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Biomedical subjects

G C Allen

Publications and source records attributed to G C Allen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Postarthroscopy analgesia with intraarticular bupivacaine/morphine. A randomized clinical trial.

BACKGROUND: Postarthroscopy analgesia has been provided with intraarticular bupivacaine, but the duration of analgesia may be only a few hours. More recently, longer-lasting analgesia has been achieved using intraarticular morphine, although the onset of analgesia may be delayed. The combination of intraarticular morphine and bupivacaine has been suggested as an ideal analgesic after knee arthroscopy. METHODS: One hundred and twenty ASA Physical Status 1-2 outpatients, age 18-60 yr, having knee arthroscopy, were randomized into one of four treatment groups. Exclusion criteria included relevant drug allergy, extensive debridement or synovectomy, arthrotomy, postoperative intraarticular drainage, tracheal intubation, and patient refusal. All patients received general anesthesia with intravenous fentanyl, propofol, N2O, O2, and isoflurane. At the end of surgery, before tourniquet release, the following were injected intraarticularly through the arthroscope: group 1, 0.25% bupivacaine; group 2, 1 mg morphine in saline; group 3, 2 mg morphine in saline; and group 4, 1 mg morphine in 0.25% bupivacaine. The volume injected was 30 ml, and all solutions contained 1:200,000 epinephrine. Postoperative analgesia was provided with intravenous fentanyl and/or oral acetaminophen/codeine, and was recorded for 24 h. Visual analog pain scale (VAPS) scores and the McGill Pain Questionnaire (MPQ) were performed hourly from 1-6 h, and at 24 h postoperatively. RESULTS: Visual analog pain scale and MPQ scores were lowest in groups 1 and 4 at 1-6 h, but at 24 h, VAPS scores were lowest in groups 2, 3, and 4. Analgesic requirements were lower for the first 12 h in groups 1 and 4, but no difference was seen between groups over the 24-h study period. No adverse effects were noted. CONCLUSIONS: Morphine, 1 mg intraarticular, in 30 ml 0.25% bupivacaine, with 1:200,000 epinephrine, may provide superior postoperative analgesia for up to 24 h versus bupivacaine or morphine alone.

Adolescent↗
PubMed1993

Malignant hyperthermia and associated disorders.

Malignant hyperthermia is a pharmacogenetic disorder of skeletal muscle that may cause a life-threatening reaction during administration of general anesthesia. It is inherited in an autosomal dominant pattern and, at least in some families, is caused by a mutation in the ryanodine receptor-calcium-release channel gene on chromosome 19. Malignant hyperthermia displays heterogeneity, making the development of a simple screening test difficult. Malignant hyperthermia may be caused by other biochemical defects affecting intramyoplasmic calcium. Some myopathies, such as central core disease, are frequently associated with malignant hyperthermia susceptibility. In other myopathies, like Duchenne muscular dystrophy, unusual compensatory mechanisms may produce a hypermetabolic state identical to that of malignant hyperthermia.

Calcium↗
PubMed1993

Scaffold attachment regions increase reporter gene expression in stably transformed plant cells.

The yeast ARS-1 element contains a scaffold attachment region (SAR) that we have previously shown can bind to plant nuclear scaffolds in vitro. To test effects on expression, constructs in which a chimeric beta-glucuronidase (GUS) gene was flanked by this element were delivered into tobacco suspension cells by microprojectile bombardment. In stably transformed cell lines, GUS activity averaged 12-fold higher (24-fold on a gene copy basis) for a construct containing two flanking SARs than for a control construct lacking SARs. Expression levels were not proportional to gene copy number, as would have been predicted if the element simply reduced position effect variation. Instead, the element appeared to reduce an inhibitory effect on expression in certain transformants containing multiple gene copies. The effect on expression appears to require chromosomal integration, because SAR constructs were only twofold more active than the controls in transient assays.

Base Sequence↗
PubMed1991

Fine balance in the regulation of DnaB helicase by DnaC protein in replication in Escherichia coli.

The DnaC protein of Escherichia coli is essential for replication in vivo and in vitro. In the initiation of replication of a minichromosome at its origin, DnaC delivers the DnaB helicase from a DnaB.DnaC complex to the future replication fork and then departs. However, if an excess of DnaC was present in subsequent steps, it severely inhibited replication by slowing the DnaB helicase at the replication fork. When DnaB was present at a level equimolar with the excess DnaC, the inhibition was relieved, implying that the ratio of DnaC to DnaB is critical for achieving optimal replication activity and avoiding inhibition by DnaC. In vivo, overproduction of DnaC slowed cell growth. This slowing was alleviated by overproducing DnaB at the same time. E. coli strains with a dnaCts gene defective in chromosomal initiation were complemented by the wild-type gene in trans. On the other hand, strains with an elongation-defective dnaCts gene were not complemented by the wild-type dnaC gene. The dominance of the mutant protein suggests that it remains tightly complexed with DnaB at the replication fork, inhibiting elongation even in the presence of the wild-type DnaC.

Alleles↗
PubMed1991

Nuclear scaffolds and scaffold-attachment regions in higher plants.

DNA in the nuclei of eukaryotic organisms undergoes a hierarchy of folding to be packaged into interphase and metaphase chromosomes. The first level of packaging is the 11-nm nucleosome fiber, which is further coiled into a 30-nm fiber. Evidence from fungal and animal systems reveals the existence of higher order packaging consisting of loops of the 30-nm fibers attached to a proteinaceous nuclear scaffold by an interaction between the scaffold and specific DNA sequences called scaffold-attachment regions (SARs). Support for the ubiquitous nature of such higher order packaging of DNA is presented here by our work with plants. We have isolated scaffolds from tobacco nuclei using buffers containing lithium diiodosalicylate to remove histones and then using restriction enzymes to remove the DNA not closely associated with the scaffold. We have used Southern hybridization to show that the DNA remaining bound to the scaffolds after nuclease digestion includes SARs flanking three root-specific tobacco genes. This assay for SARs is termed the endogenous assay because it identifies genomic sequences as SARs by their endogenous association with the scaffold. Another assay, the exogenous assay, depends upon the ability of scaffolds to specifically bind exogenously added DNA fragments containing SARs. The tobacco scaffolds specifically bind a well-characterized yeast SAR, and cloned DNA fragments derived from the 3'-flanking regions of the root-specific genes are confirmed to contain SARs by this exogenous assay.

Journal Article↗
PubMed1991

The priB gene encoding the primosomal replication n protein of Escherichia coli.

The gene encoding protein n of the Escherichia coli primosome has been discovered in the rpsF-rpsR-rplI ribosomal protein operon and designated priB. The low copy number of PriB protein and the distinctive codon usage of its gene argue against its being a ribosomal protein. A strain which overproduces PriB was constructed and has been used to purify the protein to homogeneity. The overproduced protein behaves like that purified from wild-type cells.

Amino Acid Sequence↗
PubMed1991

Oxygen Uptake and Hydrogen-Stimulated Nitrogenase Activity from Azorhizobium caulinodans ORS571 Grown in a Succinate-Limited Chemostat.

Succinate-limited continuous cultures of an Azorhizobium caulinodans strain were grown on ammonia or nitrogen gas as a nitrogen source. Ammonia-grown cells became oxygen limited at 1.7 muM dissolved oxygen, whereas nitrogen-fixing cells remained succinate limited even at dissolved oxygen concentrations as low as 0.9 muM. Nitrogen-fixing cells tolerated dissolved oxygen concentrations as high as 41 muM. Succinate-dependent oxygen uptake rates of cells from the different steady states ranged from 178 to 236 nmol min mg of protein and were not affected by varying chemostat-dissolved oxygen concentration or nitrogen source. When equimolar concentrations of succinate and beta-hydroxybutyrate were combined, oxygen uptake rates were greater than when either substrate was used alone. Azide could also used alone as a respiratory substrate regardless of nitrogen source; however, when azide was added following succinate additions, oxygen uptake was inhibited in ammonia-grown cells and stimulated in nitrogen-fixing cells. Use of 25 mM succinate in the chemostat resevoir at a dilution rate of 0.1 h resulted in high levels of background respiration and nitrogenase activity, indicating that the cells were not energy limited. Lowering the reservoir succinate to 5 mM imposed energy limitation. Maximum succinate-dependent nitrogenase activity was 1,741 nmol of C(2)H(4)h mg (dry weight), and maximum hydrogen-dependent nitrogenase activity was 949 nmol of C(2)H(4) h mg (dry weight). However, when concentration of 5% (vol/vol) hydrogen or greater were combined with succinate, nitrogenase activity decreased by 35% in comparison to when succinate was used alone. Substitution of argon for nitrogen in the chemostat inflow gas resulted in "washout," proving that ORS571 can grow on N(2) and that there was not a nitrogen source in the medium that could substitute.

Journal Article↗
PubMed1990

Phaeochromocytoma presenting as acute malignant hyperthermia--a diagnostic challenge.

We report a case of acute hypermetabolism following the induction of general anaesthesia in an 11-yr-old boy. This episode was diagnosed and managed as an acute malignant hyperthermia crisis. However, severe hypertension during the episode led to the discovery of an unsuspected phaeochromocytoma. A hypermetabolic state during anaesthesia has several aetiologies, but correct diagnosis during the acute episode may be difficult.

Adrenal Gland Neoplasms↗
PubMed1990

Does forehead liquid crystal temperature accurately reflect "core" temperature?

Liquid crystal thermometry (LCT) is a non-invasive alternative to temperature monitoring. We evaluated the ability of forehead LCT, rectal temperature, and axillary skin temperature to trend distal oesophageal temperature during rapid warming on cardiopulmonary bypass. In 24 patients undergoing open heart surgery, temperatures were measured during the rapid warming phase on bypass (12-35 min). Scattergrams of temperature vs time for the four temperature sites each contained 150 data points. Polynomial regression analysis revealed that LCT, but not axillary or rectal temperatures, correlated with oesophageal temperature. We conclude that forehead LCT may be useful to monitor temperature trends and to detect rapid elevations in body temperature when more invasive temperature monitoring is inappropriate or unavailable.

Analysis of Variance↗
PubMed1990

Malignant hyperthermia susceptibility in adult patients with masseter muscle rigidity.

We sought to determine the incidence of malignant hyperthermia (MH) susceptibility in adult patients with a previous episode of masseter muscle rigidity (MMR). The medical records and in vitro contracture test results of all patients over 15 years of age tested for MH because of previous MMR from 1985 to 1988 were reviewed. The number of children (age less than 16 yr) tested for MH because of previous MMR was also determined for the same four-year period, for comparison of coincidence rates. Six of 24 adult patients (25 per cent) were proved MH-susceptible by in vitro contracture testing. No clinical sign associated with the episode of MMR was predictive of MH-susceptibility. Two of six MH-susceptible patients developed acute MH following MMR. In the same four-year period, 75 children were tested for MH-susceptibility because of previous MMR; 44 (59 per cent) had a positive in vitro contracture test. We conclude that the coincidence of MMR and MH-susceptibility is lower in adults than children. Episodes of acute MH do occur after MMR, but the onset of MH may be delayed. Conservative management of MMR in adult patients is recommended.

Adult↗
PubMed1990

The priA gene encoding the primosomal replicative n' protein of Escherichia coli.

The Escherichia coli gene encoding protein n' has been isolated and named priA for primosomal protein A. Protein n' is absolutely required for the conversion of single-stranded phi X174 DNA to the duplex replicative form in an in vitro-reconstituted system. The gene maps to 88.7 minutes on the chromosome adjacent to the cytR locus. Soluble protein extracts from cells harboring the priA gene on a multicopy plasmid contained 45-fold more n' replication activity than wild-type extracts. Enhanced overproduction of greater than 1000-fold was achieved by replacing the natural Shine-Dalgarno sequence with that of the phage T7 phi 10 gene and placing this priA under the control of the T7 phage promoter and RNA polymerase. The priA sequence reveals a 732-amino acid open reading frame and a nucleotide-binding consensus site consistent with the size and ATPase activity of the purified protein. The gene for protein n has been named priB and the putative gene for protein n", priC.

Amino Acid Sequence↗
PubMed1990

Caffeine and halothane contracture testing in swine using the recommendations of the North American Malignant Hyperthermia Group.

Caffeine and halothane contracture testing is widely used to detect malignant hyperthermia (MH) susceptibility. The accuracy and reliability of the 3% halothane test and the incremental caffeine test, as recommended by the North American MH Group, were assessed in 11 swine (five MHS, six control). Nine swine were tested twice, 4-6 weeks apart. Accuracy of the in vitro diagnosis was also assessed by in vivo anesthetic challenge. Of all muscle bundles from MH-susceptible swine, 65% reacted positively to 3% halothane and 70% to 2 mM caffeine. Only 35% had a positive caffeine-specific concentration, and 25% developed an increase in baseline tension greater than or equal to 7% at 2 mM caffeine. However, when only the most positive response to 3% halothane or to 2 mM caffeine was used (a minimum of three fresh muscle strips is recommended), these two tests were highly sensitive and specific. In control swine one of 30 muscle bundles reacted positively to 3% halothane. A positive caffeine-specific concentration developed in one of 25 control muscle bundles exposed to caffeine. The variability in the results of these tests mandated that at least three muscle bundles be used for each test. Nonviable muscle bundles could not be relied upon to provide accurate results. In this porcine model, MH susceptibility could be detected by performing the Caffeine Halothane Contracture Test (CHCT) according to the guidelines of the North American MH Group. However, only the 3% halothane test and the response to 2 mM caffeine produced adequate diagnostic results in this breed of swine.

Animals↗
PubMed1990

Safety of general anesthesia in patients previously tested negative for malignant hyperthermia susceptibility.

Anesthetic management and outcome were examined in patients with negative in vitro contracture tests for malignant hyperthermia (MH). Contracture testing was performed in a standardized fashion using 3% halothane alone and incremental doses of caffeine alone. Medical records were examined for 54 anesthetic exposures in 42 MH(-) patients who had received anesthesia since their MH testing. Sixteen patients received anesthesia with known MH triggering agents on 23 occasions, all without incident. In six MH(-) patients with previous masseter muscle rigidity, no adverse reactions occurred in response to volatile anesthetic agents. Succinylcholine was avoided in these patients. Eleven MH(-) patients were managed as if MH-susceptible, although it was known that these patients had tested MH(-). Two of these patients also receive prophylactic iv dantrolene. These results suggest that "triggering" anesthetic agents may be safely administered to patients who test MH(-) by in vitro contracture testing. However, until the anesthetic experience of larger numbers of MH(-) patients is known, these results should be interpreted cautiously.

Anesthesia, General↗
PubMed1990

Importance of fasting in the lymphocyte calcium test for malignant hyperthermia.

Anaesthetic-induced increases in cytoplasmic free Ca2+ have been reported to be greater in lymphocytes from malignant hyperthermia (MH) susceptible patients than in those from controls, suggesting that this may be the basis for a less invasive test for MH susceptibility. In the present study the cytoplasmic Ca2+ concentrations of lymphocytes were monitored with indo-1 in 14 control subjects (nine fasted and five nonfasted) and five fasted MH susceptible and three fasted nonsusceptible patients, diagnosed by the halothane and caffeine contracture tests. No relationship was observed between MH susceptibility and Ca2+ concentrations in lymphocytes in the absence or presence of halothane. There was, however, a relationship in control subjects between fasting and the response of lymphocytes to halothane, with the halothane-induced Ca2+ increase being considerably larger in nonfasted subjects.

Adolescent↗
PubMed1990

Growth, Respiration, and Polypeptide Patterns of Bradyrhizobium sp. (Arachis) Strain 3G4b20 from Succinate- or Oxygen-Limited Continuous Cultures.

Succinate- or oxygen-limited continuous cultures were used to study the influences of different concentrations of dissolved oxygen and ammonia on the growth, respiration, and polypeptide patterns of Bradyrhizobium sp. (Arachis) strain 3G4b20. During succinate-limited growth, molar growth yields on succinate (Y(succ)) ranged from 38.9 to 44.4 g (dry weight) of cells mol of succinate and were not greatly influenced by changes in dilution rates or changes in the oxygen concentrations that we tested. Succinate, malate, and fumarate induced the highest rates of oxygen uptake in all of the steady states in which the supply rates of (NH(4))(2)SO(4) ranged between 322 and 976 mumol h. However, the amino acids aspartate, asparagine, and glutamate could also be used as respiratory substrates, especially when the (NH(4))(2)SO(4) supply rate was decreased to 29 mumol h. Glutamine-dependent respiration was seen only when the (NH(4))(2)SO(4) supply rate was 29 mumol h and thus appears to be under tight ammonia control. Nitrogenase activity was detected only when the culture was switched from a succinate-limited steady state to an oxygen-limited steady state. Comparison of major silver-stained proteins from three steady states by two-dimensional gel electrophoresis revealed that nearly 60% were affected by oxygen and 24% were affected by ammonia. These data are consistent with reports that oxygen has a major regulatory role over developmental processes in Rhizobium sp. and Bradyrhizobium sp.

Journal Article↗
PubMed1989

Rewarming following hypothermic cardiopulmonary bypass in the malignant hyperthermia-susceptible patient: implications for diagnosis and perioperative management.

A 55-year-old, malignant hyperthermia-susceptible patient underwent myocardial revascularization without incident. Six hours postoperatively, he developed what was initially diagnosed as an MH crisis, for which he received intravenous dantrolene. The resultant muscle weakness prolonged the duration of postoperative mechanical ventilation and likely contributed to the development of a postoperative pneumonia. Plasma dantrolene levels were measured for the first 48 hours postoperatively and correlated with clinical findings. On reviewing the patient's perioperative course, it was felt that the hypermetabolic state was not due to MH. The patient's pattern of rewarming following hypothermic cardiopulmonary bypass was similar to non-MH-susceptible patients. Because of the difficulty in diagnosing a MH crisis after hypothermic bypass, it is recommended that patients receive prophylactic dantrolene preoperatively and after bypass. Nondepolarizing muscle relaxants should be given postoperatively to prevent shivering and respiratory acidosis while patients rewarm.

Cardiopulmonary Bypass↗
PubMed1988

Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients.

Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.

Administration, Oral↗