Caring for the hypochondriac

The patient's manner and the content of his complaints offer early diagnostic leads. The hypochondriac clings to his symptoms. Rather than relief, his goal is forming a relationship with the doctor that provides care and understanding. The physician's goal must be the provision of this care in such manner as to reassure, treat sparingly and convert this potentially fatal illness to a chronic disorder with which the patient can function to the limits of his capabilities.     

Activin A and transforming growth factor-beta stimulate heart formation in axolotls but not rescue cardiac lethal mutants

The cytotoxicity of transforming growth factor beta 1 (TGF beta 1) was assessed in rat hepatocytes cultured under periportal (PP)-or pericentral (PC)-equivalent conditions. TGF beta 1 induced a 5-fold greater DNA fragmentation and LDH release in PC cultures than in PP cultures. At low exposure level (1 ng/ml TGF beta 1), albumin secretion and mitochondrial activity (rhodamine-123 uptake) were selectively reduced in PP cultures, whereas the incidence of apoptotic cells in PC cultures was about 10-fold higher than that in PP cultures. The time profiles of TGF beta 1-induced apoptotic and necrotic events and the concentration-response relationship differed in PC and PP cultures. In PC cultures the early appearance of cells with apoptotic nuclei was not associated with DNA fragmentation nor with an increase in LDH release or impaired mitochondrial function. At a high exposure level (5 ng/ml TGF beta 1), again cells with apoptotic nuclei were much more strongly induced in PC cultures but DNA fragmentation, LDH release, and impairment of mitochondrial activity all increased in an exposure-time dependent manner in both PP and PC cultures. At this exposure level 48 and 72% of the apoptotic cells detected in PC cultures after continuous exposure for 24 hr were induced within an exposure of 1 and 4 hr, respectively. Aurintricarboxylic acid (50 microM), an inhibitor of endonucleases, significantly inhibited the appearance of apoptotic cells and the progression in apoptosis. Clearly, TGF beta 1 preferentially induced apoptotic cell death in hepatocytes with PC-equivalent metabolism at low exposure levels. High exposure levels or prolonged exposure periods produced both apoptosis and necrosis.     

Quantitative study on the effect of osthole on proximal tibiae in ovariectomized (OVX) rats

OBJECTIVE: To determine if a correlation exists between the level of maternal serum alpha-fetoprotein (MSAFP) elevation and the rate of adverse pregnancy outcome, to examine the timing of pregnancies ending in fetal or neonatal death, and to develop a protocol for antepartum surveillance in an effort to prevent these adverse outcomes. STUDY DESIGN: Singleton pregnancies with a single second-trimester elevated MSAFP > or = 2.0 multiples of the median (MoM) were eligible if a targeted ultrasound evaluation (< 24 weeks) was in agreement with the dates and no fetoplacental anomaly was detected. Three groups were established based on the second-trimester MSAFP elevation: 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM. RESULTS: Among the 383 patients enrolled, delivery data were available on 333 infants. Stratified by MSAFP elevations of 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM, the rates of adverse pregnancy outcome were: (1) preterm birth: 14.3%, 15.6%, 20.3%; (2) small for gestational age at birth: 7.4%, 11.1%, 22.2%; and (3) perinatal deaths (neonatal and fetal): 2.6%, 3.3%, 5.6%. Seven pregnancy losses (three neonatal and four fetal deaths) occurred prior to 28 weeks. Of these seven, six fetuses exhibited intrauterine growth retardation by 23-26 weeks' gestation, and five of six were associated with MSAFP levels > or = 2.5 MoM. Four losses (two neonatal and two fetal deaths) occurred after 28 weeks. Of these, three involved structurally normal infants with normal growth who died after 34 weeks. All three of these pregnancies exhibited MSAFP elevations < 2.5 MoM. CONCLUSION: In pregnancies with an unexplained elevated second-trimester MSAFP, the rate of adverse pregnancy outcomes is increased with higher elevations. Any proposed program to improve pregnancy outcome in patients with unexplained MSAFP elevations must include efforts aimed at preventing preterm delivery, repeat ultrasound at 24-26 weeks to rule out early-onset intrauterine growth retardation in pregnancies with elevations > or = 2.5 MoM and fetal biophysical monitoring, even in normally grown fetuses, instituted at 32 weeks to detect fetuses at risk for intrauterine death.