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Biomedical subjects

E Busch

Publications and source records attributed to E Busch.

At least 37 records · Page 2Linked to original sources

Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York.

Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.

Adipose Tissue↗

Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat.

We report the technical details and validation of an improved rat model for thromboembolic stroke and rt-PA induced reperfusion, which closely resembles clinical embolic stroke. The middle cerebral artery (MCA) was proximally occluded by injection of twelve medium sized (1.5 x 0.35 mm), fibrin-rich autologous blood clots. On inspection, densely packed clot material was found at the ipsilateral MCA origin in all untreated animals. Autoradiographic rCBF measurements showed severe ischemic deficit throughout the ipsilateral MCA territory in untreated animals. The volume in which flow values fell below 30 ml/100 g per min was 54 +/- 14% of the hemispheric volume. In all rt-PA treated animals the proximal MCA was recanalised, and the volume with flow values below 30 ml/100 g per min was reduced to 29 +/- 17%. Histological findings paralleled the spatial spread of the CBF deficit. The rat model presented is well-suited for investigations of the specific pathophysiology of thromboembolic stroke. Furthermore it allows detailed studies of thrombolytically induced reperfusion, beyond the question of successful recanalisation.

Animals↗

Blood-brain barrier disturbances after rt-PA treatment of thromboembolic stroke in the rat.

We studied the effects of rt-PA (recombinant tissue type-plasminogen activator) treatment on the blood-brain barrier (BBB) after thromboembolic stroke in rat. New MRI methods of diffusion and perfusion imaging to observe the hemodynamic and biophysical effects of thrombolysis were combined with methods for assessment of BBB disturbances. In untreated animals clot embolism produced a rapid drop in MRI perfusion values and the ADC (apparent diffusion coefficient), with subsequent infarction. BBB disturbances, visualised as extravasation of serum proteins on cryostat sections, were manifest in nearly all animals in the borderzone of infarcts. In animals treated with rt-PA 15 min after clot embolism thrombolysis resulted in reperfusion of affected brain regions with subsequent improvement of ADC values. Final lesion size on ADC maps was reduced by 36% relative to untreated animals. However, BBB disturbances were not improved after treatment. To the contrary, rt-PA treated animals showed further regions with serum protein extravasation in the infarcted territories and in distant non-ischemic brain regions. MR imaging with the BBB tracer GdDTPA showed more pronounced and widespread contrast enhancement in the rt-PA treated than in the untreated group. Increased blood-brain barrier disturbances have to be taken into account even when thrombolytic therapy is started very early after the onset of stroke.

Animals↗

Inhibition of nonselective cation channels reduces focal ischemic injury of rat brain.

The effect of the novel inhibitor of receptor-activated and calcium store-operated nonselective cation channels, (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma 1)-2-phenyl-N, N-di-[2(2,3,4-trimethoxyphenyl) ethyl]acetamide (LOE 908 MS), on focal cerebral ischemia was studied in halothane-anesthetized rats submitted to permanent suture occlusion of the right middle cerebral artery (MCA). The treated group (n = 7) received subcutaneous injections of 30 mg/kg LOE 908 MS (in 1 ml saline) 10 min after vascular occlusion and again after 3 h. The untreated group (n = 11) was injected subcutaneously with 1 ml saline at the same times. Evolution of infarct was monitored by electrophysiological recording of EEG and cortical steady potential and by diffusion-weighted magnetic resonance imaging during the initial 6 h of vascular occlusion. The hemodynamic, biochemical, and morphological changes were studied after 6 h by combining autoradiographic measurement of blood flow with histological stainings and pictorial measurements of ATP, glucose, and tissue pH. In the untreated animals, the ischemic lesion volume [defined as the region in which the apparent diffusion coefficient (ADC) of water declined to below 80% of control] steadily increased by approximately 50% during the initial 6 h of vascular occlusion relative to the first set of data 10 min postocclusion. In the treated animals, in contrast, the ADC lesion volume declined by approximately 20% during the same interval. Treatment also led to a significant reduction in the number of periinfarct depolarizations. After 6 h of vascular occlusion, blood flow was significantly higher in the treated animals, and the volume of ATP-depleted and morphologically injured tissue representing the infarct core was 60-70% smaller. The volume of severely acidic tissue, in contrast, did not differ, indicating that LOE 908 MS does not reduce the size of ischemic penumbra. These findings demonstrate that postocclusion treatment of permanent focal ischemia with LOE 908 MS delays the expansion of the infarct core into the penumbra for a duration of at least 6 h and therefore substantially prolongs the window of opportunity for the reversal of the ischemic impact in the peripheral parts of the evolving infarct.

Acetamides↗

Thread occlusion but not electrocoagulation of the middle cerebral artery causes hypothalamic damage with subsequent hyperthermia.

Moderate changes in body temperature can influence the outcome of cerebral ischemic insults and the effect of drugs. Body temperature was measured continuously for 24 hours in rats subjected to permanent occlusion of the middle cerebral artery (MCA) by either coagulation or thread insertion, and the results correlated with the histology of the hypothalamus. The body temperature did not change after MCA occlusion by coagulation and the hypothalamus was intact in all rats. In contrast, the body temperature rapidly increased from about 38 degrees C to more than 39.5 degrees C after MCA occlusion using intraluminal thread, and hyperthermia continued for at least 6 hours in all rats. Histological evaluation revealed neuronal damage in the preoptic area of the hypothalamus in all rats undergoing thread occlusion. Long duration hyperthermia must be prevented after permanent MCA occlusion when the intraluminal thread occlusion model is used in chronic experiments.

Animals↗

Oligoclonality of CD8+ T cells in breast cancer patients.

Substantial evidence has suggested that T cells play an important role in antitumor immunity. T cells with cytotoxic activity against tumors have been isolated from in vitro culture of tumor-infiltrated lymphocytes of cancer patients. In addition, clonal expansions of T cells have been identified in lesions of tumors by using a PCR-based CDR3 analysis of T cell receptors (TCR). Since the CDR3 region of the T cell receptor directly interacts with the antigen-MHC complex and is thus highly polymorphic, a dominant CDR3 length in a particular TCR V beta population will indicate the clonal expansion of a specific T cell clone. Utilizing this technique, we have analyzed the T cell repertoire in lymph nodes (LNs) and peripheral blood of 20 breast cancer patients. Our results show that in most cases, peripheral blood mononuclear cells (PB-MCs) and LN express dominant CD8+ T cell clones in different V beta gene families, and the number of dominant clones is higher in PBMC than in the LN. Furthermore, in 7 out of 16 patients' lymph nodes, there is a dominant V beta 18 T cell clonal expansion in the CD8+ T cell subset. The frequency of an oligoclonal expansion of V beta 18 CD8+ T cells in non-breast cancer lymph nodes is 1 out of 9, but no obvious motif in the CDR3 region of V beta 18 TCR can be identified. The prevalence of the clonal dominance found in breast cancer is discussed in the context of a possible tumor-related antigen stimulation.

Adult↗

Patterns of breast cancer care in the elderly.

BACKGROUND: The elderly represent a large proportion of the women with breast cancer. However, there is a lack of information regarding breast cancer care in the elderly. METHODS: A patient care evaluation survey for breast carcinoma was conducted by the Commission on Cancer of the American College of Surgeons for 1983 and 1990. Data were obtained from hospital tumor registries from all 50 states, Puerto Rico, and Canada. Information regarding presentation, diagnostics, staging, treatment, recurrence, and survival were analyzed. Comparisons were made between women 75 years and older and those younger than 75 years. RESULTS: Included were 17,029 diagnosed with breast carcinoma during 1983 and 24,004 diagnosed during 1990. In 1983 and 1990, 20.4% and 23.4% of women, respectively, were 75 years or older. Fewer cancers were detected mammographically and needle localized biopsies were performed less often in the elderly. There was no difference in tumor location or histology. Stage at diagnosis appeared more advanced in the elderly. Most women regardless of age, underwent modified radical mastectomy. Of the elderly who did undergo breast conserving surgery in 1983 and 1990, 72% and 39%, respectively, did not receive radiation therapy. No difference was found in the local recurrence rates between the elderly and younger groups. In the elderly, 20% of deaths occurred from causes other than breast cancer. Overall disease specific survival was worse in the elderly but, when analyzed by stage, was significantly different for only certain stages. CONCLUSIONS: There are several differences in the detection, diagnostic methods, stage at diagnosis, treatment approaches, and outcome of breast cancer in elderly women compared with younger women.

Age Factors↗

Ultrafast perfusion-weighted MRI of functional brain activation in rats during forepaw stimulation: comparison with T2 -weighted MRI.

A fast version of the arterial spin tagging technique for the detection of cerebral perfusion is presented. Based on adiabatic spin inversion in combination with snapshot FLASH imaging, our technique allows the recording of perfusion changes with a temporal resolution of about 3 s. Differences of cerebral perfusion dependent on the choice of anesthesia were observed in rat brain. Furthermore, with this arterial spin tagging method we demonstrated perfusion increases in the somatosensory cortex of anaesthetized rats during forepaw stimulation. Comparison of the activated areas in the T2 -weighted BOLD images and the perfusion-weighted images showed good spatial correspondence, but the sensitivity to the functional activation was more than ten times higher in the perfusion technique.

Anesthesia↗

Potassium-induced cortical spreading depressions during focal cerebral ischemia in rats: contribution to lesion growth assessed by diffusion-weighted NMR and biochemical imaging.

In focal ischemia of rats, the volume of ischemic lesion correlates with the number of peri-infarct depolarizations. To test the hypothesis that depolarizations accelerate infarct growth, we combined focal ischemia with externally evoked spreading depression (SD) waves. Ischemic brain infarcts were produced in halothane-anaesthetized rats by intraluminal thread occlusion of the middle cerebral artery (MCA). In one group of animals, repeated SDs were evoked at 15-min intervals by microinjections of potassium acetate into the frontal cortex. In another group, the spread of the potassium-evoked depolarizations was prevented by application of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801). The volume of ischemic lesion was monitored for 2 h by diffusion-weighted imaging (DWI) and correlated with electro-physiological recordings and biochemical imaging techniques. In untreated rats, each microinjection produced an SD wave and a stepwise rise of the volume and signal intensity of the DWI-visible cortical lesion. The volume of this lesion increased between 15 min and 2 h of MCA occlusion from 19 +/- 15% to 66 +/- 16% of ipsilateral cortex. In dizocilpine-treated animals, microinjections of potassium did not evoke SDs, nor did the volume and signal intensity of the DWI-visible cortical lesion change. At 15 min after MCA occlusion, the DWI-visible lesion was larger than in untreated animals-43 +/- 16% of the ipsilateral cortex; however, after 2 h, it increased only slightly further to 49 +/- 21%. Slower lesion growth in the absence of SDs was also reflected by the volume of ATP-depleted tissue, which, after 2 h of MCA occlusion, involved 26 +/- 12% of the ipsilateral cortex in treated and 49 +/- 9% in untreated animals (p < 0.01). These observations support the hypothesis that peri-infarct depolarizations accelerate cerebral infarct growth.

Animals↗

Functional restoration in chronic low back pain.

Conventional treatments have not slowed down the ever expanding low back pain (LBP) problem. Traditional treatment has most probably contributed to the growth of the problem. Therefore, in a search for new solutions, 'functional restoration' has been devised. In connection with chronic LBP the term has been associated with a full-day program lasting from 3 to 5 weeks. It includes multidisciplinary treatment of patients in groups with intensive physical and ergonomic training, psychological pain management, back school, as well as teaching in social/work related issues. The key concepts are 'acceptance of the pain', 'activity', 'self-responsibility', 'multidisciplinary' and 'quantitative functional evaluation (QFE)'. The latter is aimed so that the participants can feel the physical improvement, encouraging them to be able to go back to work, or at least to lead a more active life style. Several controlled studies suggest a lasting effect in terms of regaining their ability to work and improving pain behavior for a good part of disabled chronic LBP patients. However, it is noteworthy that randomized studies seemingly show poorer results than studies not employing randomized controls.

Ergonomics↗

Simultaneous recording of EEG, DC potential and diffusion-weighted NMR imaging during potassium induced cortical spreading depression in rats.

Electrophysiological recording during in vivo NMR imaging for correlation of electrophysiological events with changes in NMR parameters has, until now, not been satisfactory. Here we present a method that uses specially prepared calomel electrodes for the continuous monitoring of both cortical steady potential and EEG during in vivo NMR imaging studies of experimental animal models. In order to demonstrate the reliability of this approach we elicited single episodes of cortical spreading depression in rats by intracortical potassium acetate injection, using an intracerebral micropipette. During the passage of DC potential shifts and associated reduction in EEG amplitude, hyperintense regions, reflecting the progression of cortical spreading depression over the cortex, were visible in diffusion-weighted images of the rat brains. No susceptibility artifacts due to the electrodes and micropipette were visible in the NMR data. Thus, we have demonstrated under controlled experimental conditions, that electrophysiological recording with calomel electrodes can be performed simultaneously with diffusion-weighted NMR imaging. The described method enables further NMR investigations of phenomena which are detectable by electrophysiology.

Animals↗

Evolution of acute focal cerebral ischaemia in rats observed by localized 1H MRS, diffusion-weighted MRI, and electrophysiological monitoring.

Focal cerebral ischaemia was produced in 11 rats by permanent occlusion of the right middle cerebral artery (MCA) using a suture model modified to enable manipulation with the animals in situ in an NMR spectrometer. The development of the ischaemic insults and the resultant infarcts were observed for up to 6 h by localized 1H MRS and diffusion-weighted MRI while performing continuous monitoring of electroencephalogram and extracellular DC potential. The ischaemic areas were depicted as regions of hyperintensity in the diffusion-weighted images. Signals due to lactate became visible in the 1H spectra after MCA occlusion indicating the onset of anaerobic glycolysis. A depletion of N-acetylaspartate was seen in all animals post-occlusion. Transient or stepwise increases of lactate were observed to occur coincidentally with the events of spontaneous transient peri-infarct depolarization detected by the electrophysiological measurements. Expansion of the ischaemic area delineated in the diffusion-weighted images also accompanied peri-infarct depolarizations. These observations are consistent with transient peri-infarct depolarization playing a role in the growth of infarcts.

Acute Disease↗

Therapy for inflammatory breast cancer: impact of doxorubicin-based therapy.

BACKGROUND: Inflammatory breast cancer (IBC) carries an ominous prognosis. Before 1988, women with IBC at our institution were treated with neoadjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without vincristine and prednisone (CMF/VP). After 1988, women with IBC were treated with cyclophosphamide, doxorubicin, and 5-fluorouracil (FAC). This study compares these two regimens with regard to response and survival. METHODS: The records of all women presenting between January 1973 and December 1991 with a stage IIIB (T4d, any N, MO) breast cancer with proven dermal lymphatic invasion by tumor cells were reviewed retrospectively. RESULTS: The study comprised 38 women; 28 received CMF (22 CMF, 6 CMF/VP), and 10 received FAC. The overall response rate to induction chemotherapy in the CMF/VP group was 57% (40% PR, 17% CR), and 100% (60% PR, 40% CR) in the FAC group. The median overall survival for women receiving CMF/VP was 18 months compared with 30 months for women receiving FAC (p = 0.02). The median disease-free survivals for the CMF/VP and FAC groups were 6 and 24 months, respectively (p < 0.001). When comparing responders and nonresponders with CMF/VP induction therapy, the responders had a significantly longer overall median survival (24 versus 10 months) (p < 0.001) and disease-free median survival (8 versus 2 months) (p < 0.001). All of the five patients remaining alive received FAC with 80% (four of five) having a complete response. These four patients subsequently underwent mastectomy and radiation. CONCLUSION: This study suggests that a doxorubicin-containing chemotherapy regimen improves overall and disease-free median survivals when compared with the previously used CMF combination in the treatment of IBC. A favorable response to induction chemotherapy also appeared to be associated with an improved survival.

Antineoplastic Combined Chemotherapy Protocols↗

[Intensive multidisciplinary treatment of back pain--2 controlled prospective studies].

The aim of this study was to evaluate an intensive, multidisciplinary functional restoration program for people with chronic low back pain. The program was compared to a non-treated control group in project A, and to less intensive treatment programs in project B. Both projects were randomized and observer blinded. Two hundred and thirty-eight patients were included, 106 entering project A and 132 project B. All had had chronic low back disability of at least six months duration, with an average of one year's sick leave due to low back pain over the last three years. Their average age was 41 years. The results at follow-up (conducted four months after treatment, follow-up rate 90% in project A and 86% in project B) showed that 67% of the treated patients in project A were able to work compared to 28% in the control group. In project B, 75% of the patients treated in the functional restoration program were able to work, the corresponding numbers from the less intensive programs being 48% and 40%. Numbers of days of sick leave, contacts to the health-care system and pain- and disability-scores were significantly lower for the patients treated in the functional restoration program compared to the other groups in both projects. Functional restoration is more expensive to carry out, but the long-term benefits in form of reductions in pensions, sick leave and contacts to the health-care system, not to mention reduced pain for the patients, seems to justify this expenditure.

Adult↗

Primary colorectal non-Hodgkin's lymphoma.

BACKGROUND: The gastrointestinal tract is the most common site of extranodal involvement in non-Hodgkin's lymphoma (NHL). Primary colorectal NHL comprises 13-18% of all gastrointestinal NHL but is not commonly reported as a separate entity. METHODS: This was a retrospective review of the medical records of 19 patients over a 16-year period to evaluate the clinical features and behavior of colorectal NHL. RESULTS: A pediatric group of seven male patients presented at an early stage with acute symptomatology. The primary tumor was located in the ileocecum in all cases and intussusception was common. An adult group of 12 patients presented at a later stage with chronic symptomatology. Staging study results were positive by bone marrow biopsy in four of 16 patients (25%), by lymph-angiography in six of 11 patients (54.5%), and by gallium scan in eight of 10 patients (80%). Seven patients relapsed a median of 8 months after treatment. Three other patients died during treatment, one died of other causes, and one died without receiving treatment. The remaining seven patients are alive from 41 to 231 months without evidence of disease. Five of these patients are in the pediatric group, where the median survival was > 72 months. The overall median survival was 45 months. CONCLUSION: Colorectal NHL is a disease that affects both the pediatric and adult population. Although pediatric patients have an excellent prognosis with anticipated long-term survival after treatment, long-term survival can be expected in approximately 50% of adult patients. In both groups of patients, multimodality therapy with surgery, chemotherapy, and radiation is the treatment of choice.

Adolescent↗

The use of videotaped lectures in surgical oncology fellowship education.

A video library of surgical oncology topics was initiated in 1991 as an educational forum for fellows in a surgical oncology training program. First-year and second-year fellows presented formal medical lectures on specific surgical oncology topics that were based on a comprehensive literature review. An abstract of the discussion, a list of references, and a copy of the presented slides were submitted at the time of presentation of each lecture. The lectures were videotaped in front of an audience made up of faculty and fellows of the Department of Surgical Oncology, The videotapes were subsequently edited to incorporate the presented slides, and these versions were shown separately to allow critique of presentation style and content by the faculty and the fellows within the Department. Nineteen videotaped presentations from academic years 1991-1992 and 1992-1993 were evaluated. These videotaped lectures are an informational resource, and, of equal importance, they provide an assessible record for self-analysis of lecturing technique and effectiveness.

Audiovisual Aids↗

Pulmonary complications in patients undergoing thoracotomy for lung carcinoma.

One hundred three consecutive patients undergoing 106 thoracotomies for primary lung carcinoma were reviewed to determine factors associated with the development of postoperative pulmonary complications. Pulmonary complications occurred in 40 of 104 (39 percent) patients. Minor complications occurred in 17 of 104 (16 percent) patients and major in 23 of 104 (22 percent). There were six deaths in the entire series of 103 patients (6 percent), two of which were directly caused by a pulmonary complication and one where it was a contributing factor. Extended surgical resections were associated with an increased risk of complications. Pulmonary complications occurred in 9 of 11 (82 percent) patients undergoing extended resections involving chest wall resection. The use of neoadjuvant chemotherapy also was associated with an increase in the rate of major complications. Poor nutritional status as measured by a history of weight loss and preoperative serum albumin levels also was associated with an increased risk of any pulmonary complication. Cardiac complications were significantly increased in the group of patients having pulmonary complications. Pulmonary complications continue to present a major source of morbidity and mortality for patients undergoing thoracotomy for lung carcinoma. Determination of factors associated with increased risk is important in order to identify patients who might be predisposed to the development of these complications.

Age Factors↗