Professional education in audiology. Survey of California audiologists.
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Audiology↗
Biomedical subjects
M Robinson
Publications and source records attributed to M Robinson.
O-side chain of Escherichia coli endotoxin 0111:B4 is transported across the intestinal epithelium in the rat: evidence for increased transport during total parenteral nutrition.
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Animals↗
Manometry during food ingestion aids in the diagnosis of diffuse esophageal spasm.
It has been shown that food ingestion can provoke esophageal motor abnormalities in patients with otherwise normal manometry. Such motor abnormalities are usually nonspecific in character. We now report water swallow and food ingestion data on 12 patients with a history of dysphagia and/or chest pain who satisfied strict manometric diagnostic requirements for diffuse esophageal spasm. Three of these patients had normal water swallow manometry, yet, during food ingestion, showed manometric evidence of diffuse esophageal spasm. In the other nine patients, the occurrence of nonperistaltic contractions was greater, and there was a greater incidence of nonperistaltic contractions of 100 mm Hg or more after ingestion of food. We conclude that food ingestion increases the diagnostic yield of manometric testing for diffuse esophageal spasm and, not infrequently, magnifies an abnormality seen during standard water-swallow testing.
Adult↗
A method for the simultaneous determination of alkylacylglycerol, diacylglycerol, monoalkylglycerol, monoacylglycerol, and cholesterol by high-performance liquid chromatography.
We describe a method for the quantitative analysis of the individual subclasses (1-O-alkyl and 1-acyl) of diradylglycerols and monoradylglycerols. These lipids, along with cholesterol, were separated from other neutral and polar lipids on silica columns and analyzed by normal-phase high-performance liquid chromatography (HPLC) as their benzoate derivatives. Cholesterylbenzoate, alkylacylglycerolbenzoate, diacylglycerolbenzoate, monoalkylglyceroldibenzoate, and monoacylglyceroldibenzoate eluted from HPLC in five distinct zones. The derivatives of diradylglycerols and monoradylglycerols were further separated within each discrete zone on the basis of the total number of aliphatic carbons at the sn-1 and sn-2 positions. Radiolabeled cholesterol and dihexadecanoylglycerol were used to monitor recovery. Amounts of synthetic alkylacylglycerol, diacylglycerol, monoalkylglycerol, and monoacylglycerol as low as 0.2 nmol per subclass could be accurately quantified. The technique was used to determine the content of diradylglycerol and monoradylglycerol subclasses in Madin-Darby canine kidney and CFTL-12 mast cells. This method should prove useful for the quantitation of lipid second messengers in cultured cells.
Animals↗
IL-3-induced generation of alkylacylglycerol and diacylglycerol in an IL-3-dependent cell line.
The hematopoietic growth factor IL-3 promotes the proliferation and development of several hematopoietic lineages. Inasmuch as protein kinase C has been suggested to mediate the response of IL-3, we examined the accumulation of diradylglycerols (DG) in response to IL-3 in CFTL-12 cells, a murine mast cell line that requires IL-3 for growth. Exposure of CFTL-12 cells to IL-3 resulted in the conversion of [3H]myristate-labeled lipids to DG. Mass analysis of the DG of CFTL-12 cells cultured in the presence of IL-3 showed that 58% was the ether-linked form, alkylacylglycerol, and 42% was diacylglycerol. The levels of both alkylacylglycerol and diacylglycerol declined when CFTL-12 cells were withdrawn from IL-3 and became quiescent. Stimulation of quiescent cells with IL-3 produced an acute increase in the mass of both alkylacylglycerol and diacylglycerol, consistent with phosphatidylcholine as a significant source. The effects of PMA on the generation of DG were examined to explore the role of protein kinase C activation in the response to IL-3. PMA stimulated an increase in DG accumulation that was not augmented by the simultaneous addition of IL-3. Down-modulation of protein kinase C by long term PMA treatment reduced, but did not eliminate, the IL-3-stimulated increase in DG, suggesting that protein kinase C activation results in an amplification of the initial accumulation of DG. These results indicate a role for DG, generated through the hydrolysis of phosphatidylcholine, in the induction of protein kinase C activity and the events leading to cell proliferation in response to IL-3.
Acylation↗
Effects of intracisternal endothelin-1 injection on blood flow to the lower brain stem.
The central effects of endothelin-1 (Et-1, 10-30 pmol in 2.5 microliters injected intracisternally) have been investigated in the conscious rat. With 10 and 20 pmol Et-1, no significant change in blood pressure was observed. With 30 pmol Et-1, mean arterial blood pressure rose by 40 +/- 10 mm Hg with an accompanying modest, short-lived bradycardia at 2 min post-injection. Cerebral blood flow [( 14C]iodoantipyrine autoradiography), measured simultaneously with the hypertensive response, was markedly reduced throughout the caudal medulla and cerebellum (by up to 85%), while significant hyperaemia was evident in a number of forebrain structures (e.g. an increase of 78% in sensorimotor cortex). These observations have relevance to two distinct scientific areas. Concerning the significant effect of Et-1 in central cardiovascular control, these results caution against drawing conclusions from ventricular application with knowledge only of cardiovascular parameters. These results also illustrate the profound effects of Et-1 which is uniquely capable of overriding cerebral autoregulatory mechanisms.
Animals↗
Sources of diradylglycerols generated during cell growth and phorbol ester stimulation in Madin-Darby canine kidney cells.
The molecular species of diacylglycerol and alkylacylglycerol of Madin-Darby canine Kidney (MDCK) cells were analyzed to determine the sources of diradylglycerols generated during cell growth and phorbol ester stimulation. MDCK cells in log phase growth contained higher levels of diacylglycerol and alkylacylglycerol than confluent cells. Both subclasses of diradylglycerol showed higher levels of saturated and monoenoic species during log phase. Glycerol incorporation into diradylglycerols was increased during growth, consistent with an increase in their synthesis de novo. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, caused an increase in the level of diacylglycerol but not alkylacylglycerol. Log phase MDCK cells showed a greater response to TPA treatment than confluent cells. The molecular species of diacylglycerol generated during stimulation with either TPA or dioctanoylglycerol closely resembled the species of phosphatidylcholine. These results indicate that TPA and synthetic diacylglycerol stimulate endogenous diacylglycerol production through the hydrolysis of phosphatidylcholine. In contrast, the higher content of diacylglycerol and alkylacylglycerol in replicating MDCK cells is the result of an increase in their synthesis de novo.
Animals↗
A novel gamma subunit of the GABAA receptor identified using the polymerase chain reaction.
We have utilized a polymerase chain reaction (PCR) strategy to identify a novel subunit, gamma 3, of the GABAA receptor. The gamma 3 cDNA encodes a mature protein of 450 amino acids that contains structural features typically conserved among subunits of the GABAA receptor family. The gamma 3 subunit shares approximately 66% sequence identity with the gamma 2 subunit but only 38% and 29% with alpha 1 and beta 1 subunits, respectively. Localization of the gamma 3 mRNA indicates that it is widely distributed throughout the mouse brain in a pattern similar to that observed for mRNAs encoding the gamma 2 subunits.
Amino Acid Sequence↗
Ninety-day toxicity study of sodium monochloroacetate in Sprague-Dawley rats.
Male and female Sprague-Dawley rats were administered the sodium salt of monochloroacetic acid (SMCA) by oral gavage for a period of 90 consecutive days. Dosage levels of 15, 30, 60 or 120 mg/kg per day were employed. SMCA clearly induced toxicity in both females and males, with the greatest severity in the male animals. Both the liver and kidneys were identified as target organs. At 120 mg/kg per day, 30% of females and 80% of the males died, most within the first 2 days of treatment. Hemorrhagic and congested lungs (possibly a postmortem change) were seen in the early deaths (1-3 days) whereas liver lesions were observed in later deaths. In addition, there was nephrotoxicity as evidenced by elevated creatinine, blood calcium (BCAL), and blood urea nitrogen (BUN) levels. Hepatotoxicity was indicated by increases in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both organs showed increased organ-to-body weight ratios. Microscopic examination revealed a significant (P less than or equal to 0.001) increase in chronic renal nephropathy and increased splenic pigmentation at 60 mg/kg per day in the males. Based on the observation of toxicity at all treatment levels in males, a lowest observed adverse effect level (LOAEL) of 15 mg/kg per day is proposed for a 90-day exposure to SMCA by oral gavage to the Sprague--Dawley rat.
Acetates↗
Cardiopathic effect of 1,2,3-trichloropropane after subacute and subchronic exposure in rats.
1,2,3-Trichloropropane (1,2,3-TCP) is an industrial water contaminant with potential for human exposure by the oral route. The systemic toxicology of 1,2,3-TCP was evaluated after subacute or subchronic exposure in male and female Sprague-Dawley rats. Animals were treated with 0.01, 0.05, 0.20 and 0.80 mmol kg-1 day-1 for 10 days and 0.01, 0.05, 0.10 and 0.40 mmol kg-1 day-1 for 90 days. Chemical exposure was by oral gavage in corn oil. Lethality did not occur in either study. Toxicity was observed primarily in the high dose group of subacute and subchronically treated rats of both sexes. Weight gain suppression occurred at a dose of 0.8 mmol kg-1 (118 mg kg-1) after 10 days. After 90 days of exposure to 0.40 mmol kg-1, the final body weights were 81% and 86% of control values for males and females, respectively. When major organ weights were normalized by body weight, liver and kidney values were generally increased relative to control in the two highest dose groups after 10- and 90-day chemical exposure. Serum chemistries and histopathology indicated a mild hepatotoxic response to 1,2,3-TCP in the high dose group of each study but did not support any renal toxicity. Thymic weight reduction due to atrophy occurred at 10 days of exposure in high dose groups but was normal in all groups after the 90-day treatment. The primary histological finding in this study was an inflammation-associated cardiopathy produced by 1,2,3-TCP. Myocardial necrosis and degeneration occurred in a diffuse pattern with marked eosinophilia of affected cells. Male and female animals showed a cardiopathic response only at a dose of 0.8 mmol kg-1 1,2,3-TCP after the 10-day exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas.
A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment--both healing spontaneously. Fourteen patients developed an area of moist desquamation--11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evaluation of cell attachment matrix (CAM) coated plates for primary culture of human tumour biopsies.
Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (ATCCS) using a culture surface coated with a cell attachment matrix (CAM). The ability of CAM-coated plates to support the growth of cells from human tumour biopsies has been evaluated. Successful growth was obtained in 9/22 samples (41%), but fibroblasts, rather than tumour cells, grew in the majority. Comparison of CAM with other surfaces showed that CAM was no better for establishing tumour cell growth than the presence of feeder cells or an alternative attachment factor vitronectin.
Animals↗
The OR record. Developing a format for documenting care.
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Humans↗
Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure.
Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Kidney Injury↗
Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment.
Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life.
Adolescent↗
Blood mononuclear cells from patients with psoriasis exhibit an enhanced adherence to cultured vascular endothelium.
Blood mononuclear cells (MNC) from patients with psoriasis were more adherent to monolayers of endothelial cells prepared from human umbilical cord vein than otherwise similar cells from control subjects. This increase in adherence occurred in the presence (mean 37% increase; p less than 0.01) and absence (mean 47% increase; p less than 0.05) of 10% autologous serum and was not related to the disease severity of the patients. The augmented adhesiveness of the patients' cells was also apparent when using monolayers of endothelial cells isolated from human skin. The levels of immune complexes, complement, alpha 2-macroglobulin, acute phase proteins (alpha 1-acid glycoprotein, C-reactive protein and alpha 1-antitrypsin), and tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interleukin-1 beta (IL-1 beta) in the patients' sera were within normal limits. When MNC were added to endothelial monolayers that had been incubated with either TNF alpha or the highest concentration of rIL-1 beta used in the study, both the patients' and control's cells exhibited a similar increase in attachment (p less than 0.01). Pretreatment of endothelium with interferon-gamma did not enhance the attachment of MNC from either group of subjects. The augmented adherence of the patient's MNC appears to be due to an abnormal adhesiveness of the lymphocytes rather than the monocytes and is not related to an enhanced expression of the cell-surface adhesion molecules CD11a/CD18. It is likely that the circulating MNC of psoriatic patients may be predisposed for extravasation into skin.
Cell Adhesion↗
Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy.
The results of four similarly designed, randomized, double-blind, placebo-controlled studies conducted to evaluate ranitidine as prophylaxis for NSAID-associated damage are reviewed. A total of 673 patients receiving therapeutic dosages of NSAIDs for arthritic or musculoskeletal conditions also received either ranitidine 150 mg twice daily (n = 343) or placebo (n = 330) for four weeks (two studies) or eight weeks (two studies). Endoscopic grading of mucosal lesions was based on a modified Lanza scoring system. All patients had normal baseline endoscopies. After four weeks of treatment a significant protective effect against duodenal mucosal lesions including duodenal ulcers (three studies) and gastric mucosal lesions including gastric ulcers (one study) was observed in patients who received ranitidine compared with those who received placebo. A meta-analysis of the four studies confirmed that significantly fewer patients receiving ranitidine than placebo developed duodenal ulcers (1% vs. 6%, P = 0.01). Endoscopic data at eight weeks from the two longer-term studies showed that duodenal ulcers occurred in ranitidine- and placebo-treated patients at a rate of 1% (2/137) vs. 8% (10/126) (P = 0.02), respectively, in one trial, and 0% (0/57) vs. 8% (4/49) (P = 0.02), respectively, in the other trial. No protective effect in the stomach was evident at eight weeks. We conclude that ranitidine is effective in preventing NSAID-associated duodenal ulcers and may be appropriate prophylaxis for certain high-risk patients.
Adult↗
Effect of different doses of omeprazole on 24-hour oesophageal acid exposure in patients with gastro-oesophageal reflux.
To define the optimum doses of omeprazole appropriate for acute and long-term therapy of patients with gastro-oesophageal reflux disease, 24-h oesophageal pH was measured in 12 patients with symptomatic reflux and an abnormal 24-h oesophageal acid exposure time (greater than 6%) in a randomized, double-blind, four-way crossover study comparing the effects of omeprazole 10, 20, or 40 mg/day and placebo. Total reflux time over 24 hours, number of reflux episodes per hour, and the number of reflux episodes lasting greater than 5 minutes were measured by ambulatory 24-h oesophageal pH monitoring. All doses of omeprazole were superior to placebo in decreasing gastro-oesophageal reflux as measured by each index. With placebo, oesophageal acid exposure was 16.3% of the 24 hours, 10 mg omeprazole/day reduced that to 6.3%, 20 mg/day lowered acid exposure to 0.9%, and 40 mg/day to 0.6%. Thus only the 20 and 40 mg doses reduced acid exposure to within the normal range. Similar results were obtained with the other indices of reflux. These data suggest that a rational dose regimen for reflux oesophagitis is 20 mg/day, a regimen that has proved effective in clinical trials. The present study indicates that 24-hour oesophageal pH monitoring is a practical approach to the determination of drug dosage in patients with gastro-oesophageal reflux.
Adult↗