Careful QA program key to decreasing medication errors.
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Centers for Medicare and Medicaid Services, U.S.↗
Biomedical subjects
D Sherman
Publications and source records attributed to D Sherman.
Successful interaction with physicians.
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Communication↗
Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity.
We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated.
Animals↗
Varicella-zoster virus glycoprotein oligosaccharides are phosphorylated during posttranslational maturation.
Varicella-zoster virus (VZV)-infected human embryonic lung fibroblasts (HELF) do not release infectious virions into their growth medium. Extracellular virions are pleomorphic, suggesting that they are partially degraded before their release from cells. To examine the intracellular pathway of viral maturation, [2-3H]mannose-labeled virus-encoded glycoproteins were isolated from VZV-infected HELF. Oligosaccharides attached to the glycoproteins were processed to complex-type units, some of which were phosphorylated. The major intracellular site of accumulation of VZV gpI was found to be perinuclear and to correspond to that of the cation-independent mannose 6-phosphate (Man 6-P) receptor. Subsets of VZV-containing cytoplasmic vacuoles were coated, Golgi-associated, or accessible to endocytic tracers. Phosphorylated monosaccharides protected HELF from the cytopathic effect of VZV in proportion to their ability to block Man 6-P receptor-mediated endocytosis. These data suggest that the unusual phosphorylated oligosaccharides mediate an interaction between VZV and Man 6-P receptors of the host cell; this interaction may be responsible for withdrawal of newly synthesized virions from the secretory pathway and for their diversion to prelysosomal structures.
Cytopathogenic Effect, Viral↗
Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma.
European and American investigators have reported response rates of 38% to 83% for ifosfamide alone in pretreated sarcomas. In a phase II trial of ifosfamide 2.0g/m2 days 1 to 4 with mesna uroprotection in 124 patients with previously failed sarcomas, four (3%) responded completely (95% exact confidence interval, 1% to 8%) and 26 (21%) had a complete or partial response (95% exact confidence interval, 14% to 29%). The median time to progression was 5 and 9 months for partial and complete responders, respectively. In the subset of soft tissue sarcomas, the response rate for the patients receiving bolus administration was 26%, compared with 9% for the patients receiving a continuous infusion schedule (P = .03). The response rates among patients with soft tissue and bony sarcomas with a performance score of 0-2 and 0-1 prior to chemotherapy administration were 20% and 40%, respectively. Somnolence or confusion developed in 19%. Neurotoxicity was significantly associated with poor performance status (P less than .01), elevated creatinine (P less than .01), and low bicarbonate levels (P = .05). A serum bicarbonate less than 20 developed in 31% of the patients and was significantly associated with older age (P = .01), elevated creatinine (P = .02), and female sex (P = .06). Hematuria was significantly associated with no uroprotection (the first four patients did not receive mesna because it was unavailable), but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus v continuation infusion schedule. Thus, ifosfamide is active in failed sarcomas and warrants further study in previously untreated patients with sarcoma.
Adolescent↗
Fetal plasma and renal responses to ruminal fluid.
Amniotic fluid homeostasis is dependent on a balance of fetal fluid production and absorption. The fetal gastrointestinal tract is believed to resorb 500 to 1000 ml of amniotic fluid per day during 7 to 10 bouts of swallowing activity. However, the impact of ruminal fluid on fetal plasma composition and fluid homeostasis is largely unknown. Seven ovine fetuses (120 +/- 1 day) received intraruminal infusions of 0.9% or 3% saline solution on alternate days. In response to successive 40-minute intraruminal infusions of 0.9% saline solution (0.5 and 1.0 ml/kg/min), there was no change from basal levels of fetal plasma osmolality (295.7 +/- 2.9 mosm), plasma arginine vasopressin (1.45 +/- 0.29 pg/ml), urine osmolality (150 +/- 8 mosm), or urine volume (0.49 +/- 0.10 ml/min). In response to the 3% saline solution infusion, significant increases were noted in fetal plasma osmolality (295.4 +/- 3.1 to 302.6 +/- 2.6 mosm), plasma arginine vasopressin (1.77 +/- 0.31 to 4.84 +/- 0.79 pg/ml), and urine osmolality (157 +/- 13 to 342 +/- 25 mosm), whereas fetal urine volume significantly decreased (0.35 +/- 0.05 to 0.15 +/- 0.06 ml/min). These results indicate that hypertonic, but not isotonic, saline solution infusion into the fetal gastrointestinal tract may affect fetal plasma composition and urine production. Under conditions of significant plasma to luminal osmotic gradients, fetal gastrointestinal water and electrolyte transfer may be more rapid than can be compensated by either fetal renal function or placental equilibration.
Animals↗
Ovine fetal and adult atrial natriuretic factor metabolism.
Studies were conducted to quantify ovine fetal and adult atrial natriuretic factor (ANF) metabolism. A total of 14 pregnant ewes with singleton fetuses were prepared with vascular catheters. In protocol 1, six fetuses (mean gestation, 131 +/- 1 days) received intravenous infusions of synthetic human ANF (hANF, 100 ng.min-1.kg-1) for 60 min. Mean basal fetal plasma ANF levels increased from 180 +/- 44 pg/ml to a steady-state level of 1,233 +/- 192 pg/ml. In protocol 2, five fetuses (mean gestation, 130 +/- 1 days) received successive 40-min infusions of hANF at 5, 25, and 100 ng.min-1.kg-1. Although basal fetal plasma ANF levels (522 +/- 135 pg/ml) were greater than those observed in protocol 1, fetal plasma ANF levels increased to 1,580 +/- 295 pg/ml at the highest infusion rate. In both protocols 1 and 2, basal fetal plasma ANF levels were three- to fourfold greater than maternal levels. The fetal plasma ANF clearance rates calculated from protocol 1 and from the 25- and 100-ng.min-1.kg-1 infusions from protocol 2 were similar (89 +/- 10, 120 +/- 31, and 116 +/- 38 ml.min-1.kg-1, respectively) and were combined to yield a mean estimated fetal plasma ANF clearance rate of 102 +/- 11 ml.min-1.kg-1. In protocol 3, adult plasma ANF levels increased from 137 +/- 36 to 4,142 +/- 776 pg/ml in response to ANF infusion at 200 ng.min-1.kg-1. The mean plasma ANF clearance rate calculated for the adult animals was 59 +/- 12 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Reproductive outcome after fimbrial evacuation of tubal pregnancy.
Thirty-one ectopic pregnancies were manually expressed (i.e., "milked out") by the tubal fimbria during a 13-year period. Reproductive histories and operative findings were unremarkable when compared with the general population with ectopic gestation. The subsequent reproductive performance was evaluated in 27 patients who attempted conception. Twenty-five (92%) of the 27 patients subsequently conceived, 23 (85%) had at least one successful term pregnancy, and the remaining 2 (7%) had abortions only. There was no repeat ectopic pregnancy. Average follow-up time was 38.5 months. Previous experience with this technique has been disappointing with low postoperative rates of successful term pregnancies. Favorable outcomes after fimbrial expression have been reported only in small numbers of patients. It is suggested that the procedure is appropriate for distal tubal gestations that are loosely adherent within the tubal lumen; these are usually expressed with minimal efforts. However, if the gestational mass does not yield to gentle milking of the tube or evacuation has been incomplete, the surgeon can always use a linear salpingotomy. More experience is obviously needed to verify these preliminary results, suggesting that fimbrial evacuation is simple, safe, and advantageous in properly selected cases.
Adult↗
Tubal abortion and infundibular ectopic pregnancy.
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Abortion, Induced↗
Enalapril, hydrochlorothiazide, and combination therapy in patients with moderate hypertension.
Using a placebo baseline, positive controlled, double-blind, randomized titration to effect our study protocol, we assessed the antihypertensive actions of enalapril, hydrochlorothiazide, and their combination in 37 patients with moderate essential hypertension. Patients were maintained on their regular diets and received a placebo for 4 weeks. Patients with moderate systemic hypertension were randomized to receive enalapril monotherapy at a dose of 10 mg twice daily (n = 16), hydrochlorothiazide monotherapy at a dose of 25 mg twice daily (n = 15), or combination therapy consisting of 10 mg enalapril and 25 mg hydrochlorothiazide twice daily (n = 6). Therapy could be titrated to twice the starting dose. All treatment regimens reduced blood pressure, but only one patient had blood pressure normalized (diastolic blood pressure less than or equal to 90 mmHg) with enalapril (7%), two patients with hydrochlorothiazide (15%), and 80% of patients with combination therapy. The patients who had not achieved normal blood pressure received combination treatment, and after 8 additional weeks, more than 70% showed normal blood pressure. After one year of combination therapy, 92% of the patients continue to have normal blood pressure. Both the monotherapy and combination regimens were very well tolerated in this study. In conclusion, enalapril, hydrochlorothiazide, and their combination are effective in reducing blood pressure in patients with moderate hypertension. However, monotherapy is successful in normalizing blood pressure only in a small percentage of patients. Combination therapy achieved normalization of blood pressure in almost all patients, suggesting that most patients on regular diets with moderate hypertension may require a diuretic-ACE inhibitor combination rather than monotherapy to achieve effective blood pressure control.
Adult↗
Innovative drug delivery systems in cardiovascular medicine: nifedipine-GITS and clonidine-TTS.
Innovative drug delivery systems have been developed for nifedipine and clonidine that prolong the pharmacologic activity of the medications, allowing once daily dosing. The nifedipine-GITS (gastrointestinal therapeutic system) tablet formulation and the clonidine-TTS (transcutaneous delivery system) patch may also reduce side effects in patients while preserving the therapeutic efficacy of the origin drug formulations (nifedipie capsule, clonidine tablet).
Administration, Cutaneous↗
[Carotid endarterectomy under local anesthesia supplemented with neuroleptic analgesia].
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Anesthesia, Local↗
A combined light and electron microscopic immunocytochemical method for the simultaneous localization of multiple tissue antigens. Tyrosine hydroxylase immunoreactive innervation of corticotropin releasing factor synthesizing neurons in the paraventricular nucleus of the rat.
In order to study the morphological interrelationships between immunocytochemically identified neuronal systems, a double labelling procedure - suitable for correlative light and electron microscopic observations - is introduced. The technique is based on the consecutive use of the silver-gold (SG) intensified and non-intensified forms of the oxidized 3,3'-diaminobenzidine (DAB) chromogen in the framework of the peroxidase-antiperoxidase complex (PAP) indirect immunocytochemical procedure. The first tissue antigen is detected by the SG intensified DAB chromogen, which has a black color and high electron density. The structures containing the second antigen are visualized by the non-intensified DAB-endproduct, which is less electron-dense than the silver-gold amplified form and is brown. The metallic shield that forms around the labeled antibody sequences associated with the first antigen prevents non-specific binding of immunoglobulins used for the detection of the second tissue antigen. The application of this method for the simultaneous detection of tyrosine hydroxylase (TH)- and corticotropin releasing factor (CRF)-immunoreactive structures revealed that black colored TH-immunopositive fibers contacted brown colored CRF-synthesizing neurons in the hypothalamic paraventricular nucleus. The juxtaposition of TH- and CRF-containing elements was apparent in both thick vibratome (40 micron) and semithin (1 micron) sections. At the ultrastructural level, TH-positive terminals - labeled by silver-gold grains - were observed to establish asymmetric synapses with both CRF- and TH-immunoreactive neurons. The former finding indicates a direct, TH-immunopositive, catecholaminergic influence upon the hypothalamic CRF system, while the latter demonstrates the existence of intrinsic connections between TH-positive elements.
Animals↗
Development of the monoaminergic innervation of the avian gut: transient and permanent expression of phenotypic markers.
Specific cellular accumulation of [3H]5-hydroxytryptamine ([3H]5-HT) occurs during development of the avian gut. This accumulation is transient in extraganglionic mesenchymal cells (TES cells) but is a permanent characteristic of enteric serotonergic neurons (ESN). Species-specific differences were found in the location of TES cells and ESN. In chicks TES cells surrounded myenteric ganglia and ESN were restricted to the myenteric plexus. In quails TES cells surrounded submucosal ganglia and [3H]5-HT-labeled submucosal as well as myenteric neurons. [3H]Norepinephrine accumulated only in noradrenergic terminals and not in TES cells or ESN. The origins of TES cells and ESN were studied in chimeras, in which neuraxis from appropriate or inappropriate axial levels was grafted from quail to chick. Both types of chimeric bowel contained TES cells and ESN. Most TES cells in chimeras were chick in origin and distributed as in chicks (around myenteric ganglia); however, some TES cells and all ESN were quail cells. To test whether crest cells are required for development of TES cells and ESN, aneuronal chick hindgut was explanted and grown alone, or with quail neuraxis, as chorioallantoic membrane (CAM) grafts. TES cells appeared in CAM grafts whether or not crest cells were present; however ESN only appeared in explants when quail neuraxis was included. In addition, an ectopic [3H]5-HT-labeled chromaffin-like cell, also of quail origin, was found in enteric plexuses in these combined explants of crest and gut. Most TES cells, therefore, are neither derived from nor dependent on the presence of crest cells in the gut wall. Since even an inappropriate axial level of crest was found to produce ESN when it was experimentally induced to colonize the bowel the enteric microenvironment probably plays a critical role in serotonergic neural development. The species-specific location of TES cells and ESN is consistent with the hypothesis that TES cells constitute an important component of this microenvironment.
Animals↗
Malnutrition after gastric surgery. Association with exaggerated distal intestinal hormone release.
This study was designed to investigate the mechanism of excessive weight loss following gastric surgery. Twelve weight-stable and six weight-losing postoperative subjects were studied. The weight-losing subjects had lesser body mass based upon anthropometric measurements. All weight-losing subjects and six weight-stable subjects excreted excess breath hydrogen after a standard meal. The quantities of hydrogen excreted by the weight-losing subjects and weight-stable subjects with positive tests were not different, implying similar degrees of carbohydrate malabsorption. Peak breath hydrogen concentration occurred earlier in weight-losing subjects than in weight-stable subjects (2 vs 5 hr), indicating more rapid oral-cecal transit of the test meal in weight-losing subjects. Analyses of postprandial blood samples for eight different gastrointestinal hormones demonstrated exaggerated postprandial elevations in the concentrations of enteroglucagon and neurotensin. The results of these studies demonstrate close correlations between excessive weight loss after gastric surgery, rapid gastrointestinal transit as measured by excess breath hydrogen excretion, and increased release of hormones from the distal intestine. We conclude that these hormones are secreted in excess due to the rapid gastrointestinal transit and that rapid gastrointestinal transit may play a role in excessive weight loss after gastric surgery.
Aged↗
Evolution and expression of the transplantation antigen gene family.
We have cloned 26 different class I genes that are located in the major histocompatibility complex of the C57BL/10 mouse. Two of the three class I genes found in the H-2 complex encode the H-2Kb and H-2Db antigens; the other 23 class I genes map to the adjacent Tla complex. We have grouped the cosmids containing these genes into three clusters: one cluster links the H-2K and I-A regions, one cluster links the H-2D and Qa-2 regions, and the final cluster maps to the TL region. The class I gene organizations in the Qa-2 and TL regions of the C57BL/10 and BALB/c mice are generally similar, but there are several polymorphic segments. The Qa-2 region of both mice seems to have evolved by the duplication of gene pairs; furthermore, the H-2K region may have been generated by the translocation of a gene pair from the Qa-2 region. We have evidence that several of the genes in the Qa-2 region are expressed.
Animals↗
Morphology and serotonergic innervation of physiologically identified cells of the guinea pig's myenteric plexus.
Ganglion cells of the myenteric plexus of the guinea pig were physiologically classified as to cell type using intracellular microelectrodes containing horseradish peroxidase (HRP). Interganglionic fiber tracts were then stimulated in an attempt to elicit slow excitatory postsynaptic potentials (EPSPs) in the impaled cells. The presence or absence of a slow EPSP was noted, following which the cells were injected with HRP through the recording micropipette and finally were incubated with tritiated 5-hydroxytryptamine ([3H]-5-HT; 0.5 microM) and desmethylimipramine (10 nM). The preparations were examined by light and electron microscopy (EM) for which the physiologically identified, HRP-injected neurons were demonstrated histochemically and serotonergic nerve terminals were simultaneously demonstrated radioautographically. Forty-seven cells were physiologically identified, injected with HRP, and studied by light microscopy. Of these, 22 were also fully analyzed by electron microscopy. The sample included 13 type I/S cells (6 analyzed by electron microscopic radioautography), 16 type II/AH cells (10 analyzed by electron microscopic radioautography), and 18 nonspiking (NS) cells (6 analyzed by electron microscopic radioautography). Slow EPSPs were only observed in type II/AH cells. All five of the fully analyzed subset of type II/AH cells that manifested a slow EPSP were contacted by serotonergic terminals. These terminals were found on 7 of 10 type II/AH cells, 2 of 6 type I/S cells, and 0 of 6 NS cells. Serotonergic terminals, therefore, contacted type II/AH cells (p less than 0.05) and especially those that showed a slow EPSP (p less than 0.005) more frequently than other types of ganglion cells. Morphologically, cells with short, stubby dendrites were reproducibly found to be type I/S cells, and glia could be recognized by their astrocytic appearance; however, cell shape did not otherwise correlate with physiological cell type. These data are compatible with and provide support for the hypothesis that 5-HT is one of the mediators of slow EPSPs in the myenteric plexus.
Animals↗