Isoprenoid synthesis gene for geranylgeranyl diphosphate synthase from a hyperthermophile, Pyrococcus sp. strain OT3

Visual Evoked Potentials (VEP) were measured in 9 new-diagnosed hypothyroid female patients--mean age 46 +/- 12 ys--before treatment, during (with monthly evaluations) thyroid hormone replacement therapy and after long-term therapy, at the achievement as well as one year after having achieved and maintained euthyroidism. Three of the hypothyroids had abnormally prolonged latencies (m.v. 131.7 +/- 7.9 ms), while 7 had lower than normal amplitude (m.v. 2.3 +/- 2.8 microV). No remarkable change of amplitude was observed after the achievement of euthyroidism, after a mean time of 5.9 +/- 4.9 months (range 2-14 months). A significant shortening of latency (m 128.3 +/- 7.6 ms), even still higher than the control value (m 122.7 +/- 3.7 ms) was found. Significant correlation between P100 latency and thyroid hormone levels was found for TT4 (r = 0.3353; p = 0.005), TT3 (r = 0.2568; p = 0.032) and FT4 (r = 0.3572; p = 0.002). No further improvement in P100 latency (m 129.5 +/- 7.2 ms; p = 0.037) was found one year after the achievement of euthyroidism, while a remarkable amplitude increase (m 9.2 +/- 3.4 micro; p = 0.001) was observed. Our findings indicate that, as well as other studied parameters, VEP are reversibly alterated in hypothyroidism, probably in relation to metabolic rather than to structural alterations. Moreover, VEP can represent a useful neurophysiologic parameter for quantitation of SNC involvement in hypothyroidism.     

Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation

Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.     

Potential pitfalls of initiating a newborn hearing screening program

To compare auditory and visual P300 amplitude and latency magnitudes and topographies in patients with narcolepsy and normal subjects, 20 patients with polysomnographically-confirmed narcolepsy and 40 normal subjects were administered auditory and visual P300 testing using 31 evenly spaced scalp electrodes. Patients with narcolepsy were then administered baseline polysomnograms and objective (MSLT, Maintenance of Wakefulness Test or MWT) and subjective tests (Epworth Sleepiness Scale, Clinical Global Impression) of daytime sleepiness. Patients had longer 31-electrode mean age-adjusted auditory P300 latencies (406.0 +/- 27.8 vs. 385.7 +/- 28.9 ms, p = 0.012) and visual P300 latencies (427.3 +/- 29.0 vs. 411.4 +/- 27.7 ms., p = 0.044) than 40 normal subjects in the same age range. Age-adjusted auditory P300 latency was correlated with MWT (r = -0.49, p = 0.028), but not with any other clinical variable or measure of sleepiness. Age-adjusted visual P300 latency was not correlated with any clinical variable or measure of sleepiness. Patients with narcolepsy had longer auditory and visual P300 latencies than normal subjects.     

Bone metabolism markers in patients with Basedow-Graves disease

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.     

Event-related potentials as an index of cognitive function during recovery from severe closed head injury

OBJECTIVE: To evaluate the utility and neuropsychological correlates of serially performed recordings of event-related potentials (ERPs) in patients recovering from a severe closed head injury (CHI). DESIGN: Prospective longitudinal study. SETTING: Brain injury rehabilitation unit based in a national rehabilitation hospital. SUBJECTS: Sixteen patients with severe CHI (significant degree of impaired consciousness greater than 24 hours) subclassified into two severity groups according to initial Glasgow Coma Scale (GCS) score: those with initial GCS score < 9, consistent with a more severe injury; and those with initial GCS score > 8, indicating a less severe injury. METHODS: ERPs were elicited using the standard auditory P300 "oddball" detection paradigm. ERP recordings were carried out three times: 2 months after injury, 1 month later, and 2.5 months or more after the initial study. Parameters analyzed included latencies and amplitudes of the P3, N2, P2, and N1 components of the ERPs. Correlations between changes in these ERP parameters and specific neuropsychological test results were evaluated. RESULTS: Initial P3 latencies in the more severely injured group were significantly longer (P < .05) than those recorded in the less severely injured patients. In subsequent recordings, P3 latency was found to be significantly shorter compared with the initial P3 latency, and the difference in P3 latency between the two patient groups was no longer statistically significant by the time of the third recording. For the group as a whole, P3 latency decreased significantly on each repeated recording. N2 latency was found to be significantly shorter (P < .05) between the first and third recordings. Cognitive performance significantly improved between the first and third recordings. P3 latency shortening was correlated with improvement in neuropsychological test scores for short-term and long-term story recall and for word recall. N2 latency shortening was correlated with improvement in the neuropsychological test scores for word recall only. CONCLUSION: ERP recordings performed in the subacute stage after CHI may assist in evaluating injury severity. Moreover, serially performed recordings of P3 latency may be used as a physiologic index of brain activity that correlates with recovery from CHI.     

Cognitive impairment in schizophrenic patients on event-related potentials component P300

There have been many reports on the Event-Related Potentials (ERPs) abnormalities, especially P300 amplitudes reduction, in schizophrenic patients. However the relationships between P300 abnormalities and schizophrenic subtypes have not been clarified. This study aims to investigate the relationships in a relatively large number of drug free schizophrenics. Seventy three unmedicated schizophrenic patients (45 males, 28 females) who met the DSM-III-R criteria for schizophrenia were tested. Twenty seven of the schizophrenics were paranoid type according to the DSM-III-R, 23 were undifferentiated, 19 were disorganized, 2 catatonic and 2 residual. Seventy three healthy controls were age and gender matched to the patient group. All the ERPs were recorded during auditory odd ball task. Stimuli consists of 2 kHz and 1 kHz tone bursts, and the respective probabilities of the rare and frequent stimuli were 0.2 and 0.8. They were presented random order. The duration of each stimulus was 90 msec with rise and fall times of 10 msec, and the intensity was approximately 70 dB SPL for all the stimuli. The inter-stimulus intervals were 1.7 +/- 0.1 seconds. The subjects were instructed to count the numbers of rare tones. The scalp EEGs were recorded from Ag-AgCl electrodes at 16 sites that referred to linked earlobes. P300 amplitudes reduction [F (1,144) = 39.33, p < 0.001] and P300 latencies prolongation [F (1,144) = 12.41, p < 0.001] were found in schizophrenic group as a whole. Lower amplitude of P300 was observed at both right and left temporal sites in the subjects with undifferentiated type and disorganized type. Although in the subjects with paranoid type, the reduction was recognized at left temporal region, reduced amplitude was not seen at right temporal site. While no relationships between P300 amplitudes, the score of BPRS and SAPS were detected, in the patient with paranoid type, significant negative correlation between P300 amplitudes and SANS total scores was observed (r = -0.425, p = 0.03) at Pz site. These results were discussed with respect to cognitive impairment of schizophrenia.     

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Event-related potentials (ERPs) evoked by light flashes and auditory tones in a standard odd-ball procedure were recorded from Fz, Cz and Pz scalp sites. Tonic pain was evoked by immersion of the hand in cold water (5 degrees C). Significant effects of pain were found in responses to target stimuli but not in responses to non-target stimuli. P300 wave was affected more than the earlier P200 component. The reduction of P300 amplitude was the strongest effect, both in auditory and visual tests. P300 latency was not significantly affected. Difference curves (target minus non-target ERPs) showed the additional effects: latency of P200 component was elongated and its amplitude enlarged but only in auditory experiments. In control experiments with warm water stimulation no significant alterations of P300 or P200 components were found. The results show that the effect of tonic pain is specific: it predominantly affects the processes that manifest themselves as amplitude changes of P300 components in responses to target stimuli.     

Markers of bone turnover in hyperthyroidism and the effects of treatment

Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary pyridinoline cross-link (Pyr) excretion, reflecting bone resorption, have been measured in 27 patients with hyperthyroidism and 30 age-matched controls using direct and novel immunoassays. Hyperthyroid patients had higher (P < 0.001) levels of all 3 markers compared with control values: Pyr, 246 +/- 181 nmol/mmol creatinine vs. 40 +/- 12 (+515%); OC, 55 +/- 23 vs. 23 +/- 7.4 micrograms/L (+139%); and B-ALP, 22 +/- 17 vs. 10.0 +/- 5.0 micrograms/L (+120%). OC and Pyr levels were elevated above the normal range in most patients and were significantly correlated with serum free T3 concentrations (r = 0.53; P < 0.01 and r = 0.76; P < 0.001; for OC and Pyr, respectively). B-ALP levels were elevated in 11 of the 27 patients and did not correlate with serum thyroid hormone concentrations. After therapy for hyperthyroidism, Pyr and OC levels returned to normal within 1 month, whereas B-ALP transiently increased after 1 month before falling to baseline levels. The relapse of hyperthyroidism observed in 1 patient was associated with a steep increase in bone markers. These results indicate that Pyr, measured using a new and convenient immunoassay, is a highly sensitive marker for altered bone metabolism in hyperthyroidism. The increases in OC and B-ALP were less impressive, suggesting an imbalance between resorption and formation with subsequent rapid bone loss in untreated hyperthyroidism. OC and B-ALP also appear to reflect different aspects of osteoblast metabolism during the treatment of hyperthyroid patients.     

Recurrent hyperthyroidism after thyroidectomy

For 53 patients with toxic recurrent goiter (TRG), the interval between thyroidectomy and recurrent hyperthyroidism range from six months to 50 years (average, 12.4 +/- 11.9 years). Recurrent hyperthyroidism may occur in older patients for whom cardiac decompensation may be the initial manifestation. Reports on surgically treated hyperthyroid patients may underestimate the incidence of TRG unless follow-up is extended for many years.     

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.     

Median nerve somatosensory evoked potentials during isoflurane anaesthesia

PURPOSE: The effect of isoflurane on the subcortical P14 component of the median nerve somatosensory evoked potential (SEP) is poorly known. We studied whether the P14 wave from the upper brainstem, recorded with a nasopharyngeal electrode, was attenuated at the isoflurane-induced EEG burst-suppression level. We also compared the effect of isoflurane on the P14, cervical N13 and cortical N20, N35 and N6, components. METHODS: Seventeen elective patients were anaesthetized with isoflurane. Somatosensory evoked potentials were recorded prior to anaesthesia, at 0.5 MAC and 1 MAC end-tidal isoflurane as well as at the level when EEG was in burst-suppression (mean 1.9 vol% end-tidal isoflurane). RESULTS: Isoflurane had varying effects on the subcortical components of median SEP. The amplitude of nasopharyngeal P14 was stable, but the mean latency increased from 14.4 +/- 1.2 msec at 0.5 MAC to 15.2 +/- 1.1 msec at burst-suppression level (P < 0.05). In contrast, the N13 neck response amplitude was attenuated from 3.3 +/- 0.6 microV to 2.6 +/- 0.5 microV (P < 0.005) without latency changes. The latency of the cortical N20 wave was increased from 19.7 +/- 1.1 msec at awake to 24.4 +/- 1.6 msec at burst-suppression level (P < 0.0001) and amplitude was reduced from 3.3 +/- 1.1 microV to 1.3 +/- 0.6 microV (P < 0.0001). The later cortical components were attenuated even during 0.5 MAC isoflurane and were not recordable during EEG burst-suppression. CONCLUSION: We conclude that P14 can reliably be recorded with nasopharyngeal electrodes during isoflurane anaesthesia, even during EEG burst-suppression, when the N20 wave is attenuated. In contrast, the middle-latency SEP components are sensitive to isoflurane anaesthesia.     

Surgeons--the presidents and commanders of the former Medical Surgical Academy--of the Military Medical Academy

BACKGROUND: To examine the prevalence of atrial fibrillation (AF) in cardiopathic patients with hyperthyroidism. METHODS: The data concerning the patients had been derived from registers of the Laboratory of Radioimmunoassay where cardiopathic patients' blood samples were referred from the Cardiology Unit to evaluate thyroid function, consecutively from January 1992 to December 1997. Of the 443 patients, 303 (68.4%) were classified as being euthyroid, 23 (5.2%) hypothyroid, 117 (26.4%) hyperthyroid. Thyroid function was diagnosed clinically and confirmed by serum TSH and free thyroid hormone (FT3, FT4), levels. RESULTS: Among hyperthyroid patients, the more frequent arrhythmia was AF (54.7%). After excluding from the study those hyperthyroid patients with rheumatic disease, hypertension, myocardial infarction, 37 hyperthyroid patients were selected; 18 (48.6%), (mean age 63.4 +/- 10.8 yrs), showed sinus rhythm and 19 (51.4%), (mean age 66.0 +/- 12.1 yrs), showed AF. FT3 and FT4 were higher in patients with AF than in those without AF, whereas TSH was not significantly different between the groups. Left ventricular (LV) mass index was significantly increased in hyperthyroid women with AF compared with hyperthyroid women without AF (109.80 +/- 22.33 g/m2 vs 84.50 +/- 6.20 g/m2; p < 0.005). A significant correlation was found between FT3 levels and LV mass index in the hyperthyroid women with and without AF (r = 0.77; p < 0.001). CONCLUSIONS: In this study the prevalence of AF is 51.4% in hyperthyroid patients. FT3 is higher in patients with AF than in those without AF. Finally, the correlation between FT3 and LV mass index suggests that cardiac hypertrophy is associated with thyroid hyperfunction.     

Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin

The phenomenon of macrore-entry (Re) within the His-Purkinje system (HPS) was consistently observed in 10 of 19 patients during retrograde refractory period studies. Effects of intravenous infusion of diphenylhydantoin (DPH) on Re were studied in these 10 patients 10 minutes after completion of infusion (mean plasma level equal to 17.0 microgram/ml). Diphenylhydantoin modified determinants of Re in seven patients (group I) and abolished Re in the remaining three patients (group II). In group I, DPH shortened the critical V1 V2 from 310.0 +/- 30.5 to 292.9 +/- 25.6 msec (P less than 0.025) and critical V2 H2 intervals for Re from 201.4 +/- 18.4 to 185.0 +/- 13.8 msec (P greater than 0.05). In group II, DPH abolished Re in two of three patients by precluding attainment of critical V2 H2 intervals whereas Re was abolished in the remaining one patient despite attainment of critical V2 H2 intervals (vs control). For both groups, DPH significantly shortened functional and effective refractory periods of the HPS (P less than 0.001 and less than 0.01, respectively) without significantly affecting the effective refractory period of the ventricular muscle. Diphenylhydantoin either completely abolished or significantly shortened the retrograde gap zones in the HPS. It is concluded that diphenylhydantoin significantly shortens His-Purkinje system refractoriness, abolishing Re in the patients with higher degree of improvement in refractoriness.     

Sinus node recovery time and abnormal postpacing phase in the aged patients with sick sinus syndrome

The sinus node function was evaluated by rapid atrial pacing in 35 aged patients (mean age 78.2 years) including 10 aged controls, 12 cases with various degrees of AV block, 6 with bradycardia-tachycardia syndrome (BTS), and 7 with sinus bradyarrhythmia (SB). AV block was further divided into A-H block (7 cases) and H-V block (5 cases) by His bundle electrogram which was simultaneously recorded with 3 leads of surface electrocardiogram. Sinus node recovery time (SRT) was measured and its maximum value (SRTmax) was selected from SRTs obtained after pacing with various rates and durations in each patient. SRTmax was also expressed as percentage of the control P-P interval (%SRTmax). For patients in whom the study was repeated 3 to 8 months later, %SRTmax was reproducible in 9 of 14 instances. Prolongation of SRT was not always observed as the rate and/or duration of pacing was increased. SRTmax and %SRTmax were 1,363 +/- 188 msec and 147 +/- 19% (mean +/- SD), respectively, for aged controls, 1,597 +/- 442 msec and 156 +/- 31% for patients with AV block, 2,087 +/- 1,315 msec and 203 +/- 132% for those with BTS, and 3,069 +/- 1,287 msec and 247 +/- 115% for those with SB. SRTmax exceeding the range for aged controls was noted in 4 of 7 cases (57%) with A-H block, 2 of 6 (33%) with BTS, and 5 of 7 (71%) with SB; normal SRT was not infrequently observed in patients with sick sinus syndrome, especially in those with BTS. Analysis of 10 consecutive atrial cycles following cessation of pacing revealed that in 8 cases the first P-P interval (SRT) was followed by longer ones in some occasions (secondary suppression). It was observed almost exclusively in patients with sick sinus syndrome. The possibility of this phenomenon to reflect another feature of sinus node abnormality was discussed.     

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A modification of the standard electrodiagnostic test was developed in an effort to provide a more sensitive electrodiagnostic evaluation in radial tunnel syndrome. Radial motor nerve latency recordings were obtained in 3 different forearm positions: neutral, passive supination, and passive pronation. The maximal difference in these recordings, the differential latency, in 25 patients with radial tunnel syndrome of greater than 6 months duration (test group) was compared with those in 25 asymptomatic volunteers (control group). Differential latency recordings were obtained in all patients in the test group before and after surgery. Radial nerves that were compressed demonstrated a significantly greater differential latency (0.44+/-0.12 ms) versus controls (0.12+/-0.008 ms). Following radial nerve decompression, differential motor latencies in the test group decreased below control values, demonstrating a resolution of the provoked electrical response with a postoperative differential latency of 0.07+/-0.05 ms. Our results demonstrate the differential motor latency of the radial nerve to be a sensitive electrodiagnostic tool in patients with radial tunnel syndrome. A differential latency of > or =0.30 ms was considered indicative of radial tunnel syndrome.     

Symptomatic and asymptomatic high-grade unilateral internal carotid artery stenosis: scalp topography of event-related potentials (P300) and psychometric testing

Unilateral internal carotid artery (ICA) stenosis may be accompanied by widespread atherosclerosis of extra- and intracranial vessels leading to subtle cognitive disorders. We applied multichannel recording of P300 in 28 patients (68.3 +/- 8.1 years; 15 asymptomatic, 13 with a history of transient ischemic attack (TIA)) and compared them with an age- and sex-matched control group. All underwent a visual "odd-ball paradigm" as well as a psychometric test, the Cognitive Performance Test (CPT), testing mainly visual attention and memory. The potentials were derived from 16 electrodes according to the 10/20 system against linked mastoids. The latencies and amplitudes of N250 and P300 were measured and their amplitudes additionally mapped. Furthermore, the early sensory exogenous potentials, P1 and N1, within the P300 potentials as well as conventional pattern reversal visual evoked potentials (PVEPs) were evaluated. (1) Both the early exogenous potentials and the conventional PVEPs showed no significant differences among all groups. (2) There were no significant differences between asymptomatic patients and those with a TIA history in all parameters of the P300 complex so that one total patient group was constructed and compared to the controls. (3) Patients' P300 amplitudes showed significant reductions over hemispheres ipsilateral (P < or = 0.014) and contralateral (P < or = 0.044) to the stenosis. (4) The N250 amplitudes were reduced only in the central leads (P < or = 0.05). (5) The latencies of N250 potentials were significantly prolonged at many electrodes, not only ipsi-(P < or = 0.0007) but also contralateral (P < or = 0.022) to the stenosis. (6) The patients' P300 latencies showed significant lengthening only at occipital sites (P < or = 0.05) compared to controls. (7) In all measured parameters, within the patient group, the differences between hemispheres ipsilateral versus contralateral to the ICA stenoses did not reach statistical significance. (8) The CPT values detected slight cognitive disorders for both patient groups and they correlated significantly with the latencies in many leads. (9) The highest test sensitivity to classify patients versus controls (z score > 2) was reached in P300 maps of TIA patients (77%). An altered P300 indicates electrophysiologically, and CPT behaviorally, subclinical cognitive deficits even in asymptomatic patients with unilateral tight ICA stenoses. Interestingly, no differences between asymptomatic and TIA patients with a high-grade unilateral ICA stenosis could be found.     

Lymphocyte recirculation, exercise, and immune responses

OBJECTIVES: Visual evoked potentials (VEPs) show abnormal responses in newly-diagnosed insulin-dependent diabetic (IDDM) patients. Electrophysiological methods allow one to dissect and explore different structures contributing to neural conduction in the visual pathways. The aim of our work was to assess whether the VEP abnormalities are due to impaired function of the retinal layers and/or a delayed conduction in the postretinal visual pathways. METHODS: Simultaneous recordings of VEP and pattern-electroretinogram (PERG) were performed at two intervals (at entry of the study and after 3 months) in 14 newly-diagnosed IDDM patients (age: 24.8+/-6.8 years; duration of disease: 3+/-1.5 months), and in 14 age-matched control subjects. RESULTS: In comparison with control subjects, IDDM patients showed: VEP P100 latencies significantly delayed (P < 0.01), a significant impairment of all PERG parameters (P < 0.01) and retinocortical time (RCT, difference between VEP P100 and PERG P50 latencies) and latency window (LW, difference between VEP N75 and PERG P50 latencies) also significantly increased (P < 0.01). All electrophysiological parameters were not significantly changed when retested after 3 months. No correlations were found between VEP P100 latency, RCT, LW and PERG parameters. CONCLUSIONS: Impaired PERG indicates an involvement of the innermost retinal layers; increased values of RCT and LW represent an index of delayed neural conduction in the postretinal visual pathways. Therefore two sources, one retinal (impaired PERG) and one postretinal (delayed RCT and LW), may independently contribute in to the abnormal responses of VEP observed in newly-diagnosed IDDM patients. Three months of relatively-stable metabolic control have not normalized the VEP and PERG impairment.     

Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis

We studied thrombopoietic activity in hyperthyroidism by determination of reticulated platelet counts. At the time of hyperthyroidism 14/15 patients had higher reticulated platelets than after achievement of euthyroidism (P<0.001). There was no difference in peripheral platelet counts and mean platelet volumes at the time of hyperthyroidism when compared to euthyroidism. Three patients had pan- and auto-reactive platelet antibodies during hyperthyroidism. These antibodies were directed against GPIIb/IIIa in two patients and against GPIb/IX in one patient. Our findings provide direct evidence that hyperthyroidism is associated with increased platelet production, as reflected by an increase in reticulated platelets.     

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The effects of intravenous MS-551, a new class III antiarrhythmic drug, on atrium and ventricle were evaluated in 6 patients with ventricular tachyarrhythmias (4 males and 2 females; mean age 45 +/- 21 years) in an electrophysiologic study. Two patients had sustained ventricular tachycardia (VT) and 4 patients had ventricular fibrillation (VF). Electrophysiologic study was performed before and after the administration of MS-551 (loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min). The QT and QTc intervals were significantly prolonged by MS-551 from 359 +/- 52 to 411 +/- 63 msec (p = 0.01) and from 410 +/- 36 to 452 +/- 47 (p = 0.0172), respectively. No effect was observed on the sinus cycle length, QRS duration, or AH and HV intervals in sinus rhythm. The effective refractory periods of the right atrium (AERP) were significantly prolonged at paced cycle lengths of 600 (from 222 +/- 19 to 250 +/- 23 msec, p = 0.0009), 400 (from 207 +/- 15 to 228 +/- 15, p < 0.0001) and 300 (from 193 +/- 10 to 205 +/- 8 msec, p = 0.0127) msec. Similarly, the right ventricular ERP (VERP) were significantly prolonged at paced cycle lengths of 600 (from 240 +/- 23 to 268 +/- 23 msec, p < 0.0001), 400 (from 225 +/- 22 to 250 +/- 24 msec, p = 0.0007), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, p = 0.0071). MS-551 prolonged AERP and VERP in a "reverse" use-dependent manner without changing the conduction time in patients with ventricular tachyarrhythmias. MS-551 prevented the induction of VT in 1 patient and VF in only 1 patient in this electrophysiologic study. Further evaluation of the therapeutic potential of MS-551 using higher dosages is necessary.     

Electrophysiological characteristics of the human atria after cardioversion of persistent atrial fibrillation

BACKGROUND: In animal models, induced atrial fibrillation shortens the atrial effective refractory period (ERP) and reverses its physiological adaptation to rate. It is not clear whether this process, known as "electrical remodeling," occurs in humans. METHODS AND RESULTS: We determined the ERPs, at 5 pacing cycle lengths (300 to 700 ms) and in 5 right atrial sites, after internal cardioversion of chronic atrial fibrillation in 25 patients (14 in pharmacological washout and 11 on amiodarone). The ERPs were 195.5+/-18.8 ms in the washout and 206.3+/-17.9 ms in the amiodarone patients (P<0.0001). ERPs were closely correlated with the stimulation rates (r=0.95 in the washout and r=0.94 in the amiodarone group), and slope values indicating a normal (>/=0.07) or nearly normal (0.05 to 0.06) adaptation of ERP to rate were found in 77% of the 84 paced sites. The mean ERP was shorter in the lateral wall (198.1+/-17.9 ms) than in the atrial roof (203.3+/-21.5 ms) and in the septum (210.5+/-20.0 ms) (P<0.03). After 4 weeks of sinus rhythm, the mean ERP, determined again in 8 patients (4 in wash-out and 4 on amiodarone), was significantly increased compared with the basal study (221. 4+/-21.4 versus 197.8+/-18.3 ms, P<0.0001). CONCLUSIONS: After cardioversion of chronic atrial fibrillation, (1) atrial ERP adaptation to rate was normal or nearly normal in the majority of the cases, (2) a significant dispersion of refractoriness between different right atrial sites was present, and (3) ERPs were significantly increased after 4 weeks of sinus rhythm in both washout and amiodarone patients.