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Biomedical subjects

A Gelb

Publications and source records attributed to A Gelb.

At least 19 recordsLinked to original sources
PubMed2001

Lung volume reduction surgery for chronic obstructive pulmonary disease: where do we stand?

Lung volume reduction surgery (LVRS) is a promising new treatment for selected patients with moderate to severe symptoms of emphysema. Medical management, including pulmonary rehabilitation, has been shown to reduce oxygen requirements during exercise and probably to reduce hospitalization for patients with severe emphysema, but it does not improve pulmonary function. By improving the elastic recoil of the lung, LVRS is the first treatment to demonstrate substantial improvement in pulmonary function and quality of life for selected patients with emphysema. The most important selection factor for LVRS is the presence of a heterogeneous pattern of emphysema. Because it is found in only 20% of patients with emphysema, only a small number of patients are candidates for the procedure. Published reports indicate that the optimal operative technique appears to be a bilateral staple operation during a single anesthetic. This procedure offers a 68% chance of oxygen independence, 85% chance of prednisone independence, and 60% to 70% improvement in pulmonary function for patients with an upper lobe distribution of emphysema. The long-term benefits of the procedure are currently unknown, so several randomized, prospective studies are now comparing LVRS with maximal medical management.

Contraindications↗
PubMed2001

The prehospital treatment of status epilepticus (PHTSE) study: design and methodology.

Status epilepticus is a neurological emergency that is typically first encountered and managed in the prehospital environment. Although aggressive pharmacological treatment of status epilepticus is well established in the emergency department and hospital settings, the relative risks and benefits of active therapy for status epilepticus in the prehospital setting are not known. The Prehospital Treatment of Status Epilepticus (PHTSE) study is a prospective, randomized, double-blind, placebo-controlled study designed to address the following aims: (1) to determine whether administration of benzodiazepines by paramedics is an effective and safe means of treating status epilepticus in the prehospital setting and whether this therapy influences longer-term patient outcome, (2) to determine whether lorazepam is superior to diazepam for the treatment of status epilepticus in the prehospital setting, and (3) to determine whether control of status epilepticus prior to arrival to the emergency department influences patient disposition. The initial phase of the PHTSE study began in January 1994 and was completed in February 1999 after the successful enrollment of 205 patients into the three treatment arms. In this paper, we describe the rationale for the conceptualization of the study and details of the study design and methodology, and emphasize some aspects of study implementation that are unique to research involving the emergency medical system.

Adult↗
PubMed2000

The effects of clinical case management on hospital service use among ED frequent users.

This study examined the impact of case management on hospital service use, hospital costs, homelessness, substance abuse, and psychosocial problems in frequent users of a public urban emergency department (ED). Subjects were 53 patients who used the ED five times or more in 12 months. Utilization, cost, and psychosocial variables were compared 12 months before and after the intervention. The median number of ED visits decreased from 15 to 9 (P < .01), median ED costs decreased from $4,124 to $2,195 (P < .01) and median medical inpatient costs decreased from $8,330 to $2,786 (P < .01). Homelessness decreased by -57% (P < .01), alcohol use by -22% (P = .05) and drug use by -26% (P = .05). Linkage to primary care increased 74% (P < .01). Fifty-four percent of medically indigent subjects obtained Medicaid (P < .01). There was a net cost savings, with each dollar invested in the program yielding a $1.44 reduction in hospital costs. Thus, case management appears to be a cost-effective means of decreasing acute hospital service use and psychosocial problems among frequent ED users.

Adult↗
PubMed1999

Pulmonary artery pressure: an intraoperative guide to limiting resection volume.

Lung volume reduction surgery (LVRS) has shown promising results in severe emphysema. However, intraoperative indicators are needed to define optimal resection volumes. Diffusing capacity (DLCO) worsens with larger LVRS and may correlate with pulmonary artery (PA) pressure. We hypothesized that there would be a greater increase in PA pressures with larger volume LVRS in an inhaled elastase animal emphysema model. Twenty-one rabbits were induced with 15,000 units of elastase via an endotracheal tube. Four weeks later, bilateral LVRS was performed through a median sternotomy using an endoscopic stapler. PA pressures were measured prior to LVRS, immediately after LVRS, and at sacrifice. Single-breath DLCO, static pressure-volume relationships, and forced expiratory flows were measured prior to induction and at corresponding times to PA pressures. Systolic PA pressures increased in both groups immediately after LVRS (small: 2. 67 +/- 9.2 mm Hg, ANOVA, P = 0.023; large: 3.8 +/- 8.5 mm Hg, P = 0. 002), and then decreased at time of sacrifice 1 week later (small: 9. 43 +/- 4.8 mm Hg, ANOVA, P = 0.053; large: 5.2 +/- 7.3 mm Hg, P = 0. 552). The decrease, at sacrifice, in PA pressures was greater for small LVRS animals than large LVRS animals. The mortality rate (MR) for the small resection group was 0%, whereas that for the large resection group was 24%. The MR associated with larger LVRS was appreciably greater than that associated with small LVRS. These studies suggest that PA pressures may prove to be a useful intraoperative indicator for limits of resection.

Animals↗
PubMed1999

Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema.

OBJECTIVE: The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS: Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS: Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION: Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.

Animals↗
PubMed1999

Propofol prevents peroxide-induced inhibition of glutamate transport in cultured astrocytes.

BACKGROUND: Glutamate transporters located in the plasma membrane of cerebral astrocytes take up excitatory neurotransmitters from the synaptic cleft. In diseases characterized by oxidative stress, the extracellular glutamate concentration increases and contributes to neuronal death. The authors wanted to determine whether propofol defends brain cells against oxidant-induced changes in their transport of glutamate. METHODS: Primary cultures of rat cerebral astrocytes were exposed to tert-butyl hydroperoxide (1 mM) to serve as an in vitro model of oxidative stress. Astrocytes were incubated with propofol for 2 h and tert-butyl hydroperoxide was added for the final hour. Alternatively, astrocytes were incubated with tert-butyl hydroperoxide for 30 min and then with propofol for another 30 min. Control cells received drug vehicle rather than propofol. The rate of uptake of glutamate, the efflux of the nonmetabolizable analog D-aspartate, and the intracellular concentration of the endogenous antioxidant glutathione were measured. RESULTS: Tert-butyl hydroperoxide decreased the glutathione concentration and inhibited glutamate uptake but had a negligible effect on D-aspartate efflux. At clinically relevant concentrations, propofol did not affect the glutathione concentration but did prevent the effect of tert-butyl hydroperoxide on glutamate transport. Furthermore, the addition of propofol after tert-butyl hydroperoxide reversed the inhibition of glutamate uptake. CONCLUSIONS: Propofol prevents and reverses the inhibition of excitatory amino acid uptake in astrocytes exposed to tert-butyl hydroperoxide. The ability of propofol to defend against peroxide-induced inhibition of glutamate clearance may prevent the pathologic increase in extracellular glutamate at synapses, and thus delay or prevent the onset of excitotoxic neuronal death.

Anesthetics, Intravenous↗
PubMed1998

Effect of lung volume reduction surgery on pulmonary diffusion capacity in a rabbit model of emphysema.

BACKGROUND: While there is renewed interest in lung volume reduction surgery (LVRS) for treatment of emphysema, many aspects of the operation such as patient selection and surgical end points of excision are uncertain. We studied the effects of LVRS on measured lung volumes and diffusion capacity in an animal model to investigate optimal resection volumes. METHODS: Emphysema was induced in 32 New Zealand white (NZW) rabbits using aerosolized elastase. Helium dilution lung volumes and single breath DLCO were measured concurrently at baseline, following induction of emphysema (preop), and 1 week postoperatively (postop) following LVRS. Bilateral upper and middle lobe stapled lung resections were performed through midline sternotomies with excision of variable amounts of lung tissue from 1.8 to 5.8 g. RESULTS: FRC increased following induction of emphysema and decreased postoperatively. DLCO improved with increasing lung tissue resection up to 3 g of tissue and then decreased as even greater amounts were removed (r = 0.54). CONCLUSIONS: Measured lung volumes increase with development of emphysema and appropriately decrease in response to LVRS in this rabbit model. DLCO improves with moderate resection but then decreases with excessive excision of lung quantities and may help define one physiologic operative end point. In this rabbit model, excision of approximately 30% of lung volume was optimal and prevented further decrease in diffusion capacity.

Animals↗
PubMed1998

Changes in pulmonary physiology after lung volume reduction surgery in a rabbit model of emphysema.

OBJECTIVE: The purpose of this study is to investigate the effects of lung volume reduction surgery on pulmonary compliance, airway flow, and helium lung volumes in an elastase-induced emphysema animal model. METHODS: A 15,000-unit bolus of elastase was aerosolized through an endotracheal tube in 14 New Zealand White rabbits to induce emphysema. Stapled lung volume reduction of bilateral upper and middle lobes was performed through a midline sternotomy at 4 weeks after induction of emphysema. Lung functions were measured at baseline before induction of emphysema, preoperatively at 4 weeks, and 1 week postoperatively. RESULTS: Compliance increased after induction of emphysema and decreased in response to lung volume reduction surgery. Functional residual capacity decreased after lung volume reduction surgery in proportion to the amount of excised lung tissue. Expired flows suggested improvement in response to lung volume reduction surgery. Histologic examination confirmed presence of diffuse heterogeneous emphysema in each animal at necropsy. CONCLUSIONS: The decreased compliance and increased airway flow after volume reduction surgery in this model parallels findings in human studies and suggests that similar mechanisms of increased elastic recoil and airway support contribute to improvement.

Animals↗
PubMed1998

Insight on emphysema--the first 300 cases of surgical treatment.

Our experience with lung volume reduction surgery for emphysema now encompasses more than 300 cases, including several prospective trials. We have a 3.5% operative mortality rate and, with aggressive use of Heimlich valves over the past 6 months, an average hospital length of stay of 8 days. Proper patient selection is essential and can be based primarily on results of pulmonary function tests (PFTs), ventilation/perfusion (V/Q) scans, and computed tomography (CT) scans. We have found that bilateral is more effective than unilateral staple lung volume reduction surgery, which is in turn better than unilateral laser surgery. In patients with bilateral upper lobe disease, average FEV1 (forced expiratory volume in a 1-second interval) improvement is 82%; overall, it is 61% (range -33 to 217%). We conclude that lung volume reduction surgery can be performed safely with acceptable mortality and excellent clinical results in properly selected, motivated patients.

Aged↗
PubMed1997

Magnesium deficiency increases ketamine sensitivity in rats.

PURPOSE: Inhibition of the NMDA receptor likely contributes to ketamine's neurodepressive properties. Magnesium also inhibits the NMDA receptor by binding to a site associated with the ketamine-binding domain. Electrophysiological studies suggest that magnesium prevents ketamine from binding to the NMDA receptor and thereby prevents ketamine inhibition. We undertook an in vivo study to determine if magnesium deficiency was associated with an increased sensitivity to ketamine. METHODS: Weanling rats were maintained on a Mg(2+)-deficient or control diet for 14 days. In Study I, rats were anaesthetized then sacrificed and the Mg2+ concentrations in the brain and plasma were measured. In a second prospective study, experimental animals were rendered hypomagnesaemic and the potency of 125 mg.kg-1 ip ketamine was evaluated. Animals were then were fed a Mg(2+)-containing diet and ketamine sensitivity was re-examined 14 days later. RESULTS: The Mg(2+)-deficient diets rendered the rats hypomagnesaemic as indicated by the brain and plasma concentration of Mg2+. In Study 2, the time to loss of righting reflex was shorter; 1.9 +/- 0.3 min (n = 12) and 2.6 +/- 0.2 min (n = 16, P < 0.05), whereas the latency to toe pinch was prolonged: 25.0 +/- 5.8 min (n = 12) vs 3.1 +/- 2.1 min (n = 16, P < 0.05) in the Mg(2+)-deficient compared with age-matched control animals, respectively. The hypomagnesaemic animals had a higher death rate following ketamine injection. The increased sensitivity to ketamine was no longer apparent when the animals were re-tested following replenishment of Mg2+. CONCLUSION: Hypomagnesaemia is associated with an increased sensitivity to ketamine.

Anesthetics, Dissociative↗
PubMed1997

Objective predictors of response for staple versus laser emphysematous lung reduction.

Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of staple versus laser volume-reduction surgery in order to help define patient selection criteria for these procedures. Seventy-two patients with severe symptomatic emphysema without bullae were entered into the protocol (39 staple, 33 laser). Preoperative objective variables (pulmonary function tests, smoking history, demographics, and graded chest computed tomographic [CT] scans) were evaluated as predictors of response to treatment (defined as a change in FEV1) at 3- to 6-mo follow-up, using linear and multivariate regression analysis. Follow-up pulmonary function was obtained on 90% of the 68 patients surviving at 6 mo. Overall improvement was significant only for staple-treated patients, and improved outcome correlated with greater smoking history and younger age for staple-treated patients. When physiologic variables were analyzed, greater smoking history, lower DL(CO), and younger age predicted improved outcome for laser-treated patients. Preoperative FEV1 and gas-exchange variables did not predict outcome in staple-treated patients. When CT scan grading was included in multivariate regression analysis, hyperinflation (increased thoracic gas volume) was the primary predictor of response for laser-treated patients. These findings suggest that younger patients with evidence of advanced emphysematous lung disease and hyperinflation are optimal candidates for lung-volume-reduction surgery, particularly by staple-reduction techniques. Additional studies with long-term follow-up, bilateral procedures, and assessment of other outcome measures must be performed to further define operative criteria for lung-volume-reduction surgery for emphysema.

Age Factors↗
PubMed1996

Predictors of carbon monoxide and hydrogen cyanide exposure in smoke inhalation patients.

OBJECTIVE: A prospective study of civilian (nonfirefighter) smoke inhalation patients was carried out to test the hypotheses that: 1) absorption of carbon monoxide and hydrogen cyanide from smoke can be predicted by clinical examination and historical data; and, more specifically 2) a history of exposure to burning synthetic polymers is an important predictor of systemic cyanide levels. METHODS: The study was conducted over a three-year period at six urban hospitals. Patients with or without burns who were exposed to smoke within five hours of hospital arrival were sampled for carboxyhemoglobin, whole blood cyanide, urine cotinine and urine creatinine. Controls consisted of a smaller group of smoking status-matched, nonsmoke-exposed burn patients. ANALYSIS: Historical information was obtained on SMOKING status, FIRETYPE (structural vs other), MATERIAL burned (natural vs synthetic) and LAGTIME (from exposure to sampling). A smoke inhalation SCORE (0-10) was assigned to each case, based on physical examination findings and changes on chest X ray, and carboxyhemoglobin and cyanide levels were entered into various multivariate linear regression models. RESULTS: A total of 40 cases and 9 controls were recruited, ranging in age from 15 to 92 years. Thirty-four cases were discharged alive and six expired in-hospital. Observed carboxyhemoglobin levels ranged from 1.2% to 41.6% in cases (mean 8.6%), and from 0.5 to 7.3% in controls (mean 2.9%). Observed cyanide levels ranged from nondetectable (< 0.05 micrograms/mL) to 2.79 micrograms/mL in cases (mean 0.25 micrograms/mL), and from nondetectable to 0.11 micrograms/mL in controls (mean 0.03 micrograms/mL). Among cases, linear regression models explained up to 35% of the observed variance in carboxyhemoglobin levels (p < 0.001) and up to 48% of the variance in cyanide levels (p = 0.0001). CONCLUSIONS: SCORE was the strongest predictor of both carboxyhemoglobin and cyanide levels; LAGTIME also explained significant variance for [log-transformed] carboxyhemoglobin. Historical factors, such as FIRETYPE, MATERIAL, and SMOKING status, did not explain significant variance in most of the statistical models employed.

Adolescent↗
PubMed1994

Crohn's ileitis in a patient with longstanding HIV infection.

The differential diagnosis of diarrhea in patients infected with HIV is broad, and includes a variety of bacterial, viral, and parasitic pathogens, as well as malignancies including lymphoma and Kaposi's sarcoma. Idiopathic non-specific inflammatory bowel disease rarely occurs in association with HIV infection. A recent case report described a patient with longstanding Crohn's disease who experienced remission of his bowel disease upon infection with HIV (6). The authors inferred that the remission was secondary to a depressed CD4 (T helper) lymphocyte count. We report the first case of Crohn's ileitis developing in a patient with established HIV infection, depressed CD4 lymphocyte count, and no prior history of inflammatory bowel disease. This case raises questions about the role of CD4 cells in the pathogenesis of Crohn's disease.

Acquired Immunodeficiency Syndrome↗