problem with great morbidity, but there has been no effective screening method to identify these patients and target them for treatment. OBJECTIVES: We tested a hypothesis that we could identify high utilizing somatizing patients from a management information system (MIS) by total number of visits and what we termed "somatization potential," the percentage of visits for which ICD-9 primary diagnosis codes represented disorders in the musculoskeletal, nervous, or gastrointestinal systems or ill-defined complaints. METHODS: We identified 883 high users from the MIS of a large staff model HMO as those having six or more visits during the year studied (65th percentile). A physician rater, without knowledge of hypotheses and predictors, then reviewed the medical records of these patients and identified somatizing patients (n = 122) and nonsomatizing patients (n = 761). In two-thirds of the population (the derivation set), we used logistic regression to refine our hypothesis and identify predictors of somatization available from the MIS: demographic data, all medical encounters, and primary diagnoses made by usual care physicians (ICD-9 codes). We then tested our prediction model in the remaining one-third of the population (the validation set) to validate its usefulness. RESULTS: The derivation set contained the following significant correlates of somatization: gender, total number of visits, and percent of visits with somatization potential. The c-statistic, equivalent to the area under the ROC curve, was 0.90. In the validation set, the explanatory power was less with a still impressive c-statistic of 0.78. A predicted probability of 0.04 identified almost all somatizers, whereas a predicted probability of 0.40 identified about half of all somatizers but produced few false positives. CONCLUSIONS: We have developed and validated a prediction model from the MIS that helps to distinguish chronic somatizing patients from other high utilizing patients. Our method requires corroboration but carries the promise of providing clinicians and health plan directors with an inexpensive, simple approach for identifying the common somatizing patient and, in turn, targeting them for treatment. The screener does not require clinicians' time.

Adult↗

Parenteral nutrition with lipid or glucose suppresses liver growth and response to GH in adolescent male rats.

Our aim was to investigate the effects of modifying the carbohydrate-to-lipid ratio of parenteral nutrition (PN) on body composition and the anabolic actions of insulin-like growth factor I (IGF-I) and growth hormone (GH). Adolescent male Sprague-Dawley rats were randomized to receive 7 days of GH, IGF-I (3.5 mg. kg(-1). day(-1) for both) or placebo while receiving high-carbohydrate PN (CHO-PN), high-lipid PN (L-PN), or an oral diet (chow) (the PN protocols were isonitrogenous and isocaloric). PN impaired muscle growth, which was reversed by GH in the CHO-PN group only (P < 0.03). PN increased carcass lipid (P < 0.02), the effect being greater in the L-PN than in the CHO-PN group (P < 0.001). Visceral lean tissue growth was significantly impaired by PN (P < 0.001). IGF-I reversed this impairment, but GH had no effect. PN impaired the normal increase in hepatic protein and DNA (P < 0.001) and produced liver steatosis (P < 0.001). However, this steatosis was less in L-PN than in CHO-PN (P < 0.001). Serum IGF-I and the acid-labile subunit (ALS) were decreased by PN (P < 0.001) and were not affected by GH during PN treatment. However, GH significantly increased serum ALS concentrations in the chow-fed rats (P = 0.032). In conclusion, modifying the CHO-to-L ratio of PN had no significant effect on IGF-I action, but CHO-PN increased the peripheral effect of GH. L-PN increased carcass lipid significantly and decreased hepatic steatosis. Nevertheless, PN caused significant liver steatosis and profound impairment of hepatic cell growth, which was associated with relative hepatic GH resistance.

Animals↗

Incidental enhancing lesions found on MR imaging of the breast.

OBJECTIVE: This study was undertaken to determine the frequency and significance of foci of enhancement having no corresponding mammographic or clinical abnormality that are encountered on MR imaging of the breast performed to evaluate mammograms with equivocal findings. MATERIALS AND METHODS: Reports from MR examinations of 103 patients who underwent MR imaging of the breast to evaluate questionable mammographic findings were retrospectively reviewed. We identified cases that had focal enhancing lesions without a corresponding mammographic or palpable abnormality. Clinical history, mammograms, MR images, and follow-up information were reviewed. RESULTS: Of the 103 patients, 30 (29%) had incidental foci of enhancement. These women were significantly younger, more often premenopausal, and more likely to have dense breasts than those who did not have incidental foci. Tissue confirmation of the incidental foci was available for seven patients, mammographic follow-up was available for a mean interval of 22 months for 22 patients, and no follow-up was available for one. Cancer at the incidental sites was diagnosed in one of the 30 patients with multiple foci. She was also shown to have cancer at the site originally questioned mammographically (index site). None of the remaining patients has had a diagnosis of malignancy at the incidental sites. CONCLUSION: Incidental enhancing foci are common in women undergoing breast MR imaging for questionable findings on mammography, occurring in 29% of our patients. Our results suggest that unless malignancy is diagnosed elsewhere in the breast, these incidental foci are unlikely to be malignant.

Breast Neoplasms↗

Relationship between duration of pain and secondary signs of obstruction of the urinary tract on unenhanced helical CT.

OBJECTIVE: The objective of this study was to investigate the relationship between duration of flank pain and the frequency of secondary signs of ureteral obstruction on unenhanced helical CT. SUBJECTS AND METHODS: The duration of flank pain was prospectively determined in 227 consecutive patients diagnosed with acute ureterolithiasis on unenhanced helical CT. These CT studies were evaluated for the presence or absence of perinephric stranding, ureteral dilatation, perinephric fluid, collecting system dilatation, periureteral stranding, and nephromegaly. The frequency of each sign was determined as a function of the duration of pain. RESULTS: The frequency of moderate or severe perinephric stranding increased from 5% at 1--2 hr to 51% at 7--8 hr (p < 0.001); ureteral dilatation increased from 84% at 1--2 hr to 97% at more than 8 hr (p < 0.03); moderate or severe perinephric fluid increased from 0% at 1--2 hr to 22% at 3--4 hr (p < 0.03); collecting system dilatation increased from 68% at 1--2 hr to 89% at 7-8 hr (p < 0.03); periureteral stranding increased from 35% at 1--2 hr to 76% at 7--8 hr (p < 0.004); and nephromegaly increased from 40% at 1--2 hr to 54% at 7--8 hr (p < 0.36). CONCLUSION: All CT secondary signs of ureteral obstruction except nephromegaly showed a significant increase in frequency as duration of flank pain increased. This observation may explain why the CT studies of some patients with acute ureterolithiasis show negative findings for some or all CT secondary signs of obstruction. Therefore, knowledge of the duration of pain is important when interpreting unenhanced CT studies in patients with acute ureterolithiasis.

Adult↗

Imaging options.

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Artifacts↗

Hyperglycemia associated with the use of atypical antipsychotics.

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitus and taking antipsychotic medication further increases the chance of developing non-insulin-dependent hyperglycemia. Case reports, chart reviews, and some results from clinical drug trials implicate a relationship between glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia, although a few cases of hyperglycemia have also been reported in patients taking risperidone and quetiapine. These studies indicate that hyperglycemia is not dose dependent, is reversible on cessation of treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies. The postulated underlying mechanisms involved in this process in patients with schizophrenia include (1) a decreased sensitivity to insulin that is independent of atypical medication, (2) an increased insulin resistance related to atypical medications, (3) the effects of atypical medications on serotonin receptors, and (4) overuse of insulin due to weight gain. These mechanisms are discussed in detail, and recommendations for the administration of atypical antipsychotics are offered. Overweight, ethnicity, family or personal history of diabetes mellitus or hypertension, and weight gain during the course of treatment have all been identified as risk factors in the development of hyperglycemia in patients with schizophrenia. However, it is difficult to statistically assess the true incidence of diabetes within each type of antipsychotic medication group with the exclusive dependence on available case studies and without proper epidemiologic research.

Adolescent↗

Gastric lipoma causing gastroduodenal intussusception.

A case of gastroduodenal intussusception caused by a submucosal gastric lipoma in a 48-year-old man is presented. He had intermittent symptoms of regurgitation and heartburn for a period of three years. Barium meal and CT scan showed a mass in the first part of duodenum. At laparotomy there was intussusception of gastric antrum into the duodenum with a submucosal lipoma in the antrum which formed the apex of the intussusception.

Duodenal Diseases↗

Expression of wild-type and noncleavable Fas ligand by tetracycline-regulated adenoviral vectors to limit intimal hyperplasia in vascular lesions.

Proliferation of vascular smooth muscle cells (VSMCs) and the infiltration of T cells and macrophages into vessel wall are considered to be important for intimal lesion formation after balloon angioplasty. Previous studies have shown that Fas ligand (FasL) gene transfer to balloon-injured vessels inhibits lesion formation by killing both proliferating VSMCs and infiltrating inflammatory cells. Here, we describe the construction and utility of a binary, tetracycline-regulated adenovirus system that provides controlled transgene expression in vitro and in vivo. In this system, optimal transgene expression required cotransfection with an adenovirus encoding the tetracycline-dependent trans-activator (rtTA) and induction with doxycycline hydrochloride (DOX), an analog of tetracycline. Using this system, adenovirus constructs were designed that allow regulated expression of wild-type FasL and a noncleavable mutant of FasL (FasL-NC). Transduction of FasL and FasL-NC induced similar extents of apoptosis in proliferating VSMCs in vitro in a manner that was dependent on the doses of the rtTA adenovirus and the presence of DOX in the medium. Furthermore, inhibition of intimal hyperplasia in injured carotid arteries by FasL or FasL-NC transduction was also dependent on cotransfection with the rtTA adenovirus and administration of DOX by subcutaneous injection. In contrast to wild-type FasL, transduction of FasL-NC did not result in the production of soluble (cleaved) FasL in the medium of infected cells in vitro, or in the serum of rats after local gene transfer to carotid arteries. In conclusion, this binary tetracycline-inducible adenovirus system may allow for safer delivery of cytotoxic genes for therapeutic purposes.

Adenoviridae↗

The predictive value of body protein for chemotherapy-induced toxicity.

BACKGROUND: The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy-induced neutropenia was examined in the current study. METHODS: TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy (median age, 48 years; range, 26- 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2-6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 x 10(9)/L. The nitrogen index (NI) (TBN expressed as a percentage of age-, gender-. and height-matched healthy patients) then was compared with the corresponding ANCN values. RESULTS: Using receiver operating characteristics analysis, a "cut-off" value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 x 10(9)/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 x 10(9)/L (P < 0.0001). CONCLUSIONS: In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF-based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy-induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens.

Adenocarcinoma↗

Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients.

BACKGROUND: The American College of Chest Physicians addressed the dilemma of identifying optimal therapy for venous thromboembolism (VTE) prophylaxis and published their Fourth Consensus Conference on Antithrombotic Therapy in 1995, with recommendations for prophylactic therapy. Despite these recommendations, appropriate VTE prophylactic therapy is underused. OBJECTIVES: To examine routine practices in the prevention of VTE in high-risk surgical patients and to determine the extent of adoption of grade A prophylactic therapies as recommended by the American College of Chest Physicians. METHODS: Retrospective medical record review in 10 teaching or community-based hospitals located in the United States. Medical charts of 1907 patients were randomly selected for review from the population of patients who underwent high-risk major abdominal surgery, total hip replacement, hip fracture repair, or total knee replacement between January 1, 1996, and February 28, 1997. RESULTS: Of 1907 patients, VTE prophylaxis was used in 89.3%; use was 93.7% in each of the 3 orthopedic surgery groups and 75.2% in the high-risk major abdominal surgery group. The percentage of patients receiving grade A therapy was highest in the hip replacement group (84.3%) vs. the other groups (knee replacement, 75.9%; hip fracture repair, 45.2%; abdominal surgery, 50.3%). CONCLUSIONS: The use of grade A prophylaxis was related to the type of surgery, with the highest use seen in total hip replacement and the lowest in hip fracture repair. One in 4 patients who underwent high-risk major abdominal surgeries failed to receive any form of VTE prophylaxis. Publication of consensus statements alone may be insufficient to ensure the incorporation of important new clinical information into routine practice.

Adult↗