Do laboratory species protect endangered species? Interspecies variation in responses to 17ß-estradiol, a model endocrine active compound.

Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio Grande silvery minnow. However, this study supports the continued use of surrogate species for the beneficial implementation of water-quality regulations for the protection of threatened and endangered species if phylogenetic relationships are taken into consideration.

Incidence of post-anaesthetic arrhythmias in dogs.

OBJECTIVES: To assess the use of Holter monitoring for evaluating the incidence of post-anaesthetic cardiac arrhythmias and associated anaesthetic risk for two different anaesthetic protocols. METHODS: Patients undergoing orthopaedic surgery were randomly divided into two groups with different anaesthetic regimens (group A, isoflurane n = 30; group B, propofol n = 30). Two 24-hour Holter recordings were performed for each patient: the first directly following anaesthesia and the second, as a comparison, on the fifth postoperative day. RESULTS: Although all dogs were healthy on pre-anaesthetic cardiac evaluation, 56 dogs showed arrhythmias in the two 24-hour (Holter) electrocardiograms performed. However, the number of arrhythmias recorded was low in most cases (less than 10 supraventricular extrasystoles and less than 100 ventricular extrasystoles). One patient in group A showed 94 supraventricular extrasystoles during the second monitoring period. Three patients in each group developed more than 100 ventricular extrasystoles during both Holter recordings. There were no statistically significant differences between the two anaesthetic regimens or between the two recordings in both groups. CLINICAL SIGNIFICANCE: The two anaesthetic protocols investigated in this study did not induce an increased incidence of severe arrhythmias in healthy dogs in the post-anaesthetic phase.

[Relevance of surgical outpatient clinics in academic university centers to health care in Germany]. / Stellenwert einer allgemeinen chirurgischen Hochschulambulanz für die medizinische Patientenversorgung Eine ergänzende Erhebung zur "Deutschen Hochschulambulanzenstudie".

During the observation period between 2001 and 2003, all outpatient surgical therapy, including degrees of urgency, surgical care volume, regional provenance of patients, diagnoses, and referral channels were prospectively analysed at the Surgical Department of the University of Heidelberg, Germany. The data gathered do not merely describe the volume and characteristics of care encountered at this academic surgical institution but also provide further insight into the variability of resource utilisation and associated patient flow. Additionally, a retrospective evaluation using structured interviews and questionnaires was performed to differentiate and quantify patient care, teaching, and research activities. This study illustrates the high relevance of academic outpatient institutions to regional provision of general surgical care in Germany. There is a clear dominance of medical support functions, while research and teaching activities are of only minor relevance and realised particularly in subspecialty clinics. These data should give important stimuli for the future planning of health care in Germany. Outpatient clinics for general surgery appear to be an excellent basis for regional models of integrated health care delivery in the future.

Techniques of reconstruction after total gastrectomy for cancer.

BACKGROUND: Jejunal pouch formation and restoration of duodenal transit have been suggested for reconstruction after total gastrectomy. Opinions about the clinical value vary. METHODS: The literature was searched for prospective randomized trials comparing reconstructive procedures after total gastrectomy for malignancy. Reports with at least an English or German abstract were included. Immediate results were evaluated in terms of postoperative deaths and complications. Long-term outcome was analysed using trends in bodyweight and quality of life. RESULTS: A total of 19 randomized trials including 866 patients was identified. The operative risk of total gastrectomy was low, with a median mortality rate of 0 (range 0-22) per cent, irrespective of the method of reconstruction. Neither gastric substitution nor restoration of duodenal transit was associated with significant procedure-related complications. Results for specific reconstructions varied considerably within and between individual trials. Jejunal pouch reconstruction, but not restoration of duodenal passage, was associated with improved food intake and a tendency for weight gain in the early postoperative months. A favourable perception of quality of life persisted in the long term in some studies. CONCLUSION: Preservation of duodenal transit offers little clinical benefit. Construction of a small-bowel reservoir after total gastrectomy should be considered to improve early postoperative eating capacity, bodyweight and quality of life.

Hematogenous tumor cell dissemination during colonoscopy for colorectal cancer.

BACKGROUND: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy. METHODS: Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts. RESULTS: Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar's test: tumor cell detection before after colonoscopy). All control samples consistently tested negative. CONCLUSIONS: Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.

Immunocytological confirmation of bone marrow metastases in a dog with cholangiocarcinoma.

The case history of a four-year-old, male Bernese mountain dog is presented. Carcinoma cells were detected in the liver by ultrasound-guided fine-needle aspiration. Bone marrow aspirated from the iliac crest and the left femur showed a distinct infiltration by carcinoma cells. Immunocytological examination of the liver and bone marrow metastases showed a negative staining result for large spectrum cytokeratin (CK) KL1, a strong positive result for CK7 and a focal weak positive result for CK20. The dog was euthanased due to the grave prognosis. Histopathological examination revealed metastatic cholangiocarcinoma. The authors conclude that cytological and immunocytological examination of bone marrow aspirates should be used more frequently for the detection of distant metastases of carcinomas in small animal medicine.

Surgical therapy for loco-regional recurrence and distant metastasis of gastric cancer.

The appearence of distant metastases or local recurrence is assumed to render gastric cancer incurable. However, experience with colorectal cancer has shown that patients with recurrent disease may have a chance for cure, if recurrent or metastatic disease can be completely resected. Since improved imaging allows detection of ever smaller tumour deposits, we have reviewed the pertinent literature to determine the current surgical options for recurrent or metastatic gastric cancer. Metastatic disease or local recurrence is rarely resectable. Tumour recurrence in the remnant stomach after partial gastrectomy can be treated by secondary total gastrectomy and may occasionally result in long-term survival. Other types of local recurrence are generally not amenable to complete resection. The same is true for distant metastases. If, however, distant metasases are technically resectable, 5 year survival of approximately 20% has been documented. Solitary and late appearing metachronous tumours are associated with an improved prognosis. As a consequence resection of distant metastases should be considered, because the risk of metastasectomy is generally low and there is no alternative treatment with a chance for cure.

Impact of diagnostic laparoscopy on the management of gastric cancer: prospective study of 120 consecutive patients with primary gastric adenocarcinoma.

BACKGROUND: Peritoneal seeding or liver metastases found at laparotomy usually preclude curative treatment in patients with gastric adenocarcinoma. Such exploratory laparotomies may be avoided by diagnostic laparoscopy. However, routine diagnostic laparoscopy does not benefit those patients who proceed to laparotomy after negative laparoscopy. The aim of this study was to evaluate prospectively the selective use of laparoscopy in uncertain situations. METHODS: One hundred and twenty consecutive patients with primary gastric adenocarcinoma were studied prospectively. Diagnostic laparoscopy was performed in patients with clinical T4 tumours or suspected metastases, unless laparotomy was required for symptomatic disease. RESULTS: Ninety-six of 120 patients were selected for immediate laparotomy with curative intent (n = 81) or for palliation (n = 15). In two of the 81 patients gastrectomy was abandoned because of unexpected peritoneal carcinomatosis. Fifteen patients underwent diagnostic laparoscopy, which identified intra-abdominal metastases in six; the other nine patients proceeded to laparotomy, which revealed peritoneal metastases not detected at laparoscopy in four patients. The remaining nine patients had overt metastases and were referred for systemic chemotherapy without abdominal exploration. CONCLUSION: Diagnostic laparoscopy in selected patients effectively limits the number of unnecessary invasive staging procedures. Routine use of diagnostic laparoscopy in all patients with gastric adenocarcinoma is not warranted.

Two-stage radical gastrectomy for perforated gastric cancer.

INTRODUCTION: Perforation represents a severe complication of gastric cancer. Because it is rare, only few data are available regarding treatment and prognosis. METHODS: Patients with perforated gastric cancer were identified from two prospective registers of gastric cancer and of gastroduodenal ulcer. RESULTS: Between February 1982 and June 1999 23 patients with perforated gastric cancer were treated surgically. This corresponds to only 1.8% of 1273 patients presenting with gastric cancer, but to 14% of 161 patients presenting with gastric perforation during this time period. Overall, post-operative mortality was 13% (3/23). Initially, 21 patients had palliative operations. Two patients had a potentially curative procedure at the emergency operation and one of the two died post-operatively. Another six patients had potentially curative gastrectomy at a second stage and no patient died post-operatively. The 5-year overall survival was estimated at 50% for all eight curatively-treated patients. Median survival of palliatively treated patients was 6 months. CONCLUSIONS: Perforation of the stomach should raise suspicion of malignancy, particularly in elderly patients. At the time of perforation radical gastrectomy with lymphadenectomy is mostly not advised, either because a diagnosis of gastric cancer is not confirmed or because the patient's condition does not allow extended surgery. In this situation it is suggested to consider a two-stage procedure and direct the primary operation at the treatment of perforation and peritonitis. Tumour staging can be completed when the patient has recovered and a radical operation with curative intent can be planned without compromising long-term prognosis. Our observations and a review of the literature confirm that perforation of gastric cancer does not preclude long-term survival per se in a substantial number of patients.

[The long gamma nail--indications, technique and results]. / Der lange Gammanagel--Indikationen, Technik und Ergebnisse.

The introduction of the Gamma nail (GN) as an intramedullar implant for pertrochanteric femoral fractures that allowed full weight bearing decreased the death rate from 17% (methods without full weight bearing) to 6%. The long Gamma nail (LGN) is a logical supplement of the standard version, designed to treat unstable per-, subtrochanteric and segmental fractures. This study evaluated 44 consecutive operations. Seventy percent of the patients had to be classified ASA III and IV, due to their high morbidity. The median age was 73.5 years. Multiple injuries occurred in 30.2%. All fractures were considered unstable. Surgery was usually performed within 24 h. The median duration of the surgical treatment was 120 min. In five cases technical problems were observed. Radiological controls showed a good positioning of the head screw. Early complications consisted of four local wound infections, three of them deep infections with a osteomyelitis. Deep venous thrombosis was observed in four cases, two of which included a pulmonary embolism (conservative treatment). The 30-day death toll was 2.3% (one patient). The median survival time (using Kaplan-Meier) in the study was 46 months, compared to 80 months in a matched population. This difference has to be linked to high premorbidity. The median duration of admission was 15 days. Mobilisation with full weight bearing was theoretically possible in all cases, but additional injuries or preoperatively impaired walking ability prevented full mobilisation in 15 cases. Functional assessment uncovered a decrease in Merle d,Aubigne score of 26.7% due to an impaired walking ability. Seventy-three percent of the patients regained their preoperative social status. In conclusion the long Gamma nail is a universal, less invasive implant with high early weight bearing. It thus allows early remobilization and reduces lethality in the treatment of complex, unstable coxal fractures.

Bone structural and mechanical properties are affected by hypotransferrinemia but not by iron deficiency in mice.

Hypotransferrinemia is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. We used this mutant mouse in conjunction with dietary iron deficiency to study the influence of Tf and iron on bone structural and mechanical properties. Twenty-one weanling wild-type BALB/cj +/+ mice and 21 weanling +/hpx mice were fed iron-deficient or iron-adequate diets for 8 weeks. Twelve hpx/hpx mice were fed the iron-adequate diet. Hypotransferrinemia resulted in increased tibia iron and calcium concentrations, lower femur failure load, and extrinsic stiffness. Because the femurs of the hpx/hpx mice were disproportionately small, these bones actually had increased tissue material properties (ultimate stress [US] and modulus of elasticity) than those of wild-type mice. This is the first report on the effect of dietary iron deficiency on bone structural and mechanical properties. Dietary iron deficiency in +/+ and +/hpx mice decreased tibia iron concentrations but had no effect on tibia calcium and phosphorus concentrations or femur structural or mechanical properties. Because the bones of the hpx/hpx mice were small, but had superior tissue mechanical properties, we conclude that Tf is important for normal bone mineralization.

Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer.

In animal studies, glutamine (Gln) reduces chemotherapy-associated mucositis and mucosal atrophy. Therefore, this study examined the protective effects of a parenteral Gln supplementation in patients with metastatic colorectal carcinoma receiving 5-fluorouracil (5-FU)/calcium-folinate (CF) chemotherapy. In a prospective study, a total of 24 patients underwent three courses of 5-FU/CF chemotherapy and were randomised with (n = 12) or without (n = 12) glycyl-L-glutamine. Effects on gastrointestinal mucosa were assessed by endoscopic examinations and histomorphometric measurements. Clinical side-effects were documented according to the World Health Organisation grading. In the Gln group, a significant reduction in mucositis and ulcerations of the gastric (P < 0.01) and duodenal mucosa (P < 0.05) was documented after the third course of chemotherapy. In the same group, the villus height/crypt depth ratio was significantly higher after therapy than in the unsupplemented group (1st course P < 0.01; 3rd course P < 0.05). However, there were no significant differences in the incidence and severity of clinical side-effects. The results suggest that parenteral Gln supplementation protects the gastrointestinal mucosa against 5-FU/CF chemotherapy-induced damage.

[Hydrosonography as an alternative or supplement to endosonography in stomach carcinoma]. / Hydrosonographie als Alternative oder Ergänzung zur Endosonographie beim Magencarcinom.

Transabdominal ultrasound in the hydrotechnique (hydrosonography) was compared with endosonography for the locoregional staging of gastric cancer. For this purpose 52 consecutive patients were examined by endosonography (7.5 and 12 MHz) and hydrosonography (3.75 MHz). Forty-nine of the 52 tumors could be examined by endosonography and 41 by hydrosonography. The T-staging accuracy rate of endosonography was 74% and 46% for hydrosonography. Carcinoma of the cardia are often classified as uT3 and hT3 preoperatively and pT2 postoperatively due to infiltration of the subserosal fat. The N-staging accuracy rate of endosonography was 86% and 61% for hydrosonography. Based on these results, transabdominal ultrasound in the hydrotechnique (hydrosonography) cannot replace endosonography in gastric cancer staging. However, when performed in conjunction with conventional ultrasound, hydrosonography provides useful information about the local tumor stage, especially in cases of advanced and stenotic tumors.

[Pigmented villonodular synovitis. Case reports and review of the literature]. / Pigmentierte villonoduläre Synovitis. Kasuistiken und Literaturüberblick.

Because this disease is so rare the optimum treatment of pigmented villonodular synovitis (PVNS), in particular the diffuse form differs in the literature. The most important surgical procedures are arthroscopic and open synovectomy. The prevention of disease progression, as well as joint destruction and dysfunction, depends upon the early diagnosis of PVNS. During 1994 and 1995, we treated four cases of PVNS surgically and followed the patients for a time period of more than 12 months. Two patients were treated with complete synovectomy, one patient underwent partial synovial resection, and in the final case an arthrodesis was performed. Our results indicate that an MRI is essential for diagnosis and treatment planning. For the localized form of PVNS, it appears that a partial synovectomy is appropriate. However, in the event of diagnostic uncertainty or obvious diffuse involvement of the synovium, a total synovectomy is indicated because of the high recurrence rate. In our study, all four patients had disease involving secondary bony lesions and, in one case, joint destruction. Based on our findings, it is clear that early surgical therapy is the only recommended curative intervention. The decision regarding the surgical approach, arthroscopic versus open, depends on the form of PVNS, the extent of the disease and secondary changes of the joint.

Relative sensitivity of three endangered fishes, Colorado squawfish, bonytail, and razorback sucker, to selected metal pollutants.

The acute toxicity of four metal pollutants to larval and juvenile stages of endangered Colorado squawfish (Ptychocheilus lucius), bonytail (Gila elegans), and razorback sucker (Xyrauchen texanus) were determined in a water quality representative of that in the Green River, Utah. The rank order of toxicity (96-hr LC50) of the metals to all species and life stages from most toxic to least toxic was mercury (57-168 micrograms/liter) > cadmium (78-168 micrograms/liter) > hexavalent chromium (32,000-123,000 micrograms/liter) > lead (> 170,000 micrograms/liter). In tests with lead, a precipitate formed in all test solutions and no mortalities occurred in these treatments. The larvae of each species were as sensitive or more sensitive than the juveniles to cadmium, hexavalent chromium, and mercury. Overall, the three species exhibited similar sensitivities to cadmium, hexavalent chromium, and mercury. Comparison of test results for the juveniles with toxicity values reported for other freshwater fishes tested in different water qualities indicates that the endangered fishes are more sensitive to cadmium than other cyprinids and centrarchids and less sensitive than salmonids, whereas their sensitivity to hexavalent chromium and mercury is similar to that of other cyprinids, centrarchids, and salmonids.

Flexible endoscopic ultrasonography of colonic tumors: indications and results.

BACKGROUND AND STUDY AIMS: Based on the positive results of endorectal ultrasound we evaluated flexible colonic endosonography for colonic tumors. At present there are no generally accepted indications for this procedure. Moreover, it is unclear whether the results are valid enough to warrant specific therapeutic interventions. PATIENTS AND METHODS: Over a one-year period we performed flexible colonic endosonography (12 MHz rotating scanner) on 31 patients with colonic tumors. The examination was only performed when therapeutic implications were expected (e.g. endoscopic procedure when there was no sign of malignancy; oncological resection when there were signs of malignancy in ulcerative colitis or familial polyposis). RESULTS: Of 40 tumors examined, 36 were correctly staged by endosonography, compared to postoperative histology as the gold standard (16 of 17 adenomas, 5 of 5 pT1 carcinomas, 8 of 8 pT3 carcinomas). In two cases pT4 carcinomas were wrongly classified endosonographically as uT3 carcinomas, because the infiltration of the visceral peritoneum was technically not recognizable. Overall the accuracy rate of staging was 85%. Lymph node staging was correct in 36 of 40 patients, amounting to an accuracy rate of 90%. CONCLUSION: Because of its high accuracy rate flexible colonic endosonography has a place in the preoperative staging of colonic tumors in selected patients, especially those with ulcerative colitis, familial adenomatous polyposis or macroscopically suspicious adenomas. It helps to clarify the extent (oncological resection, lymphadenectomy) of resection required in conventional surgery and helps to avoid laparoscopic procedures in advanced colonic cancer.

Reconstruction after gastrectomy and quality of life.

To evaluate quality of life and functional results following surgery for gastric cancer we studied 104 patients with no evidence of disease at a minimum of 12 months postoperatively. Patients were treated with total gastrectomy and jejunal pouch reconstruction according to Hunt-Lawrence-Rodino (n = 59) or simple esophagojejunostomy (n = 24) and distal subtotal gastrectomy (n = 21). No significant differences were found between total gastrectomy with pouch reconstruction and distal gastric resection with respect to dumping or heartburn, whereas patients with total gastrectomy and restoration with esophagojejunostomy suffered from both. The latter group of patients also had reduced nutritional status. Although there is a lack of a proper definition of quality of life, all instruments applied to its measurement indicated improved results for patients with pouch reconstruction and those after distal gastrectomy, but we could not state any significant differences. We conclude that in terms of postoperative functional results as well as quality of distal gastric resection has no advantage over total gastrectomy with pouch reconstruction; hence a reduction of surgical radicality in an attempt to improve postoperative results is not justified. Pouch reconstruction should be considered the treatment of choice for reconstruction after total gastrectomy.

Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies.

In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval). Pharmacokinetic parameters (apparent volume of distribution Vd, total plasma clearance CL) needed for individualization of dosage were evaluated by the Bayesian approach and a model-(in)dependent pharmacokinetic program (TOPFIT). Comparison of both methods revealed some small differences in the pharmacokinetic parameters for all three drugs. Mean deviations of the Bayesian estimates from the pharmacokinetic calculations of the three drugs ranged between 20 and 38% for Vd and between 13 and 22% for CL, indicating that the Bayesian approach provided reliable pharmacokinetic estimates for individualizing drug dosage under routine conditions. Therefore, it is suggested that routine TDM combined with Bayesian-based analyses can be regarded as an alternative to pharmacokinetic studies in clinically relevant populations.

Inhibition of gastric tumorigenesis by alpha-difluoromethylornithine in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

Male Wistar rats were treated concurrently with a combination of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7) and the polyamine-synthesis inhibitor alpha-difluoromethylornithine (DFMO) at two different doses of 0.5% and 1.0% (w/v). Experimental groups were treated with (I) MNNG alone (n = 25), (II) MNNG plus 0.5% (w/v) DFMO (n = 25), (III) MNNG plus 1.0% (w/v) DFMO (n = 25), (IV) 1.0% (w/v) DFMO alone (n = 25). Group V represented untreated controls (n = 20). Both the carcinogen and DFMO were administered in drinking water. The treatment time with the carcinogen and DFMO was 35 weeks. After treatment was completed animals were followed for an additional 50 weeks to cover a total observation time of 85 weeks. Significantly fewer animals developed gastric adenocarcinoma in the two groups of animals that received a combined treatment of MNNG plus DFMO compared to animals treated with the carcinogen alone (P < 0.05 and 0.005). No benign or malignant neoplastic lesions were observed in the stomach or duodenum of animals treated with DFMO alone or in untreated controls. It is concluded that concurrent treatment with DFMO prevents the development of malignant gastric epithelial tumors induced by MNNG in rats.