Pathologic seminal vesicle invasion after radical prostatectomy for patients with prostate carcinoma: effect of early adjuvant radiation therapy on biochemical control

BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.     

Differential effects of prenatal stress in two inbred strains of rats

Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted in vagotomized patients, suggesting that fundic chief cells, from which gastric lipase is released, or neighboring inhibitory cells could be equipped with GLP-1 receptors. Vagotomized patients had significantly higher plasma concentrations of gastrin and secretin. No significant changes of gastrin, secretin, and CCK secretion were seen during GLP-1 infusion in the vagotomized patients, whereas secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal mechanism. Our results indicate that gastric lipase secretion is subject to hormonal stimulatory as well as inhibitory mechanisms.     

Fimbria-fornix cut affects spontaneous activity, two-way avoidance and delayed non matching to sample, but not latent inhibition

Latent inhibition (LI) consists of a decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. Based on evidence pointing to the involvement of the hippocampus and the nucleus accumbens (NAC) in LI disruption, it has been proposed that LI depends on the integrity of the subicular input to the NAC. Since fibers originating in the subiculum and destined for the NAC run through the fimbria-fornix, we assessed the effects of fimbria-fornix lesion, made using a knife cut, on LI. In addition, we assessed the effects of the fimbria-fornix cut in three tests known to be sensitive to lesions to the hippocampal region, namely, spontaneous activity, two-way active avoidance and delayed-non-matching-to-sample. In accord with previously documented effects of lesions to the hippocampus and related structures, the fimbria-fornix cut increased spontaneous activity (Experiment 1), facilitated the acquisition of two-way active avoidance (Experiment 3), and produced a delay-dependent deficit in the delayed-non-match-to-sample task (Experiment 4), demonstrating that it disrupted hippocampal functioning. In contrast, LI remained unaffected by the fimbria-fornix cut (Experiment 2), indicating that disruption of subicular input to the NAC is not responsible for the attenuation of LI following non-selective hippocampal lesions. The implications of these results for the neural circuitry of LI are discussed.     

Effects of acute and chronic morphine on rotational behavior in nigral-lesioned rats

Stimulation of mu-opioid receptors located on dopaminergic neurons in the striatum and the nucleus accumbens increases dopamine release, which may account for some of the behavioral effects of morphine. In this study, we examined the effects of acute and chronic morphine treatment on rotational behavior in rats with unilateral 6-hydroxydopamine dopamine (6-OHDA)-induced lesions of the nigrostriatal pathway. Rats receiving morphine acutely (0.3-10 mg/kg) did not show a significant bias toward contralateral or ipsilateral turning. Mini osmotic pumps dispensing morphine continuously (20-24 mg/kg/day) were implanted s.c. in these animals. This treatment induced tolerance to the behavioral depression produced by the highest dose of morphine (10 mg/kg) when it was given acutely. A slight but significant increase in ipsilateral turning occurred over the range of morphine doses examined. The effects of morphine on rotational behavior are slight, and do not correlate well with the reported increase in locomotor activity or extraneural dopamine in the striatum that are produced by doses of morphine similar to the ones tested in this study.     

Influence of fathers' social class on cardiovascular disease in middle-aged men

BACKGROUND: The independent effect of early life circumstances on adult cardiovascular risk is still unresolved. We assessed the associations of father's social class with cardiovascular risk factors and with risk of ischaemic heart disease and stroke in adult life. METHODS: We did a longitudinal study of cardiovascular disease in 5934 men aged 40-59 years at enrollment. A cross-sectional measurement survey was done between 1978 and 1980 and a follow-up questionnaire was completed in 1992. The main endpoints were non-fatal myocardial infarction and stroke based on general practitioners' reports obtained between screening and 1992 and on recall of physician-diagnosed ischaemic heart disease in the 1992 questionnaire. FINDINGS: Father's social class was strongly associated with social class in adulthood (fathers' occupation was manual for 41.3% of professionals [I] vs 89.1% for unskilled manual workers [V]) and was significantly related to height (non-manual vs manual 175.4 cm [SE 0.2] vs 172.9 cm [0.1], p < 0.0001) and obesity (213 [14.1%] vs 804 [20.1%], p < 0.0001) irrespective of adult social class; no association was found with blood glucose (log, 1.69 [0.005] vs 1.70 [0.003], p = 0.22) or cholesterol (6.34 [0.03] vs 6.29 mmol/L [0.02], p = 0.16. Men whose fathers' social class was manual had significantly higher rates of non-fatal myocardial infarction (342/4006 vs 92/1510) and self-reported physician-diagnosed ischaemic heart disease (686/4006 vs 192/1510) than men whose fathers' social class was non-manual, even after adjustment for adult social class and other established risk factors (relative odds 1.3 [95% Cl 1.0-1.7], p < 0.05 and 1.3 [1.1-1.6], p < 0.01, respectively). The influence of father's social class on non-fatal myocardial infarction and ischaemic heart disease was only seen in men whose adult social class was non-manual. No association was seen between father's social class and non-fatal stroke. INTERPRETATION: Father's social class is strongly associated with adult social class. The higher risk of non-fatal myocardial infarction and self-reported physician-diagnosed ischaemic heart disease seen in men whose father's social class was manual suggests that socioeconomic status early in life has some persisting influence on ischaemic heart disease risk in adult life.     

Family structure and the mental health of children. Concurrent and longitudinal community-wide studies

This study provides a map of variations of families and some of the core relationships between types of family and the mental health of children. Family types in a poor, black urban community were defined in terms of the adults present at home. The resulting taxonomy is based on two populations: half of the community's 1964 first-grade children and families and the entire 1966 first-grade children and families. Eighty-six family types were found, falling into ten major classes. Family type was found to be strongly related over time to the child's social adaptational status (SAS) and his or her psychological well-being. The results suggest that (1) mother alone families entail the highest risk in terms of social maladaptation and psychological well-being of the child; (2) the presence of certain second adults has important ameliorative functions--mother/grandmother families being nearly as effective as mother/father families, with mother/stepfather families similar to mother alone in regard to risk; and (3) the absence of the father was less important than the aloneness of the mother in relation to risk.     

Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure

Eleven patients with chronic renal failure and presumed secondary hyperparathyroidism developed a syndrome of medial calcinosis of the arteries and painful ischemic ulcers of the fingers, legs, or thighs, or any combination of the three. Five patients required maintenance hemodialysis; six had functioning renal homografts. Severe hyperphosphatemia had existed in each; seven showed roentgenographic evidence of subperiosteal resorption. Similarities are evident between the lesions and experimentally produced calciphylaxix. The lesions demonstrated a relentless, progressive course, with serious morbidity and mortality. Hyperplastic or adenomatours parathyroid tissue was removed from ten of 11 patients unergoing surgical procedures; healing followed in seven patients. Treatment with phosphate-binding antacids to lower serum phosphorus levels may prevent this syndrome. Total or subtotal parathyroidectomy should be considered when ischemic skin lesions appear in uremic patients or in renal transplant recipients.     

Blockade of the specific lethal effects of narcotic analgesics in the mouse

The capacity of the narcotic antagonists naloxone and nalorphine and the benzodiazepine derivatives diazepam and oxazepam to increase the LD50s of the narcotic analgesics morphine and methadone administered at convulsant doses was eveluated in the mouse. Naloxone produced a dose-related increase in the LD50s of both morphine and methadone. Iiazepam and oxazepam were also effective in increasing the LD50s of the narcotics; this effect was additive with that of naloxone. However, the maximal increase in the LD50s of the narcotics produced by pretreatment with naloxone alone was not increased further by the combined pretreatment of naloxone and a benzodiazepine. The anticonvulsant trimethadione did not elevate the LD50s of methadone, nor did it potentiate the effects of naloxone. These results suggest that the benzodiazepines may reduce the lethality of narcotic analgesics administered at high doses by a mechanism other than by an anticonvulsant effect alone. Therefore, the present results support the conclusion that the capacity to increase the convulsant LD50 of the narcotic analgesics is a general property of the narcotic antagonists.     

Involvement of 4-hydroxymandelic acid in the degradation of mandelic acid by Pseudomonas convexa

A microorganism capable of degrading DL-mandelic acid was isolated from sewage sediment of enrichment culture and was identified as Pseudomonas convexa. It was found to metabolize mandelic acid by a new pathway involving 4-hydroxymandelic acid, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, and 3,4-dihydroxybenzoic acid as aromatic intermediates. All the enzymes of the pathway were demonstrated in cell-free extracts. L-Mandelate-4-hydroxylase, a soluble enzyme, requires tetrahydropteridine, nicotinamide adenine dinucleotide phosphate, reduced form, and Fe2+ for its activity. The next enzyme, L-4-hydroxymandelate oxidase (decarboxylating), a particulate enzyme, requires flavine adenine dinucleotide and Mn2+ for its activity. A nicotinamide adenine dinucleotide-dependent, as well as a nicotinamide adenine dinucleotide phosphate-dependent, benzaldehyde dehydrogenase has been resolved and partially purified.     

Dependence of centriole formation on protein synthesis

Electron microscope observations were made of rat peroneal nerve after crushing using intravenously injected horseradish peroxidase (HRP) as a tracer protein to indicate changes in vascular permeability. At 1/2 h and 2 d after the crush there was gross leakage of HRP from damaged capillaries at the site of injury but none from vessels above or below this. Ultrastructurally vessels at the site of crush showed broken and separated endothelial cells. Proximally and distally there was little abnormal in the vessel walls; vesicles containing HRP were absent and tight-junctions between cells remained intact. Twenty-one days after the crush, leakage of HRP was found both at the site of crush and along the distal segment. The only change in vessel walls was an obvious increase in vesicles filled with HRP. Tracer was also found both in perivascular locations and throughout the endoneurial space.