Biomedical subjects
Publications and source records attributed to J Smith.
The objective of this paper is to report the uncommon association of hyperparathyroidism (one case resulting from an adenoma and the other from chief cell hyperplasia) and sarcoma of bone. The radiographic appearances of both cases were thought to be a little unusual and are discussed in detail. The possible relationship of the sarcomas to brown tumors is discussed.
A bulky tumor of the first lumbar vertebra is described. The case is the 21st to be reported. The tumor resembled an aneurysmal bone cyst radiologically. It was resected without incident. The previously reported cases are reviewed and the literature discussed.
PURPOSE: Blood pressure in individuals who have sickle cell disease has been reported to be lower than published normal values. We determine whether and to what degree this is true, using data obtained as part of a large natural history study. PATIENTS AND METHODS: Blood pressure was measured annually for 3,317 subjects with sickle cell disease who were 2 years old or older. Values obtained were compared with those reported by the National Health and Nutrition Examination Survey I and II (NHANES I and II). They were further analyzed with respect to age, sex, height, weight, hematologic diagnosis, blood urea nitrogen and creatinine, stroke, and death. RESULTS: Blood pressure was significantly lower in subjects with sickle cell anemia than published norms for age, race, and sex, a difference that increased with age. It correlated with body mass index, hemoglobin, measures of renal function and age, but the strength of the correlation varied among age and sex subgroups. The risk for occlusive stroke increased with systolic but not diastolic pressure. Mortality was related to elevated blood pressure in males (P < 0.05) and to a lesser extent in females (P = 0.10). In subjects with hemoglobin SC disease, blood pressure also deviated from normal but to a lesser degree. CONCLUSION: Blood pressure is generally lower than normal in individuals with sickle cell anemia. Those with high values relative to this population had an increased risk of stroke and death. Blood pressure should be monitored but values obtained must be assessed relative to the lower values expected for patients with this disease. Those with blood pressure values above 140/90 mm Hg should be evaluated and considered for treatment.
Assessments for blood-injury-injection phobia measure feared stimuli and overt behaviours, but they have not systematically addressed the symptoms of fear and faintness. The Blood-Injection Symptom Scale (BISS) was developed to overcome this omission. An exploratory factor analysis grouped symptoms triggered by blood and injections into three internally consistent factors (faintness, anxiety and tension). A confirmatory factor analysis replicated the factor structure in a new sample. To test the construct validity of the BISS, an attempt was made to reproduce Ost's (1992, Journal of Abnormal Psychology, 101, 68-74) finding that fear was stronger among people with concerns about injections, while faintness was stronger among people with concerns about blood. A community sample of 80 individuals with concerns (i.e. fear or fainting) about blood or injections completed the BISS. Controlling faintness, individuals with concerns about injections reported more fear than people with concerns about blood. In contrast, controlling for fear, the latter reported more symptoms of faintness. These data suggest that the BISS generates stable and internally consistent subscales useful in the measurement of symptoms elicited by blood and injections.
BACKGROUND: There are no published, detailed assessments of the direct costs of endoscopic hemostasis for actively bleeding peptic ulcers. We compared the direct costs of care for patients with active ulcer hemorrhage treated with endoscopic or medical-surgical therapies and correlated these costs with patient outcomes. METHODS: In a prospective, randomized, controlled trial, 31 patients with active ulcer hemorrhage at emergency endoscopy were randomly assigned to heater probe, injection, or medical-surgical treatment. For further ulcer bleeding, heater probe and injection patients were re-treated endoscopically and medical-surgical patients were referred for surgery. Direct costs were estimated using fixed and variable costs for resources consumed and Medicare reimbursement rates for physician fees. RESULTS: Compared to medical-surgical treatment, the heater probe and injection groups had significantly higher primary hemostasis rates (100% and 90% vs 8%) and lower rates of emergency surgery (0% and 10% vs 75%), blood transfusions, and median direct costs per patient ($4153 and $5247 vs $11,149). Furthermore, compared to medical-surgical treatment, the heater probe group had a significantly lower incidence of severe ulcer rebleeding (11% vs 75%). CONCLUSIONS: Heater probe and injection sclerosis are similarly efficacious treatments for active ulcer hemorrhage, and both treatments yield significantly lower direct costs of medical care and cost savings.
Six 6-week-old Beagle dogs were fed Cryptosporidium parvum oocysts of calf origin. All 6 dogs shed oocysts in faeces. Greater numbers of oocysts were detected with a Weber concentration technique (formalin-ethyl acetate extraction and NaCl centrifugal flotation) stained with either fluorescent antibody or modified Ziehl-Neelsen than with other formalin-ether or -ethyl acetate extraction methods. Oocyst numbers g-1 of faeces rose from days 3 to 5 to a first and highest peak lasting to days 7-9, and 5 of the 6 dogs passed oocysts for at least 80 days. However, the numbers of oocysts detected in the dogs' faeces were low, only 16.1% of the samples in the first month after infection and 2.5% thereafter contained > or = 10000 oocysts g-1 of faeces. Oocyst production was cyclical, with 19.3% of samples negative in the first month after infection and 42.5% thereafter.
We compared the potencies of systemic administration of bombesin (BN) and its mammalian homologue gastrin-releasing peptide (GRP) to decrease sham feeding in rats. Bombesin (at doses of 8, 16 and 32 micrograms/kg, intraperitoneally) inhibited sham feeding by 37% (p < 0.001), 58% (p < 0.001) and 65% (p < 0.001), respectively, confirming previous results. Gastrin-releasing peptide (16, 32, and 64 micrograms/kg) failed to affect sham feeding. Bombesin (16 micrograms/kg) and gastrin-releasing peptide (32 micrograms/kg) inhibited real feeding by 64% (p < 0.001) and 44% (p < 0.004), respectively. Pregastric food stimulation is not sufficient for the inhibitory action of GRP.
Infections by human schistosomes, in particular Schistosoma mansoni, account for significant morbidity and mortality every year in tropical and sub-tropical areas. The eggs of the parasite induce pathological changes in the infected host; in chronic and heavy infections, these changes may lead to death. A well-designed anti-schistosomal vaccine, alone or in concert with existing control measures such as chemotherapy, may prove to be a safe, inexpensive, and effective means of reducing the occurrence of severe disease and death in S. mansoni infection. Previous studies have demonstrated the importance of the syncytial layer containing the apical plasma membrane (APM) of S. mansoni in both the survival of the parasite in the mammalian host and as a potential source of immunogens which may be utilized as vaccine candidates. In this paper, we present evidence for the protective capacity of several schistosomal antigen preparations, including a calcium binding protein of the APM, S. mansoni calpain (GenBank accession no. M74233). We have constructed and characterized expression of a recombinant baculovirus expressing the large subunit of S. mansoni calpain, Sm-p80. This recombinant Sm-p80 is recognized by IgA, IgM, IgG1, and IgG3 isotype antibodies found in S. mansoni-infected human sera and partially-purified recombinant Sm-p80 provided a 29-39% reduction in worm burden in immunized mice challenged with S. mansoni. Our data indicate that Sm-p80 may be a useful vaccine antigen for the reduction of the morbidity associated with S. mansoni infections of mammalian hosts.
The objective of this study was to assess the prophylactic efficacy of cefoxitin, ceftizoxime, and metronidazole-gentamicin in colorectal surgery. A double-blind, randomized prospective clinical trial design was used in a Canadian tertiary care teaching hospital. Patients were randomized to one of three treatment groups and received three doses of a study drug (30 min preoperative and 2 postoperative doses at 12 and 24 h). Cefoxitin and ceftizoxime were given as 1000-mg doses. Metronidazole-gentamicin was given as 500 mg of metronidazole plus 120 mg of gentamicin in a minibag. High-risk patients (bowel ischemia, diabetic, current steroid use, etc.) received 10 postoperative doses. Patients with infections, prior antibiotics, or study drug allergies were excluded. Over 30 months, 153 patients were enrolled. Thirty-one patients were excluded for protocol violations. Of the 122 evaluable patients (38 ceftizoxime, 45 metronidazole-gentamicin, 39 cefoxitin), there was no difference across groups regarding sex, age, weight, preoperative Apache II score, and prior history of bowel surgery. Groups were equivalent regarding surgeon, nursing unit, high-risk status (six ceftizoxime, seven metronidazole-gentamicin, seven cefoxitin), bowel preparation, and procedure (including blood loss, drains, organ injury, intraoperative complications). Clinically significant infection requiring systemic antibiotics (7-day hospital and 30-day follow-up) was identified in 0% of ceftizoxime, 15% of metronidazole-gentamicin, and 26% of cefoxitin receiving patients (p = 0.005). Mean ASEPSIS scores for each group were 2.3 (range 0-15) for ceftizoxime, 9.2 (range 0-45) for metronidazole-gentamicin, and 10.4 (range 0-75) for cefoxitin (p = 0.01). Ceftizoxime patients tended to have a shorter total hospital stay (12.2 days versus 19.7 days for cefoxitin versus 13.9 days for metronidazole-gentamicin; p = 0.04), although the procedure to discharge interval was not significantly different (p = 0.09). There was no difference in clinical outcome according to risk status. Anaerobic bacteria were observed more commonly in the ceftizoxime and cefoxitin groups, whereas enteric Gram-negative aerobes were observed most often in the metronidazole-gentamicin group. The study regimens were generally well tolerated. Drug costs were equivalent between ceftizoxime and cefoxitin and lowest with the metronidazole-gentamicin regimen. Ceftizoxime appears to be more effective for the prevention of infection in colorectal surgery than either cefoxitin or metronidazole-gentamicin in the dosage regimens studied.
PURPOSE: To determine the incidence of particulate embolization after carotid endarterectomy (CEA), the effect of dextran-40 infusion in patients with sustained postoperative embolization, and the impact of transcranial Doppler (TCD) monitoring plus adjuvant dextran therapy on the rate of postoperative carotid thrombosis. METHODS: Prospective study in 100 patients who underwent CEA with 6-hour postoperative monitoring using a TCD that was modified to allow automatic, intermittent recording from the ipsilateral middle cerebral artery waveform (10 minute sample every 30 minutes). An incremental dextran-40 infusion was commenced if 25 or more emboli were detected in any 10-minute period. RESULTS: Overall, 48% of patients had one or more emboli detected in the postoperative period, particularly in the first 2 hours. However, sustained embolization that required Dextran therapy developed in only five patients. In each case, the rate of embolization rapidly diminished. CONCLUSIONS: A small proportion of patients have sustained embolization after CEA, which in previous studies has been shown to be highly predictive of thrombotic stroke. Intervention with dextran reduced and subsequently stopped all the emboli in those in whom it was used and contributed to a 0% perioperative morbidity and mortality rate in this series.
PURPOSE: Endovascular aneurysm repair has been advocated as a "minimally invasive" alternative to conventional aneurysm surgery. However, because of manipulation within the aneurysm sac, endovascular techniques may result in massive microembolization. METHODS: In this study lower limb microemboli were quantified in 29 patients undergoing conventional (11 straight and 7 bifurcated grafts) and endovascular aneurysm repair (8 aortoiliac, 1 straight, and 2 bifurcated grafts) by insonation of the superficial femoral artery with a 2 MHz Doppler probe. Emboli were detected as high-intensity, short-duration signals on the background Doppler trace. Differentiation of gaseous emboli from particulate emboli was achieved by calculation of the sample volume length (emboli velocity x duration = sample volume length) for each embolus (N = 4927). Previous experiments had determined that a sample volume length < 1.4 cm represented particulate embolization. RESULTS: The number of gaseous, particulate, and total emboli were significantly greater in the endovascular group compared with the conventional group (p < 0.05). CONCLUSIONS: These data demonstrate that peripheral microembolization is significantly higher during endovascular aneurysm repair than during conventional surgery. Methods to reduce embolization must be developed before endovascular aortic surgery is widely adopted.
Burkholderia cepacia isolates from patients with cystic fibrosis (CF) attending five CF centers were studied for relatedness by cellular fatty acid methyl esters (FAME) and by chromosomal DNA restriction analysis. Twenty-eight of 32 (87.5%) isolates tested were grouped in cluster group 1 based on their FAME profiles. DNA analysis revealed that 29 of 32 (90.6%) B. cepacia isolates from five CF centers had one closely related DNA pattern. To examine strain variation over a time period, FAME profiles and DNA patterns of isolates from serial cultures on seven patients from center D were studied. For four patients, all serial B. cepacia isolates belonged to a single FAME cluster group; for the remaining three patients, all serial isolates belonged to any two of the four cluster groups. On serial culture isolates, a single DNA pattern (pattern A) was found in 31 of 32 isolates demonstrating a close genetic relatedness. These data corroborate the observations that the majority of patients colonised with B. cepacia in a CF center harbor strains genetically closely related as determined by FAME profiles and DNA patterns.
Brachyury, or T, is the founder member of a family of transcription factors that share the so-called T-box-a 200 amino acid DNA-binding domain. Recent work has addressed the regulation of Brachyury expression and its function in the embryo. New T-box family members have been found in vertebrate and invertebrate embryos and the importance of this gene family is illustrated by the discovery that mutations in human TBX5 are responsible for Holt-Oram syndrome, which is characterised by abnormalities in heart and forelimb development.
Introduced are articles from the Berlin Aging Study (BASE) that collectively illustrate systemic-wholistic approaches to psychological functioning in old age. A systemic-wholistic perspective aims to elucidate structural and functional interdependencies between domains and to provide an integrative account of individual functioning. The special features of BASE (age range, 70-105 years; heterogeneous sample stratified by age and gender; and multidisciplinary data collection) are suited to this purpose. This article outlines the design of BASE, describes the cross-sectional sample (N = 516: 258 men and 258 women), and reports sample selectivity analyses on 25 criterion variables in which the Pearson-Lawley selection formulas were used. Although the BASE sample is positively biased, it is not restricted in heterogeneity and does not exhibit major differences in patterns of covariation among variables. This finding supports the use of BASE data for the intended systemic-wholistic analyses.
Cluster analysis was applied to 12 measures of intellectual, personality, self-related, and social functioning collected in the 1st cross-sectional wave of the Berlin Aging Study (BASE; N = 516). Central questions concerned the number, profile desirability (functional status), and the membership of the subgroups obtained. Of the 9 subgroups extracted, 4 reflected different patterns of desirable functioning (47% of the sample), and 5 reflected less desirable functioning (53%). Relative risk of a less desirable profile was 2.5 times higher for the oldest old (85-103 years) than for people between the ages of 70-84 years and was 1.25 times higher for women compared with men. Relationships with education, health, and mortality suggested underlying systemic differences. Consistent with theoretical propositions about a "4th age" and the incomplete architecture of life span development (P.B. Baltes, 1997) the oldest old appear to have a distinct and less desirable psychological profile.
This study assesses the effect of adding continuous-infusion fluorouracil to palliative thoracic radiation therapy (RT) on the rate and duration of symptom relief in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred eligible patients with NSCLC were randomized to receive either 20 Gy in five daily fractions as palliation for intrathoracic disease or the same RT with concurrent continuous infusion of 1 g m(-2) day(-1) fluorouracil for 5 days. Survival, response and rates of symptom relief in the two groups were compared according to treatment intent, and toxicities were compared according to treatment received. The overall response rate was higher in patients randomized to the combination (29%) than in patients randomized to RT alone (16%) (P = 0.035). However, there were no significant differences between the treatment arms in terms of overall or progression-free survival or in palliation of symptoms. Patients treated with RT plus fluorouracil had significantly more acute toxicity, including nausea and vomiting (P = 0.01), oesophagitis (P = 0.0003), stomatitis (P = 0.0005) and skin reaction (P = 0.003). This study suggests for the first time an interaction between RT and infusional fluorouracil in NSCLC. Although RT plus fluorouracil resulted in a significantly higher response rate than achieved with RT alone, this did not translate into more effective palliation. Because the combination produced significantly more toxicity than RT alone, it is not recommended for the palliative treatment of NSCLC. Nevertheless, these results suggest that opportunities may exist for exploitation of the observed enhancement of antitumour effect in the setting of high-dose radical RT for NSCLC.
Monocytes/macrophages and pro-inflammatory cytokines such as interleukin (IL)-1 are important in the pathogenesis of acute glomerulonephritis. The aim of this study was to examine whether IL-4, a cytokine with anti-inflammatory activity, could modulate glomerular inflammation and reduce injury in vivo. Treatment with recombinant rat IL-4 in a model of anti-glomerular basement membrane (GBM) antibody mediated glomerulonephritis in rats reduced glomerular injury. Albuminuria was less (73% less at day 4) and a lower proportion of glomeruli had capillary thrombi (79% less at day 4). In IL-4 treated rats, there was a moderate reduction in the number of macrophages in the glomeruli and also suppression of pro-inflammatory activities of the macrophages. Northern blot analysis of glomerular RNA showed that treatment with IL-4 up-regulated mRNA levels of type II IL-1 receptor (IL-1RTII). IL-1RTII, also known as IL-1 decoy receptor, may act as a decoy molecule to inhibit the effect of IL-1 beta. To our knowledge, this is the first demonstration of (i) recombinant IL-4 reducing glomerular inflammation in vivo and (ii) a treatment that increases IL-1RTII expression in association with reduction of tissue injury in vivo.
Interleukin-6 (IL-6) has been reported to have pro- and anti-inflammatory effects. It has also been shown to cause mesangial cell proliferation in vitro and has been suggested as a mediator of injury in proliferative nephritis. We have assessed the effects of continuous infusion of human recombinant (hr) IL-6, by osmotic minipump, on the degree of glomerular injury, and on glomerular and interstitial cell proliferation, in the accelerated autologous phase of nephrotoxic nephritis. Two groups of rats were pre-immunized with 1 mg of normal rabbit IgG in Freund's complete adjuvant. One week later, nephritis was induced by an intravenous injection of 1 ml of rabbit nephrotoxic serum. One day before the induction of nephritis, group 1 (N = 9) was subcutaneously implanted with osmotic minipumps filled with 50 micrograms (200 microliters) of IL-6 (equivalent to a dose of 6 micrograms/day), while in group 2 (N = 11) the minipumps were filled with 200 microliters of normal saline. In group 3 (N = 6) normal rats were infused with 50 micrograms of IL-6 alone. The rats were killed seven days after implantation of minipumps. The administered hrIL-6 was detectable in the circulation within the pathophysiological range, and induced a hepatic acute phase response, as assessed by alpha 2-macroglobulin levels. Continuous treatment with IL-6 resulted in a significant reduction in albuminuria (from 195 +/- 37 mg/20 hr to 60 +/- 15 mg/20 hr on day 1, and from 494 +/- 52 mg/20 hr to 238 +/- 30 mg/20 hr on day 7, P < 0.002) and in the prevalence of glomerular capillary thrombosis (from 19 +/- 3% to 5 +/- 1%, P < 0.002). There was also a reduction in macrophage infiltration (ED1 + ve cells from 524 +/- 34 to 466 +/- 14 per 50 glomeruli, P < 0.02) and activation (ED3 + ve cells from 106 +/- 13 to 42 +/- 5 per 50 glomeruli, P < 0.002). Immunohistology showed fewer interstitial Ia + ve cells (OX3 and OX4) in the IL-6 treated group. Similar results were obtained in a second set of experiments in which the IL-6 treatment was extended until day 14. Kidney sections taken from nephritic rats infused with IL-6 showed no increase in glomerular or interstitial cell proliferation when stained with antibodies to proliferating cell nuclear antigen. There was no difference in the deposition of rabbit IgG or rat IgG along the glomerular basement membrane (GBM), and the titer of rat anti-rabbit IgG was similar in the IL-6 and control treated rats. Infusion of IL-6 alone in normal rats had no functional or pathological effects. In conclusion, these results show that IL-6 has powerful anti-inflammatory effects in a rat model of anti-GBM nephritis, and does not induce mesangial cell proliferation in vivo.