For a physician with the signature scar of the CABG club, a friend's death brings not only grief but also memories and fear.
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Biomedical subjects
Publications and source records attributed to D Rapoport.
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We report the isolation of the genes encoding the beta 1 and beta 2 adrenergic receptors from dog genomic DNA. Sequence analysis of both genes revealed intronless open reading frames of 473 and 415 amino acid residues, receptively. Heterologous expression of both receptors in CHO cells indicated that both receptors are functionally similar to the human homologs. Comparing the dog beta 1 and beta 2 adrenergic receptors, the beta 1 receptor appears to bind to G proteins more tightly than the beta 2 receptor. Heterologously expressed receptors provide a convenient system for evaluating novel receptor agonists and antagonists.
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UNLABELLED: A retrospective study was performed on the clinical outcome and long-term treatment of 17 patients with propionic acidaemia diagnosed during the last 20 years in our hospital. The study group consisted of 12 patients with early onset type of disease and 5 patients with late onset. Seven (41%) patients died, five with early onset and two with late onset. The deceased early onset patients had a median survival of 0.4 years while the deceased late onset patients died at the age of 2.8 and 4 years respectively. Median age of the living early onset patients was 5.2 (1-9.25) years, the late onset patients were 4, 7 and 23 years old. Patients were all treated with natural protein restriction and in most cases carnitine and metronidazole were added. The early onset patients were almost all treated with daily home tube feeding. The mean natural protein intake of early onset patients (6.3 +/- 1.5 g/day) was significantly lower than the natural protein intake of late onset patients (17.6 +/- 5.3 g/day). Supplemental protein intake was higher in early onset patients. The general neurological outcome of our study group was satisfactory with a better outcome for early onset patients. As to growth, many patients showed a failure to thrive, this was particularly for height. The strong protein restriction during the first years of life probably contributed to this. CONCLUSION: The prognosis for patients with propionic acidaemia appeared to be satisfactory in terms of survival and outcome characteristics such as neurological and mental development. Despite these results the authors feel that the prognosis and quality of life of these patients might be improved with liver transplantation or possibly somatic gene therapy in the future.
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The effect of nefazodone on the pharmacokinetics and pharmacodynamics of theophylline was evaluated in a multiple-dose, randomized placebo-controlled, double-blind two-period crossover study in 13 patients who were undergoing theophylline therapy for chronic obstructive pulmonary disease. Two treatments were administered, each for 7 days: theophylline + 200 mg nefazodone twice daily (every 12h) and theophylline+matching nefazodone placebo capsule twice daily (every 12h). Mean peak and trough plasma concentrations of theophylline ranged from 13.1 to 14.5 micrograms ml-1 and 11.6 to 14.2 micrograms ml-1, respectively, at steady-state when theophylline was administered with or without concurrent dosing of nefazodone. Similarly, the mean area under the curve for theophylline ranged from 93.5 to 103 micrograms ml-1 h. When nefazodone and theophylline were co-administered, theophylline pharmacokinetic parameters did not significantly differ from those obtained when theophylline was administered with placebo. Forced expiratory volume in one second (FEV1) measurements taken when nefazodone or placebo were administered with theophylline did not differ from those obtained at baseline. The plasma concentration-time profiles for nefazodone and its metabolites were similar to those in other studies where nefazodone was administered alone. Since nefazodone did not affect the pharmacokinetics or the pharmacodynamics of theophylline, no change in theophylline dose should be needed as a consequence of nefazodone co-administration.
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We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.
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The prospective follow up of abused children after their hospitalization is illustrated by the report of a sibship. Dysfunction in management and therapy is often observed and is detrimental to the children. Many levels of our society are implicated. This means that there is still a lot to do to obtain adequate therapy for these children.
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