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Biomedical subjects

R M Kotloff

Publications and source records attributed to R M Kotloff.

33 records · Page 2Linked to original sources
PubMed1998

Comparison of short-term functional outcomes following unilateral and bilateral lung volume reduction surgery.

STUDY OBJECTIVES: To compare short-term functional outcomes following unilateral and bilateral lung volume reduction surgery (LVRS) performed in patients with advanced emphysema. METHODS: LVRS was performed unilaterally in 32 patients and bilaterally in 119 patients. Pulmonary function testing and 6-min walk test (6MWT) were performed preoperatively and repeated at 3 to 6 months postoperatively. RESULTS: Bilateral LVRS was associated with increased in-hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There was no significant difference in duration of air leaks between unilateral and bilateral groups, but the mean hospital stay was significantly longer following bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively, there was no significant difference between the unilateral and bilateral groups with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of these parameters, the magnitude of improvement was significantly greater following bilateral LVRS. Notably, the magnitude of improvement in each parameter following unilateral LVRS exceeded half that following bilateral LVRS, suggesting that functional outcomes after the unilateral procedure were disproportionate to the amount of tissue resected. Serial functional assessment of seven patients undergoing staged unilateral procedures (two unilateral procedures separated in time by at least 3 months) demonstrated somewhat unpredictable responses; failure to achieve a favorable response to the initial procedure did not necessarily portend a similar outcome with the contralateral side, and vise versa. CONCLUSIONS: Bilateral LVRS produces a greater magnitude of short-term functional improvement than does the unilateral procedure and should be considered the procedure of choice for most patients. Unilateral LVRS should be reserved for patients in whom factors contraindicating entrance into one hemithorax exist.

Endoscopy↗
PubMed1998

Primary graft failure following lung transplantation.

STUDY OBJECTIVES: To determine the incidence of primary graft failure (PGF) following lung transplantation, assess possible risk factors, and characterize its effect on outcomes. METHODS: Retrospective review of 100 consecutive patients undergoing lung transplantation at the University of Pennsylvania Medical Center. Fifteen patients meeting diagnostic criteria for PGF (PGF+ group) were compared with 85 patients without this complication (PGF- group). RESULTS: The incidence of PGF was 15%. There was no significant difference in age, sex, underlying pulmonary disease, preoperative pulmonary artery systolic pressure, type of transplant, allograft ischemic times, use of cardiopulmonary bypass, or use of postoperative prostaglandin E1 infusion between the PGF+ and PGF- groups. Induction therapy with antilymphocyte globulin was used less frequently in the PGF+ group (p<0.005). Duration of mechanical ventilatory support was 36+/-43 days vs 4+/-6 days for the PGF+ and PGF- groups, respectively (p<0.0001). Hospital stay was significantly longer in the PGF+ group, averaging 75+/-105 days, compared with 27+/-38 days in the PGF group (p<0.005). One-year actuarial survival for the PGF+ group was only 40% compared with 69% for the PGF- group (p<0.005). Five of the six PGF+ survivors were ambulatory by 1 year; three were completely independent while two continued to require assistance with activities of daily living. Six-minute walk test distance among the ambulatory patients averaged 883+/-463 feet (range, 200 to 1,223 feet) compared with 1513+/-424 feet for the PGF- group (p<0.005). Among the subset of survivors who underwent single lung transplantation for COPD, the mean percent predicted FEV1 at 1 year was 43% for the PGF+ group and 55% for the PGF- groups, but this difference was not statistically significant. CONCLUSIONS: PGF is a devastating postoperative complication, occurring in 15% of patients in the current series, and it is associated with a high mortality rate, lengthy hospitalization, and protracted and often compromised recovery among survivors.

Activities of Daily Living↗
PubMed1998

Surgical approaches to advanced emphysema.

The care of patients with advanced emphysema requires an understanding of both medical and surgical therapy for this disease. Current surgical approaches to advanced emphysema include bullectomy, lung volume reduction surgery, and lung transplantation. Each procedure is applicable to a specific subset of patients. This article reviews the evaluation and selection of patients for each procedure, as well as operative and postoperative management, mechanisms by which surgery improves function, and overall outcomes after each procedure.

Female↗
PubMed1997

Fatal hyperammonemia following orthotopic lung transplantation.

There have been anecdotes of unexplained coma and death in patients after otherwise successful orthotopic lung transplantation. A patient with primary pulmonary hypertension who underwent a technically uncomplicated single orthotopic lung transplantation is described. The patient developed intractable status epilepticus 4 days after surgery in association with the presence of a markedly elevated plasma ammonium level. Despite multiple therapeutic interventions, the hyperammonemia ultimately resulted in the patient's death. Both metabolic and enzymatic studies showed that the unique physiological disturbance in this disorder results at least in part from defective in vivo conversion of waste nitrogen to urea and increased production of waste nitrogen. Although the rate of hepatic ureagenesis was therefore insufficient to prevent accumulation of ammonium, the cause was not severe liver disease. Liver histology showed widespread, microvesicular steatosis on light-microscopic examination, but only electron-microscopic examination showed severe microvesicular steatosis with severe mitochondrial injury. As in Reye's syndrome, it was unclear whether the hepatic mitochondrial injury played a role in development or if it was the result of hyperammonemia. We recommended that any patient with an unexplained alteration of mental status after solid organ transplantation be evaluated for hyperammonemia.

Ammonia↗
PubMed1997

Lung transplantation. A disease-specific approach.

Lung transplantation has emerged as a viable option for the treatment of end-stage disease attributable to a wide spectrum of primary disorders. Although many aspects of patient management are indifferent to the underlying indication, important differences related to timing of transplantation, selection of candidates, choice of procedure, and post-transplant complications exist among the various primary disease groups. Optimal utilization of transplantation for these challenging patient populations with advanced lung disease mandates a thorough appreciation of those differences.

Heart-Lung Transplantation↗
PubMed1997

Radiographic pulmonary infiltrates.

The finding of a pulmonary infiltrate on chest radiograph may represent a spectrum of pathologic entities in the acutely ill hospitalized adult. Timely intervention depends on the advanced practice nurse's ability to devise a differential diagnosis based on the characteristics of the infiltrate and the clinical setting. Pulmonary infiltrates are described as interstitial or alveolar, diffuse or focal. Their presentation may be chronic or acute in nature. Understanding the nuances of chest radiographic interpretation provides the foundation on which the infiltrate is described and is therefore the first step in establishing the differential diagnosis. Thorough clinical assessment and thoughtful requisition of diagnostic studies are used to discriminate the disorders found in the differential diagnosis. Using an organized approach to describe the radiographic abnormality and define its clinical context, the advanced practice nurse can efficiently establish a diagnosis so that the work of treatment may begin.

Acute Disease↗
PubMed1997

Bilateral sequential lung transplantation for pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is characterized by deposition of calcium phosphate within the alveolar airspaces. There is currently no effective medical therapy and affected individuals may progress to end-stage lung disease requiring transplantation. Two patients with PAM underwent bilateral sequential lung transplantation. This study reviews the clinical manifestations of PAM and discusses the particular difficulties that may be encountered in the use of lung transplantation as treatment for this uncommon disease. Also addressed is the question of recurrence in the allograft.

Adult↗
PubMed1996

Bilateral lung volume reduction surgery for advanced emphysema. A comparison of median sternotomy and thoracoscopic approaches.

STUDY OBJECTIVES: To compare short-term outcomes following bilateral lung volume reduction surgery performed by median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). METHODS: Bilateral lung volume reduction surgery was performed by MS in 80 patients and by VATS in 40. All patients underwent preoperative assessment with pulmonary function testing, arterial blood gas determination, and 6-min walk test (6MWT). Pulmonary function testing and 6MWT were repeated at 3 to 6 months postoperatively. RESULTS: The mean age of the VATS group was lower than that of the MS group (59.3 +/- 9.4 vs 62.4 +/- 6.9 years; p = 0.001), but there were no differences in baseline functional parameters of disease severity (FEV1, FVC, residual volume [RV], arterial PCO2, or 6MWT). All patients in both groups were extubated at the completion of surgery, but 17.5% of patients in the MS group and 2.5% in the VATS group (p = 0.02) subsequently required reintubation at some point during the postoperative course. Thirty-day operative mortality was 4.2% for the MS group and 2.5% for the VATS group (p = not significant). However, total in-hospital mortality was 13.8% for the MS group, while it remained 2.5% for the VATS group (p = 0.05). Mortality was largely confined to patients 65 years of age or older. There was no significant difference in duration of air leaks or length of hospital stay between the two groups. Functional outcomes achieved with the two techniques were similar. Specifically, there was no difference between the two groups in mean postoperative FEV1, FVC, RV, or 6MWT, or in the magnitude of change in these parameters over preoperative values. CONCLUSIONS: Bilateral lung volume reduction surgery performed by either MS and VATS approaches leads to similar improvements in pulmonary function and exercise tolerance. VATS is associated with a significantly lower incidence of respiratory failure and a trend toward decreased in-hospital mortality and may be the preferred technique, particularly for high-risk patients.

Carbon Dioxide↗
PubMed1994

Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts.

IL-6 is a multi-functional cytokine that plays an important role in normal biologic homeostasis and disease pathogenesis. Retinoids are vitamin A analogs that regulate the function of a wide variety of inflammatory and structural cells. To further understand the biology of retinoids and IL-6 we determined whether all-trans-retinoic acid (RA) and other retinoids regulate lung fibroblast IL-6 production. RA did not stimulate fibroblast IL-6 production. Instead, it inhibited the production of IL-6 by IL-1-stimulated cells. This effect was dose-dependent with an IC50 of 10(-7) M RA and significant inhibition being noted with doses of RA as low as 10(-8) M. These inhibitory effects could not be explained by cytotoxicity or a shift in the kinetics of IL-6 production. They also did not appear to involve alterations in the early events in IL-1-induced IL-6 production, because RA inhibited IL-6 production even when added 6 h after IL-1 and RA did not inhibit IL-1 binding to cell surface IL-1 receptors. RA inhibition of IL-6 protein production was associated with a comparable decrease in IL-6 mRNA accumulation and gene transcription. 13-cis-retinoic acid, retinol, retinaldehyde, all-trans etretin, Ro 13-6298, and 9-cis retinoic acid also inhibited IL-1-induced IL-6 production. However, 4-hydroxyphenyl retinamide and etretinate did not share this property. The inhibitory effects of these analogues may be mediated by nuclear retinoic acid receptors as mRNA encoding RAR-alpha, RAR-gamma, and RXR-alpha were present, and RAR-beta was induced by RA in human lung fibroblasts. These studies demonstrate that RA and other retinoid analogs inhibit IL-1-induced IL-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated.

Cell Line↗
PubMed1993

Chronic beryllium disease in a dental laboratory technician.

Workers involved in the manufacture of dental prostheses are exposed to a number of potentially harmful substances capable of inducing lung disease. In this report, we describe a dental laboratory technician who developed chronic beryllium disease as a result of exposure in the workplace. The diagnosis of chronic beryllium disease was suspected from the clinical, radiographic, and histologic features and confirmed by the in vitro proliferation of lung lymphocytes to beryllium salts. The potential risks of beryllium use in the dental industry have been recognized for some time, but this is the first documentation of chronic beryllium disease in this population of workers. Since chronic beryllium disease may be easily confused with sarcoidosis, awareness of this occupational association is essential in preventing misdiagnosis and in providing appropriate management.

Adult↗
PubMed1992

Fertility and pregnancy in patients with cystic fibrosis.

Issues related to fertility and pregnancy, once moot, are now extremely relevant to the care of a growing number of CF patients entering adulthood. With rare exception, men are infertile, due to the almost universal presence of malformations of the reproductive tract causing obstructive azoospermia. Emphasis in the care of these patients should be directed toward confirmation of infertility and counseling to allay anxieties. In contrast, a significant albeit unknown proportion of women are fertile and a steadily increasing number of these women are conceiving. The accumulated clinical experience has demonstrated that pregnancy is well-tolerated by patients with mild disease while associated with increased maternal and fetal complications in those with severe disease. In light of current uncertainties in accurately predicting outcome in all but the most clear-cut cases, the physician must exercise clinical judgment in providing a realistic assessment of the medical risks involved and of the advisability of pregnancy. This assessment should be based on a thorough and objective evaluation of the pulmonary, cardiac, and nutritional status of the patient. Future efforts, assisted by data collected for the national CF patient registry, should be directed toward better defining the long-term impact of pregnancy on the natural history of CF and more precisely defining the pregravid parameters useful in predicting outcome for both mother and child.

Counseling↗
PubMed1990

Human alveolar macrophage and blood monocyte interleukin-6 production.

Interleukin-6 (IL-6) modulates a number of processes relevant to host immunity and inflammation. We investigated the capacity of the human alveolar macrophage to elaborate IL-6 in response to lipopolysaccharide (LPS), recombinant interleukin-1 (rIL-1), and recombinant tumor necrosis factor (rTNF), and compared macrophage IL-6 production to that of blood monocytes and lung fibroblasts. Unstimulated and TNF-stimulated alveolar macrophages and monocytes produced little or no detectable IL-6. In contrast, macrophages and monocytes produced large amounts of IL-6 in response to LPS and monocytes produced lesser but readily detectable amounts in response to rIL-1. Monocytes and alveolar macrophages differed significantly in their capacity to produce IL-6, with macrophages making more IL-6 in response to LPS and less IL-6 in response to rIL-1 than autologous blood monocytes. Monocytes aged in vitro produced little detectable IL-6 in response to LPS or rIL-1, suggesting that differences in cell maturity may account for the diminished capacity of the alveolar macrophage to produce IL-6 in response to IL-1 but not its enhanced capacity to produce IL-6 in response to LPS. Mononuclear phagocytes and lung fibroblasts also differed in their ability to produce IL-6. Lung fibroblasts produced more IL-6 in response to rIL-1 and less IL-6 in response to LPS than monocytes and macrophages. In addition, monocytes and macrophages elaborated electrophoretically identical IL-6 moieties that differed from those produced by lung fibroblasts. These differences could be at least partially attributed to differences in sialylation and/or glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1989

Fibroblast interleukin 1 beta: synergistic stimulation by recombinant interleukin 1 and tumor necrosis factor and posttranscriptional regulation.

To understand the role fibroblasts play in mediating and amplifying the effects of inflammatory cytokines, we determined whether recombinant interleukin 1 (IL-1) and recombinant tumor necrosis factor (TNF), alone and in combination, stimulated fibroblasts to produce IL-1 beta. Recombinant IL-1 (alpha and beta) stimulated fibroblast IL-1 beta mRNA accumulation, whereas recombinant TNF did not. In addition, simultaneous stimulation with recombinant IL-1 (alpha or beta) and recombinant TNF resulted in a synergistic increase in IL-1 beta mRNA levels. However, in all cases, IL-1 beta mRNA accumulation was not associated with fibroblast production of soluble IL-1 beta protein. Lysates of unstimulated, recombinant IL-1-stimulated, and recombinant TNF-stimulated fibroblasts did not contain IL-1 beta prohormone. In contrast, IL-1 beta prohormone was detected in lysates of fibroblasts incubated simultaneously with recombinant IL-1 and recombinant TNF. These studies demonstrate that recombinant IL-1 stimulates fibroblast IL-1 beta mRNA accumulation and that recombinant IL-1 and recombinant TNF synergize to further up-regulate IL-1 beta mRNA levels. In addition, they show that IL-1 beta production by human lung fibroblasts is inhibited at a posttranscriptional level. Translational control appears to be important in recombinant IL-1-stimulated fibroblasts and posttranslational control is important in fibroblasts stimulated simultaneously with recombinant IL-1 and recombinant TNF.

Antibodies↗