Ex vivo culture of peripheral blood CD34+ cells: effects of hematopoietic growth factors on production of neutrophilic precursors

A major potential application for ex vivo culture of hematopoietic progenitor cells is the treatment of cytopenia following high-dose chemotherapy and hematopoietic transplantation. We have previously postulated that infusion of a sufficient number of neutrophil postprogenitor cells generated by ex vivo culture of CD34+ cells may be able to abrogate neutropenia. In this article, we describe further development of an efficient stromal-free, cytokine-dependent, static culture system for generation of these cells. Our previous studies indicated that maximal production of nucleated cells and myeloid progenitor cells from PB CD34+ cells occurred with multiple hematopoietic growth factor (HGF), notably the 6-HGF combination of interleukin (IL)-1, IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and stem cell factor (SCF). In the present study, we determine the contribution of each of these 6 HGF in generation of neutrophilic precursors. SCF, G-CSF, and IL-3 were found to be the most important HGF for production of neutrophilic cells. The 4-HGF combination of IL-3, IL-6, G-CSF, and SCF was optimized by performing dose-response experiments and shown to be as potent as 6 HGF for production of nascent CFU-GM and neutrophilic precursors.     

Axis II psychopathology as a function of Axis I disorders in childhood and adolescence

OBJECTIVE: To examine the occurrence of elevated personality disorder (PD) dimensional scores in a community sample of young adults as a function of the occurrence of Axis I disorders through age 18 years. METHOD: 299 individuals who had been interviewed regarding Axis I disorders twice while in adolescence (first when 14 through 18 years of age) were carefully assessed regarding Axis I and II psychopathology at age 24. RESULTS: The prevalence of PD diagnoses was relatively low (3.8% in participants with a history of Axis I versus 1.7% in participants with no Axis I history). The occurrence of all four Axis I diagnostic categories (major depression, anxiety disorders, disruptive behavior disorders, substance use disorders) in childhood and adolescence was associated with elevated PD dimensional scores. The likelihood of elevated PD dimensional scores increased as a function of the number of Axis I disorders. Elevated PD scores were significantly associated with a negative course of major depression. CONCLUSIONS: Although the rates of PDs were low, the findings suggest a substantial degree of association between early-onset Axis I disorders and Axis II psychopathology in young adulthood. More research is needed to develop assessment and treatment recommendations addressing the early manifestations of PDs.     

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

Community respiratory viral infection in adult lung transplant recipients

STUDY OBJECTIVE: To define the epidemiology, clinical manifestations, and long-term complications of respiratory viral infections in adult lung transplant recipients. DESIGN: Retrospective review of the records of 122 adult lung transplant recipients over a 5-year period at one institution. RESULTS: Ten episodes of infection with respiratory syncytial virus, parainfluenza, influenza, or adenovirus were identified. All patients presented with symptoms of respiratory tract infection. Two patients died acutely and four patients subsequently had development of obliterative bronchiolitis (OB). CONCLUSIONS: These data suggest community respiratory viral infections cause significant morbidity and mortality in lung transplant recipients. Further prospective studies are warranted to clarify the relationship between respiratory viral infection and OB and to define the optimal therapy for these viral infections.     

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.     

Learning curve for oesophageal cancer surgery

BACKGROUND: Surgical training and experience are frequently claimed to influence early and late outcome measures. The aim of this study was to examine any improvement in an individual surgeon's performance in one operation over a period of 7 years from initial appointment to date. METHODS: Patients undergoing Ivor Lewis subtotal oesophagectomy performed by a single surgeon between April 1990 and December 1996 were identified from a prospectively compiled oesophageal cancer database. Operating time (abdominal, thoracic and 'one-lung time'), blood loss, transfusion requirements (intraoperative and total), extent of lymphadenectomy (number of lymph nodes sampled), intensive treatment unit (ITU) stay, hospital stay, postoperative morbidity and mortality, pathological stage, grade and survival were recorded. RESULTS: The records of 150 patients were identified for analysis. The cohort was split into five groups, each of 30 patients operated on consecutively. Each of the groups was comparable for age, sex, smoking history, preoperative haemoglobin and creatinine levels, weight loss, American Society of Anesthesiologists' grade, and histological stage and grade of disease. Analysis of the variables pertaining to operation revealed a significant improvement with time including reduced single-lung operating time (P=0.01), reduced blood loss (P=0.03), reduced transfusion requirement (P < 0.0001), reduced ITU stay (P< 0.0001), reduced inpatient stay (P< 0.0001) and an increased yield of lymph nodes (P < 0.0001). CONCLUSION: This study showed a continuing improvement in a surgeon's performance over a 7-year period. With the current trend to shorter training periods there is a case for continuing supervision of the 'fully trained' surgeon within highly specialist units.     

Evaluation of an adenosine 5'-triphosphate assay as a screening method to detect significant bacteriuria

The bioluminescent reaction of adenosine 5'-triphosphate (ATP) with luciferin and luciferase has been used in conjunction with a sensitive photometer (Lab-Line's ATP photometer) to detect significant bacteriuria in urine. This rapid method of screening urine specimens for bacteriuria was evaluated by using 348 urine specimens submitted to the clinical microbiology laboratory at the University of Minnesota Hospitals for routine culture using the calibrated loop-streak plate method. There was 89.4% agreement between the culture method and the ATP assay, with 7.0% false positive and 27.0% false negative results from the ATP assay using 10(5) organisms/ml of urine or greater as positive for significant bacteriuria and less than 10(5) organisms/ml as negative for significant bacteriuria.