Growing number of elderly patients will mean more ethical issues for MDs, conference told.
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Advance Directives↗
Biomedical subjects
S Katz
Publications and source records attributed to S Katz.
Intraluminal Ca2+ dependence of Ca2+ and ryanodine-mediated regulation of skeletal muscle sarcoplasmic reticulum Ca2+ release.
The action of ryanodine upon sarcoplasmic reticulum (SR) Ca2+ handling is controversial with evidence for both activation and inhibition of SR Ca2+ release. In this study, the role of the intraluminal SR Ca2+ load was probed as a potential regulator of ryanodine-mediated effects upon SR Ca2+ release. Through dual-wavelength spectroscopy of Ca2+:antipyrylazo III difference absorbance, the intraluminal Ca2+ dependence of ryanodine and Ca(2+)-induced Ca2+ release (CICR) from skeletal SR vesicles was examined. Ryanodine addition after initiation of Ca2+ uptake (a) increased the intraluminal Ca2+ sensitivity of CICR and (b) stimulated spontaneous Ca2+ release with a delayed onset. These ryanodine effects were inversely proportional to the intraluminal Ca2+ load. Ryanodine also inhibited subsequent CICR after reaccumulation of Ca2+ released from the initial CICR. These results provide evidence that ryanodine inhibits transitions between low and high affinity Ca2+ binding states of an intraluminal Ca2+ compartment, possibly calsequestrin. Conformational transitions of calsequestrin may be reciprocally coupled to transitions between open and closed states of the Ca2+ release channel.
Adenosine Triphosphate↗
Calcium-activated neutral protease effects upon skeletal muscle sarcoplasmic reticulum protein structure and calcium release.
In this study, the effects of Ca(2+)-activated neutral protease (CANP) upon skeletal muscle heavy sarcoplasmic reticulum (HSR) structure and function were investigated. CANP was immunolocalized to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid detergent-insoluble fraction of purified HSR membranes. Ca2+ activation of the endogenous membrane-bound CANP produced a characteristic partial fragmentation of the HSR 565-kDa Ca2+ release channel. Similarly, the major substrate for both micromolar and millimolar Ca(2+)-sensitive isoforms of exogenous CANP was the Ca2+ release channel with proteolysis of a 88-kDa HSR protein also observed. Ca2+ release channel proteolysis was initiated at a single cleavage site with coincidental production of 410- and 150-kDa peptide fragments. Appearance of 160- and 137-kDa limiting peptides accompanied secondary proteolysis of the primary 410- and 150-kDa fragments, respectively. Despite extensive proteolysis of the Ca2+ release channel, CANP did not dramatically alter the Ca2+ handling and ryanodine binding properties of HSR membranes. The association of CANP with isolated HSR membranes suggests that, in vivo, this protease may modify an additional property of the Ca2+ release channel. This may be related to the CANP-susceptible structural association of the Ca2+ release channel with dihydropyridine receptors at T-tubule/sarcoplasmic reticulum junctions.
Adenosine Triphosphate↗
MD-patient communication key to reducing asthma's toll, seminar told.
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Adolescent↗
Regulation of calcium transport in pancreatic acinar plasma membranes from guinea pig.
The regulation of the guinea-pig pancreatic acinar plasma membrane Ca2+ pump by protein kinase A, protein kinase C and calmodulin was investigated. The results were compared with the effects of these regulators on the high affinity Ca(2+)-ATPase found in this membrane preparation. The catalytic subunit of cyclic AMP-dependent protein kinase stimulated Ca2+ transport 2-fold, but had no effect on Ca(2+)-dependent ATPase activity. Purified protein kinase C, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate and diacylglycerol derivative, 1-stearoyl-2-arachidonoyl-sn-glycerol, failed to stimulate the Ca(2+)-uptake but augmented the Ca(2+)-dependent ATPase activity. Exogenously added calmodulin failed to stimulate either activity. In addition, two antagonists of calmodulin activity, trifluoperazine and compound 48/80 produced a concentration-dependent inhibition of Ca(2+)-transport. These data suggest the presence of endogenous calmodulin within guinea-pig pancreatic acinar plasma membranes. Both calmodulin antagonists failed to influence the Ca(2+)-dependent ATPase activity. The ability of boiled extracts from guinea-pig pancreatic acinar plasma membranes to stimulate the Ca(2+)-ATPase activity in calmodulin-depleted erythrocyte plasma membranes confirmed the presence of endogenous calmodulin. Our results imply a role for calmodulin and cAMP-dependent protein kinase, but not protein kinase C, in the regulation of Ca2+ efflux from pancreatic acinar cells. These results also provide further evidence suggesting that the high affinity Ca(2+)-ATPase does not catalyze the plasma membrane Ca(2+)-transport activity observed in pancreatic acini.
Animals↗
[Nonoperative treatment of pancreatic pseudocyst in children].
3 children with pseudocyst of the pancreas resulting from blunt abdominal trauma are described (boys 6 and 8.5 years old, and a 6.5-year-old girl). Based on abdominal ultrasound and CT findings, nonoperative treatment was elected. There was spontaneous resolution in 1 and in the other 2 the pseudocyst was successfully drained. Previous reports and our own results indicate that it is safe to treat pancreatic pseudocysts in children after blunt abdominal trauma.
Abdominal Injuries↗
Addiction can take many forms, experts warn MDs at conference.
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Adult↗
Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor.
The nuclear oncogenes v-myc or v-myb specifically transform avian myeloid cells. In both cases, the transformed cells remain dependent on chicken myelomonocytic growth factor (cMGF). This factor dependence can be relieved by expression of kinase-type oncogenes such as v-mil or v-erbB, leading to expression of cMGF and autocrine growth stimulation. In erythroid cells the same kinase-type oncogenes cause transformation but do not induce cMGF expression. Here we investigated the molecular mechanisms of the observed lineage specific oncogene collaboration. We found that kinase-type oncogenes and TPA activate the cMGF promoter via AP-1 like transcription factors. The activation of the cMGF promoter is, however, strictly dependent on the binding of nuclear proteins to both halves of an inverted repeat adjacent to the AP-1 binding site. These proteins are related to C/EBP. They are expressed exclusively in myeloid cells and were therefore termed NF-M. Our results indicate that the lineage specific cooperation of kinase type oncogenes with v-myb or v-myc in leukemia formation is based on the concerted action of AP-1 and NF-M on the cMGF promoter.
Animals↗
Renal trauma with posttraumatic hypertension in a neonate.
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Female↗
Giant cystic hygroma associated with venous aneurysm.
Complete excision of giant cystic hygroma requires meticulous dissection of the multilocular lymphatic cysts from the adjacent vascular and neural structures. The association of venous aneurysms with cystic hygroma is extremely rare. We report two infants with cystic hygroma in whom preoperative diagnosis of venous aneurysm was helpful in planning complete excision of the lymphatic lesions.
Aneurysm↗
Inhalation toxicity of chromium from Whetlerite dust in rats.
The acute inhalation toxicity and metabolic fate of chromium and copper from Whetlerite dust in rats were investigated. Groups of male and female, Sprague-Dawley rats were exposed to Whetlerite dust and base carbon dust as outlined in the OECD Limit Test guidelines. At 14, 28 and 180 days post-exposure, rats were evaluated for gross pathological changes and tissues were collected for chromium and copper determination. Four deaths occurred during or post-exposure, but did not appear to be compound related. No gross pathological changes were observed at necropsy in either group. Organ chromium concentrations were below detection limits of 0.5 micrograms Cr/g dry tissue in both exposure groups. According to OECD guidelines, neither Whetlerite dust nor base carbon dust demonstrated an acute inhalation toxicity.
Administration, Inhalation↗
Pharmacokinetic strategies for cyclosporin therapy in organ transplantation.
Marked interindividual variations in cyclosporin (CsA) produce disparate clinical results in organ transplant recipients. In an attempt to eliminate marked deviations of insufficient or excessive CsA concentrations consequent to the administration of uniform drug doses, test dose pharmacokinetics were performed on each potential organ transplant candidate. An intravenous 3 mg/kg test dose delivered over 3 h proved to be readily performed, namely 53% perfect studies, and relatively reliable, namely 73% of observed concentrations within 10% of the predicted values. Furthermore, the use of CsA doses predicted by pretransplant studies reduces the incidence of delayed graft function, early rejection episodes and transplant loss. The oral test dose study predicted a suitable amount of CsA to achieve sufficient gastrointestinal absorption but was less accurate than the iv prediction method: namely, 40% of observed post-transplant concentrations were within 10% of the predicted target value. Furthermore, patients who received oral doses predicted by the test dose strategy showed no improvement in the incidence of acute rejection episodes between 7 and 60 days, and only modestly improved serum creatinine values. The lower accuracy of predictions from oral test dose studies may reflect the impact of non-linear oral (as opposed to iv) drug pharmacokinetics, of variable diet, and/or of altered postoperative gastrointestinal function.
Administration, Oral↗
Initial organ localisation of blood-borne Candida albicans in a rat model of disseminated candidosis.
The rat was evaluated as an experimental model for disseminated candidosis by quantitating blood clearance and initial organ localisation of 3H-leucine-labelled Candida albicans after intravenous injection into the tail or portal vein. Viable or formalin-killed blastoconidia or viable blastoconidia with germ tubes were injected into experimental animals. Blood and tissue samples were obtained up to 24 h after injection and processed for liquid scintillation counting (to determine the distribution of labelled yeasts) and quantitation of viable organisms. Yeasts were cleared rapidly after intravenous (i.v.) injection by either route, i.e., < 5% of the radioactivity was detected in the blood after 5 min. The liver and lung were the major organs that sequestered blood-borne yeasts 1 h after tail vein injection (42.5 SD 15% and 41.4 SD 6.4% of labelled yeasts injected, respectively). However, injections via the portal vein resulted in trapping of the yeasts predominantly by the liver. Recovery of radioactivity and viable yeasts from all organs except the kidneys decreased with time. Overall, the results indicated that the rat might serve as a reliable model for short-term studies on organ distribution and thus contribute to our understanding of tissue trophism in candidosis.
Animals↗
Critical analysis of methods for assessing regional blood flow and their reliability in clinical medicine.
The advantages and inadequacies of the currently available techniques to measure regional blood flow in the lower limbs are being reviewed. Thermodilution technique and local 133xenon washout technique have the advantage of allowing determination of blood flow during exercise, while venous occlusion plethysmography and pulsed-Doppler duplex ultrasonography only allow determination of blood flow at rest. Overall, measurements of lower limb blood flow are not highly reproducible by any technique, and the variability in measurements of regional blood flow should lead to careful interpretation of derived parameters such as vascular conductance and resistance. Determination of vascular input impedance by Fourier analysis of pressure data, recorded with high fidelity catheter, and flow velocity measurements obtained transcutaneously by Doppler ultrasonography, may offer a more accurate quantitative analysis of the characteristics of the lower limb vascular system.
Catheterization, Peripheral↗
Mechanisms and amelioration of acute renal allograft failure in the cyclosporine era.
The fairly wide-ranging spectrum of tactics under investigation for ameliorating acute renal allograft dysfunction caused by harvest/preservation-related ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact that no single approach has emerged as universally useful for mitigating the vasomotor nephropathy produced by the combined effects of each of these vectors of vasomotor renal allograft injury. Given the clinical heterogeneity of patients and allografts, it is the author's bias that, in addition to careful donor and recipient hemodynamic management, induction immunosuppressive regimens should be individualized on the basis of allograft function in the immediate postreperfusion period (judged by rate of diuresis, intraoperative parenchymal tone, renal scan profiles, and rate of decline of serum creatinine concentration) as well as patient-specific immunologic and general medical risk factors. Promising laboratory and clinical investigations of such agents as calcium channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor prostaglandin formation, and atriopeptins have the potential to provide clinically helpful options with regard to adjunctive therapy for ameliorating acute renal allograft dysfunction associated with INF and ACR.
Acute Kidney Injury↗
Crohn's disease associated with cyclic neutropenia.
Crohn's disease and neutropenia unrelated to drug therapy is a rare association. We present a case of Crohn's disease associated with cyclic neutropenia. Our patient, observed over 10 yr, is unique due to the lack of recurrent bacterial infections or other associated sequelae of the neutropenic state. There was no consistent association between white blood cell cycling and exacerbations of her Crohn's disease. However, the latter did appear to worsen the neutropenic state. A clear pattern of cyclic neutropenia became apparent only when the disease was quiescent and all medications had been discontinued. We report this case for its value in pursuing clinically and therapeutically appropriate options, including surgery and drugs with neutropenic potential, in patients with Crohn's disease and, possibly, white blood cell abnormalities.
Child↗
Pneumococcal empyema following endoscopic sclerotherapy in a child with cavernous transformation of the portal vein.
Esophageal sclerotherapy is widely used in the treatment of bleeding esophageal varices. Complications vary from chest pain to esophageal perforation. Our patient, suffering from cavernous transformation of the portal vein, developed massive empyema following sclerotherapy. Although small asymptomatic pleural effusions have been reported, massive empyema requiring surgical drainage, without evidence of esophageal perforation, has, to our knowledge, not been described.
Anti-Bacterial Agents↗
The use of epidural anesthesia and analgesia in aortic surgery.
During a 3-year period, sixty-four consecutive patients, who had elective aortic reconstruction were investigated to determine whether epidural anesthesia and analgesia, combined with light general anesthesia, would lower the rate of perioperative complications in this high-risk group of patients. The epidural group comprised 32 consecutive patients who had surgery during the 20-month period from July 1986 to December 1987. These patients were compared with the previous 32 patients who had aortic reconstruction at Huntington Memorial Hospital (Pasadena, CA) using conventional general anesthetic techniques. Cardiovascular and respiratory morbidity, length of hospital stay, length of intensive care unit stay, and duration of endotracheal intubation were compared. There was no statistically significant difference in cardiovascular morbidity, length of hospital stay, or intensive care unit stay between the two groups. There was however, a striking decrease in respiratory complications and length of intubation in the epidural anesthesia group (P less than 0.005). The authors conclude that epidural anesthesia and analgesia, combined with a light general anesthetic may confer benefits over conventional general anesthesia in patients undergoing aortic surgery.
Analgesia, Epidural↗