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Biomedical subjects

C Ferguson

Publications and source records attributed to C Ferguson.

At least 55 records · Page 3Linked to original sources

Bedside measurement of intra-abdominal pressure (IAP) via an indwelling naso-gastric tube: clinical validation of the technique.

OBJECTIVES: To compare measurements of intraabdominal pressure (IAP) via a naso-gastric tube with the previously validated technique of IAP measurement via a urinary bladder catheter. To examine an association between elevated IAP and oliguric acute renal failure. DESIGN: Simultaneous paired measurements of gastric and urinary bladder pressures in supine patients. SETTING: The general intensive care units of two London hospitals. PATIENTS: 141 Paired measurements of intragastric and urinary bladder pressures were obtained in 26 general intensive care patients. MEASUREMENTS AND RESULTS: With the patient lying supine, 50 ml of sterile water were instilled via manometer tubing into the stomach and bladder following drainage of each viscera. The mid-axillary line was used as the zero reference, and cavity pressures noted in centimeters of water (cmH2O) at end expiration. The results were compared using the technique of Bland and Altman. RESULTS: Gastric pressure may be approximately 2.5 cmH2O above or below urinary bladder pressure. Manometric measurement of the gastric pressure via a naso-gastric tube provides a simple, reliable, non-invasive technique of IAP measurement. IAP should be regularly monitored in patients with abdominal distension at risk of acute renal failure.

Acute Kidney Injury↗

Factors associated with successful laparoscopic cholecystectomy for acute cholecystitis.

OBJECTIVE: This article determined which preoperative data correlated with successful completion of a laparoscopic cholecystectomy in patients with acute cholecystitis. SUMMARY BACKGROUND DATA: Although laparoscopic cholecystectomy is the procedure of choice in chronic cholecystitis, its use in acute cholecystitis may be associated with higher costs and complication rates. It is not known which patients with acute cholecystitis are likely to require conversion to open cholecystectomy based on preoperative data or if a cooling-off period with medical therapy can diminish inflammation and increase the chance of successful laparoscopic cholecystectomy. METHODS: All laparoscopic cholecystectomies done by the authors between 10/90 and 2/92 were reviewed. Data on cases of acute cholecystitis were prospectively collected on standardized data forms. RESULTS: Twenty of 281 laparoscopic cholecystectomies were done for acute cholecystitis; 7/20 patients with acute cholecystitis required conversion to open cholecystectomy compared with 6/281 patients undergoing elective operation for chronic cholecystitis. In patients with acute cholecystitis the interval from admission to cholecystectomy in the successful cases was 0.6 days vs. 5 days in the cases requiring conversion to open cholecystectomy (p = .01). Cases requiring conversion to open cholecystectomy also had higher WBC (14.0 vs. 9.0, p < .05), alkaline phosphatase (206 vs. 81, p < .02, and APACHE II scores (10.6 vs. 5.1, p < .05). Ultrasonographic findings such as gallbladder distention, wall thickness, and pericholecystic fluid did not correlate with the success of laparoscopic cholecystectomy. Patients converted from laparoscopic to open cholecystectomy required more operating room time (120 min vs. 87 min, p < .01) and more postop hospital days (6 vs. 2, p < .001). CONCLUSIONS: Laparoscopic cholecystectomy for acute cholecystitis should be done immediately after the diagnosis is established because delaying surgery allows inflammation to become more intense, thus increasing the technical difficulty of laparoscopic cholecystectomy.

Acute Disease↗

Exertional heat stroke induced by amphetamine analogues. Does dantrolene have a place?

There are increasing numbers of patients admitted to hospital as a result of ingesting amphetamine-like drugs. The most severe cases exhibit hyperthermia, rhabdomyolysis, coagulopathy and renal failure. We describe six such patients with varying severity of intoxication, and have reviewed the recent literature with particular reference to the use of dantrolene. One of our patients died but the others all survived. There is little evidence that dantrolene influenced the outcome in patients reported to date. We believe that a controlled trial should be carried out in amphetamine-related hyperthermia before the use of dantrolene becomes widespread.

3,4-Methylenedioxyamphetamine↗

The substitution of glycine 661 by arginine in type III collagen produces mutant molecules with different thermal stabilities and causes Ehlers-Danlos syndrome type IV.

Previous studies have shown that Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutations of type III collagen (COL3A1). Here we have characterised the most amino-terminal glycine substitution so far described in a patient with EDS IV. A combination of peptide mapping and chemical cleavage analysis of cDNA localised the mutation in cyanogen bromide peptide CB5. Sequence analysis showed a G to A mutation, converting glycine 661 to arginine, which was a new dominant mutation. Analysis of type III collagen secreted by cultured fibroblasts showed an overmodified mutant protein with normal thermal stability. However, the intracellularly retained form melted 2 degrees C lower than normal. This indicated that molecules resulting from the same mutation can differ in their thermal stabilities.

Arginine↗

Staurosporine, a protein kinase C inhibitor, decreases the general anesthetic requirement in Rana pipiens tadpoles.

Protein kinase C, the intracellular effector for the inositol phosphate-mediated signal transduction pathway, plays a key role in neurotransmission in the central nervous system. Although the in vitro activity of protein kinase C is inhibited by therapeutic concentrations of volatile anesthetics, the relation of this effect to in vivo obtundation has not been established. If obtundation by volatile anesthetics involves protein kinase C inhibition, then an inhibitor of this enzyme should decrease the anesthetic requirement. To test this hypothesis, we compared the EC50S of halothane and diethylether for loss of the righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Anesthetic concentrations were confirmed by gas chromatography and staurosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained in more than 1000 animals indicated that pretreatment with staurosporine concentrations in the nanomolar range significantly decreased the EC50 for both halothane (68% of control; P < 0.035) and diethylether (41% of control; P < 0.001). This finding implies that protein kinase C inhibition may play a role in general anesthetic-induced obtundation.

Alkaloids↗

[Opinions of Honduran adults about street children].

The purpose of this study was to determine the beliefs parents of working children and business people have about two types of street children, those who work on the street and those who are abandoned and live on the street. In 1991 forty-nine parents of working children and 49 business people from Tegucigalpa were administered a questionnaire listing 36 beliefs about the lifestyles of abandoned and working children and causes of children adopting these ways of life. Among parents of working children, education was significantly lower and mothers were more likely to be single women than in the business people sample. There were many beliefs about the lifestyles of street children on which both groups agreed, but parents of working children held the youngsters more accountable for choosing to work or live in the street. Parents also seemed to be more aware of the health risks to both types of street children than business people who felt working children were at less risk than abandoned children. Business people perceived abandoned children to be victims of single parenthood and solvent abuse. A deeper exploration of the views held by families of street children may assist those seeking to help them.

Adult↗

Functional expression of plant plasma membrane H(+)-ATPase in yeast endoplasmic reticulum.

Recombinant plant plasma membrane H(+)-ATPase has been produced in a yeast expression system comprising a multicopy plasmid and the strong promoter of the yeast PMA1 gene. Western blotting with a specific monoclonal antibody showed that the plant ATPase is one of the major membrane proteins made by the transformed cells, accounting for about 1% of total yeast protein. The plant ATPase synthesized in yeast is fully active. It hydrolyzes ATP, pumps protons, and the reaction cycle involves a phosphorylated intermediate. Phosphorylation is possible from both ATP and Pi. Unlike the situation in plants, however, most of the plant ATPase is not expressed in the yeast plasma membrane. Rather, the enzyme appears to remain trapped at a very early stage of secretory pathway: insertion into the endoplasmic reticulum. This organelle was observed to proliferate in the form of stacked membranes surrounding the yeast nucleus in order to accommodate the large amount of plant ATPase produced. In this location, the plant ATPase can be purified with high yield (70 mg from 1 kg of yeast) from membranes devoid of endogenous yeast plasma membrane H(+)-ATPase. This convenient expression system could be useful for other eukaryotic membrane proteins and ATPases.

Adenosine Triphosphate↗

Epidural analgesia.

The most frequently used postoperative analgesia techniques are intramuscular injection (IM) and patient controlled analgesia (PCA). Recently, the use of epidural catheter injection (EPI) has been done with success. This study was done to prospectively compare these three techniques for postoperative analgesia after extensive operations upon the colon and rectum. Patients were randomized to one of three analgesia groups--IM, intramuscular morphine sulfate; PCA, patient controlled morphine sulfate, and EPI, epidural morphine sulfate. Data collected included age, time to first bowel movement, amount of narcotic, number achieving 75 per cent of preoperative forced vital capacity, postoperative pruritus, headache, nausea and vomiting, respiratory depression, atelectasis or pneumonitis. A visual analog pain scale was used to evaluate postoperative pain severity (0, no; 1, partial; 2, marked, and 3, total relief). Sixty-eight patients were eligible for study (IM, 19; PCA, 22; EPI, 23, and excluded, four). The EPI group required significantly less daily narcotic compared with either the IM or PCA groups (17.0 +/- 6.12 milligrams; 67.8 +/- 26.8 milligrams; 40.5 +/- 20.6 milligrams, respectively, less than 0.05 ANOVA) and total narcotic (81.3 +/- 31.3 milligrams; 355.4 +/- 147.7 milligrams; 215.3 +/- 105.4 milligrams, respectively, p less than 0.05 ANOVA). EPI achieves excellent pain control in more patients with a significantly lower dose of narcotics and significantly fewer pulmonary complications. Therefore, epidural analgesia is the optimal method of postoperative analgesia after extensive abdominal operations.

Adult↗

Immunological approaches to the transmembrane topology and conformational changes of the carboxyl-terminal regulatory domain of yeast plasma membrane H(+)-ATPase.

Molecular genetic experiments have suggested that the carboxyl terminus of the Saccharomyces cerevisiae plasma membrane H(+)-ATPase is an inhibitory domain involved in the "in vivo" regulation of the enzyme by glucose metabolism. An antibody prepared against a fusion protein including the last 59 amino acids of the ATPase sequence has been affinity purified to yield a preparation which requires the 18 carboxyl-terminal amino acids for recognition. Antibody binding experiments show that the carboxyl-terminal domain of the ATPase can be selectively exposed by concentrations of the detergent Tween-20 which do not break down the permeability barrier of the plasma membrane to the antibody. Both enzyme-linked immunosorbent assay and immunofluorescence analysis demonstrate that the accessibility of the carboxyl-terminal domain in isolated plasma membranes depends on the physiological state of the cell being increased by glucose metabolism. Immunofluorescence analysis of isolated plasma membrane vesicles, using a dual labeling protocol with concanavalin A and antibody to reveal the orientation of individual vesicles, and colloidal gold immunoelectron microscopy of ultrathin cryosections of whole yeast cells separately demonstrate that the ATPase carboxyl terminus is located in the cytoplasmic compartment. The application of a mutant deleted of the epitope(s) recognized by the affinity purified carboxyl-terminal antibody eliminates the possibility of artifacts arising from nonspecific antibody binding. The accessibility properties and cytoplasmic location of the carboxyl-terminal domain appear to be consistent with its role as a negative regulator of the ATPase.

Blotting, Western↗

Domains of yeast plasma membrane and ATPase-associated glycoprotein.

In yeast homogenates the plasma membrane H(+)-ATPase and a major surface glycoprotein of about 115 kDa are present in two membrane fractions with peak densities in sucrose gradients of 1.17 and 1.22. Immunogold electron microscopy of frozen yeast sections indicates that the ATPase is exclusively (greater than 95%) present at the surface membrane. Therefore the two ATPase-containing fractions appear to correspond to different domains of the plasma membrane. The 115 kDa glycoprotein is tightly associated with the ATPase during solubilization and purification of the enzyme. However, in a mutant lacking the glycoprotein the activity of the plasma membrane H(+)-ATPase is similar to wild type, suggesting that this association is fortuitous. The ATPase and the glycoprotein are difficult to separate by electrophoresis and therefore binding of concanavalin A to the ATPase cannot be unambiguously demonstrated in wild-type yeast. By utilizing the mutant without glycoprotein it was shown that the ATPase band of 105 kDa binds concanavalin A.

Cell Membrane↗

Effects of inorganic lead on the differentiation and growth of cultured hippocampal and neuroblastoma cells.

Lead exposure has devastating effects on the developing nervous system, and has been implicated in variety of behavioral and cognitive deficits as well as neural morphological abnormalities. Since lead impacts many calcium-dependent processes, one likely mechanism of lead toxicity is its disruption of calcium dependent processes, among which is neuronal differentiation. We investigated the effects of inorganic lead on survival and several parameters of differentiation of cultured neurons. Three different cell types were used: Rat hippocampal neurons (a primary CNS cell type), B50 rat neuroblastoma cells (a transformed CNS-derived cell line), and N1E-115 mouse neuroblastoma cells (a transformed peripherally-derived cell line). Lead concentrations ranged from low nM to 1 mM. Lead effects differed considerably among the three cell types, with B50 cells least affected. Lead effects were generally multimodal, with fewest effects observed at intermediate concentrations. Lead inhibited neurite initiation in hippocampal neurons, but stimulated initiation in N1E-115 cells. In those cells that differentiated, lead increased dendrite numbers in hippocampal neurons and neurite numbers in N1E-115 cells. Lead exposure increased both the length and the degree of branching of axons in hippocampal neurons and the length of neurites in N1E-115 cells. We hypothesize that lead impacts multiple regulatory processes that influence neuron survival and differentiation, and that its effects show differing dose-dependencies. The differing responses of the different cell types to lead suggests that differentiation may be regulated in different ways by the three types of cells. Alternatively, or additionally, the cell types may differ in their ability to compensate for, sequester, or expel lead.

Animals↗