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Biomedical subjects

D M Lang

Publications and source records attributed to D M Lang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Theophylline improves measurements of respiratory muscle efficiency.

To determine the effect of theophylline on respiratory muscle efficiency (RME), 12 normal subjects were given theophylline vs placebo in a double-blind, randomized crossover protocol. Spirometry, resting energy expenditure, minute ventilation, RME and oxygen cost of breathing were measured at baseline, after taking theophylline, and after placebo. RME was calculated by dividing the added work required to breathe through a threshold load by the added energy consumed during loaded breathing. Oxygen cost of breathing was calculated by dividing the increase in oxygen consumption induced by breathing an air/carbon dioxide mixture by the associated increase in minute ventilation. RME increased from 3.3 +/- 1.6% at baseline to 7.9 +/- 3.2% after theophylline (p < 0.01) but did not change significantly after placebo (4.8 +/- 2.4%). Oxygen cost of breathing decreased from 3.9 +/- 2.4 mL O2 per liter at baseline to 1.7 +/- 0.7 mL O2 per liter after theophylline (p < 0.05) but did not change significantly after placebo (2.8 +/- 1.3 mL O2 per liter). Theophylline use was also associated with an 18% increase in minute ventilation (p < 0.01) and a 15.7% increase in resting energy expenditure (p < 0.01). Theophylline improves measured RME and reduces oxygen cost of breathing in normal subjects. These effects are offset by increases in resting energy expenditure and minute ventilation.

Adult↗
PubMed1996

Patellar resurfacing versus retention in total knee arthroplasty.

We studied 40 patients in whom the patella was not severely deformed and who were undergoing primary total knee arthroplasty (TKA) for osteoarthritis by one surgeon using one type of prosthesis. They were randomly allocated either to have the patella retained or resurfaced with a cemented, all-polyethylene component regardless of the state of the patellar articular cartilage. Apart from removal of osteophytes, no surgery was undertaken on the retained patellae. All 38 surviving patients were evaluated at three years using the HSS knee score and a new, specifically designed Patellar score (maximum score of 30). No TKA was revised, but two patients in the resurfacing group had a further unrelated procedure. The mean HSS and Patellar scores at follow-up were 89 and 28 in the patellar retention group and 83 and 26 in the patellar resurfacing group. Statistically significant lower scores for both were recorded in women and in heavier patients. Stair-climbing ability was significantly better in the retention group. Although there were no complications related to patellar resurfacing, in the medium term we did not find any significant benefit from resurfacing the patella during TKA for osteoarthritis if it was not severely deformed.

Aged↗
PubMed1995

Gender risk for anaphylactoid reaction to radiographic contrast media.

BACKGROUND: Female predominance has been reported previously in series of anaphylaxis cases; however, no definite precedent has been established for greater risk of anaphylactoid reaction caused by contrast media infusion on the basis of gender. OBJECTIVE: This study was designed to determine whether greater risk for anaphylactoid reaction caused by intravenous contrast media infusion exists in association with female gender. METHODS: Rates of anaphylactoid and severe anaphylactoid reaction, according to gender, were determined in a sample of 5264 consecutive patients receiving conventional radiocontrast media during performance of computed tomography. RESULTS: Of 80 adverse reactions caused by contrast media infusion, 73 (1.39%) were classified as anaphylactoid in nature. Among 5191 patients who received intravenous contrast media without experiencing an anaphylactoid reaction, there were 2642 male patients (51%) and 2549 female patients (49%); reactors included 22 male patients and 51 female patients (odds ratio = 2.40, 95% confidence interval = 1.42-4.10, p < 0.0005). Female patients also comprised 21 of 22 cases of severe anaphylactoid reaction (odds ratio = 21.77, 95% confidence interval = 3.13-435.12, p < 0.0005). CONCLUSION: Greater risk for anaphylactoid and severe anaphylactoid reaction exists in association with female gender. Further studies are needed to identify mechanisms that can explain this risk. The importance of these findings for cost-effective use of lower osmolality contrast media need to be determined.

Anaphylaxis↗
PubMed1995

Anaphylactoid and anaphylactic reactions. Hazards of beta-blockers.

Studies have demonstrated greater hazards associated with anaphylaxis in patients receiving beta-blockers. Serious anaphylaxis is more frequent. Evidence suggests this occurs via modulation of adenylate cyclase, which can influence release of anaphylactogenic mediators. Treatment of anaphylaxis in patients exposed to beta-blockers is complicated because therapeutic administration of epinephrine (adrenaline) may be ineffective or promote undesired alpha-adrenergic and vagotonic effects. Risk reduction efforts should be considered for patients receiving beta-blockers who are prone to experience anaphylaxis.

Adrenergic beta-Antagonists↗
PubMed1995

Reevaluation of the growth-permissive substrate properties of goldfish optic nerve myelin and myelin proteins.

To determine whether optic nerve myelin of goldfish carries mammalian-like neurite growth inhibitory proteins which can be neutralized by the antibody IN-1, myelin fractions of fish optic nerves were used as substrates for fish retinal ganglion cell axons and rat dorsal root ganglia (DRG). Axonal growth was monitored and compared with that of IN-1 treated preparations. Growth of fish retinal axons and rat DRG neurites was substantial on goldfish optic nerve myelin and no improvement was observed with IN-1. In contrast, rat CNS myelin allowed only poor growth, and number of axons and length of DRG neurites increased significantly with IN-1. In addition, proteins of fish optic nerve myelin and bovine CNS myelin were extracted, reconstituted in liposomes and applied to growth cones. When goldfish myelin proteins in liposomes were seeded onto growth cones, 77% of fish and 89% of rat DRG growth cones continued to elongate, and the proportion of elongating fish growth cones (80%) did not significantly change when liposomes were pretreated with IN-1. But 73% of fish and 93% of rat growth cones collapsed with liposomes containing proteins from bovine CNS myelin. Upon IN-1 treatment, only 24% of fish growth cones collapsed. Thus, axon growth in vitro indicates that goldfish optic nerves, which permit successful axon regeneration in vivo, lack mammalian-like neurite growth inhibitors which are neutralized by IN-1.

Animals↗
PubMed1995

CNS myelin and oligodendrocytes of the Xenopus spinal cord--but not optic nerve--are nonpermissive for axon growth.

In vitro assays reveal that myelin and oligodendrocytes of the Xenopus spinal cord (SC) are--unlike corresponding components of the optic nerve/tectum (OT)--nonpermissive substrates for regenerating retinal axons. The number of growth cones that crossed SC oligodendrocytes is low but increases significantly (four- to fivefold) in the presence of the antibody IN-1, in which case their numbers are similar to the number of growth cones (approximately 60%) that cross OT oligodendrocytes with or without IN-1. IN-1 neutralizes neurite growth inhibitors (NI) of rat CNS myelin, indicating that mammalian-like NI are associated with Xenopus SC myelin and oligodendrocytes but not with the OT. IN-1 immunocytochemistry on sections supports this view: SC myelin was stained with IN-1, whereas OT myelin and PNS myelin were not.

Animals↗
PubMed1994

Patterns of asthma mortality in Philadelphia from 1969 to 1991.

BACKGROUND: The rate of mortality from asthma has increased substantially in the United States since 1978. We analyzed the patterns of the rates of death from asthma in Philadelphia between 1969 and 1991. METHODS: The rates of death from asthma were analyzed and compared with trends in the concentrations of major air pollutants: ozone, carbon monoxide, nitrogen dioxide, particulate matter (particles < 10 microns in diameter), and sulfur dioxide. Univariate and multivariate analyses were used to study the rates of death from asthma from 1985 to 1991 and their association with race, poverty, sex, and other factors. RESULTS: The rate of death from asthma decreased from 1.68 per 100,000 people in 1969 to 0.68 per 100,000 in 1977, but then increased to 0.92 per 100,000 in 1978 and 2.41 per 100,000 in 1991. Between 1965 and 1990, the concentrations of major air pollutants declined substantially. From 1985 to 1991, 258 people were identified for whom asthma was the primary cause of death. According to multivariate analysis, the rates of death from asthma from 1985 to 1991 were significantly higher in census tracts with higher percentages of blacks (P = 0.032), Hispanics (P = 0.013), female residents (P < 0.001), and people with incomes in the poverty range (P < 0.001). CONCLUSIONS: The rates of death from asthma have increased in Philadelphia, whereas concentrations of major air pollutants have declined. The rates are highest in census tracts with the highest percentages of poor people and minority residents, particularly blacks. Public health efforts should target urban areas where the risk of death from asthma is highest.

Adolescent↗
PubMed1994

Origin and clonal relationship of common inhibitory motoneurons CI1 and CI3 in the locust CNS.

In the primordial thoracic ganglia of locust embryos, the bromodeoxyuridine (BrdU) technique for labelling proliferating cells and their progeny was combined with intracellular dye injection to investigate the origin and the clonal relationship of common inhibitory motoneurons. Common inhibitors 1 (CI1) and 3 (CI3) were found to be siblings, that is, they are produced by the division of one ganglion mother cell. This ganglion mother cell results from the first division of neuroblast 5-5, at about 30% of embryonic development. A large portion, at least, of the ganglion mother cells produced by subsequent divisions of neuroblast 5-5 give rise to interneurons with contralaterally ascending or descending axons and GABA-like immunoreactivity. Thus, CI1 and CI3 are more closely related to putative inhibitory interneurons than they are to other, that is, excitatory, motoneurons. Consistent with this, the CI somata are associated with cell bodies of putative inhibitory interneurons rather than with clusters of excitatory motoneuron somata. These results elicit speculations regarding the evolutionary origin of inhibitory motoneurons.

Animals↗
PubMed1994

Production and characterization of recombinant mouse brain-derived neurotrophic factor and rat neurotrophin-3 expressed in insect cells.

Bioactive brain-derived neurotrophic factor (BDNF) and neurotrophin-3 were produced using the baculovirus expression system and purified to homogeneity using ion-exchange and reversed-phase chromatography. Yields of purified neurotrophin-3 (300-500 micrograms/L) were similar to levels reported for baculovirus-expressed nerve growth factor (NGF), whereas initial yields of BDNF were significantly lower (20-50 micrograms/L). Improved production of BDNF (150-200 micrograms/L) was achieved by expressing BDNF from a chimeric prepro-NGF/mature BDNF construct using the Trichoplusia ni insect cell line. Tn-5B1-4. Examination of the distribution of BDNF protein from both the non-chimeric prepro-BDNF and the chimeric prepro-NGF/mature BDNF viruses in Sf-21- and Tn-5B1-4-infected cells suggests a specific deficiency in the Tn-5B1-4 cells in processing the nonchimeric precursor. In addition, the vast majority of the BDNF protein at 2 days after infection was intracellular and insoluble. N-terminal amino acid sequencing of purified recombinant BDNF and neurotrophin-3 demonstrated that the insect cells processed their precursors to the correct N-terminus expected for the mature protein. Bioactivity was characterized in vitro on primary neuronal cultures from the CNS and PNS.

Animals↗
PubMed1993

Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders.

BACKGROUND: A case-control study, with both retrospective and concurrent subject selection, was performed (1) to determine whether greater risk for anaphylactoid reaction from contrast media associated with beta-blocker exposure reflects presence, or is independent of underlying cardiovascular disorder; and (2) to characterize further the risk of anaphylactoid reaction from contrast media in patients with cardiovascular disorders and patients with asthma. METHODS: Adverse reactions from intravenous contrast media were recorded in accordance with quality assurance guidelines. Anaphylactoid reactions were classified as mild to moderate (urticaria/angioedema), severe (stridor, bronchospasm, or hypotension), or major and life-threatening (hypotension with or without the need for subsequent hospitalization). Medical records from reactors were compared with those from matched (gender, age, date, and type of contrast study) controls who received conventional contrast media without adverse reaction. RESULTS: Of 34,371 intravenous contrast media procedures performed, 122 anaphylactoid reactions were recorded. The risk of anaphylactoid reaction was significantly associated with asthma (odds ratio [OR], 8.74; 95% confidence interval [CI], 2.36 to 32.35; P = .0012). The risk of bronchospasm was associated with beta-blocker exposure (OR, 3.73; 95% CI, 1.18 to 11.75; P = .025) and with asthma (OR, 16.39; 95% CI, 4.30 to 62.46; P = .0001). The risk of major and life-threatening reaction was associated with the presence of cardiovascular disorder (OR, 7.71; 95% CI, 1.04 to 57.23; P = .046). Among patients with severe reactions, the risk of hospitalization was elevated by the presence of cardiovascular disorder (P = .001), exposure to beta-blockers (OR, 7.67; 95% CI, 1.79 to 32.85; P = .029), or asthma (OR, 20.7; 95% CI, 1.21 to 355.55; P = .065). Although beta-blocker exposure and the presence of cardiovascular disorder were highly associated (chi 2 = 49, P < .001), a greater risk of bronchospasm with severe reaction was observed in nonasthmatic patients with cardiovascular disorders receiving beta-blockers (OR, 15.75; P = .023). Among reactors with asthma, receiving beta-blockers, or with a cardiovascular disorder, 60.8% (31/51) experienced severe anaphylactoid reactions, compared with 35.2% (25/71) of patients without these risk factors (OR, 3.62; P = .005). CONCLUSIONS: beta-Blocker exposure and cardiovascular disorder are both statistically significant risk factors for severe anaphylactoid reaction from contrast media. Thus, patients receiving beta-adrenergic blockers and patients with asthma, on the basis of greater risk for bronchospasm, and patients with cardiovascular disorders, on the basis of elevated risk of major and life-threatening reaction, are appropriate target populations for risk reduction measures before receiving intravenous infusion of contrast media.

Adrenergic beta-Antagonists↗
PubMed1991

Increased risk for anaphylactoid reaction from contrast media in patients on beta-adrenergic blockers or with asthma.

OBJECTIVE: To determine whether greater risk for anaphylactoid reaction from intravenous urographic contrast media exists in patients receiving beta-adrenergic blockers or in asthmatic patients. DESIGN: Case-control study. SETTING: Tertiary care, referral-based medical center. PATIENTS: Of 28,978 intravenous urographic contrast media procedures done from July 1987 to June 1988, 49 patients experienced moderate to severe anaphylactoid reaction. Medical records from these 49 reactors were compared with those from a control group matched for gender, age, and date and type of contrast study who received intravenous urographic contrast media without adverse reaction. MAIN RESULTS: Patients exposed to beta-adrenergic blockers or with asthma comprised 39% (19 of 49) of reactors, compared to 16% (13 of 83) of matched controls (odds ratio, 3.43; 95% CI, 1.45 to 8.15; P = 0.005). Exposure to beta-blockers was 27% among reactors and 12% in matched controls (odds ratio, 2.67; CI, 1.01 to 7.05; P = 0.036). Asthma was found in 12% of reactors and 4% of controls; after correction for beta-blocker use, asthma was also associated with increased risk for anaphylactoid reaction (odds ratio, 4.54; CI, 1.03 to 20.05; P = 0.046). Compared with nonasthmatic patients not taking beta-blockers, asthmatic patients were at greater risk for anaphylactoid reaction with bronchospasm (P = 0.02). Five of 13 reactors receiving beta-blockers became hypotensive, and three needed hospitalization. Compared with nonasthmatic patients not taking beta-blockers, patients exposed to beta-blocking drugs were almost nine times (odds ratio, 8.7; CI, 0.81 to 93.5; P = 0.075) more likely to be hospitalized after an anaphylactoid reaction. CONCLUSION: Increased risk for moderate to severe anaphylactoid reaction from intravenous urographic contrast media exists in patients receiving beta-adrenergic blockers or with asthma. These patients are appropriate target populations for efforts to reduce risk before intravenous urographic contrast media are administered.

Adrenergic beta-Antagonists↗
PubMed1991

Structural requirements for the inhibition of human monocyte carboxylesterase by organophosphorus compounds.

Human blood monocyte carboxylesterase (CBE) is inhibited by a variety of organophosphorus compounds including arylphosphates and arylphosphites and some alkylphosphites. Triphenyl phosphate and triphenyl phosphite with Ki values of 8 x 10(-9) M and 4.8 x 10(-8) M, respectively, are the most potent inhibitors of this enzyme evaluated by this study. The arylphosphates vary in their capacity to inhibit carboxylesterase activity. Diphenyl phosphate with its strong negative charge is not a potent inhibitor (Ki = 1 x 10(-4) M), whereas if its negative charge is neutralized, as in diphenyl methyl phosphate, its capacity to inhibit carboxylesterase is significantly increased. Compounds with increased bulk, such as trinaphthyl phosphate, only inhibit the enzyme at concentrations of 10(-5) M or greater. Arylphosphites have inhibitory capacities similar to the arylphosphates. Alkylphosphites (tributyl phosphite/triethyl phosphite) inhibit carboxylesterase activity, whereas alkylphosphates (tributyl phosphate/triethyl phosphate) have no inhibitory effect. Arylphosphines and arylphosphine oxides do not inhibit carboxylesterase activity. This study demonstrates that organophosphates and organophosphites are relatively effective inhibitors of human monocyte CBE activity with the exception of the alkylphosphates which have no inhibitory activity. We conclude that molecular bulk and charge have a significant role in determining the potency of organophosphorus inhibitors of monocyte CBE. The observed variations in the degree of esterase inhibition by organophosphorus compounds as well as the differences in the pathological expression of neuropathic disorders associated with such chemicals suggest that different esterase enzymes derived from the family of esterase genes may mediate the different neuropathies observed with organophosphorus exposures. Such data also provide the rationale for the kinetic analyses of esterases and the design of non-toxic organophosphorus compounds with low or no monocyte CBE inhibitory capacity to reduce the potential of these commonly used chemicals for human toxicity.

Binding Sites↗
PubMed1991

Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction.

Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma.

Adult↗
PubMed1989

High-molecular-weight kininogen is cleaved in active erythema multiforme.

Erythema multiforme (EM) is an inflammatory disorder of the skin, which may include mucous membrane involvement, that features target (iris) lesions. Mediators specifically involved in EM are not well characterized; its pathogenesis remains enigmatic. In this study, evidence for participation of kinins in the pathophysiology of inflammation in EM was investigated by assessing cleavage of high-molecular-weight kininogen (HMWK) in plasma. These data were compared with analyses of plasmas from patients with serum sickness, chronic idiopathic urticaria/angioedema, and from normal control subjects. Patients with EM demonstrated significant levels of circulating cleaved HMWK in plasma during active disease (p less than 0.01), which declined during remission/recovery. Plasmas from patients with EM obtained during active disease also demonstrated significant levels of 94 kd C1 inhibitor (p less than 0.01) and C1 inhibitor-kallikrein complexes. Patients with serum sickness and chronic idiopathic urticaria/angioedema did not demonstrate these findings and did not differ from normal control subjects (p = not significant). Although the kininogenase responsible for HMWK cleavage in EM has not been conclusively demonstrated, these findings suggest that HMWK cleavage resulted from activation of the contact system and that some of the manifestations of EM in selected patients may in part be accounted for by inflammatory and proinflammatory actions of kinins. Based on these preliminary findings, it will be important to establish whether or not HMWK cleavage in EM is a general finding in patients with this disorder. Further investigation is needed to characterize more clearly kininogenase activity and elucidate the possible role of kinin generation in EM.

Adult↗
PubMed1988

Venous bypass for surgical resection of renal carcinoma invading the vena cava: a new approach.

A new technique is described which facilitates the surgical removal of renal carcinoma from the inferior vena cava. The use of cardiopulmonary bypass with or without cardiac arrest has been advocated but with this procedure only the inferior vena cava is bypassed, using femoral and right atrial cannulation, assisted by a closed system electromagnetic centrifugal pump. In appropriate cases this less complex technique allows prolonged access to the inferior vena cava whilst providing equal protection from pulmonary embolisation and tumour dissemination; it also reduces morbidity, operating time, difficulty and cost when compared with cardiopulmonary bypass.

Anastomosis, Surgical↗