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Further evidence for a high incidence of nocturnal hypoglycaemia in IDDM: no effect of dose for dose transfer between human and porcine insulins.

We tested the hypothesis that transfer from porcine to human insulin causes a fall in nocturnal blood glucose and an increase in the frequency of hypoglycaemic episodes. Twenty IDDM patients (age 19-55, duration 3-36 years) used Velosulin and Insulatard twice daily for 12 weeks, double-blinded to species (human (H) or porcine (P)) in a randomized crossover study. Species was changed after 4 weeks' run-in and 4 weeks later, with insulin doses unchanged on transfer. Ten patients underwent each sequence (H/P/H or P/H/P) and were admitted on the first and eighth night after transfer for hourly blood glucose measurement (22.00-07.00). Biochemical hypoglycaemia (<3.5 mmol l(-1)) was observed on 39 of the 80 patient-nights studied (48.75%). The number of episodes were similar during each night (H1 8, H8 10, P1 10, P8 11, p = 0.83). Total reported symptomatic episodes (H 51 vs P 73, p = 0.85), total HbA1 (H 9.8 +/- 0.3%, P 10.0 +/- 0.3%, p = 0.32) and daily insulin doses (H 0.63 +/- 0.04 units kg(-1) day(-1) vs P 0.63 +/- 0.05 units kg(-1) day(-1), p = 0.54) were not different. Despite an apparent fall in blood glucose levels from night 1 to 8 on transfer to human (AUC 82.3 +/- 7.8 vs 61.4 +/- 5.3 mmol.h l(-1), p < 0.05) but not porcine insulin (AUC 70.7 +/- 7.2 vs 70.1 +/- 7.5 mmol.h l(-1), p = 0.74), there was no difference when all 4 nights were considered together (p = 0.30). We conclude that dose for dose transfer to human insulin does not increase numbers of episodes of nocturnal or reported hypoglycaemia.

Adult↗

Low frequency therapeutic EMF differently influences experimental muscle pain in female and male subjects.

Effects of a pulsating, half sine wave magnetic field (MF) with a frequency of 100 pps and 15 mT rms flux density, generated by the MD TEMF device (EMF Therapeutics, Inc., Chattanooga), on subjective pain rating, heart rate, and arterial blood pressure were tested in a double blind, crossover design study employing experimental muscle pain. Each of 24 healthy volunteers (12 females and 12 males, 24.7 +/- 3.2 years of age) received painful stimulation induced by the infusion of 5% hypertonic saline (HS) into the erector spinae muscle during real and sham MF exposure, in counterbalanced order. Exposure to MF differently affects subjective pain estimates in females and males. MF exposure increased averaged pain level and time integral of pain ratings in females, whereas no statistically significant difference for these characteristics was found in males. Pain related elevation of systolic and diastolic blood pressure was observed during both real and sham EMF exposure in female and male subjects.

Adult↗

The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions.

OBJECTIVES: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. METHODS: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1beta, IL-6 and IL-8 and prostaglandin E(2) (PGE(2)) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire. RESULTS: Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1beta 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0. 01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged. CONCLUSION: The interleukins measured proved to be sensitive indicators of irritating effects of 1,1, 1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa.

Adult↗

[Knowledge of care activity: another professional factor associated with utilization?].

OBJECTIVES: To analyse the doctors' level of understanding of the use of resources in primary care and the relationship of their understanding to the proper use of resources. SETTING: Primary care in the Autonomous Community of Murcia. DESIGN: Descriptive, crossover study. RESULTS: There was little concordance between the real data contributed by the unit of information and registration of primary care management and data calculated by the doctors themselves. The best-known parameters are frequency of attendance (kappa index = 0.11) and patient pressure (kappa = 0.39). The profile of the doctors did not in general relate to this degree of understanding; it was only observed in a tendency in older doctors (p < 0.001) to overvalue frequency of attendance. The doctors with less understanding used radiology resources more with 164 requests per 1000 inhabitants per year, made more specialist referrals (826 per thousand inhabitants per year) and prescribed more medicines (21 prescriptions per inhabitant per year). Likewise, doctors who used resources most tended to underestimate their use of resources (p < 0.001). CONCLUSIONS: The doctor's understanding of his/her health-care activity and of the resources it involves is scant and independent of the doctor's professional characteristics. This is a factor, which we could call the professional factor, clearly related to resource use.

Clinical Medicine↗

Supplementation with mixed fruit and vegetable juice concentrates increased serum antioxidants and folate in healthy adults.

OBJECTIVE: Epidemiological studies have shown that low plasma levels of antioxidant micronutrients, which are commonly found in fruit and vegetables, are associated with increased risk for diseases such as heart disease, cancer, metabolic disorders and the like. The aim of this study was to monitor the dietary habits of a group of healthy, middle-aged, men and women and to assess the effect of supplementation with a natural phytonutrient preparation from fruits and vegetables, on plasma levels of various antioxidant micronutrients and oxidative stress assessed by measuring 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) in urine. METHODS: The study followed a double-blind randomized cross-over design involving 59 healthy men and women (40-60 years of age). The supplement or a placebo was given to two groups for a total period of 14 weeks (crossover week 7). Blood levels of beta-carotene, vitamin C, vitamin E, selenium and folate were measured at 0, 7 and 14 weeks. Fruit and vegetable consumption was monitored by means of a retrospective food frequency questionnaire at week 0, 7 and 14. Urinary 8-oxodGuo was also determined at these time points. RESULTS: Significant increases in blood nutrient levels after active supplementation were observed for beta-carotene, vitamin C, vitamin E, selenium and folate. Ranges measured, after supplementation, often fell into those associated with a reduced risk for disease. Our data suggests that, although generally health conscious, participants still fell short of the recommended five portions of fruit and vegetables per day. No significant group changes were noted for 8-oxodGuo concentration in urine. CONCLUSION: Supplementation with mixed fruit and vegetable juice concentrates effectively increased plasma levels of important antioxidant nutrients and folate.

8-Hydroxy-2'-Deoxyguanosine↗

Association between infectious diseases and type 1 diabetes: a case-crossover study.

BACKGROUND: To investigate the role of infectious diseases in the development of type 1 diabetes, this study estimated the relative risks of type 1 diabetes immediately after infectious diseases. RESEARCH DESIGN AND METHODS: A case-crossover design was employed. Information on infectious diseases during 407 d before the onset of type 1 diabetes was collected from medical records and parents' interviews for 260 patients in Chinese type 1 diabetes registry. The frequency of infectious diseases in 42 d before the onset of type 1 diabetes was compared with either the usual frequency of infectious diseases over the past year or the actual frequency of infectious diseases in a comparable 42-d control period. RESULTS: Forty-eight (18%) patients were reported to have infectious diseases during this period based on medical records and interviews with parents. The relative risk of type 1 diabetes onset was markedly elevated to 10.1 (5.6, 17.9) immediately after infectious diseases, suggesting the role of infections as a precipitator. The relative risk decreased gradually before and after 42 d and was similar between male and female patients. CONCLUSION: The results showed that infectious diseases are associated with a large and transient increase in the risk of type 1 diabetes during 42 d after the infection.

Causality↗

Efficacy of diltiazem for coronary artery spasm.

The introduction of calcium entry blockers which caused marked vascular smooth muscle relaxation with minimal effects on myocardial contractility have provided a new approach to the patient with angina due to coronary artery spasm. Multiple, double-blinded, randomized studies of diltiazem versus placebo have demonstrated that this agent results in reduction in angina frequency and nitroglycerin consumption by 30% to 70% with a demonstrated dose response. A long-term, open label follow-up study of 18 patients who participated in a 44-week prospective, double-blind crossover trial of 240 mg of diltiazem versus placebo for prophylaxis of angina in patients with coronary artery spasm demonstrated a 75% decrease in angina attacks during the first five months of the study and an 80% decrease compared to the placebo period during the second six months. Both the short- and long-term studies have demonstrated very few adverse side effects, less than 7%. A recent long-term study of 43 patients who took diltiazem regularly and were followed in the Coronary Artery Spasm Clinic at Stanford University Medical Center for a mean of 19.6 months (range 6 to 28.5 months) was analyzed for cardiovascular events in the 19.6 months prior to therapy and the 19.6 months after the initiation of therapy. Cardiovascular events on diltiazem, including sudden cardiac death, myocardial infarction, and hospitalization to rule out myocardial infarction utilizing a binomial distribution showed over a 90% reduction compared to the pre-diltiazem period. Adverse effects were reported in six patients who reported minimal to mild pedal oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human immunodeficiency virus type 1 transductive recombination can occur frequently and in proportion to polyadenylation signal readthrough.

One model for retroviral transduction suggests that template switching between viral RNAs and polyadenylation readthrough sequences is responsible for the generation of acute transforming retroviruses. For this study, we examined reverse transcription products of human immunodeficiency virus (HIV)-based vectors designed to mimic postulated transduction intermediates. For maximization of the discontinuous mode of DNA synthesis proposed to generate transductants, sequences located between the vectors' two long terminal repeats (vector "body" sequences) and polyadenylation readthrough "tail" sequences were made highly homologous. Ten genetic markers were introduced to indicate which products had acquired tail sequences by a process we term transductive recombination. Marker segregation patterns for over 100 individual products were determined, and they revealed that more than half of the progeny proviruses were transductive recombinants. Although most crossovers occurred in regions of homology, about 5% were nonhomologous and some included insertions. Ratios of encapsidated readthrough and polyadenylated transcripts for vectors with wild-type and inactivated polyadenylation signals were compared, and transductive recombination frequencies were found to correlate with the readthrough transcript prevalence. In assays in which either vector body or tail could serve as a recombination donor, recombination between tail and body sequences was at least as frequent as body-body exchange. We propose that transductive recombination may contribute to natural HIV variation by providing a mechanism for the acquisition of nongenomic sequences.

Base Sequence↗

Rapid onset of cutaneous anesthesia with EMLA cream after pretreatment with a new ultrasound-emitting device.

UNLABELLED: In this randomized, double-blinded, placebo-controlled, crossover trial of 42 human subjects, we examined the speed of onset of cutaneous anesthesia by eutectic mixture of local anesthetics (EMLA) cream after brief (approximately 10-s) pretreatment of the underlying skin with low-frequency (55 kHz) ultrasound. Four treatments were compared: ultrasound pretreatment followed by application of 1 g EMLA or placebo cream for 5 min, 10 min, 15 min, and 60 min without ultrasound pretreatment as positive control. Pain was tested by pricks with a 20 g needle. Pain scores and patient preference for EMLA or placebo cream were measured at each time point. Based on both pain scores and patient preference, cutaneous anesthesia was achieved in the EMLA groups as compared with placebo at all time points. After ultrasound pretreatment and then 5, 10, or 15 min after EMLA cream application, pain scores and overall preference were statistically indistinguishable from EMLA cream application for 60 min (without ultrasound pretreatment). There were no significant adverse effects. Low-frequency ultrasound pretreatment appears to be safe and effective in producing rapid onset of EMLA cream in this model, with results as early as 5 min. IMPLICATIONS: A prospective, randomized, double-blinded, placebo-controlled clinical trial demonstrated rapid onset of cutaneous anesthesia by pretreatment of the skin with ultrasound before application of EMLA cream.

Adolescent↗

Clonidine effect in chronic angina pectoris. Double-blind, crossover trial on 60 patients.

Increased adrenergic activity, often manifested in chronic angina, is likely to influence adversely the course of the disease. In view of the inhibitory effect of clonidine (CL) upon the adrenergic nervous system, the effectiveness of small doses of CL in chronic angina was evaluated in a double-blind crossover study on 60 patients suffering at least 5 coronary pains per week in spite of routine medication. CL was given orally in a dose of 2 x 75 microgram/day for a 2 wk. Reduction in frequency of coronary pains by at least 50% was observed in 53.7% of patients, total nitroglycerin consumption decreased from 322 to 174 tablets/week, and ergometric performance increased from 168 to 283 W x min/patient. Urinary excretion of adrenaline and noradrenaline diminished. Blood pressure and heart rate were not considerably changed. Mild and transient side effects occurred in 10 patients, 9 of them completed the trial. It is concluded that CL in low doses is effective and safe in patients with chronic angina, presumably by alleviating adrenergic strain.

Administration, Oral↗

Pentagastrin-induced release of free fatty acids in healthy volunteers and patients with panic disorder: effect of pretreatment with ethinyl estradiol.

OBJECTIVE: The primary objective of this study was to assess whether pentagastrin-induced panic symptoms are associated with release of free fatty acids (FFAs) in a manner that could explain the mechanism of correlations observed between serum cholesterol levels and frequency and severity of panic attacks in patients with panic disorder (PD). A secondary objective was to assess whether pretreatment with ethinyl estradiol (EE) attenuates pentagastrin-induced release of FFAs. METHODS: A double-blind, crossover, placebo-controlled study was conducted in which patients with PD and healthy volunteers received 2 injections of pentagastrin, 7-10 days apart, with randomization of the order of pretreatment with placebo and EE. RESULTS: We found a statistically significant, time-dependent release of FFAs in response to pentagastrin challenge. However, this release of FFAs was not attenuated by pretreatment with EE. CONCLUSIONS: These results support the hypothesis that release of FFAs in association with panic attacks occurs in a manner similar to the stress-induced lipolysis model. This suggests a possible mechanism for the elevated serum cholesterol levels observed in patients with PD. However, the occurrence of a delayed increase in low-density lipoprotein (LDL) cholesterol following induction of a panic attack remains to be tested in studiesincorporating a placebo injection visit and timed measurements of LDL cholesterol.

Adult↗

Uremic neuropathy. III. Controlled study of restricted protein and fluid diet and infrequent hemodialysis versus conventional hemodialysis treatment.

The effect of a treatment schedule of restricted protein and fluid intake and of infrequent hemodialysis (schedule 1) as compared to a conventional hemodialysis treatment schedule (schedule 2) on the presence and severity of peripheral neuropathy has been studied in a small group of patients using a crossover design. Using the neurologic evaluation and quantitative assessment of cutaneous sensation and of nerve conduction as indices of peripheral nerve function, we have not demonstrated any worsening of peripheral nerve function from markedly curtailing the frequency of hemodialysis and modifying the diet. Because of the small size of the study, the preponderance of patients receiving the test treatment schedule first, and the possibility that nerve function slowly worsens with time, it is not possible to say with certainty that the test or the control treatment schedule might adversely affect peripheral nerve function. If such an effect is present it would appear to be small.

Adult↗

Labetalol in the control of cardiovascular responses to electroconvulsive therapy in high-risk depressed medical patients.

Labetalol, a drug with alpha- and beta-adrenergic receptor blocking effects, was used to attenuate hypertension and tachycardia associated with electroconvulsive therapy (ECT) in a series of 11 elderly patients with refractory depression and cardiovascular disease in a placebo-controlled, double-blind crossover study design. As compared with placebo, labetalol was found to blunt mean arterial pressure (MAP) increase by up to 8.26% (p less than .001), heart rate increased by up to 26.07% (p less than .001), frequency of atrial arrhythmias by up to 100% (p less than .01), and premature ventricular contractions by 41.97%. No untoward side effects were observed, and no effect on treatment outcome was noted. Labetalol appears to be an effective and safe agent to use in decreasing hypertension, tachycardia, and possibly arrhythmias in high-risk medical patients with cardiovascular disease undergoing ECT.

Aged↗

A double blind crossover comparison of loperamide with diphenoxylate in the symptomatic treatment of chronic diarrhea.

Loperamide, a novel antidiarrheal agent, was compared with diphenoxylate in a double blind crossover study of 23 patients with chronic diarrhea of various etiologies. Both agents were found to be capable of controlling or greatly reducing chronic diarrhea. Loperamide was superior to diphenoxylate in its abiltiy to decrease the frequency and improve the consistency of the stools, even at a 2.5-fold lower dose level.

Adult↗

Heart rate variability in time and frequency domains: effects of gallopamil, nifedipine, and metoprolol compared with placebo.

OBJECTIVE: To assess the effects of three different antianginal drugs on heart rate, blood pressure, and heart rate variability. DESIGN: Randomised, single blind, placebo controlled, cross over study. SETTING: University hospital. PARTICIPANTS: Nine healthy male volunteers. INTERVENTIONS: Oral administration of either 50 mg gallopamil, 20 mg nifedipine, 100 mg metoprolol, or placebo according to a random crossover plan. MAIN OUTCOME MEASURES: Time intervals between consecutive R waves in electrocardiograms measured with an accuracy of 5 ms from digital Holter recordings. Blood pressure monitored continuously by finger plethysmography. RESULTS: Metoprolol lowered heart rate from 62(6) to 51(5) beats/min (p = 0.003) after 78(23) minutes. Nifedipine provoked reflex tachycardia from 56(5) to 94(18) beats/min (p < 0.001) at 10(3) minutes after treatment followed by an exponential decline in heart rate to baseline values with a time constant of 34(7) min in seven subjects but 83 minutes in one volunteer. One subject showed no exponential decline in heart rate. Nifedipine significantly lowered the supine mean arterial pressure from 86(6) to 67(6) mm Hg (p = 0.004) after 11(2) minutes, indicating an acute reduction in arterial resistance. Gallopamil did not significantly change mean heart rate or blood pressure. In the sitting position three hours after administration gallopamil and metoprolol significantly lowered power spectral density in the low frequency band (0.03 Hz to 0.15 Hz) compared with placebo (p < 0.05). Nifedipine did not produce such an effect. CONCLUSIONS: Gallopamil and metoprolol both inhibit cardiac sympathetic activation compared with placebo, whereas nifedipine causes reflex sympathetic activation.

Adult↗

Metabolic effects of alterations in meal frequency in type 2 diabetes.

OBJECTIVE: The effects of altering meal frequency on measures of glucose and lipid metabolism in type 2 diabetes were examined by comparing isocaloric dietary regimens in which daily food intake was provided by three or nine meals each day. RESEARCH DESIGN AND METHODS: A total of 13 free-living men and women with type 2 diabetes or persistently impaired glucose tolerance participated in a randomized crossover study in which three- and nine-meal regimes were followed for 4-week periods. Fasting plasma lipid and lipoprotein, glucose and insulin concentrations were measured at weekly intervals and glucose, insulin, and triglyceride responses following a 75-g glucose load at weeks 2 and 4 of each diet period. Dietary intake was also recorded during these weeks. RESULTS: Nutrient intakes and all measures of carbohydrate and lipid metabolism were similar on the three- and nine-meal regimes. CONCLUSIONS: This longer-term study could not confirm the potential benefits of increased meal frequency suggested by comparable 4-week studies in type 2 diabetic individuals and acute experiments in individuals with diabetes. However, as there were no adverse effects of consuming nine meals per day, it would seem appropriate that meal frequency in those with type 2 diabetes should be left to personal choice, provided that energy balance is maintained.

Aged↗

The right information may matter more than frequency-place alignment: simulations of frequency-aligned and upward shifting cochlear implant processors for a shallow electrode array insertion.

OBJECTIVE: It has been claimed that speech recognition with a cochlear implant is dependent on the correct frequency alignment of analysis bands in the speech processor with characteristic frequencies (CFs) at electrode locations. However, the use of filters aligned in frequency to a relatively basal electrode array position leads to significant loss of lower frequency speech information. This study uses an acoustic simulation to compare two approaches to the matching of speech processor filters to an electrode array having a relatively shallow depth within the typical range, such that the most apical element is at a CF of 1851 Hz. Two noise-excited vocoder speech processors are compared, one with CF-matched filters, and one with filters matched to CFs at basilar membrane locations 6 mm more apical than electrode locations. DESIGN: An extended crossover training design examined pre- and post-training performance in the identification of vowels and words in sentences for both processors. Subjects received about 3 hours of training with each processor in turn. RESULTS: Training improved performance with both processors, but training effects were greater for the shifted processor. For a male talker, the shifted processor led to higher post-training scores than the frequency-aligned processor with both vowels and sentences. For a female talker, post-training vowel scores did not differ significantly between processors, whereas sentence scores were higher with the frequency-aligned processor. CONCLUSIONS: Even for a shallow electrode insertion, we conclude that a speech processor should represent information from important frequency regions below 1 kHz and that the possible cost of frequency misalignment can be significantly reduced with listening experience.

Adult↗

Peripheral beta-adrenergic blockade treatment of parkinsonian tremor.

The effect of nadolol, a peripherally acting beta-adrenergic blocker, on resting, postural, and intention tremor was examined in 8 patients with idiopathic Parkinson's disease whose motor symptoms, other than tremor, were well controlled with conventional medications. In a double-blind, placebo-controlled, crossover design, patients received 80 to 320 mg of nadolol for six weeks while continuing their previous therapeutic regimen. Accelerometer readings showed a 34% reduction (p less than 0.025) in tremor distance, but no change in tremor frequency, during nadolol therapy. Maximum benefit was achieved with a dose of 240 mg, when resting tremor improved 54%, postural tremor 32%, and intention tremor 54%. Physician ratings and patient reports supported the accelerometer results. Nadolol appears to be a safe, effective adjunct to current dopaminergic and anticholinergic therapy for severe tremor in Parkinson's disease.

Adrenergic beta-Antagonists↗