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Biomedical subjects

S K Hall

Publications and source records attributed to S K Hall.

At least 37 records · Page 2Linked to original sources
PubMed1997

An early transient current is associated with hyposmotic swelling and volume regulation in embryonic chick cardiac myocytes.

Hyposmotically induced changes in membrane conductance were measured in embryonic chick cardiac myocytes using conventional and perforated patch-clamp recording techniques; simultaneous measurements of cell volume were made from the video image of the voltage-clamped cell. Hyposmotic challenge was associated with a rapid, transient current coincident with the onset of cell swelling; cell volume subsequently recovered towards control values (regulatory volume decrease; RVD). The transient swelling-induced current (I(swell)) reversed at +15 mV, and was not found to be carried exclusively by any single ion in the physiological solutions. I(swell) was abolished by gadolinium (Gd3+), a blocker of stretch-activated ion channels, and was absent when the cytoskeleton was disrupted by treatment with cytochalasin B. I(swell) was also prevented when intracellular [Ca2+] was buffered with BAPTA AM. Under those experimental conditions which prevented the generation of I(swell), cell volume regulation failed so that the cells remained swollen in hyposmotic solution. Our data reveal a functional relationship between I(swell) and RVD, whereby I(swell) is a necessary prerequisite, although not exclusively sufficient, for volume recovery following cell swelling. We propose that I(swell) is an important early signalling event which activates subsequent mechanisms to regulate cell volume.

Animals↗
PubMed1996

Factors affecting the variation in plasma phenylalanine in patients with phenylketonuria on diet.

The optimal dietary management of children with phenylketonuria (PKU) has rarely been rigorously explored. The aim of this study was to assess longitudinally the effects of three factors thought to influence plasma phenylalanine concentrations in PKU: total energy intake; protein intake from natural foods allowed freely in addition to allocated phenylalanine exchanges; and the distribution of protein substitute throughout the day. Nineteen subjects, 15 girls and four boys aged 1-16 years, were enrolled. Food intake was weighed, and twice daily plasma phenylalanine concentrations measured during either 3-day or 4-day periods, for a total of 21 days throughout six months. There was a negative correlation between the percentage of protein substitute eaten by the time of the evening meal and the fall in plasma phenylalanine concentration during the day (r = -0.941; p < 0.0001). On average, 49% of pre-evening meal plasma phenylalanine concentrations were less than 100 mumol/l in children who had taken at least 65% of their protein substitute by the time of their evening meal. There was no correlation between excess natural protein intake from freely allowed foods and (a) pre-breakfast or pre-evening meal plasma phenylalanine concentrations or (b) the daily change between pre-breakfast and pre-evening meal concentrations. Nor was there any correlation between excess natural protein intake on the previous day and plasma phenylalanine concentration on the following morning. Energy intake was not correlated with plasma phenylalanine concentrations. It is therefore preferable to distribute the protein substitute evenly through the day in order to achieve stable phenylalanine concentrations, rather than to carry out further fine manipulation of the phenylalanine intake, which would make management of the diet even more difficult.

Adolescent↗
PubMed1996

Screening for tyrosinaemia type I.

AIMS: To assess the incidence of tyrosinaemia type I in the West Midlands Region, and the value of current neonatal screening programmes for phenylketonuria (PKU) for its detection. METHODS: Retrospective study of results from the PKU neonatal screening programmes in Birmingham (using plasma amino acid chromatography) and in the rest of the West Midlands (using the Guthrie microbiological assay for blood spot phenylalanine) was carried out between January 1985 and March 1994. Patients with tyrosinaemia I born in the region during the same period were identified from a regional database of patients with confirmed inherited metabolic disease. The study was carried out in a specialist children's hospital; the regional centre in the West Midlands for neonatal screening and investigation of inborn errors, and a supraregional centre for liver transplantation and management of paediatric liver disease. RESULTS: Amino acid chromatography showed increased tyrosine in 447 of 145,444 neonates born in Birmingham; this was still increased at 6 weeks of age in six cases. Five had tyrosinaemia I; the sixth had tyrosinaemia type III. Two others in whom amino acid chromatography was considered normal have since presented with tyrosinaemia I. Outside Birmingham, 525,151 children were screened using the Guthrie test. Five have presented clinically with tyrosinaemia I; screening did not contribute to diagnosis in any case. The incidence of tyrosinaemia I was 1 in 20,791 live births within Birmingham and 1 in 105,037 outside. Of the total 12 patients in the West Midlands with tyrosinaemia I, 10 (83%) were of non-oriental Asian ethnicity; the incidence of tyrosinaemia I was 3.7/10(6) head of population in this group and 0.04/10(6) in the rest of the population. CONCLUSIONS: Asians in the West Midlands have a high incidence of tyrosinaemia I. Neonatal PKU screening using amino acid chromatography may contribute to diagnosis and early treatment.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Cyclic AMP prevents activation of a swelling-induced chloride-sensitive conductance in chick heart cells.

1. Changes in myocardial cell volume and whole-cell currents were measured simultaneously during hyposmotically induced cell swelling. In the conventional patch clamp configuration, hyposmotic challenge caused myocytes to swell continuously and was associated with the development of a sustained, swelling-induced chloride conductance (ICl). In contrast, perforated patch-clamped myocytes demonstrated regulatory volume decreases (RVD) during hyposmotic challenge, and ICl was not generated. 2. The swelling-induced ICl in conventionally patch-clamped myocytes was inhibited by application of forskolin (15 microM) and was prevented when the pipette filling solution contained cAMP (10 microM) and isobutylmethylxanthine (IBMX, 1 mM). ICl could also be prevented by inhibition of protein phosphatase activity, using okadaic acid (100 nM). Conversely, a swelling-induced current could be generated in myocytes under perforated patch clamp by inhibition of protein kinase A, using the antagonist Rp-cAMPS (10 microM). These data demonstrate that cAMP-dependent protein phosphorylation is both necessary and sufficient to prevent development of ICl during cell swelling. 3. Unlike other chloride currents described previously in heart muscle, generation of the novel swelling-induced ICl requires dephosphorylation of a cAMP-dependent protein phosphorylation site; hence it can be prevented by stimulation of cAMP-dependent protein phosphorylation or by inhibition of protein phosphatase activity.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Management of chemical disaster victims.

Following a hazardous chemical accident, early critical care life support is crucial to minimizing potential morbidity and mortality (1). Providing effective care to victims, however, depends on the nature of the incident, the number of victims affected, the availability of medical care, the coordination of rescue efforts, the available modes of evacuation, and the availability of post-evacuation tertiary care. The goal in mass casualty scenarios is to minimize mortality and morbidity. Consequently, the most basic emergency response must include a method for assessing the incident, the extent of injury to victims, methods for determining which victims will receive treatment first, and what types of treatment will be given during the various stages of the incident. The basic need to handle hazardous chemical incident victims exists regardless of the environment in which the incident occurs, or whether small or large numbers of victims are involved.

Critical Care↗
PubMed1994

Acute angle-closure glaucoma as a complication of combined beta-agonist and ipratropium bromide therapy in the emergency department.

Acute angle-closure glaucoma is an uncommon complication of inhaled ipratropium bromide therapy for asthma. All previously reported cases have occurred in hospitalized patients receiving continuing nebulized therapy. A 66-year-old woman with asthma returned to the emergency department with bilateral acute angle-closure glaucoma less than 48 hours after successful treatment with nebulized albuterol sulfate and ipratropium bromide given by metered-dose inhaler. Acute angle-closure glaucoma occurring after ipratropium bromide use is believed to result from local ophthalmic effects attributable to topical absorption instead of systemic action. Greater awareness of this complication and suggested preventive measures may lessen morbidity.

Acute Disease↗
PubMed1993

A microtitre plate method for measuring biopterin with cryopreserved Crithidia fasciculata.

The assay of biopterin derivatives in dried blood spots is used by us in initial screening for inherited defects in tetrahydrobiopterin synthesis. The previously described method (1) required aseptic technique and microbiological facilities. The modification detailed here has the advantages of antibiotic cover, which overcomes these needs and microtitre plate technology allowing the incubation time to be halved with precision and accuracy retained. Data reduction facilities may be applied.

Adult↗
PubMed1993

Biochemical stability during parenteral nutrition in children.

The aim of this study was to assess the frequency and importance of biochemical abnormality related to parenteral nutrition (PN) in a group of infants, and to devise an appropriate policy for routine biochemical surveillance. A standard monitoring protocol based on widely published guidelines was applied to 30 consecutive patients (age 3 days-3 years) referred to a children's hospital nutritional care team for PN. No serious biochemical abnormalities were observed to arise simply as a consequence of PN. Electrolyte disturbance most commonly occurred before starting PN. Biochemical abnormality was most likely to be found in patients with abnormal fluid and electrolyte losses. Protocols for biochemical surveillance during PN err on the side of caution and often suggest frequent and comprehensive testing. In stable patients such as the surgical newborn, this is both expensive and unnecessary, and simpler monitoring regimes may be used with safety.

Journal Article↗
PubMed1993

Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium.

OBJECTIVE: Replacement of extracellular chloride ions by some other anions exerts a positive inotropic effect on isolated cardiac muscle preparations. The aim of this study was to determine whether the increase of force was mediated by an intracellular alkalosis. METHODS: Isometric tension development was measured using guinea pig papillary muscles during replacement of superfusate Cl- with isethionate ions. Intracellular pH and L-type Ca2+ currents were measured in isolated myocytes using epifluorescence microscopy and a switch-clamp technique respectively. RESULTS: Reduction of extracellular Cl- increased tension, a phenomenon which was partially inhibited with the anion exchange blocker SITS. Force was also increased by reducing superfusate PCO2. Reduction of superfusate [Cl-] and PCO2 both produced concentration dependent intracellular alkalosis. The relationship between the changes to tension and intracellular pH was different when either the superfusate [Cl-] or PCO2 was reduced, less pronounced when the [Cl-] was reduced. An increase of the L-type Ca2+ current was produced in low [Cl-] solutions which could be attributed to the accompanying intracellular alkalosis. CONCLUSIONS: The positive inotropic effect of superfusate Cl- removal can only partially be explained by intracellular alkalosis. Other, as yet unknown, changes must determine the remainder of the inotropic response.

Animals↗
PubMed1993

A chloride current associated with swelling of cultured chick heart cells.

1. Cultured chick heart cells challenged by hyposmotic stress underwent regulatory volume decrease (RVD) that was attenuated by prior depletion of intracellular chloride. 2. During hyposmotic swelling, cell aggregates experienced an initial increase in spontaneous contractile activity followed by eventual quiescence. Conventional microelectrode studies revealed an underlying increase in spontaneous electrical activity, followed by a sustained depolarization beyond threshold. 3. Whole-cell patch clamp studies, with K+ currents blocked, indicated that exposure of cells to hyposmotic solution (NaCl reduction) resulted in a rapid osmotic swelling followed by a substantial increase in whole-cell conductance which persisted for the duration of hyposmotic exposure and was almost completely reversed on return to isosmotic bath solution. 4. For a variety of Cl- concentrations, the reversal potentials (Erev) of the measured swelling-activated current closely followed the calculated Cl- equilibrium potential (ECl) with a linear regression slope of 0.82. When estimated by the Nernst equation, the relationship between Erev and the [Cl-]i/[Cl-]o ratio fitted well with a slope of 51 mV per decade change in the concentration ratio, consistent with a Cl(-)-selective conductance. 5. The permeability ratios of this swelling-activated conductance to chloride, methanesulphonate (MSA) and aspartate (Asp) were calculated as PCl:PMSA:PASP = 1:0.36:0.02, with the ion selectivity sequence of Cl- > MSA- >> Asp-, which suggests the swelling-activated conductance is slightly permeable to other anions. 6. Application of a Cl- channel blocker, diphenylamine-2-carboxylate (DPC, 200 microM), substantially suppressed the swelling-activated current without shifting the Erev of this current. The effect of DPC was independent of membrane potential. 7. This evidence demonstrates that hyposmotic swelling of cultured chick heart cells activates a channel-mediated Cl- conductance which may be associated with the integrated response of volume-regulatory mechanisms.

Animals↗
PubMed1992

Development and validation of a robust specific enzyme mediated assay for phenylalanine in serum.

The specificity of a phenylalanine dehydrogenase, particularly with respect to cross reactivity toward tyrosine, has been shown to be pH dependent, being minimal at high pH. The dehydrogenase step has been coupled to colorimetric detection of NADH using a tetrazolium salt. The assay shows no significant cross reactivity towards a range of amino acids or drugs and correlates well with an established HPLC technique.

Amino Acid Oxidoreductases↗
PubMed1992

Magnesium affects excitation, conduction, and contraction of isolated mammalian cardiac muscle.

An increase of extracellular Mg concentration, [Mg]o, reduced myocardial excitability and conduction without affecting the resting membrane potential or action potential configuration in ventricular myocytes and papillary muscles from a number of mammalian species. Although there was a small increase of specific membrane resistance and no change to intracellular resistivity, the threshold voltage was shifted to depolarized potentials. Thus loss of excitability can be explained by a shift of the activation of inward currents to depolarized potentials, and reduced conduction velocity is due solely to a diminution of local circuit currents. Mgo also was negatively inotropic, the magnitude of this effect being species dependent. Raised [Mg]o caused a small increase of intracellular [Mg] with a small decrease of intracellular [Na+], did not affect intracellular pH, and attenuated the intracellular Ca2+ transient associated with cell shortening in rat (but not rabbit) myocytes. An increase of [Mg]o reduced the magnitude of the voltage-dependent inward Ca2+ current, ICa, in rat and rabbit myocytes, and the activation curve of ICa was shifted to more depolarized potentials. A scheme to account for the negative inotropic effect of Mg is presented.

Animals↗
PubMed1991

Self-concept and perceptions of attractiveness and body size among Mexican-American mothers and daughters.

The socialization of physical attractiveness stereotypes and its relationship to self-concept among parent/child dyads has not been previously examined. This study examined the relationship between mothers' and daughters' judgements of body size and the impact of size on subjects' judgements of attractiveness. Mexican-American mothers and their 7-12-year-old daughters completed attractiveness ratings of five figures of girls varying in body size and indicated which of these figures were closest to the perceived and ideal sizes of the daughter. One-half of the mothers were obese and had participated in a behavioral weight loss program, while the other half served as normal weight controls. Self-concept measures were also completed by all subjects. Daughters tended to prefer a thinner figure than did mothers. The control mothers indicated almost no preference for body size, with nearly uniform rankings for obese, normal and thin figures. The daughters ranked their own ideal figures as thinner than their perceived figures, but mothers' rankings of their daughters' ideal and actual sizes were congruent. Daughter's overall self-concept was predicted by age, their own size and their mother's size. Control but not intervention mothers' self-concept was negatively correlated with their size.

Adult↗
PubMed1990

Plasma chloride and alkalaemia in pyloric stenosis.

Fifty infants with infantile hypertrophic pyloric stenosis were studied prospectively to evaluate the reliability of plasma chloride estimation in the assessment of the acid-base status on admission and during correction of alkalaemia. Four cases were subsequently excluded because of a breach of the study protocol, leaving 46 cases in the study. Seventeen (37 per cent) were normoacidaemic on admission; 13 had plasma chloride concentrations of greater than or equal to 106 mmol/l and four had chloride concentrations of 100-105 mmol/l on admission. Twenty-nine (63 per cent) were alkalaemic on admission; six cases had chloride concentrations of 100-105 mmol/l and 23 cases had concentrations of less than 100 mmol/l. Of those 29 cases requiring correction of alkalaemia, normoacidaemia was achieved at a plasma chloride concentration of greater than or equal to 106 mmol/l in 21 cases (72 per cent) and at a concentration of 100-105 mmol/l in eight cases (28 per cent). Plasma chloride is a reliable parameter in the assessment and correction of alkalaemia in infantile hypertrophic pyloric stenosis provided that a concentration of at least 106 mmol/l is the goal.

Acid-Base Equilibrium↗
PubMed1990

Relationship between plasma and red cell biopterins in acute and chronic hyperphenylalaninaemia.

Biopterin concentrations in red blood cells were higher in patients with chronic hyperphenylalaninaemia than following a single oral dose of phenylalanine, although the plasma concentrations were similar. These findings suggest that tetrahydrobiopterin is synthesized in immature red blood cells in response to hyperphenylalaninaemia. The less marked increase in plasma biopterin suggests slow release from a tissue reservoir. The maintenance of a differential between erythrocyte and plasma biopterin concentrations suggests that some mechanism retains biopterin intracellularly.

Acute Disease↗