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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 703 records · Page 39Linked to original sources

Agnathia-holoprosencephaly: a new recessive syndrome?

The association between agnathia and holoprosencephaly is well documented (Pauli et al., 1981). Pauli et al. described two female sibs with agnathia and holoprosencephaly who were subsequently shown to carry an unbalanced 46,XX, der 18,t(6;18)(pter p24.1) karyotype (Pauli et al., 1983; Krassikoff and Sekhon, 1989). All other cases have been sporadic (Cohen, 1989). We present a recurrence of agnathia-holoprosencephaly in an unrelated European couple and postulate that this association may represent an autosomal recessive syndrome.

Abnormalities, Multiple↗

Long-term function of cryopreserved aortic homografts. A ten-year study.

Cryopreserved aortic valve homografts have become an accepted aortic valve substitute, but long-term studies with echocardiographic assessment of valve function are largely unavailable. Between 1981 and January 1, 1991, a total of 178 patients aged 9 months to 80 years (median 46 years) underwent implantation of a cryopreserved aortic valve homograft. Serial two-dimensional Doppler echocardiographic studies were obtained in 149 patients. Overall survival was 91% at 1 year and 85% at 8 years. Survival of patients undergoing isolated primary infracoronary aortic valve replacement was 99% at 1 month and 94% at 8 years. Twelve patients underwent homograft explanation. Freedom from explantation for leaflet degeneration was 95% at 8 years. Freedom from presumed leaflet failure (valve degeneration at explantation or aortic insufficiency grade 3/4 or more without reoperation on echocardiography) was 94% at 5 years and 85% at 8 years. By multivariable analysis younger recipient age was the only risk factor identified for leaflet failure. Ninety-five percent of patients followed up for 4 or more years were in New York Heart Association class I or II.

Actuarial Analysis↗

Identification of xanthine oxidase activity following reperfusion in human tissue.

In this series of experiments, we surveyed xanthine oxidase activity after microvascular transfer in the venous effluent after reperfusion of human rectus abdominis muscle (n = 8) and jejunum (n = 4). Enzyme activity was correlated with duration of ischemia and biochemical markers of cellular injury. Xanthine oxidase (XO) activity was measured spectrofluorometrically using a pterin assay, whereas cellular injury was measured with commercial creatinine phosphokinase activity assay and lipid peroxidation products using a spectrophotometer. The data demonstrated that XO activity was statistically significantly increased in muscle flaps kept at room temperature during ischemia compared with muscle flaps that were cooled (p < 0.05). Creatinine phosphokinase activity was also increased after 15 minutes of reperfusion in muscle flaps that were not cooled (p < 0.05). Two of the jejunal free flaps had ischemia times of > 1 hour and had elevated XO activity after reperfusion despite cooling (p < 0.05). Two other jejunal flaps had ischemia times of < 1 hour, but in one case, the XO activity was increased before harvest. The other case had no increase in XO activity.

Abdominal Muscles↗

Triple arthrodesis using internal fixation in treatment of adult foot disorders.

Forty adult patients with 44 fused feet were evaluated at an average of 4.9 years after triple arthrodesis. The average age of the patients at operation was 41 years. All operations were performed by a specific technique using rigid internal fixation with screws. Outcome was graded using the clinical criteria of Hallgrimsson as modified by Angus and Cowell. Function was evaluated according to modified Arthritis Impact Measurement Scales (AIMS). Radiographic evaluation included measurement of lateral talocalcaneal angle, lateral talometatarsal angle, and anteroposterior (AP) talometatarsal angle on standing or simulated weight-bearing radiographs. Thirty-four feet had good results, six had fair results, and there were four failures. The average patient could function painlessly on flat surfaces in nonstrenuous activities and had only occasional mild pain with more vigorous activities. In roentgenographic parameters, there was an average improvement of 17 degrees in the lateral talometatarsal angle, 11 degrees improvement in the lateral talocalcaneal angle, and an improvement of 18 degrees in the AP talometatarsal angle. There were two pseudarthroses, no recurrences, and two unsatisfactory corrections. When carefully done, triple arthrodesis can restore an adult patient with a disabling foot disorder to normal function and minimal pain.

Adolescent↗

Functional outcome of below-knee amputation in peripheral vascular insufficiency. A multicenter review.

A retrospective functional outcome study was performed on 299 patients treated with below-knee amputations for peripheral vascular disease during a three-year period in six Veterans Administration special amputee centers. Sixty-one percent of the patients were diabetic, and 25% were previously unilateral amputees. Surgery was performed with a long posterior flap in 92.3%, sagittal flaps in 20%, and guillotine open technique in 5.7%. Wound management was accomplished with rigid plaster dressings in 75.3%, pneumatic compression dressing in 14%, and soft dressings in 10.7%. At follow-up evaluation one to two years later, 36.1% had died. Thirteen percent suffered wound complications, with 6.7% requiring revision to a more proximal amputation level. Eighty-seven percent of community ambulators maintained their ambulatory status. A comparable percentage maintained their ability to walk with a prosthesis.

Amputation, Surgical↗

Microinvasive carcinoma of the cervix.

BACKGROUND: Microinvasive carcinoma of the cervix (MIC) has been poorly defined in the past and is still a focus of persistent controversy. In 1985, the International Federation of Gynecology and Obstetrics (FIGO) defined Stage IA as "preclinical invasive carcinoma, diagnosed by microscopy only," subdividing it into Stage IA1 or "minimal microscopic stromal invasion," and Stage IA2 or "tumor with invasive component 5 mm or less in depth taken from the base of the epithelium and 7 mm or less in horizontal spread." In 1974, the Society of Gynecologic Oncologists (SGO) defined MIC as any lesion with a depth of invasion of 3 mm or less from the base of the epithelium, without lymphatic or vascular space invasion. METHODS: To assess the risk of lymph node metastasis and treatment failures, pathologic material and clinical data on 370 patients with Stage I carcinoma of the cervix, who were treated by radical hysterectomy and pelvic-aortic node dissection, were reviewed. Histopathologic analysis of tumors was based on a uniform format, including measurement of the maximum depth of invasion, the width and length of the horizontal tumor spread, invasive growth pattern, cell type, tumor grade, and lymphatic or vascular space involvement. RESULTS: Of the 370 patients, 110 had a depth of invasion of 5 mm or less. Of these, 54 patients fulfilled the SGO definition of MIC; 42, the new FIGO Stage IA2 definition; and 27, both definitions. None of the patients with MIC, as defined by either the SGO or the new FIGO Stage IA2, had lymph node metastases or tumor recurrence. These data support the conclusion that MIC, defined by either the SGO or FIGO definitions, have a low risk for lymph node metastasis or recurrent carcinoma. A review of the literature indicated a recurrence rate for Stage IA2 of 4.2%. In addition to depth of invasion, lymph vascular space invasion is a better predictor of lymph node metastasis and recurrence than the surface dimension. CONCLUSIONS: The authors recommend adoption of the SGO definition of MIC. Patients with a depth of invasion of 3 mm or less without lymph vascular space invasion safely can be treated conservatively.

Carcinoma↗

Environmental and familial contributions to insulin levels and change in insulin levels in middle-aged women.

OBJECTIVE: To examine familial and environmental variables associated with elevated insulin levels and changes in insulin levels in healthy, premenopausal women. METHODS: A population-based sample of 518 women (aged 42 to 50 years) completed baseline assessments of weight, cardiovascular risk factors, exercise behaviors, and glucose and insulin levels (fasting and 2 hours after a glucose load); 495 of the women were reevaluated after 3 years. RESULTS: Plasma insulin levels were related to weight, activity level, race, body fat distribution, and weight gain since age 20 years. Parental history of either diabetes or hypertension was also related to elevated insulin levels, independent of body mass index, with the highest insulin levels occurring in those women with a parental history of both diseases. Increases in plasma insulin levels over the years of follow-up were related to weight gain. CONCLUSIONS: This study suggests that importance of using family history to identify women who may have elevated insulin levels and of intervening to prevent weight gain during middle age.

Adult↗

Pulmonary surfactant secretion is regulated by the physical state of extracellular phosphatidylcholine.

Pulmonary alveolar type II cells synthesize, secrete, and recycle the components of pulmonary surfactant. In this report we present evidence that dipalmitoylphosphatidylcholine is a potent inhibitor of surfactant lipid secretion by type II cells. Monoenoic and dienoic phosphatidylcholines with fatty acids of 16 or 18 carbons are ineffective as inhibitors of surfactant lipid secretion. In contrast, disaturated phosphatidylcholines, with either symmetric or asymmetric pairs of fatty acids of 14, 16, or 18 carbons, exhibit inhibition of surfactant secretion that correlates extremely well with the phase transition temperature (Tc) of the phospholipid. The inhibitory activity of dipalmitoylphosphatidylcholine is not dependent upon lipid stereochemistry. N-Methylated derivatives of dipalmitoylphosphatidylethanolamine are significantly less effective than phosphatidylcholine as inhibitors. Phosphatidylcholines below their phase transition temperature are inhibitors of surfactant secretion, whereas those above their phase transition temperature are either ineffective or weakly inhibitory. The phase transition dependence of inhibition is observed when type II cells are incubated at 37 degrees C with different species of phosphatidylcholine. In addition, if type II cells are stimulated to secrete at different temperatures the efficacy of a given phospholipid as an inhibitor is dependent on its relationship to Tc (i.e. dipalmitoylphosphatidylcholine with a Tc of 41 degrees C significantly inhibits secretion at 37 degrees C but not at 42 degrees C). Inhibition of surfactant secretion by dipalmitoylphosphatidylcholine is abrogated when it is incorporated into the same liposome with dioleoylphosphatidylcholine as a 50:50 mixture. In contrast, the simultaneous addition of two separate populations of liposomes, one composed of dipalmitoylphosphatidylcholine and the other composed of dioleoylphosphatidylcholine, does not significantly alter the inhibitory activity found with dipalmitoylphosphatidylcholine alone. These data provide compelling evidence that the physical state of phosphatidylcholine can regulate surfactant secretion from alveolar type II cells and suggest a unique mechanism for regulating exocytosis in the alveolus of the lung.

1,2-Dipalmitoylphosphatidylcholine↗

Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats.

In patients with ulcerative colitis, epidemiological work has suggested an association between low folate status and an increased risk of colonic neoplasia. The aim of the present study was to determine if experimental folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet containing either 8 or 0 mg/kg folic acid. After 5 weeks of defined diet, weekly s.c. injections of dimethylhydrazine (20 mg/kg) were administered to both groups. Serum, whole blood, liver, and colonic folate concentrations at the time of sacrifice were significantly lower in folate-depleted animals (P less than 0.001). There were significant differences in the incidence of colonic neoplasia between the two groups after 20 weeks of dimethylhydrazine exposure: folate-deficient rats had a greater incidence of dysplasia (6 of 7 versus 2 of 7 animals; P less than 0.05) and carcinoma (6 of 7 versus 1 of 7 animals; P less than 0.01). Furthermore, a significantly greater proportion of folate-replete rats than folate-deficient rats were free of neoplastic lesions (5 of 7 versus 0 of 7 animals; P less than 0.05). These results suggest that, in this animal model, folate deficiency increases the risk of malignancy when there is an underlying predisposition to colorectal cancer.

Animals↗