Inhibition of phorbol ester-mediated phenotypic changes in cultured cells by hypoxanthine

Hypoxanthine induces the differentiation of certain transformedcells in vitro, so analyses were undertaken to determine whetherthis purine metabolite might influence the expression of transformedphenotypes induced in normal cells by chemical agents. Chinesehamster embryo cells and human skin fibroblasts in culture weretreated with the promoting agent phorbol-12,13-didecanoate (PDD)with or without prior treatment with 3-methylcholanthrene (MCA),and various phenotypic effects were monitored. Hypoxanthinewas found to inhibit significantly the formation of type IIIfoci and the increase in saturation density observed for Chinesehamster cells treated with MCA plus the phorbol ester. Inosineand the hypoxanthine analogue aUopurinol could also mediatethe effect on saturation density, while xanthosine could not.An increase in the saturation density of human skin fibroblasts,which can be induced by the phorbol ester alone, was also inhibitedby hypoxanthine. There was no significant effect on the growthrate or the intracelhilar nucleotide pools with hypoxanthine-treatedcells. The results suggest that a normal purine metabolite,hypoxanthine, can modulate the expression of transformed phenotypesinduced in vitro by the known tumor promoter PDD. These observationscould help in elucidating the cellular basis for promotion ofcarcinogenesis.     

Therapeutic bronchoscopy in broncholithiasis.

Bronchoscopy is considered the most important diagnostic test for broncholithiasis. However, its role in the treatment of broncholithiasis in a large group of patients has not been studied. To evaluate the therapeutic role of bronchoscopy, we retrospectively reviewed the clinical data of patients with broncholithiasis who also underwent bronchoscopy at Mayo Clinic. Bronchoscopy revealed 127 broncholiths (free or partly eroded calcified material in the airway lumen) in 95 patients (49 men and 46 women) evaluated between 1954 and 1994. Bronchoscopic removal of 71 (56%) broncholiths was attempted in 48 patients (50.5%) during 61 bronchoscopy sessions. Forty-eight of the broncholiths selected for removal were partly eroding into the tracheobronchial lumen and 23 were free. Forty-eight percent (23 of 48) of the partly eroding broncholiths were successfully removed bronchoscopically, with a greater percentage removed with the rigid bronchoscope (67%) than with the flexible bronchoscope (30%). All free broncholiths were completely extracted regardless of the type of bronchoscope used. Complications occurred in only two patients (4% of the bronchoscopic broncholithectomy group), both with partially eroded broncholiths, and consisted of hemorrhage in one patient requiring thoracotomy and acute dyspnea in another patient, caused by a loose broncholith lodged in the trachea. We conclude that flexible and/or rigid bronchoscopic extraction of partly eroded or free broncholiths in the tracheobronchial tree can be considered safe and effective.     

Pers?nliche Meinung?Der symptomatische Koronarpatient mit pathologischem operationsbedürftigen Koronarangiogramm

Zusammenfassung: Die Bypasschirurgie hat sich bei exzellenten Kurz- und Langzeitergebnissen als fester Bestandteil in der Therapie der koronaren Herzerkrankung etabliert. Zur Anpassung an eine veränderte Patientenstruktur mit einem hohen Anteil an Hochrisikopatienten sind zunehmend minimalinvasive chirurgische Techniken in der Herzchirurgie zum Einsatz gekommen. Ergänzend zu chirurgischen Maßnahmen werden molekularbiologische Techniken in der Primär- und Sekundärtherapie der koronaren Herzkrankheit eingesetzt. Abstract: Bypass surgery has become a routine procedure for the treatment of coronary artery disease. Due to increase numbers of high-risk patients minimally invasive techniques were introduced in cardiac surgery with excellent clinical results. In addition molecular methods have been applied for primary and secondary treatment of coronary artery disease.     

Testicular seminoma metastatic to the prostate

A 43-year-old man had clinically manifest prostatic involvement by a metastatic testicular seminoma. The signs, symptoms, diagnosis and treatment of this entity, as well as a hypothesis regarding its development, are discussed.     

Treatment options for patients with stage D1 (T0-3,N1-2,M0) adenocarcinoma of prostate

Three hundred six patients with adenocarcinoma of the prostate underwent pelvic lymphadenectomy and had Stage D1 (T0-3,N1-2,M0) disease; 171 patients underwent radical retropubic prostatectomy with or without immediate adjuvant therapy (hormonal or radiation or both) or conservative (hormonal or radiation or both) treatment alone (n = 135). Follow-up was one-half to eighteen and one-half years (mean, 5 yrs). Immediate adjuvant orchiectomy significantly (P = 0.01) improved survival (87.4% at 10 years) and nonprogression rates for patients who underwent radical prostatectomy, but not for those who had lymphadenectomy. Overall patient survival was significantly better (P = 0.005) after prostatectomy than lymphadenectomy. Residual disease (n = 43) in patients who underwent prostatectomy and received adjuvant treatment (orchiectomy or radiation or both) did not affect disease outcome. Bilateral pelvic lymphadenectomy and radical prostatectomy with immediate adjuvant orchiectomy provided survival comparable to the expected survival; conservative treatment alone was associated with rapid disease progression and poor survival and significantly (P = 0.02) higher local morbidity.     

Native infective endocarditis: Which determinants of outcome remain after surgical treatment?

Summary Surgical therapy of native infective endocarditis is still considered as a particular challenge, due to remaining morbidity and mortality up to 20%. Further risk analysis and characterization of clinical features is of great importance for further improvement of surgical results. The aim of this retrospective study was a risk analysis concerning clinical features of the pre–, intra– and postoperative period. Between 02/1997 and 12/2003, 165 patients (130 male, 35 female, age 55.5 ± 13.8 years) were referred for surgical therapy of infective endocarditis at our institution. Preoperative, intraoperative and postoperative features were evaluated for their influence on the early postoperative course and the mid–term follow–up. In the majority of patients (pts) the aortic valve was infected (n = 83, 50.3% of pts), followed by mitral valve (n = 33; 20.0%), tricuspid valve (n = 10, 6.0%) and pulmonary valve (n = 2; 1.2%). Double valve affection was recorded in 37 pts (22.4%). Streptococci (n = 66, 40.0%) and staphylococci (n = 66, 40.0%) were the most common pathogens. The overall hospital mortality rate was 10.9% (n = 18), during follow–up (mean follow–up 3.3 ± 2.5 years) a further 20 pts (12.1%) died. Main predictors for hospital mortality in multivariate analysis were older age (p = 0.01), prolonged ICU stay, prolonged intubation (p = 0.03; p = 0.02) and the continuous postoperative need of alpha–catecholamine medication (p < 0.01). Significant predictors of overall mortality were older age (> 70 years) and diabetes (p = 0.03; p = 0.03). Reinfection occurred in 6.1% of patients (n = 10). Actuarial freedom from recurrent infection was 97% at 1 year and 93.9% at 5 years. Surgical therapy of infective endocarditis is associated with good clinical results in the early and mid–term follow–up. Predictors of outcome particular include preoperative risk constellation or comorbidity (age, diabetes) and variables of the immediate postoperative course.     

High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health,Aging, and Disease

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Treatment of osteoporosis after liver transplantation with ibandronate

Osteoporosis is a major side‐effect after liver transplantation (LTX). Therefore, the objective of the study was to evaluate the efficacy of ibandronate to reduce fractures after LTX. Seventy‐four patients after LTX were included in the study and measurements of bone mineral density (BMD) of lumbar spine and proximal femur using dual energy X‐ray absorptiometry (DEXA) were performed prior to and 3, 6, 12 and 24 months after surgery. The study group (IBA) consisted of 34 patients who received calcium (1 g/day), vitamin D3 (800–1000 IE/day) and ibandronate 2 mg every 3 months intravenously for 1 year. The control group consisted of 40 patients (CON) who received calcium and vitamin D3 at the same dosages. Prevalence of new fractures was predefined as primary endpoint. Changes of BMD and biochemical markers of bone metabolism were also investigated. In all patients, we found a reduction of BMD in the first few months after LTX. In the lumbar spine and the proximal femur the maximum reduction occurred 3 and 6 months post‐LTX. One and 2 years after transplantation, the group receiving ibandronate demonstrated a better recovery from loss of BMD and a significantly lower prevalence of fractures (IBA 2 vs. CON 10 P < 0.04, χ²). Ibandronate with calcium and vitamin D3 reduces the BMD‐loss after LTX and decreases the rate of bone fractures significantly.