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Biomedical subjects

J R Hayes

Publications and source records attributed to J R Hayes.

At least 37 records · Page 2Linked to original sources

Efficacy of amlodipine in pediatric patients with hypertension.

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.

Administration, Oral↗

Is cyclic vomiting syndrome related to migraine?

OBJECTIVE: To examine the overlap between cyclic vomiting syndrome (CVS) and migraine by comparing 2 subsets of children with migraine-associated and non-migraine-associated CVS. METHODS: We studied all children <18 years of age who met the consensus criteria for CVS after presentation to our pediatric gastroenterology service from 1986 to 1998. The clinical patterns and responses to treatment were obtained from a combination of chart reviews and structured interviews. RESULTS: Among 214 children identified as having CVS, 82% were classified as having migraine-associated CVS based on 1 of 2 criteria either a family history of migraines or subsequent development of migraine headaches. Compared with the non-migraine CVS subgroup, the migraine subset had milder episodes (20.7 27.3 SD vs 39.5 66.5 emeses/episode, P =.006); more symptoms of abdominal pain (83% vs 66%), headache (41% vs 24%), social withdrawal (40% vs 22%), photophobia (36% vs 16%, all P <.05); more frequent triggering events (70% vs 49%, P =.013) including psychologic stress (39% vs 22%), physical exhaustion (23% vs 3%), and motion sickness (10% vs 0%); and a higher positive response rate to anti-migraine therapy (79% vs 36%, P =.002). CONCLUSIONS: The majority of children with CVS were subclassified as having migraine-associated CVS. The migraine-associated subgroup had less severe vomiting, manifested symptoms typical of migraine headaches, and had higher response rates to anti-migraine therapy. These findings strengthen the relationship between migraine and CVS.

Child↗

Species differences in adrenal lipid peroxidation: role of alpha-tocopherol.

Previous reports have noted high levels of lipid peroxidation (LP) in vitro in a variety of adrenocortical preparations. However, we have observed that susceptibility to adrenal LP seems to vary considerably from species to species. The current study was done to confirm these apparent species differences in adrenal LP in vitro and to determine if they were attributable to differences in alpha-tocopherol content. Incubation of mitochondrial or microsomal preparations from guinea pig or rabbit adrenal glands with ferrous ion (Fe2+) caused a time-dependent increase in the formation of thiobarbituric acid reactive substances (TBARS) accompanied by depletion of alpha-tocopherol. By contrast, incubation of adrenal mitochondria or microsomes from rats or monkeys with Fe2+ had little or no detectable effect on TBARS and basal adrenal alpha-tocopherol levels were five to ten-fold greater than those in guinea pigs or rabbits. In addition, there was little change in alpha-tocopherol concentrations during incubation of rat or monkey adrenal tissue. Dietary alpha-tocopherol deficiency in rats reduced adrenal alpha-tocopherol to concentrations approximating those in guinea pigs. Incubation with Fe2+ induced high levels of TBARS in adrenal mitochondria and microsomes from the alpha-tocopherol deficient rats. Conversely, dietary alpha-tocopherol supplementation in rabbits increased adrenal alpha-tocopherol levels and prevented Fe2+ induced TBARS formation in mitochondria and microsomes. The results indicate that there are large species differences in adrenal susceptibility to LP in vitro and that these differences are at least partly attributable to species differences in adrenal alpha-tocopherol concentrations.

Adrenal Cortex↗

Oral candidal carriage and infection in insulin-treated diabetic patients.

AIM: To evaluate candidal load and carriage of candidal species in 414 insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated. METHODS: Candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. RESULTS: Seventy-seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non-significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis. CONCLUSION: The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.

Analysis of Variance↗

Effect of dental treatment on the lung function of children with asthma.

In this preliminary study, the authors evaluated whether dental treatment can trigger a reaction in the hyperactive airways of children with asthma, thereby affecting lung function. They also examined the variables, if any, that predict a change in lung function in relation to dental treatment. They tested the lung function of 57 6- to 18-year-old subjects with histories of active asthma, using spirometry before, immediately after and 30 minutes after routine dental treatment. Results revealed a statistically significant decrease (P < .05) in lung function and a clinically significant decrease in lung function in approximately 15 percent of the subjects.

Adolescent↗

Heterogeneity of diagnoses presenting as cyclic vomiting.

OBJECTIVE: To establish the diagnostic profile in children who present with cyclic vomiting. METHODS: We studied 225 children < 18 years of age who presented to our pediatric gastroenterology service from 1986 to 1997 with at least three discrete episodes of vomiting between which they were well. To determine the diagnoses in those presenting with a pattern of cyclic vomiting, the results of diagnostic testing and responses to various treatments were obtained from a combination of chart review and structured telephone interviews. RESULTS: The largest diagnostic category included idiopathic cyclic vomiting syndrome (88%). Extraintestinal disorders (7%) and gastrointestinal disorders (5%) constituting the probable cause of vomiting were established in those having complete cessation of episodes after therapy. In 12%, serious surgical disorders of the gastrointestinal (malrotation), renal (acute hydronephrosis), and central nervous systems (neoplasm) were found. In 2%, serious endocrine (Addison's disease) and metabolic disorders (disorder of fatty acid oxidation) were found. Among those with idiopathic cyclic vomiting syndrome, 41% had associated disorders (gastroesophageal reflux and chronic sinusitis) that could contribute to the vomiting, but, based on a partial response to therapy, were not deemed to be the main cause. Altogether 49% had an identified disorder that probably caused or could contribute to the vomiting. CONCLUSIONS: The cyclic pattern of vomiting is a symptom complex that can be induced by heterogeneous disorders that either cause or contribute to the vomiting. Once the cyclic vomiting pattern is identified, systematic diagnostic testing is warranted to look for these underlying disorders.

Central Nervous System Diseases↗

Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus.

Lipid peroxidation may be important in the development of cardiovascular disease, a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus (NIDDM). We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde, as thiobarbituric acid reacting substances (TBARS), in 23 non-insulin diabetic patients. Plasma levels of standardised alpha-tocopherol (vitamin E), lipid content of whole plasma and lipoprotein fractions, glycosylated haemoglobin, glycosylated low density lipoprotein (LDL) and fasting blood glucose were also measured. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the of the active treatment periods at 6 and 18 weeks. Treatment with olive oil did not change levels of TBARS, vitamin E or indices of glycaemic control compared with baseline. Total cholesterol and triglyceride (TG) content of plasma and lipoprotein fractions were not significantly altered. Treatment with fish oil resulted in elevation of TBARS (P < 0.001) and reduction of vitamin E (P < 0.01) compared with baseline and olive oil treatment. Plasma cholesterol was unchanged. A reduction in plasma TG compared with baseline occurred but failed to reach significance (P =0.07). Changes in apo B containing lipoproteins induced by fish oil failed to reach significance. No significant changes were observed in concentration or composition of high density lipoprotein (HDL). Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance (P = 0.06). Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil. This potentially adverse reaction may limit the therapeutic use of fish oils in such patients.

Chromatography, High Pressure Liquid↗

Impaired vasoconstriction to endothelin 1 in patients with NIDDM.

Microvascular disease is an important cause of morbidity in diabetes. There is evidence that impaired autoregulation of blood flow is involved in the pathogenesis of diabetic microangiopathy. The vascular endothelium plays a central role in the regulation of vascular tone. Endothelin (ET)-1 is a potent endothelium-derived vasoconstrictor substance that contributes to basal vascular tone. Impaired vasoconstriction in response to endogenous ET could result in hyperperfusion and subsequent microvascular damage. The purpose of our study was to determine whether vascular responses to locally administered ET-1 are impaired in NIDDM. Nine patients with NIDDM and 12 control subjects underwent cannulation of the nondominant brachial artery. Forearm blood flow (FBF) was measured at baseline and during the drug infusion using strain-gauge venous occlusion plethysmography. ET-1 (5 pmol/min) was infused for 60 min at a rate of 1 ml/min. FBF was measured during the first 5 min of the infusion and at 5-min intervals thereafter. Results were expressed as change in FBF from baseline (ml.100 ml-1.min-1) and were analyzed using repeated measures analysis of variance and Dunnett's test of multiple comparisons. Control subjects showed a gradual onset of vasoconstriction in response to ET-1, which reached maximum at 35 min (1.1 ml.100 ml-1.min-1; P < 0.01). There was no reduction in FBF in response to ET-1 in the diabetic group. The differences between the diabetic and control groups were significant (P < 0.03). In conclusion, ET-1 infused locally at 5 pmol/min does not cause vasoconstriction in patients with NIDDM.

Blood Flow Velocity↗

Differentiating cyclic from chronic vomiting patterns in children: quantitative criteria and diagnostic implications.

OBJECTIVE: To establish criteria to differentiate two patterns of vomiting and to identify the predominant diagnoses for each group. METHODS: All children 2 to 18 years of age referred to a pediatric gastroenterology service who presented with recurrent vomiting (three episodes of vomiting within a 3-month period) as a primary complaint from 1985 to 1991 were retrospectively reviewed (n = 106). The vomiting pattern (emeses per hour and episodes per month), diagnostic studies, and therapeutic responses were compared by Mann-Whitney U and chi-squared tests. RESULTS: Based on the criteria of peak intensity (four or more emeses per hour) and frequency (nine or fewer episodes per month), two subgroups were differentiated: chilcren with a cyclic pattern (n = 34), who vomited at a higher peak intensity (12.6 +/- 1.6 vs 1.5 +/- 0.1 emeses per hour) but at a lower frequency (1.9 +/- 4.8 vs 36.6 +/-0.3 episodes per month) than those with a chronic pattern (n = 72). Among children with a cyclic patern, nongastrointestinal (65%) causes, especially peptic and infectiouus disorders, predominated over nongastrointestinal ones (10%). CONCLUSIONS: On the basis of quantitative historical criteria, children with recurrent vomiting can be classified into two subgroups that seem to be clinically and etiologically distinct. Abdominal migraine was the dominant diagnosis in those with cyclic vomiting, whereas peptic and infectious gastrointestinal disorders predominated in those with chronic vomiting. This differentiation between cyclic and chronic patterns of vomiting may be a useful diagnostic clue to the clinician.

Child↗

Alcohol intake in patients admitted acutely to a general medical unit.

The role of alcohol in causing acute medical admissions is recognised but not well quantified. Using a questionnaire we have studied prospectively alcohol intake in patients aged 18-60 years admitted to a medical unit and have analysed the contribution of alcohol to their admission. One hundred and six patients (61 male: 45 female) who fulfilled our preset age criteria were studied. Alcohol intake (mean +/- SEM) was 9 +/- 1 and 12 +/- 1 units on average and heavy drinking days respectively, and 38 +/- 6 units during their last drinking week. Gamma glutamyl transferase (GGT) was > 60 U/l (upper limit of normal) in 29 (n = 92). Eighteen (30%) men had drunk > 50 units and seven (16%) women had taken > 35 units in their last drinking week. In 25 (41%) men and 11 (24%) women alcohol intake was felt to contribute to their admission. In this subgroup, intake was 15 +/- 2 and 20 +/- 1 units on average and heavy drinking days respectively, and 87 +/- 13 units in the last drinking week. GGT was available in 29 and was abnormal in 18. Admission diagnoses were drug overdose (n = 16), alcohol withdrawal symptoms (n = 7), liver disease (n = 6), haematemesis (n = 14) and others (n = 3). Fifteen (42%) felt they had a definite alcohol problem. The use and abuse of alcohol contributes significantly to the general medical workload in the age group studied.

Adult↗

Peripheral autonomic impairment in patients newly diagnosed with type II diabetes.

OBJECTIVE: To measure both peripheral and central autonomic function in patients newly diagnosed with type II diabetes. RESEARCH DESIGN AND METHODS: Measurements were made on 49 diabetic patients (8 with long-standing diabetes and neuropathic complications, 41 with newly diagnosed type II diabetes) and on 49 healthy, age- and sex-matched, control subjects. Five of the 41 newly diagnosed type II diabetic patients had retinopathy, and 4 had clinical evidence of neuropathy. No patient or control subject had significant vascular disease. Cardiac autonomic function was investigated by using standard cardiovascular reflex tests. The digital vasoconstrictor responses to deep breathing and body cooling were measured using venous occlusion plethysmography. RESULTS: The vasoconstrictor responses to a deep breath and body cooling were significantly reduced (P < 0.001) in the fingers and toes of the neuropathic patients compared with their matched control subjects, as were the heart rate responses (P < 0.02). The vasoconstrictor responses were significantly reduced in the toes (P < 0.001) and fingers (P < 0.05, P < 0.01) of the newly diagnosed patients compared with the corresponding responses in the control subjects. There was no significant difference in the heart rate or blood pressure responses of these patients and control subjects during standard tests of cardiac autonomic function. CONCLUSIONS: Patients with type II diabetes may have impaired peripheral autonomic function at diagnosis.

Adult↗

Use of PCR primers containing a 3'-terminal ribose residue to prevent cross-contamination of amplified sequences.

Cross-contamination with previously amplified products poses a serious limitation in the use of PCR for clinical testing and in certain research applications as well. In the present study we report the use of novel primers containing a 3'-terminal ribose residue to circumvent this problem. Extension of the primer by Taq DNA polymerase generates a cleavable ribonucleotide linkage within the amplified product. Cleavage of the primer by base or with a ribonuclease interferes with further replication of the product should carry over to another sample occur. Primers terminating in any of the 4 ribose residues function equally well as all DNA primers. Taq DNA polymerase is thus able to both efficiently extend and copy the single ribose residue. In translating from all DNA primers to ones containing a 3'-ribose residue no modification of the PCR protocol is required. The products formed can be used in all applications of the PCR. Since neither the original sample DNA, the primers or the extension products are modified by base or ribonuclease treatment both pre- and post-amplification sterilization can be carried out. Pre-amplification treatment with RNase A can yield as high as 10(4)-fold sterilization. Under these conditions the addition of beta-mercaptoethanol or other sulfhydryl reducing agent is necessary to inactivate the enzyme during thermocycling. Post-amplification treatment with NaOH readily yields at least 10(6)-fold sterilization. This alone is sufficient for most, if not all, applications of PCR. It is especially useful for quantitative RT-PCR, since the original target RNA sequence, which may be present in high copy numbers, is also destroyed.

Base Sequence↗

Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease. Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium. Using forearm venous occlusion plethysmography we studied vascular responses to 60, 120, 180 and 240 nmol/min of acetylcholine (an endothelium-dependent vasodilator) and 3, 6 and 9 nmol/min of glyceryl trinitrate (an endothelium-independent vasodilator) infused into the brachial artery in 23 patients with Type 2 (non-insulin-dependent) diabetes mellitus. NG monomethyl-L-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the active treatment periods at 6 and 18 weeks. Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration (p < 0.01). Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Autonomic function in neuropathic diabetic patients with foot ulceration.

OBJECTIVE: The aim of this study was to compare peripheral autonomic function in neuropathic diabetic subjects with and without foot ulceration. RESEARCH DESIGN AND METHODS: Measurements were made on 57 diabetic subjects; 35 subjects had evidence of peripheral neuropathy, 14 of these had a history of foot ulceration, and 22 subjects had no evidence of peripheral neuropathy. No patient had peripheral vascular disease. Measurements were made of motor and sensory nerve conduction. Autonomic function was investigated by using standard cardiovascular reflex tests and by measuring blood flow variability in the foot. The vasoconstrictor responses to deep breathing and body cooling were measured by using venous occlusion plethysmography. RESULTS: Peripheral sympathetic function was significantly worse in the DU group. The vasoconstrictor response to deep breathing in the DU group was significantly smaller than the response in the DN group (15.3 +/- 2.7 vs. 38 +/- 4%, P < 0.001). The response to body cooling in the DU group was significantly smaller than the response in the DN group (6.2 +/- 3.1 vs. 20.8 +/- 3.5%, P < 0.01). Tests of cardiac autonomic function and measurements of motor and sensory nerve conduction were similar in both neuropathic groups. CONCLUSIONS: Peripheral autonomic neuropathy is associated with the development of foot ulceration in diabetic subjects.

Autonomic Nervous System↗

Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus.

The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.

Acetylcholine↗

A study of experimental lancets for blood collection to avoid bone infection of infants.

We describe a study made at two pediatric centers to test experimental lancets for blood collection by skin puncture of infants' heels or fingers. Our primary goal is to decrease the hazard of osseous injury while collecting adequate blood, by using three lancet widths at a constant length of 1.0 mm. The three widths used were 1.0, 1.25, and 1.5 mm. When success at skin puncture was defined rigidly on the basis of the blood volume obtained, the data show that success was related neither to the lancets' dimensions as tested nor to the age of the child, but rather to the phlebotomist's skill and experience, which improved with time.

Blood Specimen Collection↗