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Biomedical subjects

J Lange

Publications and source records attributed to J Lange.

At least 73 records · Page 4Linked to original sources

Effects of exposure to grain dust in Polish farmers: work-related symptoms and immunologic response to microbial antigens associated with dust.

Medical examinations were performed in a group of 76 Polish farmers heavily exposed to grain dust during harvesting and threshing, and in a group of 63 healthy urban dwellers not exposed to organic dusts (controls). The examinations included: interview concerning the occurrence of respiratory disorders and work-related symptoms, physical examination, lung function tests, and allergological tests comprising skin prick test with 4 microbial antigens associated with grain dust and agar-gel precipitation test with 12 microbial antigens. As many as 34 farmers (44.7%) reported the occurrence of work-related symptoms during harvesting and threshing. The most common was dry cough reported by 20 individuals (26.3%). Dyspnoea was reported by 15 farmers (19.7%), tiredness by 12 (15.7%), chest tightness by 8 (10.5%), plugging of nose and hoarseness by 5 each (6. 5%). No control subjects reported these work-related symptoms. The mean spirometric values in the examined group of farmers were within the normal range, but a significant post-shift decrease of these values was observed after work with grain. The farmers showed a frequency of the positive early skin reactions to environmental allergens in the range of 10.8 - 45.5%, and a frequency of positive precipitin reactions in range of 3.9 - 40.8%. The control group responded to the majority of allergens with a significantly lower frequency of positive results compared to the farmers. The obtained results showed a high response of grain farmers to inhalant microbial allergens and indicate a potential risk of occupational respiratory diseases (such as allergic alveolitis, asthma, Organic Dust Toxic Syndrome) among this population

Adult↗

Activation of calcium signaling in isolated rat hepatocytes is accompanied by shape changes of microvilli.

Preceding studies using the hamster insulinoma cell line, HIT, and isolated rat hepatocytes have shown that two essential components of the Ca2+ signaling pathway, the ATP-dependent Ca2+ store and the store-coupled Ca2+ influx pathway, are both located in microvilli covering the surface of these cells. Microvilli-derived vesicles from both cell types exhibited anion and cation pathways which could be inhibited by anion and cation channel-specific inhibitors. These findings suggested that the microvillar tip compartment forms a space which is freely accessible for external Ca2+, ATP, and IP3. The entry of Ca2+ into the cytoplasm, however, is largely restricted by the microvillar core structure, the dense bundle of actin microfilaments acting as a diffusion barrier between the microvillar tip compartment and the cell body. Moreover, evidence has been presented that F-actin may function as ATP-dependent and IP3-sensitive Ca2+ store that can be emptied by profilin-induced depolymerization or reorganization [K. Lange and U. Brandt (1996) FEBS Lett. 395, 137-142]. Here we demonstrate the tight connection between microvillar shape changes and the activation of the Ca2+ signaling system in isolated rat hepatocytes. Using a combination of scanning electron microscopy (SEM) and fura-2 fluorescence technique, we confirmed a consequence of the "diffusion barrier" concept of Ca2+ signaling: Irrespective of the type of the applied stimulus, activation of the Ca2+ influx pathway is accompanied by changes in the structural organization of microvilli indicative of the loss of their diffusion barrier function. We further show that the cell surfaces of unstimulated hepatocytes isolated by either the collagenase or the EDTA perfusion technique are densely covered with microvilli predominantly of a short and slender type. Beside this rather uniformly shaped type of microvilli, a number of dilated surface protrusions were observed. Under these conditions the cells displayed the well known rather high basal [Ca2+]i of 200-250 nM as repeatedly demonstrated for freshly isolated hepatocytes. However, addition of the serine protease inhibitor, phenylmethanesulfonyl fluoride (PMSF), to the cell suspension immediately after its preparation reduced the basal cytoplasmic Ca2+ level to about 100 nM. Concomitantly, dilated surface protrusions disappeared, and cell surfaces exclusively displayed short, slender microvilli. Activation of the Ca2+ signaling pathway by vasopressin, as well as by the IP3-independent acting Ca2+ store inhibitor, thapsigargin, was accompanied by a conspicuous shortening and dilation of microvilli following the same time courses as the respective increases of [Ca2+]i induced by the effectors. Furthermore, the abundance of the large form of surface protrusions on isolated hepatocytes positively correlated with the size of a cellular Ca2+/Fura-2 compartment which is rapidly depleted from Ca2+ by extracellular EGTA. These findings support the postulated localization of the store-coupled Ca2+ influx pathway in microvilli of HIT cells also for hepatocytes and are in accord with the notion of a cytoskeletal diffusion barrier regulating the flux of external Ca2+ via the microvillar tip region in the cytoplasm.

Animals↗

[Intraoperative cholangiography as a routine method? A prospective, controlled, randomized study].

A prospective, controlled, randomized trial was conducted in 275 patients with symptomatic gall stone disease, whose history, laboratory data or sonographical findings did not suggest common bile duct stones. Of these patients, 137 did not undergo intraoperative fluoroscopic cholangiography (IOC), but in the remaining 138 patients IOC was attempted. In 111 cases (80.4%) the biliary system was sufficiently visualized. In 3 patients (2.7%) calculi in the cystic or common bile duct were diagnosed, which would have been overlooked without IOC. IOC was false-positive in one case. One year after the operation the patients were asked to return for a follow-up examination. Three patients in the group without IOC had had symptomatic passage of a stone, and one had a common bile duct stone removed by endoscopic papillotomy. A retained stone was discussed as etiology for a pancreatitis in a fifth patient in this group. No patient sustained long-term sequelae from the retained common bile duct stones. None of the patients in the IOC group had evidence of cholangiolithiasis at follow-up. There was no difference between the study groups concerning the incidence of post-operative complications. The operations with IOC lasted significantly longer (92 +/- 31 min vs 77 +/- 28 min). According to our data and those published earlier, the additional financial and logistic expenditure associated with routine IOC is not justified. Patients with the preoperative suspicion of a common bile duct stone should have endoscopic bile duct clearance (ERCP and EPT) prior to cholecystectomy.

Adult↗

[Postoperative radiotherapy in non-small cell lung cancer. Apropos of a series of 374 cases].

PURPOSE: Several randomized trials have led us to address the usefulness of post-surgical external beam therapy (EBT) in non-oat cell bronchial carcinoma. Results that were obtained in a group of 374 patients submitted between 1977 and 1994 to identical therapy-the follow-up being done by the same team-and results of six randomized trials are analyzed. PATIENTS AND METHODS: The tumor stages were the following: T1, 13%; T2, 56%; T3, 29%; and T4, 2%; N0, 31%; N1, 34%; and N2, 35%. There were 85% histologically complete resections. EBT was administered according to either the classical irradiation scheme (C) or as an 'equivalent hypofractionated dose' (H) in the case of complete resection. When resection was not complete, 60 to 65 Gy were administered according to a C or an H irradiation scheme. The irradiation scheme was C in 73% of the cases and H in 27%. The EBT technique has been chosen to ensure maximum lung sparing. Following a 45 Gy-irradiation with anteroposterior beams, orthogonal or, when necessary, oblique beams were used. Non homogeneity of the lungs was taken into account in establishing the treatment planning. The treatment file was collectively checked by the medical staff in 75% of the cases. EBT was indicated for N+(N1+N2), T3 and incomplete resections. RESULTS: The overall survival was 42% at 5 years and 27% at 10 years. The 5-year survival was 52% for stage I cancer (T1N0-T2N0), 60% for stage II cancer (T1N1-T2N1), 31% for stage IIIa cancer (T3N0, T1-3N2), 45% for complete resection and 30% when resection was not complete. CONCLUSION: Regarding the benefits of post-surgical radiotherapy, the analysis of the six randomized trials does not allow any conclusion. This might be due to either the insufficient number of cases, a follow-up time not long enough, incorrect radiotherapy, or insufficient available data. Comparison of the results pertaining to the six trials with those of our series shows an advantage for the current series, indicating that survival is likely to be improved if EBT is correctly done with regard to the dose, volume and technique used.

Actuarial Analysis↗

Phase II trial of oral piritrexim in advanced, previously treated transitional cell cancer of bladder.

UNLABELLED: Oral piritrexim (PTX), a second generation antimetabolite, has been shown to be an active agent against methotrexate refractory transitional cell cancer (TCC) of the bladder in phase I trials. We conducted a phase II trial of this drug in patients with TCC of the bladder who failed a first line chemotherapy regimen. METHODS: Oral PTX was started at the dose of 25 mg three times per day for 5 days weekly for 3 weeks followed by one week of rest. If this was tolerated the dose was increased to 50 mg three times a day. Patients were monitored for response rate and toxicity. RESULTS: Seventeen patients were entered into the trial. Two patients did not complete the required 2 courses of treatment to be evaluable. There were 13 evaluable patients. Among the 13 no one achieved a complete response (CR), however, there were 3 partial responses (PRs = RR: 23%) and 5 stable diseases (SDs). The responses lasted 2, 8 and 14 months. The major dose-limiting toxicity was myelosuppression. Two patients died on treatment. One death was due to neutropenic fever and the cause of death in the second patient is thought to be a cerebral vascular accident (CVA). CONCLUSION: PTX is an active drug in the treatment of TCC of the bladder. Bone marrow suppression is the most common dose-limiting toxicity. In view of the observed responses and toxicities in this study and other studies, we suggest that the role of PTX be further investigated in the following clinical settings: 1. Palliative initial treatment in patients with TCC of the bladder who are not candidates for more aggressive chemotherapy. 2. As first line chemotherapy in combination with other active drugs.

Administration, Oral↗

Lamivudine-resistant human immunodeficiency virus type 1 variants (184V) require multiple amino acid changes to become co-resistant to zidovudine in vivo.

Exposure of human immunodeficiency virus to the nucleoside analogue lamivudine (3TC) rapidly selects for resistant variants with a valine at codon 184 (M184V) in the catalytic site of reverse transcriptase. In vitro, 184V demonstrated increased enzyme fidelity and suppressed zidovudine resistance. Clinical trials demonstrated that 3TC-zidovudine combination therapy results in a strong and sustained antiviral response. To investigate the role of 184V on in vivo virus evolution, the effect of zidovudine addition in 3TC-pretreated patients harboring 184V was studied. In vivo, no significant change in fidelity was observed with 184V, shown by generation of the classical pattern of zidovudine mutations. Of interest, in contrast to zidovudine monotherapy, in which just one substitution is sufficient for in vivo development of significant zidovudine resistance, multiple substitutions are required for the same level of zidovudine resistance in strains harboring 184V. This need for multiple substitutions may be one of the mechanisms explaining the sustained antiretroviral response of the 3TC-zidovudine combination.

Amino Acid Sequence↗

Documenting community-level outcomes. Lessons from drinking and driving.

Alcohol-related crashes cluster on Friday and Saturday evenings. One objective of this study was to contrast the demographic characteristics of operators who drive at these times with those who do not, through the comparison of data from two of the most widely used methods for gathering information on drinking and driving: Random Digit Dialing Telephone Surveys and Roadside Voluntary Breath Test Surveys. Roadside surveys set up at locations where alcohol-related crashes occur provide a better sample of those drivers most at risk of crash involvement. Telephone surveys, because they do not generally measure the exposure of drivers both in the location of driving and the number of miles driven, are less suited to identifying the drivers at risk. However, they highlight the large number of individuals who drive during high-risk times but avoid high-risk locations.

Accidents, Traffic↗

Influence of melatonin and oestradiol on the opioidergic regulation of LH and prolactin release in pony mares.

The aim of this study was to investigate the influence of oestradiol, melatonin and season on the opioid regulation of LH and prolactin release. Effects of the opioid antagonist naloxone (0.5 mg/kg) on LH and prolactin secretion were determined in ovariectomized pony mares. In experiment 1, mares in January (n = 6) were pretreated with oestradiol benzoate (5 micrograms/kg) for 20 days. In experiment 2, beginning in May, mares (n = 7) received melatonin (15 mg) for 15 days and subsequently a combination of melatonin plus oestradiol for 20 days. In experiment 3, beginning in May, mares (n = 6) were pretreated with oestradiol for 30 days, left untreated for 12 days and then given melatonin for 35 days. In all experiments the animals were injected with the opioid antagonist naloxone and saline on 2 consecutive days prior to treatment. In experiment 1, animals received naloxone and saline on days 10 and 11 and 20 and 21 following oestradiol treatment. In experiment 2, naloxone and saline were administered on days 15 and 16 following melatonin treatment and on days 10 and 11 and 20 and 21 of melatonin plus oestradiol treatment. In experiment 3, the animals received naloxone and saline on days 10 and 11, 20 and 21 and 30 and 31 of oestradiol treatment, prior to melatonin treatment and on days 15 and 16, 25 and 26 and 35 and 36 following melatonin. In January (experiment 1), naloxone evoked a significant (P < 0.05) LH release at all times, however the LH increment in response to naloxone increased during oestradiol pretreatment (P < 0.05). During the breeding season (experiments 2 and 3), naloxone induced a significant (P < 0.05) increase in plasma LH concentrations when mares had not been pretreated with oestradiol or melatonin and after oestradiol pretreatment. Basal LH concentrations and the LH increment in response to naloxone increased significantly (P < 0.05) during the 30-day oestradiol pretreatment. Melatonin decreased the naloxone-induced LH release and the LH release in response to naloxone and saline no longer differed after 25 and 35 days of melatonin pretreatment. When melatonin was given together with oestradiol for 20 days, again a significant (P < 0.05) LH release in response to naloxone occurred. Prolactin release was significantly (P < 0.05) increased by naloxone when mares had been pretreated with only melatonin. The opioid antagonist did not affect prolactin release in mares that had not been pretreated or received oestradiol either alone or in combination with melatonin. In conclusion, in long-term ovariectomized mares, opioids inhibit LH secretion independent from ovarian factors. This opioid inhibition of LH secretion is enhanced by oestradiol and reduced by melatonin. Although short-term melatonin treatment inactivates the opioid regulation of LH release, a prolonged influence of melatonin as occurs in winter does not prevent activation of the opioid system. This indicates that effects of melatonin on the opioid regulation of LH release change with time. An opioid inhibition of prolactin secretion is activated by melatonin given for 15-35 days but is lost under the prolonged influence of a short-day melatonin signal in winter.

Animals↗

Significance of histologic criteria for the management of patients with malignant colorectal polyps and polypectomy.

BACKGROUND: The management of invasive cancer in colorectal polyps (malignant polyps) is controversial, particularly with regard to the different sets of histologic criteria for deciding whether malignant colorectal polyps should be treated by polypectomy alone or be followed by surgical resection. We report on the outcome of patients in accordance with the histologic assessment of their malignant polyps. METHODS: Malignant polyps were defined as having favourable histology (free margin, grade I or II, and no angiolymphatic invasion) or unfavorable histology (no free margin, grade III, or angiolymphatic invasion). Malignant polyps with favourable histology were treated by endoscopic polypectomy alone, whereas further therapy was recommended for malignant polyps with unfavourable histology. Residual cancer in a resection specimen and local or metastatic recurrence during the follow-up period (mean, 60 months; range, 12 - 120) were defined as adverse outcome. RESULTS: Thirty-seven malignant polyps were detected in 35 (0.5%) of 6605 patients. Five of these 35 patients were treated by primary bowel resection and analysed separately. In the other 30 patients the following unfavourable histologic signs were detected in 20 (62.5%) of 32 malignant polyps; no free margin in 16, grade III in 1, and angiolymphatic invasion in 3 polyps. Twelve polyps with favourable histology had no adverse outcome; in contrast, 5 of 20 polyps with unfavourable histology had an average outcome (P < 0.05). CONCLUSIONS: Locally excised malignant polyps without unfavourable histologic signs may not need further surgical treatment; for all other malignant polyps an ensuing bowel resection is recommended.

Adult↗

Alcohol consumption by young actively growing rats: a histomorphometric study of cancellous bone.

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease bone density. This study addresses the mechanism of alcohol action on the early phases of bone growth and development using histomorphometric techniques. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae, including epiphyseal growth plate, were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Trabecular volume and number were greatly reduced in the alcohol-fed animals; however, bone formation rates and mineralization rates were normal. Epiphyseal growth rate and proliferation rate were essentially stopped in the alcohol-fed animals.

Alcoholism↗

[Cost increase due to incorrect antibiotic prophylaxis in visceral, thoracic and vascular surgery].

We analysed retrospectively 460 patients treated between March 1991 and February 1992, in respect to a correct perioperative antibiotic prophylaxis. In our opinion a correct prophylaxis is a single-shot application, with a second dose given only during long operations (over 3 hours) or when blood loss is great. 240 of the 460 patients analysed (52.2%) were given antibiotics prophylactically. In 76.6% of the cases (n = 184) the prophylaxis was performed correctly. In 23.4% (n = 56) antibiotic application was extended indiscriminately into the post-operative phase. This calculated to costs three times higher than those actually necessary, causing us to spend 22,000-Swiss francs unnecessarily, one twelfth of the total cost of antibiotic treatment in our hospital each year. For economic reasons as well as to keep growth of resistant strains in check, an antibiotic prophylaxis should be restricted to the perioperative period in most cases as a single shot only.

Abdomen↗

[The history of laparoscopy].

Laparoscopy has for a long time been the domain of some very few people. The first physicians to perform "coelioscopy" routinely where internists about 1920. Later, gynecologists where the ones to make the most important developments and inventions. The actual start of modern laparoscopy in surgery was the first video-endoscopic cholecystectomy, performed by the french surgeon Mouret in 1987. From this time on, laparoscopy for diagnostics and cholecystectomy became a new standard within about just five years. This article summarizes the history of laparoscopy from the ancient time to the present.

History, 18th Century↗

[Indications, technique and outcome of laparoscopic splenectomy].

Since introduction of stapling instruments, which allow a safe hemostasis of hilar spleen vessels, the advantages of laparoscopic procedures are as well available for the laparoscopic splenectomy, like atraumatic dissection, reduced hospital stay, less bleeding and therefore less necessity of blood transfusion, and reduced analgetic consume. Laparoscopic splenectomy causes a lower morbidity comparing to open conventional splenectomy. Frequent indications for elective splenectomy are immune thrombocytopenic purpura, spherocytosis, Non Hodgkin Lymphoma and Hodgkin's disease. Limiting factors to laparoscopic splenectomy may be the size of spleen, concomiting diseases as portal hypertension and adhesions in upper left abdomen. To remove a big sized spleen we placed it within a large specimen retrival bag, which was partly delivered through a port in the left flank to allow digital morcellation of the spleen and piecemal removal. Eight females and fifteen males with a median age of 45 years (16-73) underwent splenectomy of immune thrombocytopenic purpura (14), spherocytosis (2), Non Hodgkin Lymphoma (5), Hodgkin's disease (1) and hair cell leukemia (1) with a spleen weight of 985 grams. The median operating time was 94 min (40-165) and median blood loss was 214 ml (50-400). Accessory spleens were removed in two cases. The median postoperative hospital stay was 5.6 days (3-10). The only complication was a parechymatous bleeding which needed conversion to open splenectomy. With careful selection of patients, laparoscopic splenectomy can be safely performed on normal and even enlarged spleens. The lateral approach is safe and offers excellent visualization of the splenic vessels, pancreas, and accessory spleens.

Adolescent↗

[Transoral video-endoscopic esophageal diverticulostomy--a new treatment method for Zenker's diverticulum].

70% of the esophageal diverticula are pharyngoesophageal diverticula. They are caused by a malfunction of the superior esophageal sphincter. Surgical treatment consisted of a myotomy of the superior esophageal sphincter and the resection of the diverticulum through a lateral cervical incision. With the described new endoscopic transoral technique the septum between the diverticulum and the esophagus is divided by a stapling device and both lumina are combined resulting in a esophago-diverticulostomy. At the same time a myotomy of the transverse part of cricopharyngeal muscle and the proximal esophageal wall is performed. Due to the design of the stapling device usually a small pouch remains at the bottom of the diverticulum. A modification of the stapler instrument allowed us to shorten the length of this pouch. The time of the endoscopic procedure is markedly reduced compared to the conventional surgical intervention. There is no necessity for special postoperative wound care and the hospital stay is considerably shortened. Furthermore serious complications like fistulas and lesions of the recurrent nerve, encountered with the open surgical intervention, are avoided. This new technique combines the advantages of a minimal invasive approach and the development of new instruments with the confided principles of the conventional operation in treating the pathogenetical mechanisms of Zenker's diverticulum. To assess the value of the technique long term follow up studies as well as comparative trials will be needed.

Endoscopes↗

[Surgical therapy of morbid obesity: indications, technique of laparoscopic gastric banding and initial results].

Severe obesity with co-morbidity such as diabetes mellitus, cardiac failure, obesity hypoventilation, degenerative bone diseases and increased incidence of malignancy give rise to shorter life expectancy and have an impact on quality of life. This results in higher costs of health care and work absence. Surgical procedures have become commonplace in the therapy of morbid obesity because of the infrequent success of medical treatment. We performed a horizontal gastroplasty by laparoscopic adjustable silicon gastric banding (LASGB) on 60 patients between 1. 11. 1995 and 28. 2. 1997. The average excess above normal weight was 62 kg, the median BMI (Body-Mass-Index) was 46.44 kg/m2. Fifty-nine procedures were performed by the laparoscopic method and one with an open technique. The average postoperative hospital stay was five days. Due to dorsal slipping or pouch enlargement the procedure had to be repeated on 6 patients (10%). The median loss of weight in the first three months was 14.78 kg, after six months 24.14 kg and after nine months 35.1 kg. Insulin treatment for three patients suffering diabetes mellitus could be discontinued-in addition blood sugar levels in six patients normalised. Two patients with obstructive sleep-apnea syndrome no longer needed a nocturnal Nasal-Continuous-Positive-Airway-Pressure-(nCPAP-)Therapy. To provide a better quality of life to this group of patients, the gastric banding is a suitable method for carefully evaluated and followed patients. In addition improved ability to work and reduction of health care costs due to co-morbidity and joint diseases have a positive economic impact.

Adolescent↗

Mechanism for cotolerance in nonlethally conditioned mixed chimeras: negative selection of the Vbeta T-cell receptor repertoire by both host and donor bone marrow-derived cells.

Bone marrow (BM) chimeras prepared by complete recipient ablation (A-->B) exhibit donor-specific tolerance, yet survival is often limited by graft-versus-host disease (GVHD). Negative selection of potentially donor-reactive T cells, as assessed by relative T-cell receptor (TCR)-Vbeta expression, is dependent on donor BM-derived deleting ligands. Mixed chimerism and tolerance for both donor and host antigens can be achieved using partial recipient myeloablation with 500 cGy total-body irradiation (TBI) before transplantation followed by cyclophosphamide (CyP) on day +2. To examine the influence of residual host elements on negative selection, the peripheral TCR-Vbeta repertoire was analyzed in partially ablated C57BL/10SnJ (B10) recipients reconstituted with BM from major histocompatibility complex (MHC)-disparate B10.BR/SgSnJ or MHC, Hh-1 and Mls-disparate BALB/cByJ donors, which delete Vbeta5+ and 11+ or Vbeta3+, 5+, and 11+ TCR subsets, respectively. As in myeloblated recipients, donor-reactive subfamilies were deleted in B10.BR-->B10 and BALB/c-->B10 chimeras, suggesting that donor I-E and minor lymphocyte-stimulating (Mls) antigens contribute to the deleting ligands in the nonmyeloablated host. In striking contrast to completely ablated B10-->B10.BR chimeras, partially ablated recipients showed intramedullary I-E expression in the thymus and deleted host-reactive Vbeta5+ and Vbeta11+ subfamilies. These data demonstrate that efficient clonal deletion occurs after partial myeloablation and that both donor and host ligands contribute to TCR repertoire selection.

Animals↗