Nonoperative management of esophageal perforations. Is it justified?

OBJECTIVE: Experiences obtained with nonoperative treatment (NOT), i.e. total prohibition of per oral food intake for a minimum of 7 days, administration of combinations of broad-spectrum antibiotics, and parenteral hyperalimentation, are described in the management of esophageal perforations. SUMMARY BACKGROUND DATA: The place, value, and indication of NOT in the management of esophageal perforation has not yet been unequivocally defined. As a result, contradictory data have been published regarding the outcome of NOT. METHODS: During the past 15 years (1979 to 1994), 20 of 86 patients (23.3%) with esophageal perforation have been treated nonoperatively from the outset. In this group, perforations were located to the upper, middle, and lower third of the esophagus in 50%, 30%, and 20%, respectively. In the operative management group (OT)--in which conservative (drainage, endeprothesis), reconstructive (suture, reinforced suture), and radical (resection) surgical methods were applied--lesions were preponderantly located in the lower one third of the esophagus (56.1%--37/66). As to the interval between the perforation and the onset of treatment, 14 patients had been diagnosed within 24 hours, whereas in 6 cases treatment had been begun beyond 24 hours. RESULTS: NOT could be successfully carried out in 16 patients; the decision to use NOT had to be revised in 4 other cases (Table 1). Two patients were lost; the mortality rate was 10% (2 of 20). The rate of complications was lower in the NOT group (20%, or 4 of 20) than in the OT group (50%, or 33 of 66). CONCLUSIONS: NOT can be suggested for the treatment of intramural perforations. In the case of transmural perforation, this approach should be taken into consideration if the esophageal lesion is circumscribed, is not in neoplastic tissue, is not in the abdominal cavity, and is not accompanied by simultaneous obstructive esophageal disease; in addition, symptoms and signs of septicemia should be absent.     

Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.     

Expression and molecular characterization of an enzymatically active recombinant human spumaretrovirus protease

A theoretical model is presented by which a true expression of pregnancy rate resulting from stimulated cycles can be calculated. This includes the transfer of both fresh and cryopreserved embryos. It is concluded that the total reproductive potential of a single cycle of stimulation can only be evaluated by including pregnancies arising from all fresh and frozen embryo transfers resulting from that cycle.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Modeling, histological study and pathogenetic aspects of experimental traumatic osteomyelitis

The tibial diaphysis osteotomy with limited separation of periosteum on the ends of the fragments with subsequent local infection by Staphylococcus aureus culture was conducted. In 90% of observations chronic inflammation was revealed in affected bones while morphological investigation conduction. An acute traumatic disorders of intraosseous blood circulation (the bone infarction) and local staphylococcal infection play the main role in the traumatic osteomyelitis pathogenesis.