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Biomedical subjects

C J Martin

Publications and source records attributed to C J Martin.

At least 19 recordsLinked to original sources

Autosomal dominant polycystic kidney disease: new information for genetic counselling.

We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which ADPKD is not co-inherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progression. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P less than 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late.

Adolescent

Environmental conditions for treatment of burned patients by the exposure method.

The influence of the thermal environment on evaporation and heat loss from patients with severe burns treated by exposure has been studied. Simple heat transfer equations can be used to predict changes resulting from alterations in environmental conditions and these have been tested using phantoms. The method relies upon the derivation of surface diffusion resistances to describe the moisture properties of burn wounds. Clinical measurements revealed wide variations in evaporation rates and diffusion resistances for different wounds. Evaporation rates changed by less than 30 per cent during the first 5-6 days following injury, after which evaporation from partial skin thickness wounds gradually fell whereas that from full skin thickness wounds tended to remain higher. Raising ambient temperature can compensate for increased evaporation heat losses. Patients can be treated at ambient temperatures of 32-35 degrees C in the intensive care room with a specially designed airflow system. However, raising the temperatures of standard wards with no special airflow or temperature control facilities often caused patients to sweat, further increasing heat loss.

Adolescent

Infrared emissivity of burn wounds.

Emissivities of burn wounds and tissue samples have been measured in the wavelength range 8-14 microns using a non-contact method. Emissivities of wound tissues studied were in the range 0.976-0.992, greater than those of intact skin by 0.01-0.03. This will result in underestimates of the difference in temperature between wounds and normal skin of 0.1-0.2 degrees C.

Burns

Collis-Nissen gastroplasty fundoplication for complicated gastro-oesophageal reflux disease.

Collis-Nissen gastroplasty fundoplication is a widely accepted operation for patients with gastro-oesophageal reflux disease complicated by oesophageal shortening. Assessment of this operation by 24 h oesophageal pH monitoring has not previously been reported. Our aim was to correlate clinical and endoscopic results with 24 h pH studies. Twenty-nine patients had a gastroplasty fundoplication, as a result of which twenty-five (86%) had an excellent clinical result, 2 (7%) had a good result and 2 (7%) had a poor result. The two poor results were in patients who had previously undergone anti-reflux surgery. All 29 patients had pre-operative pH monitoring. Twenty-three patients had postoperative pH studies. Oesophageal acidification times were normal postoperatively in 16 of 23 patients however, 7 still had an abnormal study. One of the two patients with a poor clinical result was studied and persistent severe oesophageal acidification was demonstrated. The remaining 6 patients with abnormal studies were asymptomatic. Five of the 6 asymptomatic patients also had a normal oesophagogastroscopy with no macroscopic oesophagitis. We conclude that 24 h pH monitoring after the Collis-Nissen operation should only be performed to assess clinically and endoscopically poor results.

Adult

Intra-operative enteroscopy in the management of bleeding small bowel lesions.

This paper reviews the use of intra-operative enteroscopy at St Vincent's Hospital, Melbourne between 1982 and 1990 in the management of presumed small bowel bleeding. Intra-operative enteroscopy was found to be a moderately technically demanding procedure. The diagnostic yield in this small series of nine patients was 100%. When solitary small bowel lesions are identified, resultant directed therapy should prevent further bleeding. When multiple widespread angiodysplastic lesions are identified as occurred in three cases, the bleeding is difficult to cure.

Adult

Diaphragmatic contribution to gastroesophageal competence and reflux in dogs.

Events associated with gastroesophageal reflux have been determined by concurrent diaphragmatic and esophageal body electromyography, video radiography, and manometry in four conscious dogs. Three characteristic phenomena occurred in parallel immediately before and during gastroesophageal reflux: 1) transient lower esophageal sphincter relaxation, 2) profound (99.5%) and selective inhibition of crural diaphragmatic activity, and 3) a previously unrecognized dorsal movement of the gastroesophageal junction (mean 1.3 cm) demonstrated by implanted radiological markers. The patterns associated with spontaneous acid and gas reflux were indistinguishable from those induced by gastric distension. Costolumbar diaphragmatic activity was stable up until the instant of sphincter opening, when there was a single costolumbar contraction of short duration and high amplitude. Esophageal shortening did not occur before reflux. Reflux that occurred after atropine-induced inhibition of lower esophageal sphincter tone to < 2 mmHg was intermittent and coincided with selective crural inhibition. These studies demonstrated that selective crural inhibition is a prerequisite for gastroesophageal reflux and suggest that the crural diaphragm is an important factor for the maintenance of gastroesophageal competence.

Animals

Inactivation of intestinal alkaline phosphatase by inositol hexaphosphate-Cu (II) coordinate complexes.

Alkaline phosphatase (APase) was greater than 99% inactivated upon incubation with myo-inositol hexakisphosphate (IHP) and Cu(II) ions. In the absence of Cu(II), IHP did not inactivate the enzyme. Likewise, cupric ions alone did not produce inactivation. Reactions of APase with IHP plus Cu(II) were competitively inhibited by zinc ions. In contrast to the marked effect of (IHP-Cu) chelate complexes on APase activity, the complexes of IHP with either Zn(II) or Mn(II) had no discernable effect. Both the extent and the rate of activity loss were dependent on the combined IHP and Cu(II) concentration. At an IHP to Cu(II) ratio of 11.6, the extent of inactivation was approximately proportional to the Cu(II) concentration with maximal inactivation attained above 10 microM. Under the same conditions, a nonlinear relation (saturation kinetics) was observed between the pseudo first-order rate constants for the reaction and the IHP and Cu(II) concentration. On the basis of adherence of the data to a mechanism involving an intermediate whose concentration was rate determining, it was suggested that a ternary complexes composed of the apoprotein, the catalytic site zinc ions, and one or more specific IHP-Cu(II) complex [( IHP-Cu]*) may be the first step along the reaction coordinate. Relevant to this possibility which assumes active site interaction is the fact that both IHP alone and (IHP-Cu) complexes are good competitive inhibitors of p-nitrophenyl phosphate hydrolysis under the same solution conditions wherein APase inactivation occurs in the absence of substrate. Rates of enzyme inactivation are decreased with an increase in pH from 6.5 to 8.0. They are also dependent upon buffer type and concentration, apparently related to their association constants for cupric ion binding. Over and above such specific effects, rates of inactivation are also reduced with an increase in ionic strength. Depending on the ratio and concentrations of IHP and Cu(II) used in the reaction with APase, subsequent exposure to EDTA followed by assay in the presence of Zn(II) gave recoveries of activity ranging from 60% to 100%. Both the prior inactivated enzyme (containing IHP and cupric ions) in the presence of EDTA and the native APase upon simultaneous exposure to IHP, Cu(II), and EDTA were slowly and irreversibly inactivated. Correction for this effect gave reconstitution of activity of the (IHP-Cu)-inactivated APase by Zn(II) addition equivalent to that which could be obtained by EDTA-treatment of the native enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaline Phosphatase

Reversible inhibition of intestinal alkaline phosphatase by inositol hexaphosphate and its Cu(II) coordinate complexes.

The influence of inositol hexakisphosphate (IHP) and its cupric ion chelate complexes on alkaline phosphatase (APase) catalysis of p-nitrophenyl phosphate hydrolysis at pH 7.2 has been determined. Both IHP and (IHP-Cu) complexes, but not Cu(II) alone, are effective inhibitors of the enzyme and are of the strictly competitive type with Ki values in the microM range. Without added inhibitors present, the kinetic parameters are kcat 5.7 x 10(3) min(-1); and KM, 18 microM. In the presence of 62 microM IHP, kcat was essentially unchanged with an apparent KM of 68 microM giving a Ki of 22 microM. In the presence of an (IHP-Cu) complex (62 microM IHP, 128 microM Cu(II], the apparent KM was 55 microM and Ki was 30 microM. At a ratio of Cu(II):IHP of 6.0 (372:62 microM) the apparent KM was 30 microM and Ki was 94 microM. The inhibitory effect of (IHP-Cu) complexes thus decreases as the IHP binding sites for cupric ions become saturated. A high ionic strength environment markedly reduces the inhibitory effect of IHP. Previous studies have also shown that rates of APase inactivation by (IHP-Cu) complexes are also ionic strength sensitive [1]. The inhibition of APase activity by either IHP or its coordinate complexes with cupric ions is evidence for their interaction at the enzyme's catalytic sites. Such results thus provide support for an essential element of the mechanism previously suggested for the reversible inactivation (as opposed to inhibition) of APase by (IHP-Cu) chelate complexes, viz., that it may be due to a metal ion exchange reaction leading to the formation of a Cu(II)-substituted enzyme.

Alkaline Phosphatase

Burn wound evaporation--measurement of body fluid loss by probe evaporimeter and weight change.

A knowledge of the rate of fluid loss from the body is a useful aid in planning treatment of patients with severe burns. Different methods for obtaining this data have been investigated. Evaporation rates recorded from a probe evaporimeter have been compared with gravimetric measurements. The evaporimeter underestimated evaporation, especially at high levels, but could be calibrated against known evaporation rates. Estimates of whole-body fluid loss have been made from calibrated evaporimeter data and results compared with measurements of fluid loss by weight change for three patients. Problems with assessing whole-body evaporation rates in the clinical environment are highlighted. Weight change gives a more accurate assessment of total body fluid loss, but considerable effort is necessary to record all relevant information. Probe evaporimeter measurements are simple to perform and allow local evaporation rates to be estimated, but results should be treated with caution. Evaporation rates from wounds of 17 patients with severe burns have been evaluated in terms of surface diffusion resistances. The diffusion resistances of some burn wounds increased with time, but many did not change significantly during the first ten days after injury, and there was considerable variation with burn type and severity.

Adolescent

A study of skin temperatures, sweat rate and heat loss for burned patients.

The influence of the thermal environment on heat losses from patients with severe burns has been studied. Burn wounds were several degrees cooler than intact skin when patients were admitted to hospital. Wound temperatures gradually increased, becoming similar to those of intact skin by three days after injury. Temperatures of intact skin in peripheral regions of burned patients were raised. Evaporation of fluid from wounds of patients with 15-36% burns increased heat loss by 50-120 W, but sweating could increase heat losses by several hundred watts. Patients with large percentage burns tended to sweat less than others with smaller burns, under the same conditions. Patients with over 30% burns could be treated at air temperatures up to 35 degrees C without inducing sweating in the Intensive Care Room, which had forced airflow and good temperature control. Patients treated in standard wards where it was difficult to maintain a constant air temperature were more likely to sweat.

Adolescent

Watermelon stomach: an unusual cause of chronic gastrointestinal blood loss.

Watermelon stomach, or gastric antral vascular ectasia, is an uncommon cause of gastrointestinal blood loss, which can easily be overlooked and which is eminently curable. A 76 year old woman who was repeatedly misdiagnosed as having incidental antral gastritis with occult iron deficiency is described.

Aged

Effect of increased intra-abdominal pressure on peristalsis in feline esophagus.

Our aim in this study was to determine the effect of variations in intrabolus pressure on esophageal peristalsis. In five cats, intrabolus pressure was altered by increasing intragastric pressure to 20-45 mmHg by use of a pressure cuff to compress the abdomen. In each cat, increases in intragastric pressure were associated with comparable increases in pressure of the esophageal bolus while the bolus was in the distal esophagus during esophageal peristalsis. Secondary peristalsis induced by a 5-ml injection of barium into the proximal esophagus was recorded by synchronized videofluoroscopy and esophageal manometry. Graded increases in intrabolus pressure caused an increased prevalence of ineffective, incomplete peristaltic sequences that did not completely clear barium from the esophagus. At intragastric pressures greater than 45 mmHg, 63% of the peristaltic sequences were incomplete. Increases in intrabolus pressure elicited by increased intragastric pressure also caused 1) slowing of the peristaltic wave in the distal esophagus, 2) increased pressure wave duration in the distal esophagus, 3) increased esophageal diameter, and 4) increased duration of lower esophageal sphincter opening. The incidence of retrograde bolus escape was inversely related to the difference between peristaltic wave amplitude and intrabolus pressure. A pressure difference of greater than 20 mmHg prevented retrograde barium escape at all esophageal levels, whereas a difference of less than 20 mmHg was generally associated with retrograde escape of barium in the distal esophagus. We conclude that an increase in intrabolus pressure causes an increase in esophageal distension that is transduced into alterations of esophageal peristalsis by either a myogenic or neural mechanism.

Abdomen

Design of a database with graphical analysis for X-ray quality assurance and dose information to assist in a programme for patient dose reduction.

A database system has been set up on an IBM PC to store X-ray quality assurance (QA) data and patient doses for all X-ray equipment operated by Grampian Health Board. Graphical analysis facilities have been developed to display data in a readily understandable form. Data on equipment specifications, QA test results, exposure factors for standard examinations, and thermoluminescent dosemeter (TLD) measurements of patient skin doses are stored in separate forms. X-ray machine outputs are fitted to a simple polynomial equation, and the data combined with information on exposure factors to calculate entrance doses for selected examinations. Data such as filtration and backscatter factors are derived from look-up tables for use in dose calculations. Histogram comparisons can be made between calculated doses, means of TLD measurements and National Radiological Protection Board reference levels to allow units giving high skin doses to be identified so that corrective actin can be taken.

Humans

Health-related behaviour in a small Scottish community.

A survey of health-related behaviours was carried out in a small Scottish town. A random sample stratified by age and sex was drawn from the records of the sole local health centre. A previously validated questionnaire was sent by post with a covering letter from the general practitioners and a reply paid envelope. An overall response rate of 71.3% was achieved. The results indicated very high rates of smoking for women with manual jobs, but differences between men in manual & non manual groups were not significant. Younger women reported higher alcohol consumption than older women, but there were no significant differences between occupational groups or employed and unemployed men. Only a minority of respondents reported regular consumption of high fibre products, low fat milk and polyunsaturated margarine and few claimed to undertake vigorous exercise. In general health-related behaviours showed little association with self-rated health. Whilst the data confirm the importance of socio-demographic factors in certain behaviours they also indicate that these are inadequate to predict the pattern of such behaviours within a community.

Adolescent

An evaluation of radiofrequency exposure from therapeutic diathermy equipment in the light of current recommendations.

Shortwave and microwave diathermy equipment use by physiotherapy departments in Grampian Region has been studied. Stray electric and magnetic fields close to equipment have been measured and compared with exposure levels recommended by the INIRC and the NRPB. Fields above the recommended whole body levels extend to 0.5-1.0 m from the electrodes and cables for continuous wave (cw) shortwave equipment, and up to 0.5 m for microwave units and pulsed shortwave models. Operators were exposed to local fields above these values for 2 - 3 min during cw shortwave treatments, but rarely exceeded the recommended exposure. However, short localised exposures to high fields, which can occur if the operator moves close to the electrodes or cables, could exceed these limits. Physiotherapists are advised to remain at a distance of at least 1 m during cw treatments, and not to approach within 0.5 m of the electrodes and cables even for a short period.

Diathermy

Reoperation for failed antireflux surgery.

The management of patients with an unsatisfactory result following antireflux surgery is often problematical. Ten such patients with failed antireflux surgery, for whom medical management had also subsequently failed, underwent reoperation via a thoraco-abdominal approach. The anatomical cause of the surgical failure was determined pre-operatively in most cases by endoscopy, radiology, manometry and 24-hour pH monitoring. The most common reason for failure was a slipped Nissen fundoplication. A tight wrap, a disrupted wrap and a fundoplication hernia were less common causes. At follow-up, only one patient had a poor result. Reoperation for failed antireflux surgery can yield good results and is facilitated by pre-operative definition of the cause of failure and wide operative exposure.

Adult

Oesophageal acidification does not increase lower oesophageal sphincter pressure.

We studied the effect of distal oesophageal acidification on lower oesophageal sphincter (LOS) pressure in normal human volunteers and in cats. The distal oesophagus was acidified by intraluminal injection of 0.1N HCl (pH 1.2). The LOS pressure was recorded by a sleeve device while pharyngeal and oesophageal pressures were monitored by nonperfused, water filled catheters. In normal human subjects, distal oesophageal acidification did not elicit a change in LOS pressure. In anaesthetised cats, injection of acid into the distal oesophagus elicited immediate LOS relaxation followed by a secondary peristaltic sequence. With propagation of the peristaltic sequence into the LOS, the LOS pressure abruptly increased 20-100 mmHg and gradually returned to the preinjection value over 15-180 s. In the one instance in which we were able to acidify the distal oesophagus without evoking secondary peristalsis, the LOS pressure did not change. Injection of saline into the distal oesophagus evoked a response in the LOS and oesophageal body that was indistinguishable from that seen with acid. We conclude that contrary to common belief, distal oesophageal acidification itself does not affect LOS pressure in man or the cat.

Adult

Response of canine lower esophageal sphincter to gastric distension.

The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum. After 1 mo each region was progressively distended while gastroesophageal pressures were monitored. At the time of the first TLESR, gastric wall tension was estimated from the bag pressure and volume. Distension of the intact stomach, lesser curve, or proximal stomach in 12 dogs produced a progressive increase in lower esophageal sphincter (LES) pressure, which was interrupted at low gastric wall tension (29, 35, and 40 mmHg.cm, respectively) by a superimposed TLESR. Background LES pressure fell progressively with distension of the antrum but was unchanged by distension of the fundus alone. Both the fundus and antrum had significantly higher thresholds for triggering TLESR (96 and 105 mmHg.cm). In another two dogs truncal vagotomy performed at the time of gastric partitioning prevented both the change in background LES pressure, and the triggering of TLESR, associated with proximal gastric and antral distension. We conclude that the subcardiac region of the stomach is primarily responsible for triggering TLESR induced by distension and that the effect on background LES pressure depends on the region distended.

Animals