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PubMed1985

Efficacy of low-dose methotrexate in rheumatoid arthritis.

Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.

Administration, Oral↗
PubMed1999

Mesoscopic theory of the viscoelasticity of polymers.

We have advanced our previous static theory of polymer entanglement involving an extended Cahn-Hilliard functional, to include time-dependent dynamics. We go beyond the Gaussian approximation, to the one-loop level, to compute the frequency dependent storage and loss moduli of the system. The four parameters in our theory are obtained by fitting to available experimental data on polystyrene melts of various chain lengths. This provides a physical representation of the parameters in terms of the chain length of the system. It is shown that the parameters chosen describe the crossover from an unentangled to an entangled state. The crossover is characterized by a dramatic increase in a time scale appearing in the theory, analogous to critical slowing down in phase transition theory. This result should stimulate more detailed experiments in this regime to test this concept.

Journal Article↗
PubMed2004

Kinetics of urea and beta-microglobulin during and after short hemodialysis treatments.

BACKGROUND: Daily short hemodialysis (HD) is often prescribed by simply doubling treatment frequency and halving treatment time; however, the effect of this prescription approach on the equilibrated HD dose (urea eKt/V) and whole body clearance for beta(2)-microglobulin has not been established. METHODS: We compared urea and beta(2)-microglobulin kinetics during and 60 minutes after a short HD treatment and a conventional HD treatment in a crossover study on 22 maintenance HD patients: 16 male and 6 female, 61 +/- 18 (mean +/- standard deviation) years of age. One patient in each treatment modality was excluded from certain analyses because of missing data. Short and conventional HD treatments were essentially identical, except for treatment times, which were 116 +/- 14 and 241 +/- 27 minutes, respectively. Blood samples were collected at regular intervals during and after treatments, and additional blood and dialysate samples were collected at 60 minutes of treatment to evaluate dialyzer clearances. RESULTS: Plasma water urea clearances measured directly across the dialyzer during short and conventional HD treatments were not different (255 +/- 23 mL/min and 255 +/- 28 mL/min, respectively). The 60-minute postdialysis blood urea nitrogen concentration rebounded more (P < 0.01) after short HD than conventional HD (5.9 +/- 3.1 vs. 4.0 +/- 1.5 mg/dL, respectively). Calculated urea eKt/V values using the Daugirdas-Schneditz rate equation were not different from those measured during conventional HD using the 60-minute postdialysis concentration but significantly overestimated measured urea eKt/V values during short HD. Postdialysis rebound of beta(2)-microglobulin concentrations was variable but similar after short and conventional HD treatments (0.1 +/- 3.4 vs. 0.7 +/- 1.8 mg/L, respectively). Whole body clearances of beta(2)-microglobulin calculated from predialysis and immediate (10-second) postdialysis serum concentrations during short and conventional HD treatments were not different from each other (42.9 +/- 24.1 vs. 41.9 +/- 22.4 mL/min, respectively). CONCLUSION: These observations show that the Daugirdas-Schneditz rate equation is accurate in predicting urea eKt/V during conventional, but not during short, HD. In contrast, whole body clearances of beta(2)-microglobulin during short and conventional HD treatments were similar. We conclude that calculation of accurate estimates of urea eKt/V, but not clearances of beta(2)-microglobulin, differ during short and conventional HD treatments.

Blood Urea Nitrogen↗
PubMed1989

Insertional mutagenesis by random cloning of antibiotic resistance genes into the genome of the cyanobacterium Synechocystis strain PCC 6803.

The facultative heterotrophic cyanobacterium Synechocystis sp. strain PCC 6803 was transformed by HaeII Cmr fragments ligated at random to HaeII DNA fragments of the host genome. A similar transformation was done with an AvaII Kmr marker ligated to AvaII host DNA fragments. Integration of the resistance markers into the host genome led to a high frequency of stable Kmr and Cmr transformants. Physical analysis of individual transformants indicated that this result was due to homologous recombination by conversionlike events leading to insertion of the Cmr (or Kmr) gene between two HaeII (or AvaII) sites of the host genome, with precise deletion of the host DNA between these sites. In contrast, integrative crossover of circular DNA molecules with homology to the host DNA is very rare in this cyanobacterium. Strain PCC 6803 was shown to have about 12 genomic copies per cell in standard growth conditions, which complicates the detection of recessive mutations induced by chemical or UV mutagenesis. Random disruption of the host DNA by insertional transformation provides a convenient alternative to transposon mutagenesis in cyanobacteria and may help to overcome the difficulties encountered in generating recessive mutants by classical mutagenesis.

Blotting, Southern↗
PubMed2004

Clonazepam for treatment of sleep disturbances associated with combat-related posttraumatic stress disorder.

BACKGROUND: Clonazepam is widely used for the treatment of posttraumatic stress disorder (PTSD)-related sleep disturbances despite very limited published data supporting its use for this indication. OBJECTIVE: We conducted a pilot-controlled trial to provide more data on this clinical practice and lay the foundation for more definitive studies. METHODS: The study was designed as a randomized, single-blind (ie, patient only), placebo-controlled, crossover clinical trial involving administration of clonazepam 1 mg at bedtime for one week followed by 2 mg at bedtime for one week. The following week served as a washout period before the alternate treatment was begun. Patients completed sleep diaries each morning upon awakening throughout the study. Parameters included quantity of sleep, quality of sleep, frequency and intensity of difficulty falling or staying asleep, and frequency and intensity of recurrent distressing dreams. RESULTS: Six patients with combat-related PTSD participated in the study. There were no statistically significant differences between clonazepam and placebo for any measure, although clonazepam therapy resulted in mild to moderate numeric improvements in difficulty falling or staying asleep. Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to receive further treatment with clonazepam at the conclusion of the trial. CONCLUSIONS: Clonazepam therapy was largely ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related PTSD. The small sample size was a significant limitation of this study, but the prospective design and single-blind, placebo-control parameters were strengths. Further studies are needed to further define the role of this widespread clinical practice.

Adult↗
PubMed1987

Arrhythmogenicity from combined bronchodilator therapy in patients with obstructive lung disease and concomitant ischemic heart disease.

Twenty-four patients (five women) aged 53-72 yr with both ischemic heart disease and asthma or chronic bronchitis receiving oral beta 2-agonists also received additional bronchodilating therapy with theophylline (600 mg daily), enprofylline (600 mg daily) or placebo. The study was double-blind, randomized, triple-crossover with each regimen given for two weeks. Holter monitoring was used during 48 consecutive hours in each period. Compared with placebo, addition of theophylline and enprofylline were associated with an increased mean hourly heart rate of 6 bpm (p less than 0.001). A small, but statistically significant (p less than 0.05) increase in mean hourly frequency of premature ventricular beats (PVBs) occurred with enprofylline as compared with placebo. However, in only two patients with enprofylline (and one patient with theophylline) the increase in PVBs was such that a clinically relevant proarrhythmic effect seems possible. Furthermore, ventricular tachycardia was not more frequently observed with any xanthine than with placebo. Thus, combined oral bronchodilator therapy is not contraindicated in patients with obstructive lung disease and concomitant ischemic heart disease. Holter monitoring is recommended to assess the individual patient's response to such therapy.

Aged↗
PubMedDate not supplied

Clinical experience with a new device that will simplify insulin injections.

In order to test clinically a newly developed, simple, and convenient device for giving multiple injections of short-acting insulin (Actrapid HM, Novo, Bagsvaerd, Denmark), 16 type I diabetic patients previously stabilized on intensified conventional therapy regimens participated in a randomized crossover study for a period of 6 wk. The patients used conventional syringes for injections of short-acting insulin during one period and the new device during the other. Conventional syringes were used for injections of basal insulin during both periods. Metabolic control was assessed by twice-weekly blood glucose profiles, HbA1c, and the frequency of hypoglycemic reactions; no significant differences were found during the two treatment periods. No infections at the injection sites were seen. Patients' evaluation of the new device was very positive.

Adult↗
PubMed1999

[The prevalence of urinary incontinence in a population over 60 treated in primary care].

OBJECTIVES: To determine the prevalence of urine incontinence (UI) among the over-60 population treated in primary care, identifying the types and associated epidemiological factors. DESIGN: Descriptive and crossover. SETTING: Primary care. PATIENTS: Sample of 400 people aged 60 or over, stratified by sex and chosen from those who attended their health centre spontaneously for a consultation. MEASUREMENTS AND RESULTS: Age, sex, chronic illnesses, treatments, previous childbirths, grade of immobility and presence or absence of involuntary discharge of urine. If the reply was positive: frequency, characteristics and evolution of UI, and prior consultations on the problem were also measured. 400 people (254 women and 146 men). Mean age: 71 (SD = 7.3 years). 145 people (36.2%) recognised they had UI. 43.3% of women and 23.9% of men (p < 0.001) were incontinent. UI prevalence increased with age: 31.7% among the 60-69 year old group; 35% among the 70-79 group; and 53.3% in those over 80. Among women the most common types are stress and urge incontinence, whereas among men the most common are urge and overflow UI. UI prevalence is greater among women with previous childbirths and among immobile patients. Of the 145 people who recognised their UI, only 31 (21.3%) had previously consulted the doctor on this problem, although men had consulted significantly more than women (40% vs. 15.4%; p < 0.01). CONCLUSIONS: Over a third of the people over 60 in our clinics suffer from UI. Prevalence increases with age and is greater among women, especially if there is a history of childbirth. Urge UI predominates among men and stress UI among women. Most people with UI do not consult concerning their problem, for which reason, so as to identify it and adopt corrective measures, women especially must be systematically asked about the symptom.

Age Distribution↗
PubMed1992

The use of low-dose intranasal midazolam to treat panic disorder: a pilot study.

BACKGROUND: Drug therapy of panic disorder, despite the intermittent nature of the panic attack, requires daily administration of antidepressants, which are often not tolerated, or benzodiazepines, which can result in physical dependence and withdrawal. The use of rapidly acting, low-dose intranasal midazolam to prevent incipient panic suggested itself to us as a novel alternative treatment strategy. METHOD: We conducted a 6-week double-blind, placebo-controlled, crossover-design pilot study of the safety and efficacy of p.r.n. low-dose intranasal midazolam in five patients diagnosed with DSM-III-R panic disorder. RESULTS: One to two drops of midazolam (approximately 0.25 to 0.5 mg) was well tolerated and highly effective in preventing incipient panic attacks and in reducing the overall weekly frequency of attacks. CONCLUSION: Intermittent intranasal midazolam shows promise as a novel alternative treatment for panic, but a controlled study of its efficacy and safety (including abuse potential) must be conducted.

Administration, Intranasal↗
PubMed1985

Randomized crossover trial of isosorbide mononitrate (Elantan 20) and slow-release glyceryl trinitrate in the treatment of angina pectoris.

An open, randomized, comparative crossover clinical trial was carried out to compare the clinical efficacy of 20 mg isosorbide mononitrate 3-times daily and 6.4 mg sustained-release glyceryl trinitrate 3-times daily in the treatment of angina pectoris. Fifty patients entered the trial and 48 patients completed. Each treatment was given for 12 weeks followed by crossover to the alternative drug. Both treatments resulted in marked significant improvements relative to the pre-trial baseline, but isosorbide mononitrate was shown to be significantly (p less than 0.001) more efficacious than sustained-release glyceryl trinitrate in the reduction of the number of angina attacks and sub-lingual glyceryl trinitrate consumption. Angina frequency was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 33 (69%) of the patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 3 (6%) patients (p less than 0.001). Sub-lingual glyceryl trinitrate consumption was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 36 (75%) patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 5 (10%) patients. Examination of the effect of changing from isosorbide mononitrate to sustained-release glyceryl trinitrate therapy or vice versa confirmed the clinical superiority of isosorbide mononitrate. Physical exercise capacity was reported as improved in 20 (60%) patients with isosorbide mononitrate but in only 12 (25%) patients with sustained-release glyceryl trinitrate (p less than 0.02). Neither treatment showed any tendency for a reduction in effect during 12-weeks' continuous therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Nifedipine gastrointestinal therapeutic system in stable angina pectoris. Results of a multicenter open-label crossover comparison with standard nifedipine.

To compare the clinical efficacy and dose equivalency of standard nifedipine versus a new gastrointestinal therapeutic system (GITS) formulation of nifedipine, 98 patients with chronic stable angina pectoris participated in a 14-week, multicenter, open-label, crossover trial. All patients were administered nifedipine capsules for one month prior to study entry and continued receiving other antianginal, non-calcium blocker medications. Ninety-one patients (93 percent), 80 men and 11 women, mean age 62 +/- 1 years, completed the trial, which included two weeks receiving standard nifedipine followed by 12 weeks receiving nifedipine GITS starting at a dosage equal to the 24-hour total dose of nifedipine capsules and titrated upward as necessary. However, throughout the trial, mean nifedipine dosage was similar on nifedipine GITS compared with standard nifedipine. Angina frequency was significantly less with nifedipine GITS at Weeks 6, 10, and 14 (0.8 episodes/week) compared with baseline with standard nifedipine (1.3 episodes/week, p less than 0.05). Likewise, nitroglycerin consumption was also less at Weeks 6, 10, and 14, but only significantly less at Week 6 (nifedipine 1.2/week versus nifedipine GITS at six weeks, 0.7/week; p less than 0.05). Resting hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were not significantly different with standard nifedipine versus nifedipine GITS during the 12-week study. Total incidences of side effects were similar for both treatments (standard nifedipine, 16; nifedipine GITS, 17). However, incidence of vasodilator side effects (flushing, dizziness, and light-headedness) was significantly less frequent with nifedipine GITS (standard nifedipine, 12; nifedipine GITS, six; p less than 0.05). Thus, results from this open-label, crossover trial suggest that nifedipine GITS dosing is similar to multidose standard nifedipine with equivalent 24-hour efficacy for nifedipine GITS.

Aged↗
PubMed1998

Brief twice-weekly episodes of hypoglycemia reduce detection of clinical hypoglycemia in type 1 diabetes mellitus.

We tested the hypothesis that as few as two weekly brief episodes of superimposed hypoglycemia (i.e., doubling the average frequency of symptomatic hypoglycemia) would reduce physiological and behavioral defenses against developing hypoglycemia and reduce detection of clinical hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Compared with nondiabetic controls, six patients with well-controlled T1DM (HbA1c, 7.5 +/- 0.7% [mean +/- SD]) exhibited absent glucagon responses and reduced epinephrine (P = 0.0027), norepinephrine (P = 0.0007), pancreatic polypeptide (P = 0.0030), and neurogenic symptom (P = 0.0451) responses to hypoglycemia as expected. In these patients, 2 h of induced hypoglycemia (50 mg/dl, 2.8 mmol/l) twice weekly for 1 month, compared in a random-sequence crossover design with an otherwise identical 2 h of induced hyperglycemia (150 mg/dl, 8.3 mmol/l) twice weekly for 1 month, further reduced the epinephrine (P = 0.0001) and pancreatic polypeptide (P = 0.0030) responses, tended to further reduce the norepinephrine and neurogenic symptom responses to hypoglycemia, and reduced cognitive dysfunction during hypoglycemia (P = 0.0271), all assessed in the investigational setting. In the clinical setting, induced hypoglycemia did not alter overall glycemic control, but did reduce the total number of symptomatic hypoglycemic episodes detected by the patients from 49 to 30 per month and lowered the mean +/- SE self-monitored blood glucose level during symptomatic hypoglycemia from 51 +/- 2 mg/dl (2.8 +/- 0.1 mmol/l) to 46 +/- 3 mg/dl (2.6 +/- 0.2 mmol/l) (P < 0.01). It also reduced the proportion of low regularly scheduled self-monitored values that were symptomatic by approximately 33%. Thus as little as doubling the frequency of symptomatic hypoglycemia further reduced both the key epinephrine response and clinical awareness of developing hypoglycemia, changes reasonably expected to increase the risk of severe iatrogenic hypoglycemia in T1DM.

Adult↗
PubMed1993

The effects of unequal sister chromatid exchange on length of arrays of repeated sequences.

Models of homogenization of repeated sequences by unequal sister chromatid exchange (USCE) assume that no significant changes in array length occur. The effects of successive USCEs on the lengths of arrays of repeated sequences has been examined mathematically and by simulation, assuming misalignment to be greater in longer arrays, a condition necessary for homogenization. The series of duplications and deletions gives a wide, asymmetric variation in copy number. Frequencies follow a binomial distribution, but if misalignment increases with array length, lengths become logarithmically distributed, most arrays being shorter than the original, counterbalanced by a few very long arrays. The median length, which is also the modal length, decreases exponentially or asymptotically. Given a proportional misalignment of a, the median (mode) decreases by a2/2 per unequal crossover. Since drift is a random transmission of available alleles in the population, it follows that fixation of common short arrays is much more probable than fixation of rare long arrays. This process will continue inexorably until each array is too short to undergo further unequal crossing over, and no more variation is generated. The number of unequal crossovers required by some published models of homogenization would almost certainly cause dramatic reduction in number, or complete loss, of repeats. Frequent unequal sister chromatid exchanges are not compatible with survival of arrays unless counteracted by an independent amplification mechanism or selection, so are unlikely to be important as a long-term homogenization mechanism in non-essential repeated sequences.

DNA↗
PubMed1998

Effectiveness of anxiety management training in the treatment of posttraumatic stress disorder: a preliminary report.

This preliminary study investigated the effectiveness of anxiety management training (AMT), a coping skills treatment similar to systematic desensitization, in comparison to implosive therapy (IT), an exposure-based treatment, for treating six Vietnam combat veterans with posttraumatic stress disorder (PTSD). The Clinician Administered PTSD Interview Scale (CAPS; Blake et al. (1988), The Behaviour Therapist, 18, 187-188) and a self-monitoring measure (Weathers et al., 1991) were used as dependent measures. A single-subject, multiple-baseline, crossover design (ABC/ACB) was employed. A new statistic for such designs (Mueser et al. (1991), Behaviour Modification, 15, 134-155), based on classical test theory, was used to assess treatment effects on intrusive war memories and avoidance of stimuli reminiscent of war. Within-subject results indicated that AMT and IT were similarly effective in reducing the frequency and intensity of intrusions and avoidance. This preliminary report therefore suggests that it may be productive to investigate multidimensional approaches (combining coping skills, exposure-based, and other approaches) to the treatment of combat-related PTSD as Foa et al. (1991), Journal of Consulting and Clinical Psychology, 59, 715-723 and Nishith et al. (1995), Behaviour Therapy, 26, 319-335 have for rape-related PTSD.

Adaptation, Psychological↗
PubMed2004

Multiple genetic processes result in heterogeneous rates of evolution within the major cluster disease resistance genes in lettuce.

Resistance Gene Candidate2 (RGC2) genes belong to a large, highly duplicated family of nucleotide binding site-leucine rich repeat (NBS-LRR) encoding disease resistance genes located at a single locus in lettuce (Lactuca sativa). To investigate the genetic events occurring during the evolution of this locus, approximately 1.5- to 2-kb 3' fragments of 126 RGC2 genes from seven genotypes were sequenced from three species of Lactuca, and 107 additional RGC2 sequences were obtained from 40 wild accessions of Lactuca spp. The copy number of RGC2 genes varied from 12 to 32 per genome in the seven genotypes studied extensively. LRR number varied from 40 to 47; most of this variation had resulted from 13 events duplicating two to five LRRs because of unequal crossing-over within or between RGC2 genes at one of two recombination hot spots. Two types of RGC2 genes (Type I and Type II) were initially distinguished based on the pattern of sequence identities between their 3' regions. The existence of two types of RGC2 genes was further supported by intron similarities, the frequency of sequence exchange, and their prevalence in natural populations. Type I genes are extensive chimeras caused by frequent sequence exchanges. Frequent sequence exchanges between Type I genes homogenized intron sequences, but not coding sequences, and obscured allelic/orthologous relationships. Sequencing of Type I genes from additional wild accessions confirmed the high frequency of sequence exchange and the presence of numerous chimeric RGC2 genes in nature. Unlike Type I genes, Type II genes exhibited infrequent sequence exchange between paralogous sequences. Type II genes from different genotype/species within the genus Lactuca showed obvious allelic/orthologous relationships. Trans-specific polymorphism was observed for different groups of orthologs, suggesting balancing selection. Unequal crossover, insertion/deletion, and point mutation events were distributed unequally through the gene. Different evolutionary forces have impacted different parts of the LRR.

Alleles↗
PubMed2004

Testing predictions of the double-strand break repair model relating to crossing over in Mammalian cells.

In yeast, four-stranded, biparental "joint molecules" containing a pair of Holliday junctions are demonstrated intermediates in the repair of meiotic double-strand breaks (DSBs). Genetic and physical evidence suggests that when joint molecules are resolved by the cutting of each of the two Holliday junctions, crossover products result at least most of the time. The double-strand break repair (DSBR) model is currently accepted as a paradigm for acts of DSB repair that lead to crossing over. In this study, a well-defined mammalian gene-targeting assay was used to test predictions that the DSBR model makes about the frequency and position of hDNA in recombinants generated by crossing over. The DSBR model predicts that hDNA will frequently form on opposite sides of the DSB in the two homologous sequences undergoing recombination [half conversion (HC); 5:3, 5:3 segregation]. By examining the segregation patterns of poorly repairable small palindrome genetic markers, we show that this configuration of hDNA is rare. Instead, in a large number of recombinants, full conversion (FC) events in the direction of the unbroken chromosomal sequence (6:2 segregation) were observed on one side of the DSB. A conspicuous fraction of the unidirectional FC events was associated with normal 4:4 marker segregation on the other side of the DSB. In addition, a large number of recombinants displayed evidence of hDNA formation. In several, hDNA was symmetrical on one side of the DSB, suggesting that the two homologous regions undergoing recombination swapped single strands of the same polarity. These data are considered within the context of modified versions of the DSBR model.

Animals↗
PubMed2006

[The cognitive effect of alprazolam in healthy volunteers].

Randomised, double blind placebo controlled crossover study has been performed to evaluate the effect of single dose of anxiolytic alprazolam on the cognitive function in 18 healthy male volunteers. The subject received a single dose of 0.75 mg, 1.75 mg alprazolam or placebo in randomised order. Performances on cognitive tests (immediate and delayed word recall test, digit symbol substitution test, critical fusion frequency and multiple choice reaction test) and subjective rating of the drug effect have been evaluated before and at several occasions after the administration of alprazolam or placebo. According to the results of the statistical analysis alprazolam impaired the performance in cognitive tests dose dependently and induced subjective sedation. The applied test battery proved to be capable to measure the effect of the drugs on the cognitive function in pharmacodynamic studies.

Adult↗
PubMed1995

Dopaminergic inhibition of pulsatile luteinizing hormone secretion is abnormal in regularly menstruating women with insulin-dependent diabetes mellitus.

OBJECTIVE: To examine the influence of low doses of dopamine (DA) (0.4 micrograms/kg per minute), on the secretion pattern of LH. DESIGN: Prospective randomized, single blind, placebo-controlled crossover study with infusion of DA or placebo in the follicular phase in regularly menstruating women with insulin-dependent diabetic mellitus (IDDM) and controls during 9.5 hours. SETTING: Department of Endocrinology, Odense University Hospital, Odense, Denmark. PATIENTS: Eight regularly menstruating IDDM women and eight controls. MAIN OUTCOME MEASURES: Mean LH, LH pulse amplitude, and LH pulse frequency. RESULTS: During placebo infusion no significant differences in basal LH values, pulse amplitude, and pulse frequency were seen between IDDM women and controls. In diabetics, basal LH levels and pulse amplitude decreased significantly during DA infusion (3.1 +/- 1.2 mIU/mL (conversion factor to SI unit, 1.00; mean +/- SD) and 0.9 +/- 0.3 mIU/mL, respectively) compared with placebo (4.5 +/- 1.1 and 1.2 +/- 0.4 mIU/mL, respectively). In normal women no significant changes were observed (basal LH 3.0 +/- 1.8 versus 3.2 +/- 1.6 mIU/mL and pulse amplitude 1.6 +/- 0.6 versus 1.5 +/- 0.9 mIU/mL). The LH pulse frequency during DA infusion was not different from placebo in either normal (9.0 +/- 2.7 versus 10.3 +/- 4.0) or diabetic women (11.8 +/- 2.1 versus 10.9 +/- 1.8). CONCLUSION: These results suggest that diabetic women are more sensitive to a small increase in peripheral DA concentration. An abnormal permeability of the blood-brain barrier in IDDM patients could explain a greater exposure of the hypothalamic structures, regulating the pituitary gonadotropin hormone secretion.

Adult↗