Biomedical subjects
Publications and source records attributed to K Schulze.
Fibronectin-binding protein I (SfbI) of Streptococcus pyogenes binds to mouse immunoglobulin G (IgG) but not to IgA or IgM in a nonimmune fashion. The fibronectin-binding domains of SfbI were responsible for this activity, which was targeted to the IgG F(ab')(2) fragment. SfbI also binds to B cells but not to CD4(+) or CD8(+) lymphocytes.
PURPOSE: The objective of this study is to describe the use and outcome of radical radiotherapy for bladder cancer in the province of Ontario, Canada, between 1982 and 1994. METHODS: Electronic records of invasive bladder cancer (ICD code 188) from the Ontario Cancer Registry were linked to surgical records from all Ontario hospitals and radiotherapy (RT) records from all Ontario cancer centers. We identified cases receiving radical RT by selecting RT records containing "bladder" or "pelvis" anatomic region codes and a radical or curative intent code (or dose >39.5 Gy if intent missing). We identified cases receiving salvage total cystectomy by selecting total cystectomy procedure codes occurring at any time beyond 4 months from the start of radical RT. We used life table methods to compute the following: the time from diagnosis to radical RT, the time from radical RT to salvage cystectomy, overall and cause-specific survival from radical radiotherapy to death, and overall and cause-specific survival from salvage cystectomy to death. We modeled the factors associated with time to death, time to cystectomy conditional on survival, and time to cystectomy or death, whichever came first, using Cox proportional hazards regression. RESULTS: From the 20,906 new cases of bladder cancer diagnosed in Ontario from 1982 to 1994, we identified 1,372 cases treated by radical radiotherapy (78% male, 22% female; mean age 69.8 years). The median interval to start of radical RT from diagnosis was 13.4 weeks. Ninety-three percent of patients were treated on high-energy linacs, and the most common dose/fractionation scheme was 60 Gy/30 (31% of cases). Five-year survival rates were as follows: bladder cancer cause-specific, 41%; overall, 28%; cystectomy-free, 25%; bladder cancer cause-specific following salvage cystectomy, 36%; overall following salvage cystectomy, 28%. Factors associated with a higher risk of death and a poorer cystectomy-free survival were histology (squamous or nonpapillary transitional cell carcinoma [TCC]) and advanced age. CONCLUSION: This population-based study confirms previous institutional studies and clinical trials and shows that radical RT has a curative role in the management of invasive bladder cancer and allows about one-quarter of patients receiving radiotherapy to survive 5 years while retaining the bladder. Salvage cystectomy following RT provides a chance of cure at the time of bladder relapse.
PURPOSE: The objectives of this study are to describe the utilization of surgery and of radiotherapy in the treatment of newly diagnosed rectal cancer in Ontario between 1982 and 1994, and to describe the probability of permanent colostomy at any time after the diagnosis of rectal cancer, as an outcome of the treatment of newly diagnosed rectal cancer. METHODS AND MATERIALS: Electronic records of rectal cancer (International Classification of Diseases code 154) from the Ontario Cancer Registry (n = 18,695, excluding squamous, basaloid, cloacogenic, and carcinoid histology) were linked to surgical records from all Ontario hospitals, and radiotherapy (RT) records from Ontario cancer centers. Procedures occurring within 4 months of diagnosis, or within 4 months of another procedure for rectal cancer, were considered part of initial treatment. Multivariate analyses controlled for age, sex, and year of diagnosis. RESULTS: Resection plus permanent colostomy was performed in 33.1% of cases, whereas local excision or resection without permanent colostomy was performed in 38.2%. Multivariate logistic regression demonstrated higher odds ratios (OR) for resection plus permanent colostomy in all regions of Ontario relative to Toronto. The OR for postoperative RT following local excision or resection without permanent colostomy varied among the regions relative to Toronto (e.g., OR Ottawa = 0.59, OR Hamilton = 0.76, OR London = 1.25). The relative risk (RR) of colostomy conditional upon survival within 5 years from diagnosis varied among regions relative to Toronto (e.g., RR Ottawa = 1.21, RR Hamilton = 1.20). CONCLUSIONS: There is regional variation in the utilization of resection with permanent colostomy, and in the utilization of postoperative RT among cases not undergoing permanent colostomy. Regions with higher initial rates of resection plus permanent colostomy continue to experience higher probability of permanent colostomy 5 years after diagnosis of rectal cancer. Higher initial rates of permanent colostomy may be malleable to interventions aimed at improving overall outcomes.
PURPOSE: To compare the risk of mortality from myocardial infarction (MI) after left-sided postlumpectomy radiotherapy (RT) to the risk after right-sided postlumpectomy RT. METHODS: We conducted a population-based cohort study of cases of invasive female breast cancer in Ontario, diagnosed between January 1, 1982 and December 31, 1987 (n = 25,570). Records of the Ontario Cancer Registry (OCR) were linked to hospital procedure and discharge abstracts and to RT records from Ontario cancer centers. A case was labelled as lumpectomy if this was the maximum breast surgery within 4 months of diagnosis. Postlumpectomy RT occurred up to 1 year postdiagnosis. Laterality was assigned from the laterality descriptor of the RT records. A case was labelled as having had a fatal MI if ICD code 410 (myocardial infarction) was recorded as the cause of death in the OCR. We used logistic regression to compare the likelihood of utilization of: 1. Dose per fraction > 2.00 Gy; 2. cobalt vs. linac; and 3. boost RT. We used life table analysis and the log rank test comparing the time to fatal MI from diagnosis of breast cancer between women who received left-sided postlumpectomy RT and women who received right-sided. We used Cox proportional hazards models to study the relative risk for left-sided cases overall, and stratified by age, RT characteristics, and among conditional survival cohorts. RESULTS: Postlumpectomy RT was received by 1,555 left-sided and 1,451 right-sided cases. With follow-up to December 31, 1995, 2% of women with left-sided RT had a fatal MI compared to 1% of women with right-sided RT. Comparison of the time to failure between women who had left-sided RT and women who had right-sided RT showed the left-sided RT group to be associated with a higher risk of fatal MI (p = 0.02). Adjusting for age at diagnosis, the relative risk for fatal MI with left-sided postlumpectomy RT was 2.10 (1.11, 3.95). CONCLUSION: Among women who received postlumpectomy RT for breast cancer in Ontario between 1982-1987, left-sided postlumpectomy RT was associated with a higher risk of fatal MI compared to right-sided.
OBJECTIVE: The adenine nucleotide translocator (ANT) of the inner mitochondrial membrane is an autoantigen in myocarditis and in dilated cardiomyopathy. Clinical and experimental studies showed that specific autoantibodies inhibit the transmembrane nucleotide transport. In isolated hearts of guinea pigs immunized with the ANT, energy metabolism is disturbed. This metabolic disorder is related to functionally active specific antibodies and to a reduced heart function. This study tests whether similar immunological, metabolical and functional responses also occur in experimental virus myocarditis. METHODS AND RESULTS: Experimental virus myocarditis was induced in A.SW/SnJ-mice by Coxsackie B3 virus infection. Specific antibodies against the ANT were detected by Western Blot in 14 out of 19 infected animals. In the isolated perfused hearts of five of these 14 mice cytosolic and mitochondrial ATP/ADP-ratios, determined by nonaqueous fractionation, were significantly altered, signalling a reduced ANT function [cytosolic ATP/ADP: 59 +/- 18 vs. 136 +/- 20 (controls), mitochondrial ATP/ADP: 4.2 +/- 1.0 vs. 1.1 +/- 0.3], all P < 0.05. Also, left ventricular pressure [43 +/- 9 vs. 78 +/- 6 mmHg (noninfected controls)], rate-pressure product (15.8 +/- 3.2 vs. 30.5 +/- 3.0 mmHg/min/1000), dp/dt (2410 +/- 222 vs. 3250 +/- 118 mmHg/s), and oxygen consumption (4.7 +/- 0.9 vs. 7.3 +/- 0.7 mumol/g/min), all P < 0.05, were lowered. CONCLUSION: The data support the hypothesis that a virus infection alters cardiac energy metabolism and function by an antibody-mediated modulation of the function of the ANT.
PURPOSE: A method of achieving successful completion of endoluminal repair of an abdominal aortic aneurysm (AAA) in the presence of intraoperative iatrogenic rupture of the aneurysm is reported. METHODS: An 83-year-old woman with an AAA that was 7 cm in diameter was treated electively by means of endoluminal repair with a Vanguard bifurcated prosthesis (Boston Scientific, Natick, Mass). No difficulty was experienced with the introduction of the delivery catheter, despite extreme angulation in the aneurysm. An acute episode of hypotension prompted an aortogram to be performed. Extravasation of contrast outside the aneurysm sac was demonstrated. The balloon on the delivery catheter was immediately advanced to the suprarenal aorta and inflated. Hypotension was reversed, and hemodynamic stability was restored, thus enabling deployment of the prosthesis to proceed and the repair to be completed by means of the endoluminal method. RESULTS: The patient's blood pressure remained stable after deflation of the balloon, allowing a postprocedure aortogram to be performed. Exclusion of the aneurysm sac was demonstrated. Exclusion of the aneurysm sac from the circulation and a large retroperitoneal hematoma were confirmed by means of a postoperative contrast computed tomography scan. Convalescence was complicated by acute renal failure, pneumonia, and prolonged ileus. The patient remained well and active at the follow-up examination 6 months after operation. CONCLUSION: Iatrogenic perforation of an AAA during endoluminal repair may be treated by endovascular means and does not necessarily require conversion to open repair, although this may be the safest option.
The adenine nucleotide translocator (ANT) is an autoantigen in myocarditis and dilated cardiomyopathy. Carrier-specific antibodies impair myocardial energy metabolism and heart function. They cross-react with a myolemmal calcium channel and alter calcium fluxes in isolated myocytes. To test whether antibodies against the ANT can alter calcium homeostasis in intact hearts, guinea pigs were immunized with the carrier protein and their isolated hearts loaded with the intracellular calcium indicator INDO-1. The diastolic and systolic ratios of fluorescence signals at 410 nm and 510 nm (emission wavelengths of the calcium-bound and calcium-free indicator), 'd-s410/510', were measured by excitation at 364 nm. This index of the transient calcium concentration associated with the contraction cycle correlated with the external heart work (EHW) in non-immunized controls. EHW of immunized animals was lower (76 +/- 62 vs 153 +/- 47 mJ/g/min in controls, p < 0.005) and the amplitude of d-s410/510 was elevated (27.6 +/- 4.1% of the average ratio of the whole heart cycle vs 21.7 +/- 1.2% in controls, p < 0.005) and essentially independent of EHW. Isoproterenol stimulation increased EHW in all hearts but d-s410/510 was hightened in control hearts, only. Thus, a disorder between cytosolic calcium transients and work was recorded in hearts from guinea pigs immunized with the ANT. It may contribute to an immunopathic mechanism of heart failure subsequent to myocarditis.
Laminar profiles of rises in [K+]o and slow field potentials induced by alvear stimulation were recorded in area CA1 of hippocampal slices from control and pilocarpine-treated rats in absence and presence of Ba2+. In control animals, Ba2+ augmented rises in [K+]o in stratum pyramidale (SP) as well as in stratum radiatum (SR). In pilocarpine-treated animals an augmentation of rises in [K+]o was restricted to SP and its immediate vicinity. Moreover, the effect of Ba2+ in SP was small or missing in eight out of 15 slices of pilocarpine-treated animals. In these slices laminar profiles of rises in [K+]o were not affected by Ba2+. It is suggested that spatial K+-buffering is reduced in area CA1 of epileptic animals.
HISTORY AND CLINICAL FINDINGS: Two days before admission a 22-year-old woman developed general fatigue, nausea, headache and retrosternal pain. Physical examination was unremarkable. INVESTIGATIONS: Erythrocyte sedimentation rate was increased to 20/48, C-reactive protein to 3.3 mg/dl, and there was evidence of myocardial damage (creatine kinase 609 U/l, creatine kinase-MB 42 U/l, troponine T 8.39 ng/ml); ST-segment elevations in I, II, III, aVF and V-V6 of the ECG. Echocardiography revealed clearly thickened myocardium, moderate but haemodynamically not significant pericardial effusion, as well as impaired left ventricular function. Antimyosin scintigraphy was very abnormal. Cardiac catheterization confirmed the left ventricular dysfunction, rise of left ventricular enddiastolic pressure to 17 mm Hg, and a markedly reduced cardiac output of 2.4 l/min. Myocardial biopsy showed severe myocarditis with marked myocytolysis and considerable lymphocytic infiltrations. Enteroviral RNA was demonstrated in the myocardium by polymerase chain reaction. TREATMENT AND COURSE: The haemodynamics became normal within only 3 days. Myocardial biopsy after 6 months was unremarkable histologically and immunohistologically, and left ventricular function was also normal. However, while after a further 12 months myocardial biopsy remained normal and no virus was demonstrated, there was definite, though moderate, impairment in left ventricular function, indicating a dilated cardiomyopathy. INTERPRETATION: Even when histological and immunohistological evidence of healing of an acute viral myocarditis has been achieved, with complete normalization of left ventricular function, a dilated cardiomyopathy may subsequently develop. The pathophysiological mechanism of this occurrence remains unknown.
We examined the association among elevations in acute phase proteins, reported illness, and hyporetinolemia in 234 pregnant Nepali women with (cases) and without (controls) night blindness. Serum alpha1-acid glycoprotein (AGP) and C-reactive protein (CRP) were inversely associated with serum retinol concentrations. Elevations in the concentration of CRP in both cases and controls and of AGP in cases were associated with significant reductions (approximately 0.2-0.3 micromol/L) in serum retinol. The risk of a low serum retinol concentration (< 0.7 micromol/L) with elevated AGP (> or = 1 g/L) and CRP (> or = 5 mg/L) concentrations was significantly higher in cases (odds ratios = 8.6 and 4.3, respectively) than in controls (odd ratios = 1.9 and 2.4, respectively). A 7-d morbidity history indicated that cases were significantly more likely than controls to report symptoms of infections of the urinary, reproductive, and gastrointestinal tracts. Only a few of these symptoms (diarrhea, nausea, and vomiting) were significantly associated with low serum retinol concentrations. Illness in the previous week and elevated CRP or AGP concentrations were synergistically associated with lower serum retinol. For example, the reduction in serum retinol in women with diarrhea and elevated AGP was 0.54 micromol/L, compared with a reduction of 0.03 micromol/L in those with diarrhea only. AGP and CRP may provide useful information about the effect of reported illness on hyporetinolemia in pregnancy. Infection-related hyporetinolemia may predispose women to night blindness during pregnancy in Nepal.
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Enterohemorrhagic Escherichia coli (EHEC) exhibits a pattern of localized adherence to host cells, with the formation of microcolonies, and induces a specific histopathological phenotype collectively known as the attaching and effacing lesion. The genes encoding the products responsible for this phenotype are located on a 35-kb pathogenicity island designated the locus of enterocyte effacement, which is also shared by enteropathogenic E. coli. We have identified an open reading frame (ORF) which is located upstream of the espA, espB, and espD genes on the complementary strand and which exhibits high homology to the genes spiB from Salmonella, yscD from Yersinia, and pscD from Pseudomonas. Localization studies showed that the encoded product is present in the cytoplasmic and inner membrane fractions of EHEC. The construction and characterization of a recombinant clone containing an in-frame deletion of this ORF demonstrated that the encoded product is a putative member of a type III system required for protein secretion. Disruption of this ORF, designated pas (protein associated with secretion), abolished the secretion of Esp proteins. The mutant adhered only poorly and lost its capacities to trigger attaching and effacing activity and to invade HeLa cells. These results demonstrate that Pas is a virulence-associated factor that plays an essential role in EHEC pathogenesis.
PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.
OBJECTIVE: To describe the variation in the use of radiotherapy (RT) in women in Ontario within 1 year of diagnosis of breast cancer, from 1982 to 1991, and to identify factors associated with these variations. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario. POPULATION: All women registered by the Ontario Cancer Registry (OCR) with a diagnosis of invasive breast cancer between Jan. 1, 1982, and Dec. 31, 1991. INTERVENTIONS: RT to any anatomic site within 1 year of the diagnosis of breast cancer. OUTCOME MEASURES: Odds of receiving RT within 1 year of diagnosis (from RT files from all radiotherapy departments in Ontario) associated with year and with geographic, age-related and socioeconomic factors. RESULTS: Use of RT within 1 year of diagnosis increased from 21.1% (95% confidence interval [CI] 19.8-22.4) in 1982 to 44.7% (95% CI 43.4-46.0) in 1991 (p < 0.0001). Among the regions of Ontario, the use of RT varied from 24.5% (95% CI 23.5-25.6) to 44.4% (95% CI 43.0-45.9) (p < 0.0001). Increasing age was associated with decreasing likelihood of receiving RT (test for trend p < 0.0001), as was decreasing income (test for trend p < 0.0001). CONCLUSIONS: The use of RT within 1 year of the diagnosis of breast cancer in women in Ontario varies by region, age and income. Despite universal and comprehensive health insurance coverage, women with breast cancer in some populous regions of Ontario were less likely to receive RT within 1 year of their diagnosis than women in other populous regions.
Three adenine nucleotide translocase isoforms (ANT1, ANT2 and ANT3) are coded by different genes. The relative amounts of the three ANT isoform mRNAs were determined in detail in various human tissues. ANT isoforms were co-expressed in all tested tissues revealing tissue-specific transcription patterns. The highest ANT1 mRNA proportions were found in terminally differentiated tissues like skeletal muscle, heart and brain, whereas ANT2 was mainly expressed in tissues capable of proliferation and regeneration as in the kidneys, spleen, liver, fibroblasts and lymphocytes. The ANT3 mRNA proportion was not prominently expressed in any of the tissues tested. In conclusion, tissue-specific expression of ANT isoforms is strongly related to the state of cellular differentiation.
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Patients with severe head injury run a high risk of developing secondary cerebral defects. Various methods have so far been described which vary in their continuity, invasiveness and technical aspects for the early detection and treatment of complications. Within this group of patients Jehovah's witnesses pose a particular problem due to their restriction concerning therapeutical possibilities. That may mean an additional danger to the cerebral O2-delivery. This case report highlights on the value of continuous, non-invasive cerebral O2-saturation measurement and its combination with the fiberoptical monitoring of mixed venous O2-saturation. It has been possible to recognize episodes of imbalance between O2-delivery and its demand owing to a variety of causes. Other measured parameters were unable to reliably detect the development of critical complications. Further latrogenic loss of blood by laboratory tests was significantly reduced. Despite partially insufficient circulation and anemia with a hemoglobin value of 49 g/l we were able to discharge the patient from ICU without recognizable neurological sequelae.
Rapid adaptation of ATP formation and coronary flow is required when cardiac work is altered. Cardiac energy status was proposed to control both oxygen consumption (MVO2) and release of vasoactive adenosine (AR). To investigate the hypothesis of a linear relation between free AMP and AR, we employed 31P nuclear magnetic resonance (NMR) in a newly elaborated guinea pig heart performing pressure-volume work. Under basal conditions, MVO2 was 7.8 +/- 1.0 mumol.min-1.g-1, free AMP 297 +/- 189 nM and AR 226 +/- 179 pmol.min-1.g-1 (n = 29). Decreasing arterial PO2 by 50% reduced MVO2 and increased free AMP by 29%; however, AR rose threefold (n = 5). Doubling oxygen content of the perfusion medium (fluorocarbon emulsion) did not alter MVO2, free AMP, or AR (n = 6). When afterload was doubled, MVO2 increased (+45%) and AR decreased (-60%) despite no change in ADP or AMP (n = 6). Dobutamine increased MVO2 (+50%) and AMP (-98%); however, AR rose more than five times (n = 8). Switching substrates from glucose + pyruvate to glucose diminished MVO2 and increased ADP twofold and AMP fourfold, whereas AR remained constant (n = 6). Our findings demonstrate that cardiac energy status is also not the prime regulator of oxidative phosphorylation in the isolated heart. Changes in the oxygen supply-to-demand ratio induced a rise in AR that exceeded by far the increase in free AMP. Thus, additional factors, possibly inhibition of adenosine kinase, influence the release of vasoactive adenosine.