SNM house of delegates approves physician supervision guidelines; HCFA delays physician supervision rule.
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Centers for Medicare and Medicaid Services, U.S.↗
Biomedical subjects
W J Smith
Publications and source records attributed to W J Smith.
HCFA's coverage instructions for lung PET. Health Care Financing Administration.
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Carcinoma, Non-Small-Cell Lung↗
Revisions to payment policies under Medicare physician fee schedule proposed for 1999.
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Centers for Medicare and Medicaid Services, U.S.↗
3-[[(4-Aryl-1-piperazinyl)alkyl]cyclohexyl]-1H-indoles as dopamine D2 partial agonists and autoreceptor agonists.
A series of arylpiperazines and tetrahydropyridines joined to indoles by semirigid cycloalkyl spacers were prepared. Target compounds were studied for their ability to bind to the DA D2 receptor in vitro and to inhibit dopamine synthesis and spontaneous locomotor activity in rats. Effects of tether length and relative stereochemistry were assessed for a series of 2-pyridylpiperazines. The cyclohexylethyl spacer was found to be the most active in the series. Further studies explored effects of changes in the arylpiperazine and indole portions of the molecule. From these studies trans-2-[[4-(1H-3-indolyl)cyclohexyl]ethyl]-4- (2-pyridinyl)piperazine (30a) was selected for further evaluation. It was characterized as a partial agonist of DA D2 receptors in vitro and caused decreases in dopamine synthesis and release as well as dopamine neuronal firing. Compound 30a was shown to be devoid of behavioral effects associated with postsynaptic DA D2 receptor activation. Furthermore, compound 30a was shown both to decrease DA synthesis and to inhibit Sidman avoidance responding in squirrel monkeys. These findings suggest that DA D2 partial agonists with the appropriate level of intrinsic activity can act to decrease dopamine synthesis and release and may have potential utility as antipsychotic agents.
Animals↗
Right latissimus dorsi cardiomyoplasty improves left ventricular energetics.
BACKGROUND: The mechanism by which cardiomyoplasty appears to enhance left ventricular (LV) function is not well understood. We applied the time-varying elastance model to study the effect of cardiomyoplasty on LV function, ventriculovascular coupling, and LV energetics in an acute canine model. METHODS: Right latissimus dorsi cardiomyoplasty was performed in 5 dogs. The end-systolic pressure-volume relation was generated by using brief caval occlusions. End-systolic elastance, effective arterial elastance, stroke work, internal work, total mechanical work, and stroke work efficiency (stroke work/total mechanical work) were calculated from these pressure-volume data. Myocardial oxygen consumption and overall mechanical efficiency (stroke work/myocardial oxygen consumption) were predicted using the myocardial oxygen consumption-total mechanical work relation. RESULTS: Skeletal muscle contraction significantly increased end-systolic elastance, an index of contractility. Although stroke work did not change significantly, the increase in end-systolic elastance led to a 29% decrease in total mechanical work, a 50% decrease in internal work, and an increase in stroke work efficiency from 53% to 66%. This was consistent with the observed 29% decrease in effective arterial elastance/end-systolic elastance, an indicator of ventriculovascular coupling that is related inversely to stroke work efficiency. Predicted myocardial oxygen consumption decreased by at least 22%, and predicted overall mechanical efficiency increased at a minimum from 16.1% to 18.4%. CONCLUSIONS: These results support the theory that cardiomyoplasty unloads the LV by decreasing LV volumes and increasing contractility. These effects appear to improve LV energetics by decreasing total mechanical work without significantly affecting stroke work, resulting in improved stroke work efficiency. The decrease in total mechanical work strongly suggests a decrease in myocardial oxygen consumption and an increase in overall mechanical efficiency.
Animals↗
Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.
Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to incentives and stressors.
Aging↗
L-oxothiazolidine 4-carboxylate pretreatment of isolated human peripheral blood lymphocytes reduces sulfur mustard cytotoxicity.
Sulfur mustard (HD, mustard gas) is a vesicant chemical warfare agent for which there is no specific medical countermeasure. A potential approach to combating the debilitating effects of this agent is the use of compounds that can react with this material before it interacts with critical macromolecules. Glutathione (GSH), a tripeptide that exists in high concentrations in cells, reacts with HD and is involved in HD detoxification. Pretreatment of human peripheral blood lymphocytes (PBL) with 10 mmol/L L-oxothiazolidine-4-carboxylate (OTC), a "masked" cysteine precursor, increased intracellular glutathione levels 25-50% over control values. Pretreated PBL were harvested, washed, and exposed to 10, 50, or 100 mumol/L HD. Flow cytometry was used to measure cytotoxicity by propidium iodide uptake. Pretreatment of PBL with OTC led to small decreases in cytotoxicity after HD exposure. However, treatment of cells with OTC after HD exposure was not beneficial. Compounds that can modulate GSH levels within the cell may help to reduce the cytotoxicity of HD when used a pretreatment.
Antidotes↗
Pathogenicity of three strains of Serpulina pilosicoli in pigs with a naturally acquired intestinal flora.
Serpulina pilosicoli is an anaerobic spirochete which has been isolated from the colons of pigs with enteric disease. The clinical and pathologic features of experimental infections of conventional pigs (born by normal farrowing with a naturally acquired intestinal flora) with three strains of S. pilosicoli were determined in order to confirm the enteropathogenicity of this species. Strains were derived from the colons of British pigs with colitis and passaged 8 to 10 times during expansion and purification in vitro. Eighteen ten-week-old Large White-Landrace cross pigs were each inoculated once orally with 0.7 x 10(9) to 1.6 x 10(9) of one of three strains of S. pilosicoli. Six pigs were challenged with each strain. Control pigs were dosed with uninfected broth medium or with 1.8 x 10(7) cells of the nonpathogenic Serpulina innocens. Eight pigs (two to four per S. pilosicoli challenge group) developed soft or diarrheic feces (fecal dry matter < 24%) between 3 and 8 days after challenge, which persisted for 7 to 8 days or until necropsy at 14 days after challenge. Average weight gains in two of the three groups challenged with S. pilosicoli were significantly less than controls. The feed conversion ratios of all the groups challenged with S. pilosicoli were impaired compared to controls. The mean values for daily liveweight gain (and feed conversion ratio) for the three groups challenged with S. pilosicoli were 0.799 (2.13), 0.783 (2.05), and 0.844 kg (2.10), respectively, while that of the uninoculated controls was 0.944 kg (1.70). Gross lesions with slight mucosal thickening, congestion, and multifocal erosions were evident in seven of eight diarrheic pigs. The relative weights of the large intestines of pigs challenged with S. pilosicoli were significantly less than controls. Histologic lesions with an increase in mucosal height, infiltration of the lamina propria with mononuclear cells, mucosal erosion with mixed inflammatory cell infiltration, and goblet cell hyperplasia in colonic glands were evident in 15 of the 18 challenged pigs. S. pilosicoli was recovered on bacterial culture of the colon from all except one of the pigs with these histologic lesions. Serpulina sp. was clearly visible within the colonic glands of these affected pigs in silver-stained sections of the gut. Clinical and pathologic findings in control pigs were unremarkable, with no diarrhea or colonic lesions evident. The results provide further evidence that S. pilosicoli is a specific enteric pathogen for conventional pigs. It is capable of colonizing the large intestine and causing mucosal damage, which although mild is sufficient to result in significant adverse effects on growth.
Animals↗
Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants.
To determine whether peptides of the insulin-like growth factor (IGF) system might be useful indicators of nutritional adequacy in premature infants, we studied 50 premature (25-34 weeks gestation) infants prospectively to define the relationship between nutrient intake and serum concentrations of IGF-I, IGF-binding protein-2 (IGFBP-2), and IGFBP-3. Each infant was monitored for at least 2 weeks. Nutrient intake was quantified from daily logs; weight was determined daily, and measurements of IGF-I, IGFBP-2, and IGFBP-3 in serum were made twice weekly. Serum IGF-I correlated strongly with length of gestation, increasing 4.03 +/- 0.95 ng/mL for each additional week of gestation (P < 0.0001) and 0.36 +/- 0.07 ng/mL day each day since birth (P < 0.0001). A higher intake of calories increased IGF-I by 0.07 +/- 0.01 ng/mL for each calorie per kg ingested over the previous 3 days (P < 0.0001). IGF-I increased quadratically as protein intake increased. For each change of 1% in calories as protein squared, IGF-I increased 0.36 +/- 0.11 ng/mL (P < 0.0001). Serum IGFBP-3 concentrations also correlated with length of gestation, increasing 25.06 +/- 11.83 micrograms/L.wk (P = 0.035) and 4.14 +/- 1.33 micrograms/.day since birth (P = 0.003). Unlike IGF-I, variation in the amount of protein supplied did not change IGFBP-3. As calorie intake increased, IGFBP-3 increased by 0.54 +/- 0.17 microgram/L for each calorie per kg consumed over the previous 3 days (P = 0.0015). In contrast to IGF-I and IGFBP-3, IGFBP-2 declined as the length of gestation increased (56.12 +/- 16.92 ng/mL.week; P = 0.001) and with each additional day of life (7.57 +/- 2.44 ng/mL.day; P = 0.003). Dietary protein, the predominant regulator of IGFBP-2, caused a decrease of 33.22 +/- 9.00 ng/mL with each percent increase in dietary calories as protein (P < 0.0003). Calorie intake had less effect on IGFBP-2 than protein intake. These results indicate that each of the three peptides studied is regulated in premature infants by nutritional intake, and that their regulatory patterns are qualitatively similar to those observed in older individuals. Measurements of these peptides in premature infants may be useful indicators of nutritional status and adequacy of nutrient intake.
Humans↗
Demographic change and income inequality in the United States, 1976-1989.
"The U.S. economy experienced significant increases in the degree of income inequality over the past two decades.... In this paper we consider the effects of race, age, female headship, and college education on the distribution of family income by developing a multivariate methodology that allows us to gauge the influence of one factor while holding other determinants of family incomes constant. Over the period studied we find that race had only a minor effect on the overall size distribution of income. Age had a somewhat greater effect than race. In contrast, the impact of female heads and college education were quite substantial. The multivariate estimates reveal that the effects of female heads and college education both increase the Gini to a much greater extent than the progressivity of federal income taxes decreases it. The effects of college education and female headed families on inequality have grown larger across time, while the influence of age has declined. We find that the effects of race on inequality have changed little over the 1976 to 1989 period."
Age Factors↗
HCFA's prospective payment system for hospital outpatient services.
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Centers for Medicare and Medicaid Services, U.S.↗
Differential induction of Fos in the female rat brain following different amounts of vaginocervical stimulation: modulation by steroid hormones.
Vaginocervical stimulation (VCS), produced either by copulation with intromission or by manual stimulation of vagina and cervix with a glass rod, induces neuroendocrine and behavioral responses that are critical for female reproduction in many species. We and others have shown that Fos mRNA and protein are induced within different estrogen-concentrating and -non-concentrating regions of the female rat brain following copulation with intromission and manual VCS. In the present study, we investigated the amount of distributed VCS required to induce Fos immunoreactivity within estrogen-concentrating regions of the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, medial amygdala, and mesencephalic central gray, and whether estrogen and progesterone could alter the threshold or pattern of induction. Ovariectomized rats were administered estradiol benzoate (10 micrograms) 48 h and progesterone (500 micrograms) 4 h before receiving either 0, 1, 5, 10, 20, 30, 40, or 50 manual VCSs with a lubricated glass rod. Ovariectomized hormone control rats received injections of the sesame oil vehicle 48 and 4 h before VCS. All rats were sacrificed 75 min after the first VCS. Fos immunoreactivity was induced differentially by VCS within the different regions, and the hormones either augmented, inhibited, or had no effect on the induction. These data demonstrate that cells within different estrogen-concentrating regions of the female rat brain are differentially sensitive to VCS, and that steroid hormones can either increase or decrease the amount of Fos induced by different amounts of VCS. Different brain regions may participate in gating the sensory information of VCS into different behavioral and neuroendocrine events.
Animals↗
Streptococcus suis serotypes 7, 8 and 14 from diseased pigs in Scotland.
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Animals↗
Ca2+ homeostasis and Ca2+ signalling in sulphur mustard-exposed normal human epidermal keratinocytes.
To investigate the role of increased cytoplasmic free calcium levels ([Ca]i) in sulphur mustard-induced cellular toxicity, the [Ca]i of human epidermal keratinocytes exposed to sulphur mustard concentrations between 50 and 800 microM were measured. No early increase in [Ca]i was observed during the first 20 min after application of the agent. Furthermore, at 3, 6 and 24 h after exposure to sulphur mustard, the [Ca]i of sulphur mustard-exposed cells differed only slightly from that of control cells. However, sulphur-mustard exposed cells responded with a weaker rise of [Ca]i upon stimulation with histamine and ATP than control cells. These results suggest that sulphur mustard can induce small increases in [Ca]i, which reflect abnormal cellular physiology rather than acute toxicity. In addition, it has been shown that sulphur mustard disturbs cellular Ca2+ signalling in human epidermal keratinocytes.
Calcium↗
Use of a supracondylar nail for treatment of a supracondylar fracture of the femur following total knee arthroplasty.
Treatment of displaced or comminuted supracondylar fractures of the femur following total knee arthroplasty is challenging and problematic. Closed treatment has been associated with malunion, nonunion, and loss of motion, whereas early operative treatment has been associated with infection as well as nonunion. Intramedullary fixation of these fractures has the theoretical advantage of preserving periosteal blood supply while allowing early motion. The use of a nail specifically designed for supracondylar femur fractures to treat a a periprosthetic fracture about a well-fixed total knee arthroplasty is reported. This device provides a valuable treatment option to the surgeon treating this difficult problem.
Aged↗
Complications of iliac crest bone graft harvesting.
Autologous bone grafts harvested from the iliac crest are commonly used in reconstructive orthopaedic surgery. Autologous bone is used to help promote bone healing in fractures and to provide structural support for reconstructive surgery. The results of autologous bone grafting are more predictable than the use of xenografts, cadaveric allografts, or synthetic bone substitutes because autologous bone grafts provide osteoinductive and osteoconductive properties, are not immunogenic, and are usually well incorporated into the graft site. In a retrospective review of 414 consecutive cases of iliac crest bone graft procedures performed at Brooke Army Medical Center from 1983 to 1993, 41 (10%) minor and 24 (5.8%) major complications were identified. Minor complications included superficial infections, superficial seromas, and minor hematomas. Major complications included herniation of abdominal contents through massive bone graft donor sites, vascular injuries, deep infections at the donor site, neurologic injuries, deep hematoma formation requiring surgical intervention, and iliac wing fractures. Harvesting of iliac crest bone graft can be associated with significant morbidity. However, with adequate preoperative planning and proper surgical technique, the incidence of these complications can be reduced.
Blood Vessels↗
The art of verbal engineering.
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Euthanasia, Active↗
Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization.
OBJECTIVES: The short- and long-term effectiveness of transmyocardial laser revascularization was evaluated in the setting of an acute myocardial infarction. BACKGROUND: Theoretically, transmyocardial laser revascularization allows direct perfusion of the ischemic area as ventricular blood flows through the channels to the myocardium. METHODS: Infarcts were created by coronary occlusion in 30 sheep. Eighteen of these sheep were studied to assess short-term efficacy. The infarct was reperfused after 1 h by either removing the occlusion or by laser drilling using a high power carbon dioxide laser. The occlusions were left in place for the control group. To monitor regional recovery, percent systolic shortening was measured. To evaluate long-term effectiveness, 12 additional sheep underwent creation of an infarct. Six were treated with the laser, and six were untreated. The animals were restudied 30 days later. RESULTS: In the short-term experiment, the control and reperfusion groups exhibited no recovery of regional contractility. The laser group demonstrated improvement throughout the recovery period. There was a significant difference in the area of necrosis within the same area at risk (reperfusion group 44 +/- 6% and control group 39 +/- 5% vs. laser group 6 +/- 2%). After 30 days, none of the control animals showed evidence of contraction in the infarct, whereas the laser-treated animals did. Histologic analysis of the laser-treated infarcts revealed patent channels surrounded by viable myocardium. The control-group infarcts were necrotic and scarred. CONCLUSIONS: On the basis of both short- and long-term improved contractility, as well as diminished necrosis in the area at risk, these results indicate that transmyocardial laser revascularization may be an alternative method of treating ischemic heart disease.
Animals↗