Biomedical subjects
Publications and source records attributed to R G Klein.
An accurate, simple and quick method for instillation of substances into the respiratory tract of small rodents is reported. This new method is compared with conventional techniques.
Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = -0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D(3) (0.4 mug daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.
Angiograms of 10 patients with giant cell arteritis who had large-artery and aortic abnormalities were reviewed. The affected arteries had multiple stenotic areas, and occlusions were relatively common, usually located at the end of tapered stenotic segments. Bridging collateral arteries usually refilled the distal portion of the occluded artery. The laterations were seen most frequently in the subclavian, axillary, and brachial arters, and the arteriographic lesions reflected the clinical findings. Such arteriographic abnormalities are suggestive of giant cell arteritis in a patient over the age of 50. The differential diagnosis includes Takayasu's disease, arteriosclerosis, thoracic outlet syndrome, and ergotism.
Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.
Of 248 patients with giant cell arteritis, 34 had evidence that the disease affected the aorta or its major branches. Symptoms suggestive of large artery involvement were intermittent claudication of an extremity, paresthesias, and Raynaud's phenomenon. Physical findings included absent or decreased large artery pulses and bruits over large arteries. Four patients presented with decreased upper extremity pulses as the initial manifestation of their arteritis. Nine other patients under treatment for temporal arteritis or polymyalgia rheumatica first developed evidence of large artery involvement as corticosteroid therapy was tapered or discontinued. Angiography, performed in 10 patients, was helpful in indicating arteritis rather than atherosclerosis as the cause of large artery disease. Three patients died with aortic rupture, and, at autopsy, widespread giant cell arteritis was found. However, when corticosteroids were given in adequate doses, the response was favorable in most patients; intermittent claudication decreased and the pulses improved.
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An ex vivo model to detect nonspecific DNA damage in different rat tissues has been developed and employed to study systemic properties of tobacco-specific N-nitrosamines. One hour after treatment of rats with the carcinogens, primary, intact cells were isolated from various organs. Viability of the cells was monitored by trypan blue exclusion. Genotoxicity was determined by alkaline elution, in situ nick translation or microgel electrophoresis. We found that oral application of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces genotoxic effects in the liver (3.125-50 mg/kg), whereas N-nitrosonornicotine (NNN) is only moderately active (50-100 mg/kg). Furthermore, oral administration of NNK, NNN, and of N-nitrosodimethylamine (NDMA), induces DNA damage in the nasal cavity. In peripheral blood lymphocytes genotoxicity of NDMA (less than 2 mg/kg), but not of NNK (50 mg/kg), was observed. NDMA and NNK are just as genotoxic in the liver when administered by inhalation as orally (effective doses: 0.1-1 and 50 mg/kg, respectively). For human cancer, these results indicate that in addition to the susceptibilities in local organs (oral cavity after snuff dipping and lung after tobacco smoke inhalation), these nitrosamines also pose a risk systemically for more remote organs.
OBJECTIVE: There is evidence for the efficacy and safety of clonazepam (CZP) in adult anxiety disorders, but no formal studies to substantiate clinical reports of similar benefit in children with anxiety disorders. METHOD: In this double-blind pilot study, 15 children, aged 7 to 13 years, entered a randomly assigned, double-blind crossover trial of 4 weeks of CZP (up to 2 mg/day) and 4 weeks of placebo. RESULTS: Twelve children completed the trial. All but 1 had a diagnosis of separation anxiety disorder, and all but 2 had comorbid diagnoses. Nine children appeared to have moderate to significant clinical improvement, but statistical comparisons on several ratings failed to confirm a trend in favor of CZP. Side effects of drowsiness, irritability, and/or oppositional behavior were notable in 10 children in the CZP phase compared with 5 in the placebo phase. CONCLUSIONS: Clonazepam was believed to have clinical benefit for some children, but this was not confirmed statistically in this small sample. Problematic side effects of drowsiness and disinhibition were common and possibly were due to rapid titration.
The research recently conducted and ongoing in adolescent obsessive-compulsive disorder indicates that the clinical signs and symptoms are indistinguishable from those seen in adults. Comorbidity appears to follow the same trends in adolescents and adults, with anxiety and affective symptomatology predominating. Contrary to expectation, Gilles de la Tourette disorder does not appear either as a concurrent syndrome, or as an eventual outcome in obsessive-compulsive adolescents. Males are greatly over-represented among adolescents with an early childhood onset. The neurological and neuropsychological findings are the only ones that appear to distinguish the adolescent and adult obsessive-compulsive patients. The findings point to frequent neurological abnormalities in adolescents with obsessive-compulsive disorder. The natural history over the short-term seems to be negatively affected by severity. The clinical efficacy of clomipramine and the failure of another tricyclic antidepressant parallels the therapeutic experience reported in adult patients. The presence of depression is unrelated to the efficacy of clomipramine. The neuropsychological and neurological abnormalities, together with the data from the longitudinal and treatment studies, strongly suggest that obsessive-compulsive disorder in adolescents is not a variant of the overall group of anxiety disorders.
The efficacy of methylphenidate (MTP) is amply documented for children with ADHD. In addition to modifying the central features of the disorder, inattention, impulsive behavior and excessive motor activity, the medication has been shown also to improve social behavior with peers and adults, as well as academic performance. The concerns that these benefits may not extend beyond the period of active intervention, and that treatment efficacy in only partial in some children, has led to the development of other, psychosocial interventions. Behavioral treatment by itself is ineffective, but contributes significantly to clinical change in children who derive incomplete gains from MTP alone. Cognitive training has not been shown to have therapeutic impact either as a single treatment, or as an adjunct to MTP. Clinical indications for MTP extend to children and adolescents with Conduct disorders. Treatment affects antisocial behavior regardless of the concurrent presence of hyperactivity symptomatology. Extended treatment with MTP alone is difficult to implement in older children due to lack of cooperation. MTP has been shown to be safe. Deceleration of growth velocity is the only identified long-term side effect. It occurs after more than one year of treatment at greater than low doses. It appears completely reversible with treatment cessation prior to the adolescent growth spurt. Efficacy in Attention Deficit-Hyperactivity Disorder (ADHD) is especially well demonstrated in preadolescents, with only sparse evidence for efficacy in adolescents.