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Sites of protein conservation and loss during starvation: influence of adiposity.

Previous studies have established that older (16 wk) and more obese rats conserve body protein during prolonged starvation. This adaptation is due in part to a curtailment of muscle proteolysis. To determine whether this response occurs also in younger rats and whether protein is conserved at sites other than muscle, studies were conducted in young 6-wk-old rats previously fed either a chow or a high-fat diet before starvation. Fat feeding caused a marked increase in adipose mass and prolonged survival. Whereas chow-fed rats survived the fast for approximately 5 days, fat-fed rats lived for 10 days and diminished their excretion of nitrogen for at least 6 days, indicative of protein conservation. Despite the ability of fat-fed rats to survive the fast longer, protein was conserved in only a few organs. The timing and magnitude of protein loss from liver, kidney, intestine, and lung was similar to that in chow-fed rats, and little protein was lost during the fast from brain, stomach, skin, and soleus muscle in either group. In fat-fed rats, cardiac and skeletal muscle were the principle tissues in which protein was conserved, and this adaptation was lost when body fat stores were nearing exhaustion. In both groups nitrogen excreted in the urine early in the fast was derived mainly from protein lost from muscle, liver, and to a lesser extent intestine. Later in the fast, the principal source was muscle. These findings indicate that during starvation in the rat the conservation of protein occurs principally in skeletal and cardiac muscle. They also suggest that the ability of the rat to conserve protein is dependent on the size of its lipid stores.

Adipose Tissue↗

Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

Aged↗

Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction.

BACKGROUND: When used in the setting of acute myocardial infarction, intravenous thrombolytic agents fail to achieve early infarct artery patency in 15% to 50% of patients. We tested the hypothesis that immediate balloon angioplasty applied to patients with failed early reperfusion would improve left ventricular function and clinical outcome at 30 days compared with conservative management alone. METHODS AND RESULTS: One hundred fifty-one patients with first anterior wall infarction treated with any accepted intravenous thrombolytic regimen and angiographically demonstrated to have an occluded infarct vessel within 8 hours of chest pain onset were randomized to aspirin, heparin, and coronary vasodilators (conservative therapy) or to this therapy and balloon angioplasty supplemented by further thrombolytic therapy as needed. Left ventricular function was assessed using multiple-gated equilibrium radionuclide technique to determine ejection fraction, and adverse clinical outcome was assessed evaluating death, ventricular tachycardia, and class III or IV heart failure at 30 days. Seventy-three patients were randomized to conservative therapy and 78 to angioplasty. The two groups were well balanced for patient age (59 +/- 11 years), sex (82% were male), and time to randomization (4.5 +/- 1.9 hours). Angioplasty was technically successful in 72 of 78 randomized patients (92%). Two patients randomized to conservative therapy crossed over to angioplasty within 72 hours. Resting 30-day ejection fraction was 40 +/- 11% in the angioplasty group and 39 +/- 12% in the conservative group (P = .49), but ejection fraction with exercise was 43 +/- 15% and 38 +/- 13% for the angioplasty and conservatively treated groups, respectively (P = .04). Adverse clinical outcomes included death in 5% and 10% (P = .18), severe heart failure in 1% and 7% (P = .11), and either death or severe heart failure in 6% and 17% (P = .05) of the angioplasty and conservatively managed groups, respectively. CONCLUSIONS: When applied to patients with first anterior infarction, rescue angioplasty appears to be useful in the prevention of death or severe heart failure, with improvement in exercise, but not resting, ejection fraction. This strategy deserves further study and highlights the potential advantage of early mechanical restoration of infarct vessel patency when thrombolytic therapy has failed.

Aged↗

Analysis of the recourse to conservative surgery in the treatment of breast tumors.

AIMS AND BACKGROUND: Conservative surgery is the treatment of choice for malignant tumors, at least up to stage II. The aim of this study was to analyze the recourse to conservative surgery for breast tumors and its determinants (ie, characteristics of hospitals and patients). METHODS: The study was conducted in Italy's Lazio region and was based on administrative data of the regional Hospital Information System, a database on hospitalizations. We selected all regional hospitalizations for therapeutic breast surgery over 1997, classifying them as either "conservative" or "non-conservative". The other variables considered were type of hospital, number of beds, volume of activity (average annual number of hospitalizations for breast cancer surgery), specific diagnosis, severity of cancer, and patient's age, place of residence, and socioeconomic level. A logistic model was used for multivariate analysis. RESULTS: A total of 7235 hospitalizations were analyzed, 3570 (49%) for malignant tumors and 3665 (51%) for benign disease. The logistic model showed that the factors most closely correlated with conservative surgery were age (OR = 2.2; 95% Cl: 1.8-2.6, for the age group <50 years compared to >70 years); severity of cancer (OR = 0.6; 95% Cl: 0.5-0.8, for non-localized compared to localized tumors), and volume of activity of the hospital (OR = 1.3; 95% CI: 1.0-1.6, for hospitals with >70 operations/year compared to those with <20 operations/year). The study also revealed that surgery for malignant tumors was performed by both high-volume and low-volume hospitals throughout the region. CONCLUSIONS: The association between conservative surgery and younger age, even after controlling for the severity of cancer, points to the need to encourage adherence to the existing guidelines. The association between conservative surgery and high-volume hospitals and the finding that a high proportion of breast operations is performed in low-volume facilities suggest that further efforts should be made to promote admission to high-volume hospitals.

Adult↗

Functional tests of enhancer conservation between distantly related species.

Expression patterns of orthologous genes are often conserved, even between distantly related organisms, suggesting that once established, developmental programs can be stably maintained over long periods of evolutionary time. Because many orthologous transcription factors are also functionally conserved, one possible model to account for homologous gene expression patterns, is conservation of specific binding sites within cis-regulatory elements of orthologous genes. If this model is correct, a cis-regulatory element from one organism would be expected to function in a distantly related organism. To test this hypothesis, we fused the green fluorescent protein gene to neuronal and muscular enhancer elements from a variety of Drosophila melanogaster genes, and tested whether these would activate expression in the homologous cell types in Caenorhabditis elegans. Regulatory elements from several genes directed appropriate expression in homologous tissue types, suggesting conservation of regulatory sites. However, enhancers of most Drosophila genes tested were not properly recognized in C. elegans, implying that over this evolutionary distance enough changes occurred in cis-regulatory sequences and/or transcription factors to prevent proper recognition of heterospecific enhancers. Comparisons of enhancer elements of orthologous genes between C. elegans and C. briggsae revealed extensive conservation, as well as specific instances of functional divergence. Our results indicate that functional changes in cis-regulatory sequences accumulate on timescales much shorter than the divergence of arthropods and nematodes, and that mechanisms other than conservation of individual binding sites within enhancer elements are responsible for the conservation of expression patterns of homologous genes between distantly related species.

Animals↗

Making very similar embryos with divergent genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona intestinalis.

Ascidian embryos develop with a fixed cell lineage into simple tadpoles. Their lineage is almost perfectly conserved, even between the evolutionarily distant species Halocynthia roretzi and Ciona intestinalis, which show no detectable sequence conservation in the non-coding regions of studied orthologous genes. To address how a common developmental program can be maintained without detectable cis-regulatory sequence conservation, we compared in both species the regulation of Otx, a gene with a shared complex expression pattern. We found that in Halocynthia, the regulatory logic is based on the use of very simple cell line-specific regulatory modules, the activities of which are conserved, in most cases, in the Ciona embryo. The activity of each of these enhancer modules relies on the conservation of a few repeated crucial binding sites for transcriptional activators, without obvious constraints on their precise number, order or orientation, or on the surrounding sequences. We propose that a combination of simplicity and degeneracy allows the conservation of the regulatory logic, despite drastic sequence divergence. The regulation of Otx in the anterior endoderm by Lhx and Fox factors may even be conserved with vertebrates.

Animals↗

Conservative versus radical surgery for tubal pregnancy. A review.

OBJECTIVE: The aim of this work was to analyse the fertility prognosis after conservative or radical surgery for tubal pregnancy. DATA SOURCES: Index Medicus was searched for all attainable literature on the subject. METHODS OF STUDY SELECTION: A total of 40 scientific publications through the latest 40 years were selected. For fulfilling the selection criterias the study design should appear clearly. Furthermore the rate of women obtaining intrauterine pregnancy and the rate of repeat ectopic pregnancy following radical or conservative tubal surgery was to be compared using 95% confidence limits. The results from each report were compared in four groups according to study design i.e. retrospective non-comparing materials, retrospective comparing studies, prospective selected treatment series or prospective randomized comparing investigations. DATA EXTRACTION AND SYNTHESIS: Pooling the results from the retrospective noncomparing materials revealed that there was no significant difference in intrauterine pregnancy rates, i.e. 46% following conservative tubal surgery and 44% after radical surgery. The repeat ectopic pregnancy rate was 10% following conservative surgery and 15% after radical surgery. In the group of restrospective comparing studies only one of 15 materials could document a significant better intrauterine pregnancy rate after conservative tubal surgery than following radical treatment for tubal pregnancy. There were no differences either in this group in repeat ectopic pregnancy rates. Prospective investigations were almost exclusively represented by selected conservative treatment series. In these series the average intrauterine pregnancy rate was 57% and the repeat ectopic pregnancy rate was 13%. CONCLUSIONS: In studies on fertility after radical or conservative surgical treatment for tubal pregnancy no significant difference in intrauterine pregnancy rates or repeat ectopic pregnancy rates were found. Prospective selected treatment series demonstrated higher intrauterine pregnancy rates than retrospective studies. The repeat ectopic pregnancy rate was not raised in prospective series. No prospective randomised trial was found.

Female↗

Tibial shaft fractures. A comparison of conservative treatment and internal fixation with conventional plates or AO compression plates.

Out of a series of 207 consecutive fractures of the tibial shaft, 102 were treated conservatively, 64 fractures were treated by AO compression plate osteosynthesis and 41 by internal fixation using Eggers or Lane plates. The choice of method was independent of the extent of soft tissue damage. A follow-up examination of 199 fractures, with a mean observation time of 3.4 years, revealed residual malalignment in 21 per cent of conservatively treated cases and in 8 per cent after conventional plate fixation, while the AO method resulted in anatomical restoration of the axis of the tibia in all cases. However, removal of the compression plates was followed by re-fractures, early and late, in 11 per cent. Implant failure occurred in 5 per cent of both types of plate fixation, and 3 per cent of the conservatively treated cases redislocated. Infection developed in 5 per cent of closed fractures and in 11 per cent of open fractures treated by operative means. Of the conservatively treated cases, only 3 per cent of the open fractures developed infection. The risk of infection following acute internal fixation is thus four times greater than with conservative treatment. AO compression plate fixation shortened the time of fracture healing considerably. The rate of non-union after conservative treatment was 6 per cent in closed and 21 per cent in open fractures. Similarly in conventional plate fixation there was non-union in 8 and 24 per cent, respectively. Non-union was not encountered after AO compression plate osteosynthesis. It is concluded that AO plate osteosynthesis is justified in the treatment of open tibial shaft fractures and also useful in closed fractures when conservative treatment does not lead to stable reduction with a good alignment.

Adolescent↗

[Scale development on health conservation of the institutionalized elderly].

PURPOSE: The purpose of this study was to develop a health conservation scale with high validity and reliability for institutionalized elderly. METHOD: The process of development of this scale was as follows. A conceptual framework composed of 4 phases of health conservation of institutionalized elderly was identified based on the literature review with elderlies and discussions with experts in health conservation. A total of 75 items, on a 4-point scale were developed. Through reliability testing and factor analysis, 57 preliminary items were selected. By means of internal consistency of the 57 items, 18 items whose inner-items correlation coefficient was below .40 were deleted. Through factor analysis, 2 items whose factor loading was below .40 were deleted. Finally 37 items remained. To verify the 37 items, factor analysis, reliability testing, and correlation was done. Data were collected from 207 institutionalized elderly subjects in Daegu, Kyungpook, Busan, and KyungNam Province from August. 2003 to February. 2004. RESULT: In the result of factor analysis of the 37 items, 4 factors were extracted. These factors were labeled as 'personal integrity', 'conservation of energy', 'structural integrity', and 'social integrity'. These factors included 4 phases of health conservation. Cronbach's Alpha of 37 the items was .9424 and the correlation coefficient of HPLP was .723. CONCLUSION: The researchers recommend the following: An explorative study on the variables related to health conservation is needed for criterion validity of this scale. Studies on health conservation of different age groups, and subjects are needed for verification.

Aged↗

Breast conservation therapy for breast cancer treatment in Brown County.

The Northeast Wisconsin Cancer Registry and a patient survey was utilized to examine the use of breast conservation surgery in Brown County between 1991 and 1997 and the factors influencing patients' treatment decisions. In all patients, the rate of breast conservation rose from approximately 30% to 44% during that time period. The percent of all patients with stage 0, I or II breast cancer who were potential candidates for breast conservation based on their stage rose from 89% in 1991 to 96% in 1997. The percent of Stage I and Stage II patients who underwent breast conserving surgery rose from 29% in 1991 to 38% in 1997. There was a higher use of breast conserving surgery in younger women (approximately 50% in age 35 to 49 years old in 1997) compared to women older than 62 (33% in 1997). Breast conservation surgery was used in 47% of patients with AJCC T1 (primary tumors less than 2 cm) and in 25% of patients with T2 lesions (primary tumors 2 to 5 cm); and more often in node negative than in node positive patients (51% vs. 20%). A patient survey revealed that a majority of patients felt that their surgeon's recommendation was the most important influence in making their surgical decision and that their fear of cancer recurrence most strongly influenced their decision on a personal level. Fewer than half of the women were referred to a medical oncologist, radiation oncologist, plastic surgeon or second opinion surgeon prior to surgery. Breast conservative treatment is increasingly utilized in Northeastern Wisconsin and women depend on their surgeon to give them clear, complete, non-biased information balanced with emotional support during the time when they are asked to make the complex decision of the type of breast cancer surgery they desire.

Adult↗

A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.

PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.

Aged↗

The natural history of untreated vestibular schwannomas. Is there a role for conservative management?

OBJECTIVE: The aim of this study was to investigate the natural history and outcome following the conservative management of a group of patients with unilateral vestibular schwannomas. METHODS: 72 patients with a radiological diagnosis of unilateral vestibular schwannoma were managed conservatively because of poor general health, advanced age, patient preference, small tumour size, minimal symptoms, or tumour in the only/better hearing ear. All patients underwent serial magnetic resonance imaging for assessment of tumour growth, according to American Academy of Otolaryngology-Head & Neck Surgery guidelines (1995). The mean duration of follow-up was 37.8 months (range 12-194 months). Patients were deemed to have failed conservative management if there was evidence of continuous or rapid radiological tumour growth, and/or increasing symptoms or signs. RESULTS: The mean tumour growth rate was 1.16 mm/year (range -0.75 to 9.65 mm/year). Approximately 83% of tumours grew at less than 2 mm/year. Significant tumour growth (total growth > 1 mm) was seen in 36.4%, no or insignificant growth (0-1 mm) in 50%, and negative growth (< 0 mm) in 13.6% of tumours. The growth rate of cerebellopontine angle (CPA) tumours (1.4 mm/year) was significantly greater than that of tumours limited to the internal auditory canal (IAC) (0.2 mm/year) (p = 0.001). Failure of conservative management, in which active treatment was required, occurred in 15.3%. The outcome of these patients appeared to be as favourable as those who underwent primary treatment, without a period of conservative management. The growth rate of tumours in patients who failed conservative management (4.2 mm/year) was significantly greater than that in patients who did not fail (0.5 mm/year) (p < 0.01). No factors predictive of tumour growth were identified. Deterioration of mean pure tone average (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred regardless of whether radiological tumour growth was demonstrated or not. CONCLUSIONS: The majority of vestibular schwannomas are slow growing, although, CPA tumours appear to grow faster than IAC tumours. Deterioration of auditory function occurs even in the absence of tumour growth. Although most Otolaryngologists and Neurosurgeons would agree that the treatment of choice for the majority of vestibular schwannomas is microsurgery, there remains a small group of patients in whom a conservative management approach may be a desirable alternative.

Adult↗

[Comparison of effectiveness of endoscopic injection of autologous blood and conservative therapy in the treatment of bilateral primary vesicoureteral reflux].

Vesicoureteral reflux (VUR) is one of the most frequent diseases which leads to pyelonephritis and furthermore, renal damage. The treatment of VUR (surgical or endoscopic) remains a controversial topic. Autologous blood injection--autohemotherapy (AHT) is used in the endoscopic treatment of VUR. The aim of the research was the comparison of efficacy of AHT and conservative therapy in children with bilateral VUR grade III. 125 children were treated endoscopically. The results of the AHT were compared with the results of conservative treatment in 121 children with the same kind of disease. Complete disappearance of VUR after AHT was observed in 61.6% of children and in 59.5% after two years of medical treatment. These results were not significantly different (p > 0.73) in contrast to the results reached after one year of conservative therapy (p < 0.01). After the conservative treatment in 33.5% of kidneys reflux nephropathy (NR) was observed. In the group treated by AHT NR developed in 25.2% of kidneys. The frequency of NR was significantly higher in children after conservative treatment (p < 0.001). 29.8% of children after conservative therapy and 8% of children after AHT were operated. The results of research proved that usefulness of intravesical autohemotherapy in the treatment of VUR. The method was safe with a low quantity of complications. The efficacy of AHT in the elimination of bilateral high grade VUR was comparable to this reached after two years of conservative treatment.

Blood Transfusion, Autologous↗

[Conservative treatment of placenta accreta].

OBJECTIVE: Examination of modalities and results of conservative treatment of placenta accreta. MATERIAL AND METHOD: Ten-year hospital records were reviewed, with analysis of patients who had diagnosis of placenta accreta associated with conservative treatment. RESULTS: During the study period, 21259 deliveries were registered, with an incidence of placenta accreta of 1 per 1 000 deliveries (n=23). Conservative treatment was applied in 13 patients. All of them had factors commonly associated with placenta accreta: prior cesarean sections (7/13), prior curettage or endouterine surgery (11/13), placenta praevia (11/13). Antenatal diagnosis was performed in only 64% of the cases (n=7). In our conservative strategy, placenta accreta was always left in situ, with an associated treatment in most of cases (n=10): Bilateral hypogastric artery ligation (n=7), medical treatment with methotrexate (n=5), uterine artery embolization (n=2). There was no case of maternal mortality. Conservative treatment was successful in 11 patients. It failed in 2 cases: hysterectomy was performed in one case for life-threatening hemorrhage, and in the other case for post-embolization uterine necrosis. The morbidity described was blood transfusion (n=7), endometritis (n=1), and one late hemorrhage with expelling necrotic tissue. Afterwards, 2 women became pregnant: one miscarriage and one normal term delivery. CONCLUSION: Conservative treatment of placenta accreta appears to be a efficient way to preserve fertility. Antepartum diagnosis should be improved among patients with a high risk of placenta accreta in order to optimize conservative strategy.

Abortifacient Agents, Nonsteroidal↗

Conservative regimen for chronic critical limb ischemia.

OBJECTIVE: The objective of this study was to determine the effectiveness of the treatment of chronic critical limb ischemia by conservative regimen. METHOD: Data for all patients who underwent a conservative regimen at a single institution from January 1997 to December 2001 were entered into the registry. Conservative regimen consisted of cilostazol (Pletaal) 200 mg/day, a vegetarian diet, had completely stopped smoking and had progressive walking training. RESULTS: A total of 53 patients (59 limbs) with chronic critical limb ischemia were treated with a conservative regimen. The conservative regimen failed in 19 limbs (32.2%). In the failed limbs, infrainguinal bypass was performed on 8 limbs, aortoiliac endarterectomy was performed on 1 limb and 6 had primary amputation. The other four limbs were treated conservatively until death because of very poor cardiac function. Post-operatively, 2 grafts had thrombosis and led to amputation. CONCLUSION: These early results appear to be promising with 67.8 per cent limb saving. This conservative regimen may be appropriately performed in selected chronic critical limb ischemia, especially those who presented with clinical severe claudication, rest pain or nonhealed ulcer. Cilostazol administration may play a positive role in gangrenous limbs.

Chi-Square Distribution↗

Evidence that the conserved region in the steroid binding domain of the glucocorticoid receptor is required for both optimal binding of hsp90 and protection from proteolytic cleavage. A two-site model for hsp90 binding to the steroid binding domain.

Steroid hormone receptors contain a conserved sequence of amino acids within the steroid binding domain, and we have previously speculated that this conserved region is the site of interaction of the glucocorticoid receptor with hsp90 (Danielsen, M., Northrop, J. P., and Ringold, G. M. (1986) EMBO J. 5, 2513-2522; Pratt, W. B., Jolly, D. J., Pratt, D. V., Hollenberg, S. M., Giguere, V., Cadepond, F. M., Schweizer-Groyer, G., Catelli, M.-G., Evans, R. M., and Baulieu, E.-E. (1988) J. Biol. Chem. 263, 267-273). In this work, we transfect COS-7 cells with three mutants of the mouse glucocorticoid receptor deleted for all or part of this conserved region. The mutant receptor missing the entire conserved region is very unstable and is found predominantly as cleavage products. Approximately one-third of the cleavage products have lost most or all of the steroid binding domain. This mutant receptor has a constitutive activity that is about one-third that of the steroid-bound wild type receptor in stimulating transcription from a reporter gene. We propose that the partial constitutive activity results from proteolytic cleavage of the steroid binding domain from the rest of the receptor, thus removing the functional repression determined by this domain. This mutant receptor is associated with hsp90 in cytosols prepared in the presence of molybdate but, when molybdate is not present, the receptor is unstable and there is very little receptor-associated hsp90. This observation is consistent with the proposal that binding of hsp90 helps to stabilize the glucocorticoid receptor against proteolysis, and it demonstrates that the site of molybdate interaction with the receptor lies outside of the conserved sequence. Our data are interpreted according to a two-site model in which hsp90 interacts with the steroid binding domain at two sites. One site is in the conserved sequence, and the other is at a transition metal oxyanion binding site, located between the conserved sequence and the COOH terminus.

Animals↗

[Conservative treatment of pediatric elbow fractures].

Between 1978 and 1982, 146 children with elbow fractures were treated at the Department of Traumatology of the Freiburg University Hospital. Forty-two children received conservative treatment and in 104 an operation was performed. The possibilities for conservative treatment of the elbow joint in children are discussed together with our results. Out of 47 supracondylar fractures of the humerus, 25 were treated conservatively (28%, dislocation grade 1; 48%, grade 2). Good or very good results were achieved in more than 76%. Unstable grade 3 fractures often involve rotation of the elbow; in 35% of such cases, conservative treatment leads to a cubitus varus. Operative stabilization is definitely indicated here. Neither serious changes in the carrying angle nor ischaemic contractures were seen. Out of 24 intra-articular fractures of the distal humerus, only 4 were treated conservatively; only fractures without dislocation are regarded as an indication for conservative treatment. Fractures of the neck of the radius were treated conservatively in 6 out of 12 cases. There was angulation of the radius head of more than 30 degrees in 4 cases, necessitating a closed reduction. The follow-up of these children shows very good results in all cases.

Adolescent↗

Conservative management options for cervical pregnancy; case reports and literature review.

OBJECTIVE: To describe three cases of cervical pregnancy treated successfully with different conservative methods and review the literature on conservative treatment of cervical pregnancy over the last 30 years. METHODS: Three patients treated conservatively for cervical pregnancy are reported. The literature regarding the conservative management of cervical pregnancy since 1965 was compiled using a MEDLINE search for articles published since 1980 and by reviewing the reference lists of published manuscripts. RESULTS: Three cases of cervical pregnancy were successfully treated using methotrexate with leucovorin rescue, methotrexate without leucovorin rescue, and curettage after angiographic embolization of the right hypogastric and left uterine arteries. Review of conservatively managed cases of cervical pregnancy since 1965 indicates that medical management with methotrexate and preoperative angiographic embolization of the uterine blood supply, when appropriate, results in successful treatment without the need for transfusion. CONCLUSIONS: Clinical suspicion of cervical pregnancy early in gestation with preoperative diagnosis may safely allow conservative treatment. Different clinical scenarios may preclude or limit which conservative management options are best for each case.

Adult↗