Goals of therapy in antibody deficiency syndromes.
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Agammaglobulinemia↗
Biomedical subjects
M Berger
Publications and source records attributed to M Berger.
Altered respiratory epithelial cell cytokine production in cystic fibrosis.
BACKGROUND: Reports that lung inflammation in patients with cystic fibrosis (CF) might precede infection raise the possibility that the excessive inflammatory response in lungs of patients with CF might be directly related to defects in epithelial cell cystic fibrosis transmembrane regulator. OBJECTIVE: We sought to determine the relationship of epithelial cell cytokine production to CF lung disease. METHODS: Immunofluorescence and cultures of freshly obtained bronchial epithelial cells and ELISA for IL-10, IL-8, and IL-6 were used to study alterations in epithelial cell cytokine production. RESULTS: Fresh bronchial epithelial cells from healthy control subjects (HCs) secreted 98 +/- 20 pg/mL of the anti-inflammatory cytokine IL-10 when placed in primary culture in vitro but little or no IL-8 or IL-6. In contrast, fresh epithelial cells from patients with CF did not secrete detectable IL-10 but produced 38 +/- 17 pg/mL IL-8 and 40 +/- 17 pg/mL IL-6. These data correlated very well with the immunofluorescence data. The correlation between the immunofluorescent staining of fresh bronchial epithelial cells from both the HCs and patients with CF and the concentrations of cytokines in epithelial lining fluid suggests a reciprocal relationship between anti-inflammatory (IL-10) and proinflammatory (IL-6 and IL-8) cytokine production by the epithelial cells in HCs versus patients with CF. CONCLUSIONS: Alterations in epithelial cell cytokine production in the lungs of patients with CF may contribute to the excessive local inflammation.
Adolescent↗
Health beliefs and compliance with inhaled corticosteroids by asthmatic patients in primary care practices.
The aim of this study was to determine factors associated with regular use of inhaled corticosteroids (ICS) by asthmatic patients in primary care practices. A cross-sectional survey was carried out over 12 family practices in the Philadelphia greater Metropolitan area. A total of 394 patients aged 18-49 years, who received medical care for asthma from their primary care physician and had been prescribed ICS between 1 January 1995 and 31 December 1996, were included. The study measured self-reported demographics, experience with asthma, use of and attitudes about ICS, and health beliefs in six domains. Only 38% of patients reported using ICS at least twice a day almost every day. The most frequently cited reasons for inconsistent or non-use of ICS were related to a belief that ICS were unnecessary during asymptomatic periods and to a general concern about side-effects. By logistic regression, factors associated with regular use of ICS were two patient health beliefs, namely the health belief of 'Active' participation in clinical decision-making with their physician (OR = 4.6, 95% CI 2.8, 7.5), and the health belief that asthma was a 'Serious' health problem (OR = 2.3, 95% CI 1.4, 3.7), and hospitalization for asthma within the previous 12 months (OR = 2.3, 95% CI 1.6, 4.6). Patients were more likely to report regular use of ICS if they saw themselves as active participants in their treatment planning and conceptualized asthma as a potentially serious illness. These results support the themes of patient education and shared decision-making between patients and physicians that are promoted by the Asthma Guïdelines from the National Heart, Lung and Blood Institute (NHLBI).
Administration, Inhalation↗
Independent sleep EEG slow-wave and spindle band dynamics associated with 4 weeks of continuous application of short-half-life hypnotics in healthy subjects.
OBJECTIVES: Habituation and adverse withdrawal reactions after prolonged medication with benzodiazepine (BZ) hypnotics are believed to play a role in dose escalation and the development of dependence. METHODS: In the current sleep EEG study in 43 healthy male subjects, the known property of BZ- and similar hypnotics to change the NREM sleep EEG spectrum is utilized for a detailed quantitative analysis across 4 weeks of continuous medication and a subsequent two-week withdrawal period. The BZ hypnotic triazolam and the non-BZ hypnotics zopiclone and zolpidem, differing in pharmacological properties and reported adverse effects, were examined in parallel to a placebo group. RESULTS: Reliably occurring spectral effects in the sleep stage 2 EEG were found in the 3 frequency bands 0.8-5 Hz, 5-10 Hz and 10-15 Hz. All 3 hypnotics showed the typical 'benzodiazepine signature', a 10-15 Hz increase and lower-frequency (<10 Hz) suppression relative to the preceding drug-free night. However, these effects developed differently across the first medication night, across the 4 medication weeks and after withdrawal: While the 5-10 Hz effect covaried with the blood presence of the drugs as estimated from the known plasma half-lifes, showed habituation and a rebound after withdrawal, the 10-15 Hz power increased across medication days and showed no rebound. Effects in the 0.8-5 Hz band in the first medication night correlated with the decrease of sleep efficiency at later withdrawal for triazolam and zolpidem.
Adult↗
Insulin sensitivity in patients with essential hypertension: no influence of the ACE inhibitor enalapril.
We studied the effect of an ACE inhibitor (Enalapril [ENA], 10 mg o.d.) and a calcium-channel blocker (Nitrendipine [NIT], 20 mg o.d.) on insulin sensitivity in a double-blind cross-over study. Insulin sensitivity was measured by a two-step hyperinsulinemic euglycemic clamp. Serum potassium concentrations were kept constant during the clamp procedure by means of a variable potassium infusion. Twenty patients with essential hypertension (age 35+/-12 years [mean+/-SD], BMI 31.9+/-5.0 kg m2, initial blood pressure 152+/-10/99+/-6 mmHg) were treated with ENA or NIT for 4 weeks, respectively, with a wash-out period of 3 weeks. No carry-over effects or period effects were observed. Both drugs induced a comparable decline in systolic and diastolic blood pressure (ENA - 15+/-9/ - 13+/-8 mmHg, NIT -16+/-8/- 12+/-6 mmHg). No significant change in body weight occurred with both treatments (ENA -0.4+/-2.0; NIT 0.6+/-1.1 kg). Neither drug had a significant impact on any parameter of insulin sensitivity measured (e.g. insulin sensitivity index SI: ENA 5.2+/-2.0 [basal 5.1+/-2.2], NIT 5.8+/-3.0 [basal SI 5.1+/-2.4) mi/min x m2/microU/ml). In conclusion, no significant differences between ENA and NIT on insulin sensitivity were observed. The reduction of blood pressure had no apparent effect on insulin sensitivity.
Adult↗
Peripheral progenitor cells (CFU-GM, BFU-E, CD34) are increased in untreated chronic lymphocyte leukemia patients: stage B and C display a particularly high CD34+ cell count.
No treatment has proved its efficiency in CLL. Autologous transplantation is now under consideration for the youngest patients. We assayed progenitor cells (CFU-GM, BFU-E, CD34) in the peripheral blood of 28 untreated CLL patients and found an increase of all these progenitors in CLL compared to controls. There was no statistical difference between stage A versus stages B and C for CFU-GM and BFU-E. In contrast, CD34 cells were higher in stages B and C as compared to stage A. This finding could be explained by a high number of circulating clonal cells in advanced stages of the disease.
Adult↗
The mechanism of chronic coxsackievirus B hepatitis in rabbits.
The pathophysiology of chronic hepatitis in rabbits infected with coxsackievirus B5 (CVB5), (strain Mitchell) was investigated. Three-week-old male New Zealand White rabbits were inoculated intraperitoneally with 1 x 10(5) plaque forming units of virus. Every 3 months for 15 months postinoculation (p.i.) groups of animals were sacrificed for the following tests: interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-beta cytokine levels by enzyme-linked immunosorbent assay (ELISA); splenic natural killer (NK) cell function; sequence of a 154-bp section of the 5' noncoding region; antihepatocyte autoantibodies; histologic examination; in situ polymerase chain reaction (ISPCR) of the liver; neutralizing antibody response to CVB5; and viral cultures of liver, spleen, blood, brain, heart, skeletal muscle, and pancreas samples. Histologic evidence of hepatocyte necrosis was evident at each time point, although few inflammatory cells were seen. Liver samples were positive at each time by ISPCR, with viral nucleic acid localized to hepatocyte cytoplasm. Other cells in the liver did not stain. No hepatocyte autoantibodies were detected, and there was no elevation of intrahepatic cytokine levels compared to uninfected controls. There were no mutations in the virus over time. A vigorous neutralizing antibody response to CVB5, Mitchell was generated, but splenic natural killer (NK) function and numbers of splenic NK cells were significantly decreased. Virus culture was positive at 3 months, but negative at further time points. Cultures were negative at 3 months for the other tissues tested. Thus, CVB5, Mitchell causes a chronic hepatitis in rabbits, with virus limited to hepatocyte cytoplasm and no evidence of autoimmunity.
Animals↗
Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients.
The objective of this study was to compare the effects of carbamazepine (CBZ) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this controlled clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia (N = 24) or schizoaffective disorder (N = 3) were randomly assigned to receive 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ, or haloperidol with VPA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels. Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy. VPA had no significant effect on either plasma levels or on psychopathology. Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure. This might be a result of a pharmacokinetic interaction on the hepatic level. The concomitant use of VPA with neuroleptic therapy is not impaired by clinically significant drug interactions, but it is not associated with a better outcome under our conditions.
Adult↗
Effects of intensified antihypertensive treatment in diabetic nephropathy: mortality and morbidity results of a prospective controlled 10-year study.
OBJECTIVE: The aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 (insulin-dependent) diabetic patients with kidney disease. DESIGN: The study was a controlled, prospective, parallel, 10-year follow-up trial. PATIENTS AND INTERVENTIONS: A sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospectively followed for 10 years. Forty-five patients (intensified antihypertensive therapy; IT group) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians, consultants and local hospitals (routine antihypertensive therapy; RT group). OUTCOME MEASURES: The main endpoint was death; secondary endpoints were renal replacement therapy, blindness and amputation. RESULTS: Blood pressure was reduced in the IT group and increased in the RT group. During the follow-up period, 29 patients died, seven in the IT group and 22 in the RT group. The survival curves were significantly different (P = 0.0008). The main causes of death were cardiac. In a multiple Cox proportional hazards model, allocation to the IT group reduced the mortality risk [relative risk (RR) = 0.213; 95% confidence interval 0.089-0.509, P = 0.00051, while age (P = 0.0039) and mean blood pressure (P= 0.0113) increased this risk. In multiple Cox or multiple logistic regression models, the risks of dialysis (RR = 0.269, 95% confidence interval 0.110-0.656, P = 0.0039), blindness (odds ratio = 0.158, 95% confidence interval 0.037-0.684, P= 0.0136), and amputation (RR = 0.181, 95% confidence interval 0.047-0.703, P= 0.0135) were significantly lower in the IT group compared with the RT group (log rank P = 0.0008). CONCLUSION: We conclude that intensified antihypertensive treatment, based on a hypertension teaching and treatment programme, reduces long-term morbidity and mortality in patients with diabetic nephropathy.
Adult↗
Autoregulation of glucose production in health and disease.
Plasma glucose concentration is a major regulator of glucose production in experimental animals and in humans. Hyperglycemia inhibits and hypoglycemia stimulates glucose production through mechanisms which are, in part, independent of changes in glucoregulatory hormones. Glucose production does not change when gluconeogenesis is acutely inhibited or stimulated. These observations indicate an autoregulatory process by which hepatic glucose production is altered as a direct consequence of changes in glycemia. Data obtained in patients with glucokinase gene mutations indicate that glucokinase may play a role in this regulatory process. Hyperglycemia in type 2 diabetic patients and in critically ill patients may result from a blunted effect of hyperglycemia on glucose production.
Animals↗
Association of asthma control with health care utilization and quality of life.
Asthma severity and level of asthma control are two related, but conceptually distinct, concepts that are often confused in the literature. We report on an index of asthma control developed for use in population-based disease management. This index was measured on 5,181 adult members of a large health maintenance organization (HMO), as were various self-reported measures of health care utilization (HCU) and quality of life (QOL). A simple index of number of control problems, ranging from none through four, exhibited marked and highly significant cross-sectional associations with self- reported HCU and with both generic and disease-specific QOL instruments, suggesting that each of the four dimensions of asthma control represented by these problems correlates with clinically significant impairment. Qualitatively similar results were found for control problems assessed relative to the past month and relative to the past year. Asthma control is an important "vital sign" that may be useful both for population-based disease management as well as for the management of individual patients.
Adolescent↗
IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice.
Cystic fibrosis (CF) lung disease is characterized by an excessive inflammatory response associated with chronic Pseudomonas aeruginosa endobronchial infection. Compared with bronchoalveolar lavage fluid from healthy subjects, lavage fluid from patients with CF contains elevated proinflammatory cytokines but negligible amounts of the anti-inflammatory cytokine interleukin-10 (IL-10). We sought to determine whether IL-10 deficiency results in increased local and systemic morbidity in mice with chronic endobronchial infection with P. aeruginosa embedded in agar beads and to determine if exogenous IL-10 might reduce these effects. Infected IL-10 knockout mice had more severe weight loss (p = 0.04) and increased area of lung inflammation (28 +/- 4 versus 10 +/- 2%, p < 0.002) but no alterations in bacterial burden compared with wild-type mice. Infected CD-1 mice treated with IL-10 had improved survival (p = 0. 035), less severe weight loss (p < 0.005), fewer bronchoalveolar lavage neutrophils (3 x 10(5)/ml versus 5 x 10(6)/ml, p < 0.02), and decreased area of lung inflammation (11 +/- 2 versus 35 +/- 7%, p < 0.01) but no alterations in bacterial burden compared with placebo-treated mice. These data suggest that IL-10 is an important regulator of the inflammatory response to P. aeruginosa endobronchial infection and that further investigation into the use of IL-10 in CF is warranted.
Animals↗
Noninvasive estimation of pulmonary artery diastolic pressure in patients with tricuspid regurgitation by Doppler echocardiography.
OBJECTIVES: The purpose of this study was to determine whether Doppler echocardiographic assessment of right ventricular pressure at the time of pulmonary valve opening could predict pulmonary artery diastolic pressure. BACKGROUND: Doppler echocardiography has been used to estimate right ventricular systolic pressure noninvasively. Because right ventricular and pulmonary artery diastolic pressure are equal at the time of pulmonary valve opening, Doppler echocardiographic estimation of right ventricular pressure at this point might provide an estimate of pulmonary artery diastolic pressure. METHODS: We studied 31 patients who underwent right heart catheterization and had tricuspid regurgitation. Pulmonary flow velocity was recorded by pulsed wave Doppler echocardiography, and tricuspid regurgitant velocity was recorded by continuous wave Doppler echocardiography. The time of pulmonary valve opening was determined as the onset of systolic flow in the pulmonary artery. Tricuspid velocity at the time of pulmonary valve opening was measured by superimposing the interval between the onset of the QRS complex on the ECG and the onset of pulmonary flow on the tricuspid regurgitant envelope. The tricuspid gradient at this instant was calculated from the measured tricuspid velocity using the Bernoulli equation. This gradient was compared to the pulmonary artery diastolic pressure obtained by right heart catheterization. MEASUREMENTS AND RESULTS: The pressure gradient between the right atrium and right ventricle obtained at the time of pulmonary valve opening ranged from 9 to 31 mm Hg (mean, 19+/-5) and correlated closely with invasively measured pulmonary artery diastolic pressure (range, 9 to 36 mm Hg; mean, 21+/-7 mm Hg; r = 0.92; SEE, 1.9 mm Hg). CONCLUSION: Doppler echocardiographic measurement of right ventricular pressure at the time of pulmonary valve opening is a reliable noninvasive method for estimating pulmonary diastolic pressure.
Aged↗
Intensified treatment and education of type 1 diabetes as clinical routine. A nationwide quality-circle experience in Germany. ASD (the Working Group on Structured Diabetes Therapy of the German Diabetes Association).
This contribution describes the nationwide implementation of an intensive treatment and education program for type 1 diabetic patients in the clinical routine of the German health care system. Based on the formation of a working group (Arbeitsgemeinschaft Strukturierte Diabetestherapie [ASD]) of presently 57 general internal medicine departments, mainly from secondary and tertiary care levels in city and country hospitals throughout the country, a peer-review quality circle was formed as an official working group of the German Diabetes Association. The participating institutions performed a structured program of intensive treatment and education in all type 1 diabetic patients referred to them on a routine basis. The program includes multiple daily insulin injections or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring and self-adaptation of insulin dosages and other aspects of treatment by the patients, and a far-reaching liberalization of the nutrition regimen. The group has attempted to document and to improve the quality of the structure and process of type 1 diabetes care in its participating institutions by a system of peer supervision. Furthermore, all member institutions volunteered to collect outcome data based on systematic 1-1.3 years' follow-up examinations of consecutive type 1 diabetic patients. For the 1997 evaluation of 1,103 type 1 diabetic patients, significant decreases of GHb levels and of incidence rates of severe hypoglycemia (from 0.35 to 0.16 cases per patient-year) and ketoacidosis (from 0.08 to 0.02 cases per patient-year) are presented. The ASD quality circle represents a model to improve principal aspects of type 1 diabetes care on a nationwide basis.
Cohort Studies↗
Influence of continuous combined estradiol-norethisterone acetate preparations on insulin sensitivity in postmenopausal nondiabetic women.
OBJECTIVE: Estrogen-progestogen replacement therapy (HRT) may be associated with deterioration of insulin sensitivity in comparison to estrogens alone, which tend to improve insulin sensitivity in postmenopausal women. Insulin sensitivity with the use of continuous combined 17-beta estradiol/norethisterone acetate (E2/NETA) preparations has not been examined before in postmenopausal women. DESIGN: In a double-blind randomized parallel study, we evaluated the effect of 2 mg E2/1 mg NETA (high dose E2/NETA), 1 mg E2/0.5 mg NETA (low dose E2/NETA), or placebo (P) on the insulin sensitivity index (SI) in three groups (18 women/group) of postmenopausal nondiabetic women (follicle stimulating hormone [FSH] > 40 mIU/mL, mean +/- SD) aged 56 +/- 3 years, BMI 25 +/- 4 kg/m2, cholesterol 233 +/- 42 mg/dL, and triglycerides 87 +/- 36 mg/dL. Insulin sensitivity was measured by means of a two-step hyperinsulinemic euglycemic glucose clamp (insulin infusion rate, 0.25 and 1.0 mU/kg/min for 120 min each) at baseline and after 3 months of daily administration of high dose E2/NETA, low dose E2/NETA, or P. Analysis was performed assuming equivalence of start-end changes of insulin sensitivity among treatment groups (Anderson-Hauck test). RESULTS: SI was 7.7 +/- 2.9, 7.5 +/- 3.4, 6.8 +/- 2.2 at baseline and 6.3 +/- 3.0, 7.9 +/- 2.5, 7.1 +/- 3.1 mL/min/m2 per mu U/mL 3 months after the administration of high dose E2/NETA, low dose E2/NETA, and P, respectively. The low dose E2/NETA group had start-to-end changes of SI which were equivalent to the P group (0.4 [95% confidence interval [CI] -0.8; 1.7] vs. 0.4 [-0.3; 1.0]) (p = 0.02). For the high dose E2/NETA group, equivalence could not be shown with either the P (p = 0.89) or with the low dose E2/NETA group (p = 0.90). SI within the high dose E2/NETA group decreased by -1.5 (95% CI -2.7; -0.2) mL/min/m2 per mu U/mL. HbAlc decreased from 5.3 +/- 0.3 to 5.1 +/- 0.3% within the high dose E2/NETA group (p < 0.03) and remained unchanged within the low dose E2/NETA and P group. Fasting plasma glucose, fasting serum insulin, and C-peptide, as well as triglycerides and BMI were comparable among the groups at baseline and after 3 months. Total cholesterol decreased by 12% and 8% in women treated with high dose and low dose E2/NETA (p < 0.02), respectively, and remained unchanged within the P group. CONCLUSIONS: These results indicate that 3 months use of a low dose continuous E2/NETA preparation does not change insulin sensitivity in postmenopausal women. At high dose of E2/NETA, a modest decrease seems possible. The effects of E2/NETA on other parameters of carbohydrate and lipid metabolism are neutral or favorable.
Aged↗
Rationale for the use of insulin therapy alone as the pharmacological treatment of type 2 diabetes.
Before any treatment of type 2 diabetes in accordance with the principles of evidence-based medicine can be generally recommended, the considerable disease heterogeneity must be taken into account, and randomized controlled intervention trials directed to cardiovascular and microangiopathic organ damage end points must be performed for the various subgroups of patients. Until then, it appears prudent to treat the typical Caucasian type 2 diabetic patient primarily by nondrug therapies, and if they fail to achieve the patient's individual treatment goals, then insulin treatment should be initiated. Treatment of type 2 diabetic patients with insulin alone, aimed at the patient's individual therapeutic goals, is effective and safe when conducted as an integral part of specific and structured treatment and teaching programs. Insulin treatment can be safely used to achieve near-normal HbA1c levels (< 7.0-7.5%) if prevention of diabetic microangiopathy is indicated, or to maintain HbA1c levels < 8.5-9.0% if catabolic symptoms due to insulin deficiency are to be prevented.
Demography↗
Use of host nation facilities as medical force multipliers at the Operation Joint Guard intermediate staging base, March to October 1997.
In March 1997, a transition occurred in the health service support of the intermediate staging base of Operation Joint Guard in Taszar, Hungary, by which a level III, 32-bed Deployable Medical Systems facility staffed by 178 personnel was replaced by a level II+ clinic staffed by 48 personnel with no organic surgical or blood transfusion capabilities. This was achieved by the use of local host nation facilities for surgery, sophisticated diagnostics, and medical specialty hospitalization. In the ensuing 7 months, 34 American patients were admitted to Hungarian hospitals for a total of 100 inpatient days, and 8 of them underwent surgery. This successful use of host nation facilities as medical force multipliers allowed great savings in cost and personnel and should be considered in future operations other than war that involve low-intensity conflict.
Cost Savings↗
[Amputations and mortality in elderly insulin-treated patients with type 2 diabetes].
The diabetic foot syndrome has a strong impact on the morbidity of elderly patients with type 2 diabetes, since diabetics have a 22-fold higher amputation rate. The aim of this study was to conduct a prospective evaluation of elderly insulin-treated patients with type 2 diabetes, giving special consideration to the diabetic foot syndrome. 94 consecutively admitted patients (mean age 68 years; mean diabetes duration 13 years) were re-evaluated 2, 5 and 10 years after participation in a 5-day insulin treatment and teaching programme for patients with type 2 diabetes. During the 10-year follow-up period 60 (64%) patients had died. Of the remaining 34 patients 33 were evaluated personally or by phone. All patients still alive had no acute foot complications and no amputations during the 10-year follow-up period. In these patients an acceptable level of metabolic control and acute metabolic decompensations was found. However, in 55 deceased patients (no data were available for 5 patients) 20 above-knee amputations (1 patient on both legs) and 2 fore-foot amputations were performed. This shows that severe complications as amputations associated with high mortality will be grossly underestimated, unless deceased patients are included in follow-up studies. An improved care for the feet of elderly insulin-treated patients is needed.
Aged↗