Effects of race and socioeconomic status on survival of 1,332 black, hispanic, and white women with breast cancer

Background: A survival disadvantage for black women with brest cancer, which persists after controlling for stage of the disease, has been reported. This study investigates the effects of race and socioeconomic status (SES) on breast cancer survival after controlling for age, stage, histology, and type of treatment. Methods: Kaplan-Meier and Cox proportional hazards models were used to analyze the interaction between race and SES in predicting survival in a sample of 163 black, 205 Hispanic, and 964 white women with breast cancer treated at M. D. Anderson Cancer Center (1987–1991). Results: The results of univariate and multivariate analyses indicate that race was not a significant predictor of survival after adjusting for SES and other confounding factors such as demographic and disease characteristics. SES remained a significant predictor of survival after all adjustments were made. There was no evidence of differences in type of treatment by race or SES if adjustments were made for stage. Conclusions: These results suggest that institutional factors, such as access to treatment, do not explain survival differences by race or SES. Other factors associated with low SES, such as life-style and behavior, may affect survival.     

Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations.

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ > La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ > Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.     

Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.     

Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.

Evidence exists that a norepinephrine/prostaglandin E2 (PGE2)/cAMP pathway is involved in the regulation of luteinizing hormone-releasing hormone (LHRH) secretion. The aim of the present experiments was to determine if release of LHRH from the immature rat hypothalamus could also be stimulated by activation of protein kinase C. Median eminences from 28-day-old female rats were incubated in vitro with either dioctanoylglycerol (a synthetic diacylglycerol that selectively activates protein kinase C in intact cells) or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (another protein kinase C activator). Both agents increased LHRH release, the response to dioctanoylglycerol being more pronounced than that to the phorbol ester. This direct activation of protein kinase C was not accompanied by changes in PGE2 formation. Activation of the PGE2/cAMP pathway by either norepinephrine, PGE2, or forskolin (a stimulator of adenylate cyclase) increased LHRH release. Dioctanoylglycerol or phorbol ester in conjunction with either norepinephrine, PGE2 or forskolin resulted in an additive effect on LHRH release suggesting coexistence of both pathways. Phospholipase C, which activates protein kinase C via formation of diacylglycerol, increased the release of both LHRH and PGE2. This suggests that an increase in endogenous phospholipase C activity caused by neurotransmitter inputs may lead to both activation of protein kinase C and PGE2 formation. Blockade of cyclooxygenase activity by indomethacin obliterated phospholipase C-induced PGE2 release. The same treatment reduced the LHRH response by only 50% indicating that protein kinase C activation can cause LHRH release in the absence of PGE2 synthesis. It is suggested that the median eminence of the rat possesses a protein kinase C-dependent pathway that is coupled positively to LHRH release and complements PGE2/cAMP-dependent mechanisms. Norepinephrine, however, does not appear to be the neurotransmitter responsible for activating the protein kinase C pathway. Simultaneous activation of both pathways may provide a mechanism by which a large increase in LHRH secretion occurs, such as in the afternoon of first proestrus.     

Venous skin flaps: an experimental study and report of two clinical distal island flaps

An experimental study of saphenous flaps in 26 dogs is reported, which confirmed the work of Baek et al. (1985) that venous flaps can survive. In addition, it showed that venous island flaps could survive after division of the venous pedicle proximally or distally, or as free flaps, providing through flow was re-established by venous anastomoses. In this study no flaps survived on a single venous pedicle without through flow. Two successful clinical cases of venous flaps are also reported, in which through flow was re-established by a simple venous anastomosis. One of these flaps threatened to become necrotic until the thrombosed anastomosis was successfully redone.     

Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

Central effects of systemic lidocaine mediated by glycine spinal receptors: an iontophoretic study in the rat spinal cord

The objective of this investigation was to demonstrate the possible interactions of systemic lidocaine (lido) with inhibitory receptors in the spinal cord. In the lumbar dorsal horn of anesthetized and curarized rats, 60 physiologically identified, wide dynamic range (WDR) neurons, were recorded extracellularly. Glutamate, glycine and its selective antagonist, strychnine, were iontophoretically applied onto the neurons either singularly or concurrently. The effects of systemic lido on the drug-induced frequency changes and the interaction with the glycine receptors, using strychnine as a probe, were studied. It was consistently found that (i) lido (3–4 mg/kg) inhibited the excitatory responses to iontophoretic glutamate, (ii) this inhibition was significantly antagonized by concurrent iontophoretic strychnine, (iii) iontophoretic glycine induced comparable glutamate inhibition that was reversed by strychnine. In contrast, no effect on glutamate-induced excitations was observed when lido was applied by micropressure or a different local anesthetic was systemically administered. The results suggest that central inhibitory effects of lido could by mediated by spinal strychnine-sensitive glycine receptors, activated by lido itself or possibly by its glycine residue-bearing metabolites.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.