Biomedical subjects
Publications and source records attributed to D E Cohen.
Spiny keratoderma of the palms and soles has been rarely reported. Debate exists regarding the proper nosologic classification of this disorder. We describe a patient and her mother with concurrent autosomal dominant polycystic kidney disease with liver cysts.
Recent progress has begun to elucidate molecular and cellular mechanisms whereby bile salts stimulate hepatocellular selection, transport, and biliary secretion of phospholipids, which are enriched (up to 95%) in phosphatidylcholines. This article first summarizes classical observations concerning the molecular structures of biliary phospholipids, as well as the role of bile salts in promoting their secretion into bile. New data are then reviewed and synthesized into a working model for biliary phospholipid secretion. An important feature is that this model is selective for biliary phospholipids and necessitates a largely independent pathway for cholesterol secretion into bile.
Although rotational ablation has been successful in the treatment of complex coronary lesions, periprocedural complications of microvascular-mediated ischemia (slow flow or no reflow) and coronary vasospasm may occur. In an attempt to reduce such complications, a drug cocktail consisting of a combination of verapamil 10 micrograms/ml, nitroglycerin 4 micrograms/ml, and heparin 20 U/ml was infused in 21 consecutive patients with AHA/ACC Type B2 and C lesion morphology. A total of 27 lesions were treated, with a procedural success rate of 95%. One patient required emergency bypass surgery. Coronary vasospasm occurred in 7% (2/27 lesions). Only one lesion (3.7%) was associated with a transient reduction in TIMI flow that resolved within 5 min, and none had classical no-reflow. No patient developed intraluminal thrombus, and none had hypotension requiring inotropic support. All patients had prophylactic temporary pacemakers inserted. All RCA and circumflex lesions and 50% of LAD stenoses required transient pacing. A "cocktail" infusion of verapamil, nitroglycerin, and heparin mixed in pressurized saline delivered through the 4-French Teflon sheath of the Rotablator system during rotational ablation is associated with high success and low complication rates. Transient AV block is frequent, especially when treating RCA and circumflex arteries; therefore, prophylactic pacing is indicated.
A 1917-bp cDNA clone encoding phosphatidylcholine transfer protein (PC-TP) was identified by screening a bovine liver library. Northern blot analysis demonstrated a 2-kb mRNA transcript in bovine liver, and Southern blotting was consistent with a single bovine PC-TP gene which was shown to be present in a diverse group of vertebrates, but not in yeast. Database comparisons revealed the nucleotide sequence of the clone to be unique and unrelated to other cytosolic lipid TP.
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PURPOSE: To determine whether findings on plain radiographs alter clinical care in outpatient management after hip arthroplasty. MATERIALS AND METHODS: From June 1, 1993, through February 28, 1994, one arthroplasty surgeon saw 148 outpatients (age range, 15-86 years) after hip arthroplasty (163 prostheses). The surgeon made decisions about clinical management before he reviewed the plain hip radiographs. After he reviewed the radiographs, he recorded any changes in the management plan. RESULTS: In only one case did the radiographic findings change patient treatment. The prosthesis in this relatively asymptomatic patient had been in place for over 9 years and appeared clinically to be functioning well, but radiographs demonstrated aggressive granulomatosis. Therefore, the patient underwent revision arthroplasty. In the remaining 147 patients, radiographic findings had no impact on clinical management. CONCLUSION: Radiographic evaluation may be most beneficial in patients with hip prostheses that have been in place for many years to rule out asymptomatic bone loss due to aggressive granulomatosis.
Because of recent assertions by a group of investigators that structures called "lamellae" instead of mixed micelles are present in human bile, the nature of biliary cholesterol solubilization and transport ("carriage") has again become a matter of dispute. "Lamellae" are rod- or tubular- shaped banded images observed when biles are negatively stained and dehydrated during electron microscopy; they are believed to be composed principally of biliary phospholipid (which is mostly lecithin) and cholesterol. It is well known that when mixed together in aqueous systems, lecithin and cholesterol, which are otherwise insoluble amphiphilic lipids, swell to form stacked or multilamellar liquid crystals that have regular periodicity because of the bilayer arrangement of the molecules. Provided super-micellar concentrations of cholesterol are present, multilamellar vesicles occur spontaneously in concentrated model biles, and are a frequent occurrence in human gallbladder biles that are beginning to nucleate cholesterol crystals. When multilamellar vesicles are negatively stained and dehydrated, they produce "lamellae" images by electron microscopy. Coincidentally, images of "lamellae" are also produced when purely micellar bile, either model or native is treated similarly. In this review we show that these images are an artifact. This artifact is produced by the dehydration process itself and is due to a phase change i.e. a change in molecular packing which is predicted by the appropriate phase diagram. As a consequence, a dehydrated "lamellae" phase results and the overall effect is an electron microscopic image that is identical to those produced by multilamellar vesicles in supersaturated or lithogenic biles.(ABSTRACT TRUNCATED AT 250 WORDS)
To predict bile salt-membrane interactions physiologically, we used an immobilized artificial membrane HPLC column that contains dimyristoyl-phosphatidylcholine molecules covalently linked to silica microspheres. Using a 90% aqueous (10% acetonitrile) mobile phase, 22 species of bile salts and 4 species of fusidates were eluted. Glycine conjugates displayed higher affinity for the column at pH 5.5, eluting later than their taurine-conjugated congeners, but this order was reversed at pH 6.5 and 7.4 as glycine conjugates became fully ionized. Capacity factors decreased logarithmically as functions of increasing temperature, permitting determinations of interaction enthalpies, which ranged from -2.86 to -7.67 kcal/mol. A standard curve was developed from which the enthalpy for an uncommon bile salt could be inferred from its capacity factor at room temperature. Bile salt interaction enthalpies were substantially better correlated than hydrophobic indices by octadecylsilane-HPLC (D. M. Heuman, J. Lipid Res. 1989. 30: 719-730) with equilibrium binding to small unilamellar vesicles and literature values reflecting bile salt-membrane interactions (e.g., biliary phosphatidylcholine secretion), but not with bile salt functions that do not require phospholipid (e.g., micellar cholesterol solubility). This new application should prove valuable for evaluating membrane-active physical-chemical properties as well as therapeutic potential of novel bile salts, particularly when they are available in quantities too small for study by conventional techniques.
Using model systems, we explored a potential function of hepatic phosphatidylcholine transfer protein to extract biliary-type phosphatidylcholines from intracellular membranes (e.g., smooth endoplasmic reticulum) and deliver them to canalicular plasma membranes where biliary secretion occurs. We measured transfer rates of parinaroyl phosphatidylcholine, a naturally fluorescent phospholipid, from small unilamellar vesicles composed of sn-1 palmitoyl, sn-2 parinaroyl phosphatidylcholine, and egg yolk phosphatidylcholine (molar ratio 75:25) wherein the fluorophore is self-quenched to small unilamellar vesicles composed of phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, and cholesterol (molar ratios 22:22:10:8:38) representing model microsomal and canalicular plasma membranes, respectively. Following addition of phosphatidylcholine transfer protein (purified from bovine liver), fluorescence intensity increased exponentially indicating net phosphatidylcholine transfer from donor to acceptor vesicles. Submicellar concentrations of a wide hydrophobicity range of common and uncommon taurine and glycine conjugated bile salts species (anionic steroid detergent-like molecules), sodium taurofusidate (a conjugated fungal bile salt analog), and sodium dodecyl sulfate and octylglucoside, anionic and nonionic straight chain detergents, respectively, markedly stimulated phosphatidylcholine transfer protein activity. This 40-115-fold effect was most pronounced for the common bile salts and correlated positively with bile salt hydrophobicity. Thermodynamic analysis of net transfer revealed that the rate-limiting step was extraction of phosphatidylcholine molecules from donor vesicles and that bile salts facilitated their capture by enhancing both phosphatidylcholine transfer protein binding as well as perturbing phospholipid packing in vesicle bilayers.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Multiple immunologic abnormalities such as impaired T-cell function, elevated serum IgE level, and increased interleukin 4 production have been demonstrated in patients with atopic dermatitis. OBJECTIVE: As part of a 12-week, multicenter, double-blind, placebo-controlled clinical trial, we evaluated the safety and efficacy of thymopentin (Timunox) as an adjunctive treatment in patients with severe atopic dermatitis. METHODS: Thirty-nine patients at least 2 years old with severe atopic dermatitis on a minimum of 20% of their cutaneous surface area were randomly selected to receive either thrice-weekly subcutaneous injections of thymopentin, 50 mg, or placebo. Use of triamcinolone 0.1% or hydrocortisone 1.0% cream and oral antihistamines were permitted during this trial. RESULTS: After 12 weeks, thymopentin-treated patients had significantly greater improvement than those receiving placebo. No thymopentin-related adverse events occurred. CONCLUSION: Thymopentin may be a safe effective adjunct to therapy in patients with severe atopic dermatitis.
Confluent and reticulated papillomatosis is most probably a disorder of keratinization rather than a fungal infection. We describe an 18-year-old man who was effectively treated with high-dose oral isotretinoin. Our review of the literature on confluent and reticulated papillomatosis refutes previously accepted epidemiologic data.
OBJECTIVES: To determine the significance of anti-laminin antibodies in patients with collagen vascular diseases using a large control population of normal individuals. METHODS: Anti-laminin antibodies of IgG isotypes were determined using an ELISA assay in a population consisting of 73 patients with systemic sclerosis, 10 with urticarial vasculitis, five with leukocytoclastic vasculitis, 13 with giant cell arteritis, and eight with dermatomyositis. Sera from 134 healthy individuals served as controls. RESULTS: Only eight sera in the systemic sclerosis group, one in the leukocytoclastic group and one in the giant cell arteritis group were abnormal. No other sera were abnormal. CONCLUSION: These data contradict previous studies using smaller numbers of controls. The necessity for an adequate control population to define abnormal when comparing immune responses among groups is frequently under-emphasised in rheumatological studies.
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Despite its importance in cholesterol gallstone formation, crystallization of cholesterol from bile is poorly understood, especially with respect to the influences of other biliary lipids. We reported recently (Konikoff et al. J. Clin. Invest. 1992. 90: 1155-1160) that cholesterol can crystallize from model and native biles as filamentous crystals covered by a surface layer of lecithin molecules. During growth, filamentous crystals transformed via metastable intermediates into classical plate-like cholesterol monohydrate crystals. Using the same dilute (1.2 g/dl total lipid) bile salt-rich (97.5 moles %) model bile supersaturated with cholesterol, we have studied the effects of natural egg yolk, soy bean as well as single molecular species of lecithins, other phospholipids and related lipid classes on early filamentous cholesterol crystallization, as well as transformations between crystal habits and their growth to equilibrium cholesterol monohydrate plates. After extraction and derivatization, HPLC analysis revealed that the surfaces of filamentous crystals were enriched preferentially with lecithin molecular species having longer and more saturated sn-1 and sn-2 acyl chains compared to mixed lecithin species of whole bile. In contrast, the molecular species distribution of lecithins on equilibrium plate-like crystals resembled that of whole bile. After incubation of pre-formed anhydrous cholesterol and cholesterol monohydrate crystals in cholesterol-free lipid solutions, we demonstrated that surface-adsorbed lecithins were not preferentially enriched excluding nonspecific lecithin adsorption. Time-sequences and transformations between metastable crystalline intermediates were altered markedly by specific phospholipid species: model biles composed of saturated short-chain, medium-chain, and polyunsaturated long-chain lecithins induced rapid precipitation of short filamentous crystals that became plate-like slowly by an "arborization pattern." Long-chain saturated lecithins and natural sphingomyelins retarded cholesterol crystallization markedly, and filamentous as well as metastable intermediate crystals made transient appearances only after plate-like crystals had formed. These observations suggest that phospholipid molecular species and class influence the earliest events in cholesterol crystallization from bile salt-rich model bile. Furthermore, as the molecular species of lecithins adsorbed onto filamentous cholesterol crystals were more saturated than in whole bile and essentially identical to those in biliary vesicles, this finding provides chemical evidence for a vesicular origin of the critical cholesterol nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
To delineate dose ranges, utilization patterns, and the frequency and types of problems encountered, we retrospectively reviewed the medical records of 46 patients with sickle hemoglobinopathies who used patient-controlled analgesia (PCA) a total of 92 times for the management of vasooclusive pain. Patients varied widely in the drug administered, use of basal infusion, individual dose, and total amount of drug received. On the day of heaviest use, the average maximum hourly dose was equivalent to 0.09 mg/kg of morphine. In this study, 11 patients and two families disliked PCA, one patient had respiratory compromise, and one patient tampered with the machine. Patient satisfaction with PCA probably reflects interactions among the psychosocial impact of chronic illness and chronic pain, individual psychological and temperamental factors, environmental contingencies, and the expectations and beliefs of the family and the health-care professionals. Based on this experience, recommendations can be proposed for the use of PCA in this condition.
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Advances in pediatric anesthesia can contribute to improved care of children in other environments. As an example, drugs and dosages established in preoperative sedation of children provide a base for their application in sedation and pain relief of children undergoing painful procedures in the emergency unit, oncology treatment area, and radiology suite. Midazolam, ketamine, fentanyl, propofol, chloral hydrate, and pentobarbital are reviewed from the past year's pediatric literature. Adverse sequelae of sedation including hypoxemia and hypoventilation or apnea confirm the need for an individual whose responsibility is observation and support of the sedated child rather than performing the procedure, a principle that is the cornerstone of revised guidelines for the use of sedation in children. Monitoring techniques may similarly be developed in the operating suite then applied in emergency areas or critical care units. We examine a qualitative device for detecting carbon dioxide in the exhaled gases of an intubated child.
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