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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 37 records · Page 2Linked to original sources

Endocrine responses to positive end-expiratory pressure ventilation in patients who have recently undergone heart surgery.

The effect of positive end-expiratory pressure ventilation (PEEP) on angiotensin II and atrial natriuretic factor (ANF) was studied postoperatively following heart surgery. In nine patients pressures were recorded in the radial artery, pulmonary artery and the right atrium. PEEP of 5 cmH2O (0.5 kPa) and 10 cmH2O (1 kPa) increased angiotensin II from 38.8 +/- 20.3 (mean +/- s.e.mean) to 56.7 +/- 29.6 (n.s.) and 66.7 +/- 28.7 (P less than 0.05) pmol/l, respectively. Plasma-ANF showed no significant changes during PEEP. Pulmonary artery wedge pressure increased from 12.9 +/- 2.0 to 14.1 +/- 2.0 (n.s.) and 18.5 +/- 2.1 (P less than 0.01) mmHg, and right atrial pressure from 8.3 +/- 1.7 to 9.8 +/- 1.7 (n.s.) and 12.9 +/- 1.7 (P less than 0.01) mmHg with 5 and 10 cmH2O (0.5 and 1.0 kPa) of PEEP, respectively. Systemic blood pressure tended to decrease (n.s.) with PEEP. In conclusion, PEEP markedly increased angiotensin II. This may represent an important compensatory mechanism, helping to prevent reduction in aortic pressure during PEEP. ANF, however, did not change with PEEP of 5 or 10 cmH2O (0.5 and 1.0 kPa).

Anesthesia, General

The relationship between atrial pressure, atrial dimensions and atrial natriuretic factor during pacing tachycardia in dogs.

Acute supraventricular tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The purpose of these experiments was to investigate if such an increase in plasma-ANF could be ascribed to changes in atrial pressure and atrial dimensions. Eight anaesthetized dogs were instrumented with atrial pressure catheters and sonomicrometers to measure left and right auricular and atrial free wall dimensions. An acute increase in atrial rate from 150 to 200 min-1 for 10 min did not change plasma-ANF or atrial haemodynamic variables. A further increase in atrial rate to 250 or 300 min-1 increased right and left atrial intracavitary pressures (P less than 0.01), both auricular diameters and right atrial free wall segment length (P less than 0.05). Left atrial free wall segment length remained unchanged. Plasma-ANF increased in all dogs (P less than 0.01). The change in plasma-ANF correlated well with changes in atrial pressures as well as with changes in atrial dimensions. These results support the hypothesis that release of ANF during acute atrial tachycardia may in part be attributed to atrial dilatation.

Animals

Rate-induced increase in plasma atrial natriuretic factor can occur independently of changes in atrial wall stretch.

Tachycardia is known to increase the plasma level of atrial natriuretic factor (ANF). The aim of the study was to determine whether such release of ANF can occur independently of increased atrial wall stretch. Seven anesthetized dogs were instrumented with pressure catheters and sonomicrometer crystals to measure left and right auricular and atrial free wall dimensions. During atrial pacing, the measured atrial dimensions were kept constant by adjusting vascular constrictors placed around the great vessel trunks. When atrial rate was increased progressively by pacing at 150, 200, and 250 min-1, plasma ANF increased from 40.8 +/- 5.4 to 43.0 +/- 6.0 (P = NS) and 103.1 +/- 17.6 (SE) pmol/l (P less than 0.05), respectively. Repeating the pacing sequence at two different levels of elevated left atrial pressure caused at each level a similar increase in plasma ANF at 250 min-1. The relationship between plasma ANF and atrial dimensions was shifted upward by pacing, such that ANF was higher for any given atrial dimension. In conclusion, pacing tachycardia elevates plasma ANF in the presence of constant atrial dimensions. These results support the hypothesis that chronotropic stimulation can cause release of ANF by a mechanism that is independent of atrial stretch.

Animals

Blood volume changes in liver and spleen during cardiogenic shock in dogs.

Changes in vascular capacitance of the liver and spleen were studied in seven anesthetized dogs during cardiogenic shock induced by coronary microembolization. Left ventricular end-diastolic pressure increased from 2 +/- 2 to 28 +/- 4 mmHg (P less than 0.001), and mean aortic pressure decreased from 111 +/- 7 to 56 +/- 9 mmHg (P less than 0.001). Hepatic venous pressure increased from 1.8 +/- 0.6 to 5.0 +/- 1.0 mmHg (P less than 0.05). Portal venous pressure did not change. Blood volume changes were assessed from sonomicrometric measurements of organ diameters. Hepatic diameter increased after embolization, corresponding to an estimated 54 +/- 14 ml increase of hepatic blood volume (P less than 0.01). Splenic diameter gradually decreased during shock until an estimated 33 +/- 12 ml of blood had been released (P less than 0.05). Occlusion of hepatic venous outflow by a balloon catheter was used to cause ramp changes in hepatic volume and hepatic venous pressure so that a pressure-volume curve could be estimated. Analysis of the hepatic curves showed an increase in unstressed volume with no change in vascular compliance during shock. The blood volume increase could in part be attributed to increased outflow pressure, but active dilation of hepatic capacitance vessels probably contributed. Splenic curves were shifted downward, suggesting expulsion of blood by active contraction.

Animals

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs.

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.

Animals

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.

Animals

Retinal, choroidal and total ocular blood flow response to hypercarbia during spontaneous breathing and mechanical ventilation.

The effect of hypercarbia on ocular blood flow was studied in the newborn piglet with the isotope-labeled microsphere method. Blood flow measurements were made during spontaneous breathing and during paralyzation (pancuronium) and mechanical ventilation. Retinal blood flow increased from 0.40 +/- 0.07 (mean +/- SEM) ml/min/g at baseline levels to 0.91 +/- 0.17 ml/min/g at a PaCO2 level of 11.0 kPa during spontaneous ventilation. A similar response was observed during paralyzation and mechanical ventilation (0.89 +/- 0.15 ml/min/g at a PaCO2 of 11.1 kPa). For choroidal blood flow, however, the increase caused by hypercarbia during spontaneous ventilation (16.14 +/- 3.69 to 29.15 +/- 3.22 ml/min/g) was significantly reduced when the animals were paralyzed and mechanically ventilated (15.99 +/- 2.99 to 23.51 +/- 3.41 ml/min/g). Since choroidal blood flow accounts for 60-80% of oxygen delivery to the retina, paralyzation and mechanical ventilation may significantly reduce oxygen delivery to the retina during hypercarbia.

Animals

Effect of different phototherapy lights on retinal and choroidal blood flow.

The response of retinal (RBF) and choroidal (ChBF) blood flow to illumination with light with different spectra was investigated in spontaneously breathing newborn piglets. After 1 h in complete darkness, the animals were exposed to blue, white or green light in such a manner that equal energy was delivered to the eye. RBF and ChBF showed different flow responses. After 60 min exposure to blue light, RBF increased from 0.22 +/- 0.01 ml/min/g at baseline to 0.32 +/- 0.03 ml/min/g (+/- SEM) (p less than 0.03). Apart from this increase, RBF did not change significantly during any of the experimental settings. ChBF, on the other hand, was significantly affected by illumination. Thus, at 120 min of light exposure all three types of light decreased ChBF significantly from baseline (darkness) levels. Blue light decreased ChBF (mean +/- SEM) from 13.78 +/- 0.84 to 7.61 +/- 0.67 ml/min/g (p less than 0.01), white light from 17.43 +/- 1.86 to 9.86 +/- 1.07 ml/min/g (p less than 0.01), and green light from 14.13 +/- 1.64 to 8.31 +/- 1.30 ml/min/g (p less than 0.02). The results indicate that light is an important modulator of ChBF and to a certain extent also RBF. Further, the results suggest that ChBF and RBF are regulated differently.

Animals

A multicentre controlled clinical trial of high-volume fresh frozen plasma therapy in prognostically severe acute pancreatitis.

Fresh frozen plasma (FFP) has been proposed as a specific therapy for acute pancreatitis. It may replenish important circulating proteins, particularly the naturally occurring anti-protease system. To investigate this potential therapy, 72 patients with predicted severe disease were selected from 301 admissions with acute pancreatitis using the modified Glasgow prognostic scoring system. They were randomised within 6 h of diagnosis to receive FFP (8 units daily for 3 days) or a similar volume of colloid control as part of their intravenous fluid therapy. Clinical progress was monitored and specific blood proteins were measured on days 1, 3 and 7. FFP therapy significantly increased the day 3 concentrations of some of the acute phase proteins (C1-reactive protein P less than 0.02, D-dimer P less than 0.05 and fibrinogen P less than 0.05) as well as some proteins which showed a fall in circulating concentration during the early stages of the disease (alpha 2 macroglobulin P less than 0.001, antithrombin III P less than 0.01 and fibronectin P less than 0.001). However, there was no significant difference between the two groups in terms of clinical outcome. Mortality was 20% in patients who received FFP and 18% in the colloid control group. Despite the ability of FFP therapy to supplement circulating concentrations of several potentially useful proteins during acute pancreatitis, it does not appear to improve clinical outcome.

Acute Disease

Agricultural pilot safety in Australia: a survey.

Agricultural flying is one of the most hazardous forms of aviation. The incidence of death and injury among agricultural pilots in Australia is over one hundred times the national average for work-related injury. As with most forms of aviation, the pilot's awareness of and attitude toward risk are important factors in accident prevention. However, it is difficult for others to monitor and regulate agricultural flying activity, and responsibility for safety tends to fall largely on the pilot. A 1988 survey of agricultural pilots in Australia, carried out on behalf of the Civil Aviation Authority, showed that: 1) over 50% regularly exceed regulated flying hours; 2) 90% fly on application when tired; 3) there is a systematic relation between accidents and exposure to risk; 4) pilots perceive the main factor contributing to accidents is the pilot. The practical challenge for aviation medicine is to improve occupational safety by assisting pilots to monitor their own capabilities and performance.

Accidents, Aviation

Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.

A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.

Amino Acid Sequence

Risk for systemic embolization of atrial fibrillation without mitral stenosis.

The risk for systemic embolization was studied in 272 patients without mitral stenosis or prosthetic valves who were referred to the echocardiography laboratory with atrial fibrillation (AF). During a mean follow-up period of 33 months (range less than 1 to 83), 27 (10%) patients had a systemic embolic event, which was cerebral in 23 patients (85%) and peripheral in 4 (15%). In the analysis of individual variables, the risk of embolization was increased by female sex, underlying heart disease and left atrial size greater than or equal to 4.0 cm, but not by age, hypertension or type of AF (paroxysmal vs chronic). In multivariable analysis, left atrial size greater than or equal to 4.0 cm was the single strongest predictor of increased risk for embolization (p less than 0.001), but female sex (p = 0.014) and underlying heart disease (p = 0.027) also contributed. When each of these 3 factors was assigned 1 point in a risk score, embolic events were found to occur in none (0%) of 24 patients with a risk score of 0, in 2 (3%) of 83 patients with a risk score of 1, in 13 (11%) of 118 patients with a risk score of 2 and in 12 (26%) of 47 patients with a risk score of 3. The score allows patients with AF and without mitral stenosis to be stratified into high-, medium- and low-risk groups for systemic embolization. Such information could be useful in decision making for anticoagulation in patients with AF.

Aged

Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro.

Carboxypeptidase E (CPE), which cleaves C-terminal amino acid residues and is involved in neuropeptide processing, is itself subject to intracellular processing. Human CPE cDNA was isolated and sequence comparisons were made with those of a previously isolated brain cDNA (M1622) encoding rat CPE and of other human carboxypeptidases (M and N). Human (2.5 kb) and rat (2.1 kb) CPE cDNAs approximated to the size of their respective mRNAs; additional sequences were located in putative 5' and 3' untranslated regions of human CPE mRNA. There is 79% sequence similarity between human and rat CPE cDNAs, with greater similarity (89%) over the coding region and short sections of the non-coding sequence. The predicted 476-amino acid-residue sequences of human and rat preproCPEs are highly conserved (96% identity), with lower degree of similarity of the N-terminal signal peptide (76%). Human CPE showed 51% and 43% sequence similarity to human CPN and CPM respectively, with discrete regions of divergence dispersed between the highly conserved mechanistically implicated regions. Antiserum generated from a fusion protein, synthesized in Escherichia coli from constructs of the human cDNA, recognized an approx. 50 kDa membrane protein and a smaller soluble protein in rat and human brain preparations, corresponding to the two forms of native CPE. Human CPE mRNA transcripts directed the synthesis in reticulocyte lysate of a 54 kDa translation product, which in the presence of dog pancreas microsomal membranes was co-translationally processed with cleavage, insertion into membranes and glycosylation. Three processed forms were generated, the largest (56 kDa) and smallest (52 kDa) being equally glycosylated. The membrane association of the processed translation products and of native brain membrane CPE, detected immunologically, was resistant to moderate alkali but not pH 11.5 extraction. These results are consistent with secondary-structure predictions that CPE is a peripheral membrane protein. The dissimilar regions of human carboxypeptidases may provide information on sequences responsible for their different cellular disposition.

Amino Acid Sequence

The human heat-shock protein family. Expression of a novel heat-inducible HSP70 (HSP70B') and isolation of its cDNA and genomic DNA.

The human heat-shock protein multigene family comprises several highly conserved proteins with structural and functional properties in common, but which vary in the extent of their inducibility in response to metabolic stress. We have isolated and characterized a novel human HSP70 cDNA, HSP70B' cDNA, and its corresponding gene sequence. HSP70B' cDNA hybrid-selected an mRNA encoding a more basic 70 kDa heat-shock protein that both the major stress-inducible HSP70 and constitutively expressed HSC70 heat-shock proteins, which in common with other heat-shock 70 kDa proteins bound ATP. The complete HSP70B' gene was sequenced and, like the major inducible HSP70 gene, is devoid of introns. The HSP70B' gene has 77% sequence similarity to the HSP70 gene and 70% similarity to HSC70 cDNA, with greatest sequence divergence towards the 3'-terminus. The HSP70B' gene represents a functional gene, as indicated by Northern-blot analysis with specific oligonucleotides, hybrid-selected translation with a specific 3' cDNA sequence and S1 nuclease protection experiments. In contrast with HSP70 mRNA, which is present at low concentrations in HeLa cells and readily induced by heat or CdCl2 treatment in both fibroblasts and HeLa cells, HSP70B' mRNA was induced only at higher temperature and showed no basal expression. The differences in patterns of induction may be due to the special features of the promoter region of the HSP70B' gene.

Adenosine Triphosphate

Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene.

A novel human brain complementary DNA sequence encodes n-chimaerin, a 34,000 Mr protein. A single cysteine-rich sequence CX2CX13CX2CX7CX7C in the N-terminal half of n-chimaerin shares almost 50% identity with corresponding sequences in the C1 regulatory domain of protein kinase C. The C-terminal half of n-chimaerin has 42% identity with the C-terminal region (amino acid residues 1050 to 1225) of BCR, the product of the breakpoint cluster region gene involved in Philadelphia (Ph') chromosome translocation. n-Chimaerin mRNA (2.2 x 10(3) base-pairs) is specifically expressed in the brain, with the highest amounts being in the hippocampus and cerebral cortex. The mRNA has a neuronal distribution and is expressed in neuroblastoma cells, but not in C6 glioma or primary astrocyte cultures. The similarity of two separate regions of n-chimaerin to domains of protein kinase C and BCR has intriguing implications with respect to its evolutionary origins, its function in the brain and potential phorbol-ester-binding properties.

Amino Acid Sequence

Methyl-tert-butyl-ether for treating bile duct stones: the British experience.

Methyl-tert-butyl-ether (MTBE), infused via a nasobiliary catheter, was used to treat 33 patients with bile duct stones in nine units around Britain. MTBE contributed to success in 12 (36 per cent) cases: seven passed stones spontaneously during MTBE infusion and five had partial stone dissolution allowing subsequent endoscopic extraction. MTBE was non-contributory in 21 (64 per cent) cases: four passed stones after MTBE was stopped, six were treated by subsequent endoscopic techniques without evidence of dissolution, seven underwent surgery, and four were treated conservatively (with one death). In at least ten of the 21 cases in which MTBE was non-contributory, pigment stones were present. Forty-two complications occurred in 26 (79 per cent) patients. The efficacy of MTBE for treating bile duct stones might be improved by better methods of instillation and, since success may be related to technique, the use of MTBE should be restricted to units familiar with this chemical.

Cholelithiasis