Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy

Summary Objective To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). Methods We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. Results Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. Conclusions With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event. Received: 23 February 2001 Accepted: 16 May 2001     

The effects of the stereoisomers of the alpha 2-adrenergic agonist medetomidine on systemic and coronary hemodynamics in conscious dogs.

The alpha 2-adrenergic agonist medetomidine produces systemic hemodynamic effects that are mediated by both peripheral and central nervous system actions. The current investigation was designed to characterize coronary and systemic hemodynamic effects of the D- and L-stereoisomers of medetomidine in conscious, chronically instrumented dogs with and without autonomic nervous system blockade. Dogs were instrumented for measurement of aortic pressure, coronary blood flow velocity, cardiac output, left ventricular pressure, rate of change in pressure (dP/dt), and subendocardial systolic shortening. Administration of the D-isomer of medetomidine (doses of 1.25, 2.5, and 5.0 micrograms/kg, each administered over 10 min, with 60 min between doses) significantly altered systemic hemodynamics, in a biphasic fashion. A decrease in respiratory rate without change in arterial blood gas tensions occurred. With the 5 micrograms/kg dose of D-medetomidine, an initial pressor response was followed by secondary, significant (P less than 0.05), and dose-related decreases in heart rate (74 +/- 3 to 57 +/- 4 beats per min), mean arterial pressure (109 +/- 2 to 100 +/- 3 mmHg) and the rate-pressure product (10.5 +/- 0.4 to 7.0 +/- 0.5 beats.min-1.mmHg.10(3] accompanied by a reduction in plasma concentrations of norepinephrine. No changes in left ventricular end diastolic pressure or coronary blood flow velocity occurred. In contrast to the D-isomer, the L-isomer (1.25, 2.5 and 5.0 micrograms/kg) produced no changes in hemodynamics or plasma concentrations of norepinephrine. In dogs pretreated with hexamethonium (20 mg/kg), propranolol (2 mg/kg), and atropine methylnitrate (3 mg/kg) to produce autonomic nervous system blockade, D-medetomidine also produced an initial pressor response, but no secondary reduction in heart rate or arterial pressure occurred. The results indicate that the D-isomer of medetomidine is stereospecific for alterations in hemodynamics: the active D-isomer produces decreases in heart rate, arterial pressure, and the rate-pressure product via diminished sympathetic and/or augmented parasympathetic tone. This conclusion is supported by the absence of these changes after pharmacologic blockade of the autonomic nervous system.     

Pseudomembranous supraglottitis with airway compromise in a patient with recurrent tonsillar carcinoma

PURPOSE: In this report, we discuss a patient with acute pseudomembranous supraglottitis complicating recurrent tonsillar carcinoma and describe the ramifications of these disorders on perioperative management. CLINICAL FEATURES: The patient was an acutely ill man with a history of right tonsillar carcinoma originally treated with chemoradiation therapy and a radical neck dissection who presented with a brief history of fever, dyspnea, and stridor. The soft tissue of his neck was very stiff, his neck mobility was limited, and his mouth opening was restricted by pain and radiation-induced fibrosis. A nasal flexible fibreoptic laryngoscopy revealed a very large, indurated epiglottis almost completely obstructing the glottis. The aryepiglottic folds and false cords were edematous, and a gray pseudomembranous exudate was observed on the glottic surface, epiglottis, and true vocal cords. An elective tracheostomy was performed in the operating room using local anesthesia, and conscious sedation was avoided because of the potential for complete airway obstruction. General anesthesia was induced after the airway was secured, but trismus and tissue edema resulting from the acute infection made the glottis and surrounding structures nearly impossible to visualize during direct laryngoscopy. The patient was treated with intravenous antibiotics, and a subsequent direct laryngoscopy demonstrated tumour recurrence. CONCLUSIONS: The case emphasizes that the perioperative management of imminent airway obstruction by acute supraglottitis complicating recurrent oropharyngeal cancer may optimally be approached by establishing a surgical airway under controlled operating conditions.     

Parodontaler Knochenabbau als Kriterium der forensischen Altersdiagnostik bei jungen Erwachsenen

Zusammenfassung Es wurde untersucht, ob die Bestimmung des parodontalen Knochenabbaus forensisch verwertbare Hinweise auf die Vollendung des strafrechtlich relevanten 21. Lebensjahres liefert. Hierzu wurden 650 konventionell gefertigte Orthopantomogramme deutscher Probanden der Altersgruppe 18–30 Jahre ausgewertet. Der parodontale Knochenabbau wurde an den zweiten Prämolaren aller 4 Quadranten bestimmt; hierbei wurden 4 Stadien definiert. Ein zunehmender parodontaler Knochenabbau korrelierte gut mit einem Altersanstieg der Probanden. Bei einem beginnenden parodontalen Knochenabbau (Stadium 1) war die Hälfte der Untersuchten mindestens 21 Jahre alt. Mit einem fortgeschrittenen parodontalen Knochenabbau (Stadium 2) waren 75% der Untersuchten mindestens 21 Jahre alt. Alle männlichen Probanden mit einem erheblichen Knochenabbau (Stadium 3) waren deutlich älter als 21 Jahre; dieses Stadium kam in der untersuchten Altersgruppe nur selten vor. Es wird geschlussfolgert, dass der parodontale Knochenabbau als ergänzendes Kriterium der forensischen Altersdiagnostik im jungen Erwachsenenalter geeignet erscheint. Allerdings ist die Übertragbarkeit der präsentierten Referenzwerte auf Personen anderer ethnischer Zugehörigkeit in künftigen Studien zu prüfen.     

Changes in the phenotype of polymorphic plasma proteins after liver transplantation – new data and medico-legal consequences

The genetically inherited polymorphic plasma protein types have always been considered stable for lifetime in humans. Most of these proteins are synthetised in the liver. Phenotypes for 14 plasma proteins in donors and recipients of liver transplants prior to and after transplantation were determined in 15 patients who had undergone liver transplantation at the university hospitals Charité and Rudolf Virchow in Berlin. The plasma proteins investigated were HP, TF, GC, PI, ORM1, ITI, A2HS, PLG, FXIIIB, BF, C3, C6, C8 and FH. Evidence was provided of irreversible change from the recipient type to the donor type in at least one patient for all the systems investigated. This is the first time such data have been obtained for ITI, A2HS, C8 and FH. These results clearly support the point that the dogma of life-long stability of genetically determined protein phenotypes is merely of limited validity. Against the background of good long-term results of liver transplantation, there are consequences for the practice of legal medicine in the particular context of certification of parentage, identification and stain analysis. Received: 21 November 1997 / Received in revised form: 4 March 1998     

Response times follow lognormal or gamma distribution in arthritis patients

ObjectiveThis study evaluated the statistical distribution of time to treatment response in patients with rheumatic diseases.Study Design and SettingThe study used a secondary data analysis design. Data from the trial of etanercept and methotrexate with radiographic patient outcomes were used to model the response times for etanercept (ETN), methotrexate (MTX), and combined ETN + MTX in patients with rheumatoid arthritis. The German etanercept registry was used to evaluate the response time distributions in patients with juvenile idiopathic arthritis.ResultsFor MTX, the lognormal distribution was considered to be the best model for the outcome American College of Rheumatology (ACR20), lognormal, generalized gamma, and log-logistic distributions for ACR50, and lognormal and generalized gamma for ACR70. For ETN, the lognormal model was best for ACR20, the generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For combined treatment, the best model was the log-logistic distribution for ACR20, generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For the German etanercept registry, the lognormal distribution was the best model for all three outcomes of pediatric ACR30, ACR50, and ACR70 without interval censoring.ConclusionStudy designs might be more efficient if the response distributions are taken into consideration during planning.     

Hormonal and metabolic response to operative stress in the neonate

It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin.