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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 109 records · Page 6Linked to original sources

Improvement of asthma control with a breath-actuated pressurised metred dose inhaler (BAI): a prescribing claims study of 5556 patients using a traditional pressurised metred dose inhaler (MDI) or a breath-actuated device.

A relationship has been reported between sub-optimal inhaler technique and control of asthma symptoms. Randomised controlled trials and systematic reviews may fail to accurately represent this relationship, by excluding patients who are unable to correctly use the reviewed devices. Breath actuated inhalers (BAIs) are reported to be easier to use than metered dose inhalers (MDIs). This study uses a large primary care medical record database (DIN-LINK) to examine the 'real-life' clinical effectiveness of a BAI vs. traditional MDIs. A comparison is made between the quantity of asthma-related medication (beta2 agonist, oral steroids and antibiotics) and healthcare resource use required by children (0-12 years) and adults (13+ years) using either the BAI or an MDI over a 12-month period. Out of 5556 new asthma patients who met the inclusion criteria, 306 used a BAI and 5250 used a traditional MDI. Children and adults using the BAI received fewer prescriptions for all three medication types than those using a traditional MDI (children: beta2 agonists -18% P=0.036, oral steroids -88% P<0.05, antibiotics -68% P<0.05 and adults: beta2 agonists -10.9% P=0.179, oral steroids -51.2% P<0.05, antibiotics -19.5% P=0.276). All prescription results reached statistical significance, with the exception of beta2 agonist and antibiotic prescription numbers for adult patients. Children and adults using the BAI required less GP consultations for asthma (children -30.3%, P<0.05 and adults -22.9%, P<0.05) and less GP consultations for respiratory infections than those using a traditional MDI (children -35.2%, P=0.001 and adults -10.4%, P=0.236). Adults using the BAI required less outpatient appointments than adults using an MDI (-43.7%, P=0.166). All non-prescription resource results reached statistical significance with the exception of GP consultations for respiratory infections and outpatient visits in the adult group. In conclusion, children and adults using the BAI appear to have better asthma control than children and adults using an MDI as evidenced by fewer relief medication prescriptions and less healthcare resource use.

Administration, Inhalation↗

Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis.

Thyroid abnormalities and Takayasu arteritis (TA) have been reported separately in patients with Crohn disease (CD). We report two patients with hyperthyroidism, CD and Takayasu arteritis and discuss hypothetical mechanisms. Case 1. A thyrotoxic goiter was diagnosed in 1987 in a 34-year-old woman treated since 1969 for severe CD and TA. Iodine urinary excretion was 405 microg/mL (20-500). Anti-thyrotropin receptor (TRAK) and anti-thyroid antibodies were not detectable. The ultrasonography showed a nodule in the right lobe of the thyroid and two nodules in the left lobe. A 123I thyroid scan showed a multinodular goiter with no hot nodule. She was treated successfully with propylthiouracile until 1991, when a new episode of thyrotoxicosis led to a subtotal thyroidectomy. Case 2. Hyperthyroidism was diagnosed in February 2000 in a 49-year-old woman treated for CD and TA, both diagnosed in 1980. TRAK and anti-thyroid peroxydase antibodies were not detectable. The ultrasonography disclosed a normal thyroid volume with an inhomogeneous parenchymal structure and nodular images in both lobes. A 123I thyroid scan showed one hot nodule in the lower part of each lobe. A subtotal thyroidectomy was performed. The association of these three diseases may not be fortuitous, possibly explained by genetic predisposing factors and disease-related iodine deficiency both involving Nuclear Factor kappaB pathway.

Adult↗

Physiological validation of the concept of glycemic load in lean young adults.

Dietary glycemic load, the mathematical product of the glycemic index (GI) of a food and its carbohydrate content, has been proposed as an indicator of the glucose response and insulin demand induced by a serving of food. To validate this concept in vivo, we tested the hypotheses that 1). portions of different foods with the same glycemic load produce similar glycemic responses; and 2). stepwise increases in glycemic load for a range of foods produce proportional increases in glycemia and insulinemia. In the first study, 10 healthy subjects consumed 10 different foods in random order in amounts calculated to have the same glycemic load as one slice of white bread. Capillary blood samples were taken at regular intervals over the next 2 h. The glycemic response as determined by area under the curve was not different from that of white bread for nine foods. However, lentils produced lower than predicted responses (P < 0.05). In the second study, another group of subjects was tested to determine the effects of increasing glycemic load using a balanced 5 x 5 Greco-Latin square design balanced for four variables: subject, dose, food and order. Two sets of five foods were consumed at five different glycemic loads (doses) equivalent to one, two, three, four and six slices of bread. Stepwise increases in glycemic load produced significant and predictable increases in both glycemia (P < 0.001) and insulinemia (P < 0.001). These findings support the concept of dietary glycemic load as a measure of overall glycemic response and insulin demand.

Adult↗

Calculated glomerular filtration rate is a useful screening tool to identify scleroderma patients with renal impairment.

OBJECTIVES: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.

Adolescent↗

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

OBJECTIVE: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. DESIGN: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. PATIENTS: A total of 185 infants with a median gestational age of 26 (range 23-28) weeks. RESULTS: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. CONCLUSION: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Age Factors↗

Hb Q-India: an uncommon variant diagnosed in three Punjabi patients with diabetes is identified by a novel DNA analysis test.

AIMS: An abnormality in the glycated haemoglobin peak (Hb A1c) on Diastat (Bio-Rad) cation exchange low pressure liquid chromatography (LPLC) was found in three Punjabi patients with diabetes. The aims of this study were to identify the variant by chromatography and electrophoresis and to determine whether a DNA analysis test could be designed for confirmation that could be generally applied for the identification of any unusual abnormal haemoglobin. METHODS: The presence of an Hb variant was confirmed by cellulose acetate electrophoresis at pH 8.6. The variant was characterised further by high performance liquid chromatography (HPLC; Bio-Rad Variant) and isolelectric focusing (IEF) electrophoresis. A novel DNA analysis test based on the amplification refractory mutation system (ARMS) and the polymerase chain reaction (PCR) was developed to confirm the presence of the mutation for the uncommon variant. RESULTS: Comparison of the HPLC retention time and IEF band position determined the presence of the variant Hb Q-India in all three cases. Hb Q-India is caused by the mutation GAC --> CAC at codon 64 of the alpha-1 globin gene and is clinically silent. ARMS-PCR specific primers were designed and used successfully to confirm the presence of the mutation for Hb Q-India. CONCLUSIONS: The results show that the ARMS-PCR technique, developed previously for the diagnosis of beta thalassaemia mutations, can also be adapted to provide a simple, rapid, and inexpensive approach for the identification of abnormal haemoglobins.

Adult↗

Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial.

BACKGROUND: Functional breathing disorders may complicate asthma and impair quality of life. This study aimed to determine the effectiveness of physiotherapy based breathing retraining for patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing. METHODS: 33 adult patients aged 17-65 with diagnosed and currently treated asthma and Nijmegen questionnaire scores > or =23 were recruited to a randomised controlled trial comparing short physiotherapy breathing retraining and an asthma nurse education control. The main outcome measures were asthma specific health status (Asthma Quality of Life questionnaire) and Nijmegen questionnaire scores RESULTS: Of the 33 who entered the study, data were available on 31 after 1 month and 28 at 6 months. The median (interquartile range) changes in overall asthma quality of life score at 1 month were 0.6 (0.05-1.12) and 0.09 (-0.25-0.26) for the breathing retraining and education groups, respectively (p=0.018), 0.42 (0.11-1.17) and 0.09 (-0.58-0.5) for the symptoms domain (p=0.042), 0.52 (0.09-1.25) and 0 (-0.45-0.45) for the activities domain (p=0.007), and 0.50 (0-1.50) and -0.25 (-0.75-0.75) for the environment domain (p=0.018). Only the change in the activities domain remained significant at 6 months (0.83 (-0.10-1.71) and -0.05 (-0.74-0.34), p=0.018), although trends to improvement were seen in the overall score (p=0.065), the symptoms domain (p=0.059), and the environment domain (p=0.065). There was a correlation between changes in quality of life scores and Nijmegen questionnaire scores at 1 month and at 6 months. The number needed to treat to produce a clinically important improvement in health status was 1.96 and 3.57 at 1 and 6 months. CONCLUSION: Over half the patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing show a clinically relevant improvement in quality of life following a brief physiotherapy intervention. This improvement is maintained in over 25% 6 months after the intervention.

Administration, Inhalation↗

Growth hormone (GH) secretion in patients with childhood-onset GH deficiency: retesting after one year of therapy and at final height.

BACKGROUND: Recent studies have shown that many patients treated with growth hormone (GH) during childhood because of idiopathic GH deficiency (GHD) are no longer GH deficient when retested after cessation of GH therapy when final height is achieved. These patients are labelled as transient GHD. We hypothesized that normalization of GH secretion in transient GHD could occur earlier during the course of GH treatment, which could allow earlier cessation of GH treatment. METHODS: In a retrospective study, GH secretion was re-evaluated after cessation of GH treatment at final height in 43 patients diagnosed during childhood as idiopathic GHD (10 with multiple pituitary hormonal deficiencies (MPHD) and 33 with isolated GHD (IsGHD)). In a prospective study, GH secretion was re-assessed after interruption of GH treatment given for 1 year in 18 children with idiopathic GHD (2 MPHD, 16 IsGHD). GH secretion was evaluated by glucagon or insulin stimulation tests. RESULTS: In the retrospective study, all the 10 patients with MPHD and 64% of the 33 patients with IsGHD were still deficient at re-evaluation using the paediatric criteria to define GHD (GH peak <10 ng/ml at provocative test). The proportion of persisting deficiency was greater in patients with complete IsGHD (86%, 12/14 patients) than in patients with partial IsGHD (47%, 9/19 patients). With the criteria proposed in adulthood (GH peak <3 ng/ml), all the 10 patients with MPHD were still considered to be deficient. In contrast, only 15% (5/33 patients) with IsGHD had a maximal GH value <3 ng/ml (36% of the 14 patients with complete IsGHD and none of the 19 patients with partial IsGHD). In the prospective study, after interruption of GH therapy given for 1 year, the 2 patients with MPHD were still GHD at re-evaluation and they resumed GH treatment. Among the 16 patients with IsGHD, 13 (81%) were still deficient (peak response <10 ng/ml) after 1 year. Two of the 3 patients in whom GHD was not confirmed at retesting after 1 year GH showed again a deficient response at second retesting. CONCLUSIONS: Although many patients diagnosed with IsGHD during childhood have a normalized GH secretory capacity when retested during adulthood, early retesting after interruption of GH treatment given for 1 year during childhood does not enable to determine if GH therapy has to be discontinued before cessation of growth.

Adolescent↗

Late or delayed induced or spontaneous puberty in girls with Turner syndrome treated with growth hormone does not affect final height.

Although it has been well established that GH treatment increases final height (FH) in girls with Turner syndrome (TS), the optimal ages to start GH therapy and introduce estrogens for pubertal induction have not been defined. We evaluated retrospectively the influence of the age at onset of GH treatment and age at onset of puberty on FH of 186 adult TS women treated during childhood with GH. Puberty started spontaneously in 38 patients, and it was induced in 148 girls with ethinyl estradiol (mean +/- SD starting dose, 66 +/- 32 ng/kg.d). Patients with spontaneous or induced puberty were divided into quartiles on the basis of age at initiation of GH treatment (3-10, 10-12, 12-14, and 14-19 yr). FH was 151.7 +/- 6.0 cm; there were no FH differences between patients with induced or spontaneous puberty, nor were there differences between the age quartiles. Puberty started earlier in the girls with spontaneous puberty than in those with induced puberty (12.4 +/- 1.3 yr vs. 14.5 +/- 1.9 yr; P < 0.0001). The age at onset of puberty was not related to FH. Pubertal growth was 15.4 +/- 4.6 cm in the girls with spontaneous puberty and 8.6 +/- 4.3 cm in the girls with induced puberty (P < 0.0001). We conclude that GH treatment results in a significant increase in FH in most TS girls. Under the conditions of GH treatment and induction of puberty that we have used, the age at start of GH treatment was not related to FH; in addition, late or delayed induced or spontaneous puberty did not affect FH.

Adolescent↗

Reye's syndrome.

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Adolescent↗

Morbidity predictors in ischemic stroke.

BACKGROUND: Although ischemic CVA is one of the leading causes for death and disability, parameters for predicting long-term outcome in such patients have not been clearly delineated, especially in the Indian context. METHODS: A prospective hospital-based study of 105 patients of ischemic stroke, focal neurological deficits and functional score was assessed and the C-reactive protein level (CRP) was measured. A follow-up was done at 5 days and at 6 months and outcome variable was the functional status at 6 months using Barthel Index of Activities of Daily Living. Accordingly, patients were grouped into 3 - Barthel Index < 41: Severely disabled, Barthel Index 41-60: Moderately disabled and Barthel Index > 60: Mildly disabled. RESULTS: At admission, if upper limb power was less than Medical Research Council (MRC) grade 4, or aphasia was present or CRP assay was positive, then at 6 months, these patients most likely belonged to the severely disabled group. If upper limb or lower limb power was greater than MRC grade 3 or there was no aphasia or conjugate gaze deviation or CRP assay was negative, these patients most likely belonged to the mildly disabled group at 6 months. Follow-up rate was 86%. CONCLUSION: Patients can be stratified according to the predicted prognosis. The treatment and rehabilitation can be properly planned and strictly adhered to in patients predicted to have worse prognosis.

Activities of Daily Living↗

Pentoxifylline induced signalling events during capacitation of hamster spermatozoa: significance of protein tyrosine phosphorylation.

To fertilize the oocyte, mammalian spermatozoa must undergo capacitation and acrosome reaction. These events are believed to be associated with various biochemical changes primarily mediated by cAMP, Ca2+ and protein kinases. But the precise signaling mechanisms governing sperm function are not clear. To study this, we used pentoxifylline (PF), a sperm motility stimulant and a cAMP-phosphodiesterase inhibitor, during capacitation and acrosome reaction of hamster spermatozoa. PF induced an early onset of sperm capacitation and its action involved modulation of sperm cell signaling molecules viz, cAMP, [Ca2+]i and protein kinases. The PF-induced capacitation was associated with an early and increased total protein phosphorylation coupled with changes in the levels of reactive oxygen species. Protein kinase (PK)-A inhibitor (H-89) completely inhibited phosphorylation of a 29 kDa protein while PK-C inhibitor (staurosporine) did not inhibit phosphorylation. Interestingly, PF induced protein tyrosine phosphorylation of a set of proteins (Mr 45-80 K) and a greater proportion of PF-treated spermatozoa exhibited protein tyrosine phosphorylation, compared to untreated controls (82 + 9% vs 34 +/- 10%; p < 0.001); tyrosine-phosphorylated proteins were localized specifically to the mid-piece of the sperm. The profile of protein tyrosine phosphorylation was inhibitable by higher concentrations (> 0.5 mM) of tyrosine kinase inhibitor, tyrphostin A47. However, at lower (0.1-0.25 mM) concentrations, the compound interestingly induced early sperm capacitation and protein tyrosine phosphorylation, like PF. These results show that protein tyrosine phosphorylation in the mid-piece segment (mitochondrial sheath) appears to be an early and essential event during PF-induced capacitation and a regulated level of tyrosine phosphorylation of sperm proteins is critical for capacitation of hamster spermatozoa.

Acrosome Reaction↗

Optimisation of Noosa BNR plant to improve performance and reduce operating costs.

Noosa WWTP is publicly owned and privately operated by Australian Water Services. The process includes primary sedimentation, raw sludge fermentation, biological nutrient removal (BNR), sand filtration and ultraviolet (UV) disinfection. An innovative feature of the plant is the supplementary carbon dosing facility to avoid the use of metal salts (alum or ferric) for phosphorus removal. The average flow treated during 2000 was 9.0 ML/d. The annual 50 percentile effluent quality requirements for nutrients are total N < 5 mg/L and total P < 1 mg/L. The objectives of this project were to: determine the cause of variability in phosphorus removal; develop a strategy to control the variability in phosphorus removal; and minimise the operating cost of supplementary carbon dosing while achieving the effluent quality requirements. An investigation of chemical and microbiological parameters was implemented and it was concluded that there were several factors causing variability in phosphorus removal, rather than a single cause. The following four major causes were identified, and the control strategies that were adopted resulted in the plant achieving annual 50 percentile effluent total P = 0.37 mg/L and total N = 3.0 mg/L during 2001. First, phosphorus removal was limited by the available VFA supply due to consumption of VFA by other organisms competing with phosphate accumulating organisms (PAO), and due to diurnal variations in the sewage VFA and phosphate concentrations. Therefore, supplementary carbon dosing was essential to make allowance for competing reactions. Second, increasing the fermenter VFA yield via supplementary carbon dosing with molasses was found to be an effective and economic way of ensuring reliable phosphorus removal. Third, nitrate in the RAS resulted in consumption of VFA by denitrifying bacteria, particularly with process configurations where the RAS was recycled directly into the anaerobic zone. Incorporating a RAS denitrification zone into the process rectified this problem. Finally, glycogen accumulating organisms (GAO) were observed in BNR sludge samples, and consumption of VFA by GAO appeared to cause decreased phosphorus removal. Better phosphorus removal was obtained using VFA derived from the fermenter than dosing an equivalent amount of acetic acid. It was hypothesized that GAO have a competitive advantage to use acetate and PAO have a competitive advantage to use propionate, butyrate or some other soluble COD compound in the fermenter effluent. Contrary to popular belief, acetate may not be the optimum VFA for biological phosphorus removal. The competition between PAO and GAO for different VFA species under anaerobic conditions requires further investigation in order to control the growth of GAO and thereby improve reliability of biological phosphorus removal processes.

Bioreactors↗

Gastric infarction associated with septic shock and high-dose vasopressor use.

Gastric infarction is rare, owing to the extensive collateral circulation of the stomach. A case of gastric infarction occurring in a patient with septic shock secondary to pneumonia is presented. The aetiology, diagnosis and therapy of gastric infarction are discussed, with consideration of the role of sepsis and vasopressors in pathogenesis and the concept of splanchnic resuscitation in prevention of the condition.

Aged↗

Brucella isolated from bone marrow.

A 40 year patient presented with pyrexia of one month duration. Routine work up for fever of unknown origin (FUO) was negative. Bone marrow aspiration and culture done yielded Brucella. Bone marrow cultures are recommended for patients for FUO for whom the routine workup turns out to be negative. Serological tests for brucellosis can be false-negative in some cases of brucellosis due to prozone phenomena.

Adult↗