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Biomedical subjects

C Scott

Publications and source records attributed to C Scott.

At least 145 records · Page 8Linked to original sources
PubMed1997

Postsclerotherapy pigmentation. Is serum ferritin level an accurate indicator?

BACKGROUND: Human beings have suffered and sought treatment for disease of veins as early as the recordings of the old testament. The use of irritating sclerosing agents have been and are widely used today to treat varicose veins and telangiectasia. One of the most common and cosmetically significant side effects of sclerosing agents is varying degrees of hyperpigmentation. It has been reported that elevated serum ferritin level plays a role in this postsclerotherapy pigmentation. OBJECTIVE: To support or negate the possibility of a direct correlation between serum ferritin levels and pigmentation postsclerotherapy using for our investigation a patient with hemochromatosis. METHODS: A patient with hemochromatosis having a serum ferritin level of 1200 was treated for spider veins. Clinical and histologic studies were performed pretreatment and posttreatment. RESULTS: There was no clinically apparent hyperpigmentation noted on the patient after sclerotherapy over a 6-month period. Histology reports revealed macrophagic pigmentation both pretreatment and posttreatment. CONCLUSION: Our results do not confirm the theory that lab values of elevated serum ferritin correlate with pigmentation postsclerotherapy. Further study of the correlation between postsclerotic pigmentation and serum ferritin levels are needed. One would anticipate that if a true correlation existed, then an extreme case such as this would clearly support this theory.

Ferritins↗
PubMed1997

Aortic valve replacement with a pulmonary autograft: case studies of the Ross procedure.

The Ross procedure is an old surgical technique that is gaining popularity some 30 years after its introduction. The patient's own pulmonary valve is essentially used as a "spare part" to replace the diseased aortic valve. The Ross procedure has become an accepted and attractive option for patients with a life expectancy of more than 20 years and for patients in whom long-term treatment with anticoagulants is undesirable or problematic. Careful preoperative evaluation and postoperative management, as well as proficient surgical techniques, are all necessary to achieve good outcomes.

Adult↗
PubMed1996

Nitric oxide and exercise in the horse.

1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respectively. 3. Nebulized methoxamine (40 mg ml-1 for 60 s), an alpha 1-adrenergic agonist, further reduced [NO] during the 9 m s-1 canter to 1.05 +/- 0.14 and 1.99 +/- 0.41 p.p.b. when collected at 80 and 20 l min-1, respectively, and induced cyclical changes in the breathing pattern. 4. Exercise induced a linear increase in VNO with work intensity to a maximum (428.1 +/- 31.6 pmol min-1 kg-1) which coincided with the maximal oxygen uptake for the horses (138.3 +/- 11.7 ml min-1 kg-1), although a further increase in VNO (779.3 +/- 38.4 pmol min-1 kg-1) occurred immediately after exercise. The changes in VNO correlated well with the tidal volume (r = 0.968; P < 0.01) and the haematocrit (r = 0.855; P < 0.01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0.05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83.1 +/- 7.6 mmHg compared with a control value of 94.4 +/- 6.3 mmHg, and during the second minute, 84.2 +/- 7.1 mmHg compared with a control value of 98.4 +/- 4.7 mmHg. There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise.

Adrenergic alpha-Agonists↗
PubMed1996

Human fibroblasts express functional IL-2 receptors formed by the IL-2R alpha- and beta-chain subunits: association of IL-2 binding with secretion of the monocyte chemoattractant protein-1.

Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [125I]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes.

Adult↗
PubMed1996

Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

PURPOSE: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality. METHODS AND MATERIALS: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min. RESULTS: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant. CONCLUSIONS: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.

Adult↗
PubMed1996

GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms.

During rat cortical development, when neurons migrate from the ventricular zone to the cortical plate, GABA localizes within the target destinations of migratory neurons. At this time, cells in germinal zones and along migratory pathways express GABA receptor subunit transcripts, implying that in vivo, GABA may be a chemoattractant. We used an in vitro strategy to study putative chemotropic effects of GABA on embryonic rat cortical cells. GABA stimulated neuronal migration in vitro at embryonic day 15 (E15). From E16 onward, two concentration ranges (fM and microM) induced motility. Femtomolar GABA primarily stimulated chemotaxis (migration along a chemical gradient), whereas micromolar GABA predominantly initiated chemokinesis (increased random movement). These effects were mimicked by structural analogs of GABA with relative specificity at GABAA (muscimol), GABAB (R-baclofen), and GABAC (trans- or cis-4-aminocrotonic acid) receptors. Antagonists of GABAB (saclofen) and GABAC (picrotoxin) receptors partially inhibited responses to both femto- and micromolar GABA; however, only responses to femtomolar GABA were partially blocked by bicuculline, a well established antagonist of GABA at GABAA receptors. Hence, chemotactic responses to femtomolar GABA seem to involve all three classes of GABA receptor proteins, whereas chemokinetic responses to micromolar GABA involve GABAB and GABAC receptor proteins. GABA-induced motility was blocked by loading the cells with the Ca(2+)-chelating molecule bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid, suggesting that intracellular Ca2+ mediates GABA-induced cell movement. Optical recordings of cells loaded with Ca2+ indicator dye revealed that both femto- and micromolar GABA evoked increases in intracellular Ca2+. Thus, GABA-stimulated increases in intracellular Ca2+ may mediate both chemotactic and chemokinetic responses in embryonic cortical cells.

Animals↗
PubMed1996

Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05).

PURPOSE: To determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases. METHODS AND MATERIALS: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) < or = 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery. RESULTS: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, < or = 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, < or = 20mm, 21 Gy; arm 5, 21-30 mm 18 Gy; and arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7 and 5% of patients on Arms 1, 2 and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume > or = 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) > or = 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume > or = 8200 mm(3) and MD/PD > or = 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. CONCLUSION: We found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases < or = 40 mm in maximum diameter treated according to the protocol described.

Adult↗
PubMed1996

Use of protease inhibitors increases the amounts of substance P extracted from small specimens of nerve tissue.

When using radioimmunoassay to measure the levels of peptides from small pieces of nerve tissue it is crucial to maximize the amount of peptides extracted. Here we report on the value of including protease inhibitors in the extraction buffer when extracting substance P (SP) from short lengths of rat saphenous nerve tissue. Nerve segments were removed from terminally anesthetized 13-week-old rats and directly added to acid buffer (including EDTA) either with or without 1 mM 4-(2-amino-ethyl)-benzesulfonyl fluoride-HCl, 2 micrograms/ml aprotinin, 100 microM leupeptin, 1 microgram/ml cystatin, and 1 mM benzamidine. These "direct" samples were then boiled for 10 min. With additional groups of pieces of saphenous nerve tissue the effects of leaving the samples for 10 min in both buffers at room temperature either intact ("delayed") or after mincing the tissue ("minced") were investigated. Addition of protease inhibitors increased the amount of SP extracted in both direct and delayed procedures, although the increase was only significant for the delayed situation (P < or = 0.05). "Delay" in the absence of protease inhibitors resulted in a significantly decreased amount of SP being extracted compared to the direct and minced situations (P < or = 0.05). We recommend use of protease inhibitors be included as part of the standard procedure for extracting neuropeptides from small specimens of nerve tissue for radioimmunoassay.

Animals↗
PubMed1996

Inhibition of neutrophil respiratory burst and cytokine priming by gamma-linolenic acid.

The effect of n-6 fatty acids, particularly gamma-linolenic acid (GLA), on the oxidase response and neutrophil priming by tumour necrosis factor alpha and interleukin 8 was studied in both normal volunteers and patients with obstructive jaundice. GLA inhibited the neutrophil respiratory burst at concentrations higher than 50 mummol/l, but abolished cytokine priming at concentrations as low as 1 mummol/l. Inhibition was not the result of either cytotoxicity to the neutrophils or alteration in cytosolic free calcium homoeostasis. It is concluded that GLA is a potential inhibitor of neutrophil priming by cytokines and of the oxidative response.

Aged↗
PubMed1996

Endotoxin priming exacerbates acute reflux pancreatitis in the rat.

Recently, endotoxaemia has been reported as a prognostic marker in acute pancreatitis. However, the role of endotoxin in inducing or aggravating acute pancreatitis is not fully understood. We administered endotoxin 400 micrograms/kg i.p. to rats 24 h before performing either a closed duodenal loop (group B) or a sham operation (group D). Pancreatic damage and overall survival were compared with the results obtained in rats not exposed to endotoxin undergoing either closed duodenal loop (group A) or sham treatment (group C). In a first set of experiments, 24 h after laparotomy blood samples were collected and the animals were sacrificed; survival up to 8 days was estimated in a second set of experiments. Group B had higher lipase concentrations and more severe tissue damage than group C (P < 0.05). A larger number of abscesses was observed in both group B and group D as compared to group C (P < 0.05). Survival was significantly shorter in group B (P < 0.0001). We conclude that priming with endotoxin worsens the extent of pancreatic damage induced by the closed duodenal loop procedure in the rat, possibly favouring selective homing of neutrophils to the site of inflammation, in similarity to what happens in the Shwartzman phenomenon.

Animals↗
PubMed1996

Confirmation of susceptibility locus on chromosome 13 in Australian breast cancer families.

Two major genes determining predisposition to breast cancer, termed BRCA1 and BRCA2, have been mapped to the long arms of chromosomes 17 and 13, respectively. Each locus is believed to account for approximately 40% of cases of familial breast cancer. We used linkage and haplotype analysis with simple tandem repeat polymorphisms at chromosomal bands 17q21 and 13q12 to determine the contribution of the BRCA1 and BRCA2 genes to predisposition to breast cancer in four Australian breast cancer kindreds, one of which had two male cousins with breast cancer. Surprisingly all families segregated a haplotype of markers on 13q and showed positive lod scores supporting linkage to BRCA2. In addition, haplotype analysis identified an informative recombination between D13S260 and D13S171 in one affected individual, which refines the localisation of BRCA2 to between D13S260 and D13S267; a distance of 2-3 cM. Tumours of the stomach and cervix, as well as melanoma and leukaemia/lymphoma also occur in these pedigrees but the numbers are too low to determine whether they may be significantly associated with BRCA2 carrier status. Our results confirm the existence of BRCA2 on the long arm of chromosome 13 and support previous findings that this locus is likely to confer risk in families with affected males. Furthermore, our observations suggest that the BRCA2 gene may also contribute to the development of other neoplasma.

Australia↗
PubMed1996

Frequency and effect of negative comments ("badmouthing") on medical students' career choices.

BACKGROUND: Some call it "medical bigotry," and others describe it as the "hidden curriculum," but, by any name, the superficial and demeaning comments that students hear about particular career choices are thought to play a major role in discouraging the selection of primary care careers. This paper explores the frequency and effect of "badmouthing" on career choice with the hypothesis that it is more frequently heard about primary care disciplines but has relatively little influence on actual career choice. METHOD: In 1993, 129 (79%) of the 163 University of Washington School of Medicine graduates responded to a two-page questionnaire about badmouthing. This information was used to refine the questionnaire. In 1994, 1,447 graduating students from nine medical schools were surveyed with the revised questionnaire. The schools were chosen to represent schools that had high, medium, and low proportions of students going into primary care careers. RESULTS: A total of 1,114 questionnaires were returned, for a response rate of 77%. Badmouthing was heard frequently (76% of the responding students) and often occurred as early as the first and second years of medical school. The students heard badmouthing about their career choices most frequently when they selected surgery (91%) and family medicine (87%) and least frequently when they chose pediatrics (57%), p < .001. The students reported that the influence on career choice was low in general, but 186 students (17% of all respondents) did report altering their choices based on badmouthing. CONCLUSION: Primary care fields and non-primary care fields were equally affected by career changes due to badmouthing. This study indicates that badmouthing, while pervasive across all disciplines and an unattractive aspect of the educational experience, cannot alone account for the low proportion of graduates choosing primary care careers.

Attitude↗
PubMed1996

The need for more aggressive follow-up of children born to hepatitis B surface antigen-positive mothers: lessons from the Louisiana Perinatal Hepatitis B Immunization Program.

BACKGROUND: Preventing perinatal transmission of hepatitis B virus (HBV) is an important part of strategies to prevent HBV-related disease. To help prevent perinatal transmission the Louisiana Office of Public Health began in 1990 a statewide program to track children of hepatitis B surface antigen (HBsAg)-positive mothers. We examined data from this program to evaluate the effectiveness of the program and to assess the value of serologic testing in the program. METHODS: We examined vaccination and testing records for all children listed in the program database who were old enough to have been tested, according to program recommendations, as of July, 1993. RESULTS: Of 426 children 269 (63%) had been completely vaccinated. Also of these 426 children 194 (46%) were tested for hepatitis B surface antibody (anti-HBs) and 163 (38%) were tested for HBsAg. Among tested children 6 (4%) were HBsAg-positive and 22 (11%) were anti-HBs-negative. Incompletely vaccinated children were more likely than completely vaccinated children to be HBsAg-positive (risk ratio, 7.9; 95% confidence interval, 1.5 to 41.2) and less likely to be positive for anti-HBs (risk ratio, 0.5, confidence interval, 0.3 to 0.7). Children tested > or = 18 months after the last vaccine dose were more likely than children tested earlier to be anti-HBs-negative (risk ratio, 0.8; 95% confidence interval, 0.7 to 1.1). CONCLUSIONS: Rates of vaccination completion and postvaccination serologic testing were low for children in this program. Even with these low vaccination rates, however, we estimate that the program prevented 74% of HBV infection and 87% of HBV carriage in this group of high risk children, suggesting that failure to vaccinate rather than vaccine failure was the major obstacle to prevention of perinatal HBV transmission. Serologic testing was useful in that it identified children with chronic HBV infection and children who may have needed additional doses of vaccine, but it should be performed < 18 months after the last dose of vaccine is given. More aggressive follow-up of these children for both vaccination and serologic testing is needed.

Adolescent↗
PubMed1996

Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06.

PURPOSE: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients. CONCLUSION: Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06.

PURPOSE: Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. PATIENTS AND METHODS: Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] < 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total 69.6 Gy). RESULTS: Seventy-six assessable patients with a Karnofsky performance status > or = 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of < or = 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). CONCLUSION: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.

Administration, Oral↗