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Biomedical subjects

G G Lavery

Publications and source records attributed to G G Lavery.

At least 19 recordsLinked to original sources

Thrombotic thrombocytopenic purpura secondary to Streptococcus.

We describe a 16 year old female who developed thrombotic thrombocytopenic purpura (TTP) following infection due to Streptococcus. Initially presenting a fever and systemic upset she progressed to develop dialysis dependent acute renal failure, seizures, thrombocytopenia and a haemolytic anaemia--the pentad of features seen in TTP. Prior to the diagnosis she was found to have unexplained and previously undescribed MRI findings of diffuse increased signal intensity in the white matter of the left cerebellar hemisphere posteriorly and also increased signal intensity in the overlying cortex. She was commenced on plasmapheresis, and her anaemia, thrombocytopenia, creatinine and LDH all fully responded. In addition, she had no further seizures following plasmapheresis and has not relapsed to date. We review both the rare association of TTP and streptococcal infection, and the neuroradiological findings described in the literature. This is only the third case report describing TTP following streptococcal infection, and only the second in the era of plasmapheresis.

Adolescent↗

An evaluation of protocolised weaning on the duration of mechanical ventilation.

Using a before and after study design, we compared protocolised weaning from mechanical ventilation with usual non-protocolised practice in intensive care. Outcomes (duration of mechanical ventilation, duration of intubation, intensive care stay) and complications (re-intubations, tracheostomy, mortality) were compared between baseline (Phase I) and following implementation of protocolised weaning (Phase II). Over the same period, we collected data in a second (reference) unit to monitor practice changes over time. In the intervention unit, outcomes were longer in Phase II compared with Phase I (all p < 0.005). When adjusted for admission APACHE II score and diagnostic category, only intensive care stay remained significantly longer (p = 0.002). There were significantly more tracheostomies in Phase II (p = 0.004). The reference unit demonstrated no statistically significant differences in study outcomes or complications between Phases. Protocolised weaning did not reduce the duration of mechanical ventilation and was not associated with an increased rate of re-intubation or intensive care unit mortality.

Aged↗

Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population.

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity upon the mineralocorticoid receptor (MR). Mutations in the gene encoding 11beta-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of "Apparent Mineralocorticoid Excess" (AME) where cortisol induces hypertension and hypokalaemia. We report five different mutations in the HSD11B2 gene in four families from Oman with a total of 9 affected children suffering from AME. Sequence data demonstrate the previously described L114Delta6nt mutation in exon 2 and new mutations in exon 3 (A221V), exon 5 (V322ins9nt) and for the first time in exon 1 (R74G and P75Delta1nt) of the HSD11B2 gene. These additional mutations provide further insight into AME and the function of the 11beta-HSD2 enzyme. The prevalence of monogenic forms of hypertension such as AME remains uncertain. However, our data suggests AME may be a relevant cause of hypertension in certain ethnic groups, such as the Oman population.

11-beta-Hydroxysteroid Dehydrogenases↗

Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

The effect of air fluidised bed therapy on hypermetabolism in intensive care unit patients.

Major trauma is associated with a hypermetabolic (increased resting energy expenditure) and hypercatabolic (negative nitrogen balance) response. Studies have suggested that nursing injured patients at higher temperatures reduces the metabolic response (Ryan & Clague 1990). In this study the energy expenditure and urinary nitrogen excretion of major trauma patients was examined when nursing them on an air-fluidised bed at 32 degrees C using a crossover study design. Patients were randomised into two groups. Group A patients (n = 8) remained on a standard intensive care unit bed at an environmental temperature of 22 degrees C while Group B patients (n = 6) were placed on an air-fluidised bed operating at 32 degrees C. On days 4 and 5 after injury, energy expenditure and urinary nitrogen excretion were measured. On day 6, Group A patients transferred to an air-fluidised bed and Group B patients to a standard bed. On days 7 and 8, energy expenditure and urinary nitrogen excretion were again measured. Within group comparisons of energy expenditure and urinary nitrogen excretion were made for days 3 and 4 (period 1) and days 7 and 8 (period 2). In both groups, mean energy expenditure was significantly increased in the second period irrespective of whether air-fluidised bed therapy preceded or followed a period on a standard bed. We concluded that nursing intensive care patients on an air-fluidised bed at 32 degrees C did not influence energy expenditure or urinary nitrogen.

Adult↗

The gastric tonometer. A valuable monitor of splanchnic perfusion?

Minimally invasive assessment of the adequacy of perfusion of the gastrointestinal tract has become clinically feasible with the availability of the gastric tonometer. This modified nasogastric tube permits calculation of the pH of the gut mucosal cells; a low tissue pH may indicate tissue hypoxia due to regional hypoperfusion. Such regional hypoperfusion is often undetected by other monitors and, if it occurs intra-operatively, may result in a poor outcome following major surgery. In critical illness, the splanchnic area seems to be particularly vulnerable to hypoperfusion and such a regional oxygen deficit is implicated in the causation of organ dysfunction/failure. Recent studies have begun to define the circumstances in which splanchnic tissue acidosis develops and several therapies have been proposed to reverse the regional oxygen deficit. This review seeks to clarify whether or not the tonometer is a valuable addition to our current monitoring aids.

Gastric Mucosa↗

The provision of adult intensive care in Northern Ireland with reference to the role of high dependency care.

In 1991 an audit of Intensive Care Services was carried out by the Northern Ireland Intensive Care Group. In conjunction with this regional overview, all patients in the Regional Intensive Care Unit, (RICU) in the Royal Victoria Hospital were assessed daily, over a 10 month period in 1990-91 and classified as conforming to either intensive care or high dependency status. These data were then used to compare adult intensive care service in Northern Ireland with recent national and international recommendations on intensive care. Ten units in Northern Ireland were surveyed. In regard to national or international guidelines, all ten were deficient to some degree. Four units had significant deficiencies; small patient numbers, lack of 'dedicated' 24 hr medical cover and or deficiencies in the provision of appropriate monitoring and or equipment. There was a large diversity in casemix among the ten units surveyed which suggested differing admission criteria. The bed occupancy of RICU was 100%. Refused admissions constituted a further 13% of unresourced workload. The lack of physically separate, dedicated high dependency unit facilities meant that 26% of bed days were devoted to HDU care (usually for "improved" intensive care unit patients not yet ready for discharge to a general ward. Achieving nationally recommended intensive care standards (on a regional basis) is probably only possible if a number of the smaller intensive care units are redesignated as high dependency units, and patients requiring intensive care are concentrated in a smaller number of larger ICUs. This will increase the frequency of interhospital transfer of critically ill patients.

APACHE↗

Correction of splanchnic oxygen deficit in the intensive care unit: dopexamine and colloid versus placebo.

Correction of the splanchnic oxygen deficit indicated by low gastric intramucosal pH (pHi < 7.35) appears to reduce ICU mortality. Dopexamine hydrochloride is in clinical use for this purpose but its efficacy has not been fully investigated. We report the results of a prospective, randomized, placebo-controlled study with a crossover design to assess the efficacy of dopexamine in correcting low pHi. Twelve patients in whom pHi < 7.32 was detected during eight-hourly monitoring were randomized to receive either incremental dopexamine (4-6 micrograms/kg/min) with colloid or 5% dextrose for three hours prior to crossover. There was no difference in pHi between treatments despite cardiovascular effects during dopexamine infusion. There was, however, a time-related increase in pHi suggesting a beneficial effect of conventional therapy. Dopexamine hydrochloride at 4-6 micrograms/kg/min in conjunction with colloid is not a clinically useful therapy to correct the splanchnic oxygen deficit indicated by low pHi.

Adolescent↗

Low gastric intramucosal pH: incidence and significance in intensive care patients.

Monitoring of gastric intramucosal pH (pHi) is advocated in critical illness to detect tissue acidosis due to regional hypoperfusion. However, the number of patients who may benefit from such monitoring remains unclear and the relationship between low pHi and outcome requires further definition. Sixty consecutive patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores < 30 were studied throughout ICU stay to investigate the incidence of low pHi (< 7.32 for > or = 1 hour), its relationship to outcome, and temporally associated clinical events. pHi was measured 2 to 6 hours post-ICU admission and 8-hourly thereafter. Forty-four patients (73%) exhibited low pHi. Fourteen patients died in ICU with 13 deaths occurring in the low pHi group (P = 0.05). Length of ICU stay was greater in the low pHi group (P = 0.02). The development of low pHi was temporally associated with maximal sepsis score, weaning from assisted ventilation and commencement of enteral feeding.

APACHE↗

Intensive care management of multiple-organ dysfunction due to falciparum malaria in a married couple.

A married couple presented simultaneously with malignant tertian malaria and rapidly developed septicaemia and severe multiple-system organ failure. Despite schizonticidal treatment and multisystem support in intensive care the husband died. The selection of chemoprophylactic agents for this couple was not ideal and the duration of therapy before exposure to risk was inadequate. Severe infection with plasmodium falciparum is life-threatening and requires early diagnosis. It is best managed in an intensive care unit where continuous assessment may enable rapid detection of clinical deterioration and allow appropriate treatment to be instituted. The diagnosis should be considered in symptomatic patients who have travelled through areas where malaria is endemic. Recognised guidelines for the prescription of malarial chemoprophylaxis should be followed to ensure adequate protection.

Critical Care↗

Organ donation.

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Attitude to Health↗