[Lung transplantation update. Summary and observations on the international guidelines on the selection of lung transplantation candidates].
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Humans↗
Biomedical subjects
D Kirsten
Publications and source records attributed to D Kirsten.
Efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipient.
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Acute Disease↗
HLA-DQB1 and HLA-DPB1 genotypes in familial sarcoidosis.
Numerous reports on the familial occurrence of sarcoidosis, on regionally different prevalences and on its associations with genetic polymorphisms point to the existence of predisposing genes. We have started to establish a collection of DNA from families with two or more sarcoidosis patients for the purpose of genetic linkage and association studies. In this report we present HLA class II genotypes of affected first-degree relatives from 17 families, including eight instances of affected parent and offspring, six sib pairs, and three sib triplets. Genotyping for HLA-DQB1 revealed an over-representation of DQB1*0603 and DQB1*0604 among alleles shared by affected first degree relatives. The same was found for HLA-DPB1*0201 (Glu69 positive). However, none of the sib triplets had any of these alleles in common.
Family↗
A second unrelated bone marrow transplant with an unrelated donor marrow: treatment of a patient with relapsed leukemia.
A second bone marrow transplant might be considered as an option in patients with leukemia relapsing after bone marrow transplantation. We report the successful treatment of a patient with relapsed ALL with a second BMT from the same unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. The conditioning regimen for the first transplantation consisted of BU and CY while fractionated TBI and CY were used for the second BMT. Acute skin GVHD, grade III which developed after second BMT, was successfully treated with the use of a new immunosuppressive drug, mycophenolate mofetil. Hemorrhagic cystitis and a CMV infection developed as complications during the second BMT and were successfully treated. The patient was alive and well after the second BMT with limited chronic skin GVHD up to day +170.
Adult↗
Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients.
The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD.
Acute Disease↗
Clinical pharmacokinetics of vasodilators. Part I.
Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.
Angiotensin II↗
Clinical pharmacokinetics of vasodilators. Part II.
Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy.
Adrenergic alpha-Antagonists↗
Chronic eosinophilic leukemia: successful treatment with an unrelated bone marrow transplantation.
The optimal treatment of eosinophilic leukemia is still uncertain. We report the successful treatment of a 21-year-old patient with eosinophilic leukemia, without cytogenetic abnormalities, by bone marrow transplantation from an unrelated donor. The conditioning regimen for the transplantation consisted of fractionated total body irradiation and cyclophosphamide. Acute GVHD, grade I, post-transplantation was successfully treated. No other severe complications occured. The patient is alive in complete remission 21 months after unrelated bone marrow transplantation.
Adult↗
[The German Society of Pneumology: recommendations for diagnosis and therapy of sarcoidosis].
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Germany↗
[Large, multilocular thymus cyst with compression of the left lung].
Thymic cysts are rare, generally asymptomatic lesions, which in most cases are discovered incidentally on the chest x-ray and are localized in the anterior compartment of the mediastinum or in the neck. We report the case of a 41 year old man, who developed a compression of the left lung and a protuberance of the left chest wall as a result of multilocular thymic cyst with an exceptional volume of 2 litres.
Adult↗
Effect of a nasal challenge with endotoxin-containing swine confinement dust on nasal nitric oxide production.
Inhalation of swine confinement dust containing endotoxin causes an inflammatory response in the nose as reflected by an influx of neutrophils 3 hrs after exposure (Am J Respir Crit Care Med 149: A401(1994)). As there is evidence that nitric oxide (NO) in exhaled air indicates cellular activation, we studied whether endotoxin causes an increase in nasal NO production in human subjects. Seven healthy subjects underwent a nasal challenge in which 50 mg swine confinement dust was given into each nostril (endotoxin concentration, 23.6 microg . g-1). Exhaled NO was measured before and during 3 hrs after the challenge and was compared to control values measured over the same period of time. Endotoxin produced a slight but statistically significant (p = 0.017) increase in nasal NO concentrations, mean (+/-SEM) values over 3 hrs being 367.5 +/- 7.5 ppb after endotoxin and 342.1 +/- 7.2 ppb under control conditions. The difference was most pronounced during the first hour after the challenge. We conclude that nasal administration of endotoxin causes a short-term increase in NO production which must precede cell influx or upregulation of transcription.
Adult↗
[Problems in adjustment to negative pressure ventilation].
We tried to establish a nasal intermittent positive pressure ventilation for a 54-year old patient with post-polio kyphoscoliosis. Due to intractable rhinitis the patient stopped the treatment. A negative pressure ventilation via a cuirass exhibited an inverse ventilation: during the inspiratory cycle of the ventilator the diaphragm was elevated and the patient was forced to exhale, afterwards he needs to inhale by himself. The ventilatory support is now done via a combined nasal-mouth mask and intermittent positive pressure ventilation.
Combined Modality Therapy↗
[Prospective study of the quality of life in intermittent self-ventilation].
PATIENTS AND METHOD: We assessed quality of life for 17 patients (age 14 to 74 years) before and during intermittent (nightly) nasal home mechanical ventilation with a standardized questionnaire (SF 36, Medical Outcomes Trust, Boston, USA). Underlying diseases were amyotrophic lateral sclerosis, bronchiectasis, kyphoscoliosis, pulmonary emphysema, muscular dystrophy and sequelae of tuberculosis. Blood gas and lung function data were collected during every examination. RESULTS: We observed statistically significant increases for items of general health, mental health, vitality and capillary oxygen partial pressure. CONCLUSION: The SF 36 allows to assess quality of life for patients under intermittent mechanical ventilation at home.
Adolescent↗
A short protocol for methacholine provocation testing adapted to the Rosenthal-Chai dosimeter technique.
BACKGROUND: The purpose of this study was to develop a rapid and safe methacholine provocation protocol equivalent to the standard dosimeter technique. METHODS: The rapid protocol comprised a short and a long subprotocol. The challenge was started with one of these subprotocols according to the subject's answers to a questionnaire and baseline lung function. If FEV1 dropped by 10% during the short subprotocol, the test was continued with the long subprotocol. The concentrations of methacholine and numbers of inhalations were chosen to match the concentrations of the standard method as closely as possible. To verify the protocol, we compared both methods in 38 subjects with asthma and 10 control subjects. RESULTS: The provocative concentrations of methacholine (PC20FEV1) obtained with the standard method and the rapid method were within one doubling concentration in 38 of 40 subjects. None of the subjects who were normoreactive according to the standard method (PC20FEV1 > 8 mg/mL) responded in the rapid protocol. The standard method required, on average (+/-SD), 34+/-11 min; the rapid method required 15+/-3 min. CONCLUSIONS: The rapid provocation protocol is equivalent to the standard method, without loss in precision and safety, but with considerable saving in time. Therefore, it appears to be particularly suited for studies that require comparability with provocative concentrations obtained with the Rosenthal-Chai dosimeter method.
Adult↗
[Indications and performance of a 6 minute treadmill test in pneumology].
The aim of rehabilitative measures for chronic airway and lung diseases is the restoration or improvement of disturbed lung function along with increased quality of life. The six minute walking-distance test (6 min WDT) is a suitable method for the assessment of the physical fitness of patients with chronic pulmonary diseases. The results of the 6 min WDT do not correlate strictly with lung function but correlate rather better with quality of life parameters and dyspnoea ratings; they therefore provide a better reflection of the patient's condition in daily life than is given by lung function measurements. Such a parameter may be appropriate in considerations of the potential for rehabilitation, in addition to its usefulness in questions of assessment.
Exercise Test↗
[Comparison of nasal and bronchial production of nitric oxide in healthy probands and patients with asthma].
Nitric oxide (NO) appears to play an important role in the pathophysiology of airway diseases as suggested from measurements of NO in exhaled air, animal and in vitro experiments. As NO is produced in variable amounts within the bronchial system and the nose, we studied the relationship between nasal and bronchial production of NO in patients with asthma and determined to which extent these productions were increased compared to healthy subjects. The nasal and bronchial production rates of NO as a function of breathholding time were assessed in 10 healthy subjects, 7 patients with asthma without inhaled corticosteroids, and 5 patients with asthma and a therapy of inhaled corticosteroids. After a breathhold of 10 s bronchial NO concentrations were elevated in the patients with asthma without steroids by the factor 3.5 (p < 0.005) and nasal concentrations by the factor 1.2 (n.s.) compared to healthy subjects. NO concentrations increased with time. Correspondingly, bronchial production rates were increased by factor 2.7 (p < 0.01) and nasal production rates by factor 1.1 (n.s.) in asthmatic compared to healthy subjects. The asthmatic patients with steroids showed lower production rates than those without steroids. We conclude from these data that in patients with asthma as compared to normal subjects bronchial production of NO is markedly increased, whereas the corresponding relative increase in nasal production is lower.
Adult↗
Analysis of immunoglobulins in sarcoidosis.
BACKGROUND: Assessment of local immunoglobulin(Ig)-production in sarcoidosis may be indicative of disease activity. However, in interstitial lung disease an increase in protein leakage across the alveolar-capillary membrane complicates determination of local Ig-production. In order to overcome this problem, techniques successfully used for the evaluation of local Ig-production in cerebrospinal fluid were applied to bronchoalveolar lavage (BAL)-analysis. METHODS: Ten patients with biopsy-proven sarcoidosis, seven patients with respiratory infections and ten patients as controls without any sign of interstitial lung disease or infection underwent BAL. Equal amounts of total protein (2 micrograms/lane) from BAL and serum samples were run on SDS-PAGE gradient-gel and blotted to a nitro-cellulose membrane. The blots were stained for total protein, IgA, IgM, IgG and IgG1-4-subgroups. RESULTS: Densitometric analysis revealed a significant increase of the IgG/albumin-ratio in BAL of sarcoidosis patients compared to the control group. In all control patients a single IgG band of identical molecular weight was detected both in serum and BAL. In sarcoidosis and pneumonia the serum showed multiple bands distinct from the BAL-band in regard to molecular weight. Subclass analysis of this group revealed an increased band intensity and different molecular weight of IgG1, IgG2 and IgG4-bands in BAL compared to serum indicative of local production. IgA and IgM were detected in all samples without any significant differences between the three groups. CONCLUSIONS: Molecular weight analysis of IgG-subgroups revealed local production of IgG1,2+4 in sarcoidosis and respiratory infection. This technique may prove useful with regard to the assessment of disease activity in sarcoidosis.
Adult↗
[Do patients with obstructive sleep apnea syndrome treated with nCPAP therapy lose weight?].
A simple therapy for obstructive sleep apnoea syndrome is weight reduction, which we always recommend before initiating and maintaining nCPAP-therapy. We documented the body weight of 123 patients (9 women, 114 men; age 53.8 +/- 10 years, initial apnoea-hypopnoea-index 40.7 +/- 22.6/hour) before and after 582 +/- 391 days nCPAP-therapy. Absolute and relative (Broca Index: weight [kg]/[height [cm] -100] x 100) body weight was 97.8 +/- 19.4 kg resp. 128.3 +/- 24.3 units before and 97.3 +/- 18.2 kg resp. 127.8 +/- 23.5 units during therapy (not significant). Body weight changes ranged from +22 to -26 kg. Only a subgroup of patients with a Broca index between 100-119 exhibited a significant weight change from 86.8 +/- 10.4 to 88.5 +/- 10.4 kg. We conclude that our recommendations to lose weight were unsuccessful in patients with obstructive sleep apnoea, although nCPAP-therapy generally improved well-being.
Adult↗