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Biomedical subjects

D Heimer

Publications and source records attributed to D Heimer.

At least 19 recordsLinked to original sources
PubMed1995

[Seasonal variation in hospital admissions for cardiorespiratory diseases in the Negev].

Characteristics of patients admitted to the general medical wards of this hospital during the 21 months between January 1990 and September 1991 were analyzed. Cardiovascular and respiratory disease-related (CR) admissions accounted for 46.8% of the 18,774 admissions. Using a linear model, we examined the relationship between season and clinical characteristics of the patients admitted with CR diagnoses. They were admitted more often during the winter (December-February) than the summer (June-August). The ratio of CR admissions to other causes of admission was 0.75 in the summer, 0.93 in the spring, 1.01 in the winter, and 0.82 in the autumn (p < 0.0001). Seasonality affected more patients with coronary heart disease, noncoronary cardiac disease, and chronic pulmonary disease than those with pneumonia or other pulmonary diseases, or cerebrovascular events. Those admitted during the winter were older, had more than 1 CR condition, and their hospital stays were longer. This pattern of hospitalization partly explains the increase in admissions to medical wards in the winter with increase in work load.

Cardiovascular Diseases↗
PubMed1995

Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women.

BACKGROUND: Changes in asthma activity, in part related to the female hormonal profile, have been observed during pre-menstrual periods and during pregnancy. Estrogen replacement therapy (ERT) is an accepted routine treatment for post-menopausal women. The effect of ERT on disease activity in post-menopausal asthmatic women has not been investigated in the past and is the subject of the present study. METHODS: Fifteen post-menopausal women with mild to moderate asthma completed two 30-day periods in which they measured peak expiratory flow (PEF) at home and filled in a daily diary of asthma-related symptoms. The first monitoring period was pre-ERT and the second was during ERT. In addition spirometry was performed on each woman three times, twice pre-ERT and once during ERT. RESULTS: The average daily PEF decreased from 241 (57.9, S.D.) l/min pre-ERT to 226.7 (62.7) l/min during ERT (P < 0.004). Significant differences between the two study periods were also found in morning and evening PEF values. Diurnal variation, measured as the difference between morning and evening PEF values, decreased significantly from 22.3 (26.7) l/min pre-ERT to 17.5 (26.8) l/min during ERT (P < 0.007). The average daily consumption of bronchodilator inhalers increased significantly from 3.7 puffs/day pre-ERT to 4.3 puffs/day during ERT (P < 0.006). Although the differences in spirometry between the two periods did not reach statistical significance, a trend towards a worsening of the obstructive disorder during ERT was observed. However, the general feeling of well-being of the asthmatics did not change during the two periods. CONCLUSIONS: During ERT a sub-clinical worsening of disease activity was found in postmenopausal women with mild to moderate asthma. We also detected a decrease in diurnal variation. Our findings should be substantiated by additional studies.

Asthma↗
PubMed1995

Influence of estrogen replacement therapy on airway reactivity.

The effect of estrogen on smooth muscle in various organs is unpredictable. Little is known about the effect of estrogen on respiratory tract smooth muscle, particularly in humans. In the present study we used the histamine challenge test (HCT) to assess the effect of estrogen replacement therapy (ERT) on airway reactivity in postmenopausal women who did not suffer from respiratory disease. Thirty-six women who were undergoing treatment at the postmenopausal clinic completed the study. All participants were nonsmokers whose pulmonary function tests were normal. HCT was performed twice before the inception of ERT, and a third time 4-6 weeks after ERT was begun. None of the 36 women demonstrated a 20% decrease in FEV1 values (PC20) after inhaling histamine at a concentration of 8 mg/ml, either before or during ERT. The maximal decrease in FEV1 values in response to the maximum concentration of histamine was significantly lower during ERT compared to the pretreatment period. The average maximal decrease in FEV1 during ERT was 2.63 +/- 2.72% (mean +/- DS) compared to 5.21 +/- 4.47% and 6.57 +/- 5.28% on the 2 tests prior to therapy (p < 0.0002). We conclude that ERT has an inhibitory effect on the bronchial reactivity of respiratory smooth muscle. There is no cause for concern about increased airway reactivity as an adverse effect of this therapy.

Estrogen Replacement Therapy↗
PubMed1994

The protein kinase C inhibitor, H-7, induces acute lung injury in guinea pigs.

OBJECTIVES: To determine if the protein kinase C inhibitor, H-7, alone can cause acute lung injury. In cell studies, H-7 inhibited phorbol myristate acetate-induced neutrophil oxygen radical release. Additionally, one animal study demonstrated that H-7 inhibited phorbol myristate acetate-induced lung injury. There have been no studies on the effect of H-7 alone on lung function or on neutrophil release of oxygen radicals. DESIGN: Prospective, randomized, laboratory study along with in vitro studies using flow cytometry and lucigenin-dependent chemiluminescence. SETTING: Experimental laboratory. SUBJECTS: Specific, pathogen-free guinea pigs and isolated human peripheral neutrophils. INTERVENTIONS: Guinea pigs were randomized into three experimental groups: saline control, H-7 low dose (2 mg/kg bolus + 0.2 mg/kg/hr), and H-7 high dose (6 mg/kg bolus + 0.5 mg/kg/hr). Human neutrophils were randomized into control and experimental groups. The effects of H-7 on pulmonary permeability in guinea pigs were examined over an 8-hr period. MEASUREMENTS AND MAIN RESULTS: We measured the wet/dry weight ratio as an index of pulmonary edema and we measured the concentration ratios of 125I-labeled albumin in lung tissue and in bronchoalveolar lavage fluid and compared the ratios with those values in plasma as indices of pulmonary permeability. We also studied the in vitro effect of H-7 on human neutrophil oxygen radical production, using flow cytometry and lucigenin-dependent chemiluminescence. By flow cytometry, we measured oxygen radical production using the 2',7'-dichlorofluorescin and hydroethidine assays. The 2',7'-dichlorofluorescin assay mainly measures hydrogen peroxide, while the hydroethidine assay measures either superoxide anion alone or in combination with other oxygen intermediaries like hydrogen peroxide. Neutrophils (5 x 10(5)) were obtained by Ficoll-Hypaque gradient centrifugation and were incubated with H-7 (5, 25, 100 microM). In the H-7 high-dose group, wet/dry weight ratio, and 125I-labeled albumin ratios in lung/plasma, and bronchoalveolar lavage/plasma were significantly increased (p < .05 for each ratio). Pulmonary endothelial gap and subendothelial bleb formation were demonstrated in the high-dose group by electron microscopy. One hundred micromols of H-7 caused a small, significant decrease (23.3%, p < .05) in neutrophil oxygen radical production assessed by 2',7'-dichlorofluorescin. H-7 had no other effects on neutrophil oxygen radical production. H-7 did not stimulate neutrophil chemiluminescence; it decreased chemiluminescence. CONCLUSIONS: a) Protein kinase C inhibition with high-dose H-7 increased wet/dry weight and albumin in lung/plasma and bronchoalveolar lavage/plasma ratios in guinea pigs; b) the H-7 high-dose group demonstrated damaged pulmonary endothelium by electron microscopy; and c) since neutrophil oxygen radical production was not increased by H-7 as assessed by flow cytometry and chemiluminescence, it appears that H-7-induced acute lung injury and endothelial damage are not mediated by increased neutrophil oxygen radical production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

TGF-beta 1 causes increased endothelial ICAM-1 expression and lung injury.

Neutrophil adherence to vascular endothelium is partially mediated by adhesion molecules, including intracellular adhesion molecule 1 (ICAM-1), on endothelial cells. We examined the effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of ICAM-1 in human umbilical vein endothelial cells (HUVEC). TGF-beta 1 (1 ng/ml) increased ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cytometry and Northern blot analysis, respectively. In addition, we investigated whether exogenous recombinant TGF-beta 1 can cause neutrophil-mediated lung injury in guinea pigs. The plasma half-life of 125I-labeled TGF-beta 1 in guinea pigs was 4.6 +/- 0.1 min, and the 125I activity was 2.8 +/- 0.2% 8 h after injection. The ratio of 125I-labeled albumin concentration in lung tissue and bronchoalveolar lavage (BAL) fluid to that in plasma, lung wet-to-dry weight ratio, numbers of neutrophils in BAL fluid, and numbers of neutrophils per alveolus in fixed lung sections increased in guinea pigs that received a high dose of TGF-beta 1 (25 micrograms i.v. followed by 2 micrograms/h for 8 h) compared with the control group. These results suggest that TGF-beta 1 causes neutrophil-mediated lung injury, possibly through upregulation of ICAM-1 on endothelial cells, and might be important in the pathogenesis of lung injury.

Animals↗
PubMed1994

Perceptions of asthma severity: the role of negative affectivity.

The role of negative affectivity on patients' perceptions of and behavior during asthma attacks was explored among 47 asthmatic subjects. Patients completed 17 to 30 daily questionnaires assessing negative affect, asthma perception, additional drug intake, search for medical assistance, and peak-flow measures of respiratory distress. Asthma perceptions were correlated with negative affect and educational level; the perception of the asthma severity, but not negative affect, did predict behavior during an attack. The importance of symptom perceptions for the clinical management of chronic asthma is underscored.

Adult↗
PubMed1993

Attenuation of acute lung injury and oxygen radical production by the 21-aminosteroid, U-78518F.

Oxygen radicals play an important role in the mechanism of acute lung injury. The 21-aminosteroid lazaroid, U-78518F, is a potent antioxidant. We examined the effect of intravenous U-78518F on acute lung injury in septic guinea pigs over 8 h. The experimental groups (n = 6) were 1) saline control, 2) Escherichia coli (2 x 10(9)/kg i.v.), 3) pretreatment (U-78518F 5 mg/kg bolus + 1 mg.kg-1 x h-1, 15 min before E. coli injection), and 4) posttreatment (U-78518F 30 min after E. coli injection). We measured wet-to-dry weight ratio (W/D) as an index of pulmonary edema and concentration ratios of 125I-labeled albumin in lung tissue and bronchoalveolar lavage fluid compared with plasma (L/P and BAL/P, respectively) as indexes of lung protein fluxes. In septic guinea pigs, pretreatment with U-78518F attenuated W/D, L/P, and BAL/P and posttreatment attenuated W/D and BAL/P (P < 0.05 for each). Furthermore, we studied the effect of U-78518F on human neutrophil oxygen radical production (ORP) by using flow cytometry to assess intracellular ORP and lucigenin-dependent chemiluminescence to assess extracellular ORP. Neutrophils (5 x 10(5) were stimulated with 0.5 micrograms/ml of phorbol myristate acetate. With flow cytometry, we measured intracellular ORP, cross-sectional cell area, and degranulation in neutrophils. U-78518F (minimum concn 1.0 microM) decreased intracellular ORP (n = 4; P < 0.05) when the dihydrorhodamine 123 assay was used. U-78518F (minimum concn 1.0 microM) inhibited phorbol myristate acetate-induced neutrophil chemiluminescence (n = 4; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗
PubMed1992

Effect of dietary sodium on the severity of bronchial asthma.

BACKGROUND: A high sodium intake has been found to increase bronchial reactivity in men with asthma. The effects of change in sodium intake on peak flow rate have not been determined. METHODS: The effect of changing dietary salt intake for two weeks on the severity of asthma as measured by peak expiratory flow (PEF) was studied in 17 patients with mild asthma in an open randomised crossover trial. PEF measurements were made by the patients in their own homes. Patients were placed on three levels of dietary sodium intake: normal, low, and high. Sodium intake was assessed by 24 hour urine collection. RESULTS: The mean (SD) urine sodium was 147 (45), 84 (32), and 201 (73) mmol/24 hours in the normal, low, and high sodium intake periods respectively. There were no significant differences in PEF or PEF amplitude (highest--lowest PEF), an index of asthma lability, between the three dietary salt periods. CONCLUSION A low and high dietary salt intake for two weeks has no effect on peak expiratory flow in patients with mild asthma.

Adult↗
PubMed1992

Effects of hyperphosphatemia on diaphragmatic strength and endurance.

Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue.

2,3-Diphosphoglycerate↗
PubMed1992

Polyethylene glycol-conjugated superoxide dismutase attenuates septic lung injury in guinea pigs.

Reactive oxygen species (ROS), including superoxide anions, play an important role in mediating acute lung injury. We examined whether polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) attenuates lung injury in Escherichia coli-treated guinea pigs. Twenty-four guinea pigs were divided into four groups: (1) control group; (2) septic group, in which live E. coli (2 x 10(9)/kg) were injected intravenously; (3) pretreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 15 min before E. coli; and (4) posttreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 30 min after E. coli. Lung injury was assessed by the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P), lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid. Plasma half-life of PEG-SOD in normal guinea pigs was 13.5 h. L/P, lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid decreased in both pretreatment and posttreatment groups compared with the septic group. BAL/P decreased in the pretreatment group but not in the posttreatment group compared with the septic group. After the animal model studies, we investigated the effect of PEG-SOD on the human neutrophil extracellular generation of ROS stimulated by phorbol myristate acetate (PMA) in lucigenin-dependent chemiluminescence (CL). PEG-SOD at concentrations greater than or equal to 0.1 U/ml inhibited PMA-induced CL in a dose-dependent manner. We also examined the effect of PEG-SOD on the neutrophil intracellular generation of ROS using flow cytometry to assess intracellular hydroethidine oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of chronic renal failure on skeletal and diaphragmatic muscle contraction.

The changes in muscle mechanical properties caused by the myopathy of chronic uremia was examined in the soleus and the diaphragm muscles of rats in which chronic uremia was produced by subtotal nephrectomy. Using an in vitro muscle preparation in two groups of rats (moderately and severely uremic), we determined that uremia had a significant detrimental effect on both muscles with respect to the force-frequency relationships. In the diaphragm it decreased by 15% in the moderate group and by 43% in the severe group. In the soleus it decreased by 20% in both groups. Twitch characteristics behaved differently in the soleus and the diaphragm muscles in that 1/2 RT and TPT increased significantly (p < 0.05) in the soleus (severely uremic group) but not in the diaphragm. Fatigability was increased in both muscles in the moderately uremic rats and in the diaphragm in the severely uremic rats; however, the fatigability of the soleus in the severely uremic group was not different from that in the control group. Our findings suggest that the myopathic changes occurring in chronic uremia affects the function of the soleus and the diaphragm in different ways. Other findings in the severely uremic group indicate that additional factors such as marked electrolyte imbalances may also affect the excitation-contraction coupling in different ways.

Animals↗
PubMed1991

Effect of dexamethasone on diaphragmatic and soleus muscle morphology and fatigability.

In spite of the extensive use of corticosteroids, its myopathic effect on respiratory muscle is unknown with relation to the dose and duration of therapy. The present study examined the effects of dexamethasone on the morphology and function of respiratory (diaphragm) as compared to skeletal (soleus) muscle. Control rats were compared to those that received low, high and prolonged doses of dexamethasone. Body mass was reduced proportionally to the dose and duration of therapy. Atrophy of the diaphragm was greater than that of the soleus when normalized to body mass. Absolute tension and tension as a function of cross sectional area was significantly (P less than 0.05) less in the diaphragm and soleus at the high and prolonged dosages. Dexamethasone had no effect on fatigability except in the soleus after prolonged treatment. Furthermore, after prolonged therapy, it had converse effects on the Pt and 1/2RT in the diaphragm as compared to the soleus muscle. Dexamethasone improved the recovery times in the diaphragm alone. Our data suggest that dexamethasone weakens the diaphragm and soleus by reducing its mass and apparently also through some effect on the intrinsic contractile apparatus.

Animals↗
PubMed1991

Effect of digoxin on respiratory muscle performance in patients with COPD.

The effect of 2 weeks oral digoxin administration on respiratory muscle performance (RMP) in 14 patients with chronic obstructive lung disease (COPD) was investigated in a randomized double-blind placebo-controlled cross-over study. All patients were ambulatory with severe air flow obstruction. FEV1/FVC was 0.44 +/- (SD) 0.11, FEV1 was 0.88 +/- (SD) 0.35 liter/s RMP was assessed by measuring maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and maximal voluntary ventilation. Although these parameters were significantly reduced in the COPD patients, 2 weeks of digoxin administration (with serum levels in the therapeutic range) did not alter any parameter of RMP or spirometry. We conclude that digoxin has no effect on RMP or spirometry in ambulatory patients with severe COPD.

Adult↗
PubMed1991

Comparison of a B2 adrenergic agonist and an anticholinergic agent given by sequential inhalation in patients with severe chronic obstructive pulmonary disease.

We evaluated the response of 15 male patients with severe chronic obstructive pulmonary disease (COPD) to sequential inhalations of an anticholinergic agent, ipratropium bromide 0.25 mg (IB) and a B2 adrenergic agonist, terbutalin 2.5 mg (TER), in a double-blind crossover study. We found no statistically significant difference in the bronchodilatory response between the two agents when comparing the change in forced vital capacity and forced expiratory volume in 1 sec. The subsequent effect of the sequential inhalation demonstrated some additional bronchodilatory response when IB was given after TER, but not when TER was given after IB. However, the end result after the two protocols was not statistically different. The results indicate that in COPD patients the two agents are equipotent. However, in order to prescribe the best treatment schedule for each patient, it is still necessary to evaluate how each individual patient responds to each of the agents. Sequential inhalation may be beneficial in some patients.

Adrenergic beta-Agonists↗
PubMed1990

Respiratory muscle performance in patients with type 1 diabetes.

Respiratory muscle strength and endurance were examined in 31 Type 1 diabetic patients and in age, sex, and weight matched control subjects. No significant difference in respiratory muscle strength was noted between the two groups. Maximal static inspiratory pressure was 92.3 +/- 33.9 (+/- SD) and 99.5 +/- 23.0% of the predicted values in the patient and control groups, respectively. Maximal static expiratory pressures were 75.1 +/- 14.3 and 77.4 +/- 14.0% of the predicted values in the patient and control groups, respectively. Respiratory muscle endurance was significantly lower in the diabetic patients 88.9 +/- 20.7 vs 103.9 +/- 15.8% predicted in the control group (p less than 0.01). Total lung capacity, vital capacity, and maximal voluntary ventilation were also significantly lower in the diabetic group and correlated with the duration of diabetes.

Adult↗
PubMed1990

Physiological changes in respiration associated with near drowning in the Dead Sea: a canine model.

An experimental study to elucidate the physiological changes that occur in respiration during near drowning in the Dead Sea was performed in an experimental model. Findings showed that clinical signs of respiratory failure were due to aspiration rather than ingestion of Dead Sea water and occurred within 10 min of aspiration. Physiological changes included increased ventilation, tachypnea, increased resistance, decreased compliance and hypoxia.

Airway Resistance↗