Focal source hypothesis of atrial fibrillation.
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Animals↗
Biomedical subjects
T J Wu
Publications and source records attributed to T J Wu.
Derivatization of progesterone to a neurally active steroid by pituitary neurointermediate lobe.
The melanotrophs of the neurointermediate lobe and peptidergic terminals of the neural lobe are regulated by gamma-aminobutyric acid (GABA) via GABA-A receptors and therefore, may be important sites for the modulatory actions of neurally active steroids. These steroid compounds might be produced peripherally, synthesized de novo in the pituitary, or derivatized from circulating steroids, each pathway having different physiological implications. In the present study, we show that neurointermediate lobe tissue can derivatize progesterone to the neurally active steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one. The neurointermediate lobe was found to be four times as active as anterior pituitary and mediobasal hypothalamus in conversion of progesterone to 3 alpha-hydroxy-5 alpha-pregnan-20-one; mediobasal hypothalamus was relatively more active in the production of the intermediate 5 alpha-pregnan-3,20-dione. The identity of the compounds was confirmed by the method of serial isotopic dilution. We observed rates of synthesis in the neurointermediate lobe consistent with the production of physiologically relevant quantities of 3 alpha-hydroxy-5 alpha-pregnan-20-one from concentrations of progesterone which can occur naturally. In support of these findings, we demonstrate the presence of 3 alpha-hydroxysteroid oxidoreductase in neurointermediate lobe by immunocytochemistry.
3-Hydroxysteroid Dehydrogenases↗
Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.
OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.
Adolescent↗
Suppurative Acinetobacter baumanii thyroiditis with bacteremic pneumonia: case report and review.
Suppurative thyroiditis is rare, and the major pathogens are Staphylococcus and Streptococcus species. We present a case caused by Acinetobacter baumanii, which has never before been reported. We review another 191 cases from the English-language literature (1980 to April 1997) and make a comparison with a review of 224 cases (1900-1980). As the numbers of immunocompromised patients increase, cases of suppurative thyroiditis are increasing. Pneumocystis carinii has become an important pathogen. Most patients (83.1%) with bacterial infections were euthyroid, whereas those with fungal or mycobacterial infections tended to be hypothyroid (62.5%) and hyperthyroid (50%), respectively.
Acinetobacter↗
Transmembrane potential properties of atrial cells at different sites of a spiral wave reentry: cellular evidence for an excitable but nonexcited core.
Transmembrane action potentials (TAPs) were recorded during simultaneous mapping of a reentrant wavefront induced in canine isolated atria. The activation pattern was visualized dynamically using a high resolution electrode catheter mapping system. During functional reentry (spiral wave), cells in the core of the spiral wave remained quiescent near their resting membrane potential. Cells away from the core progressively gained TAP amplitude and duration, and at the periphery of the spiral wave the cells generated TAPs with full height and duration. During anatomical reentry, when the tip of the wavefront remained attached to the obstacle (a condition of high source-to-sink ratio), the TAP near the obstacle had normal amplitude and duration. However, when the tip of the wavefront detached from the obstacle (condition of lowered source-to-sink ratio) the TAP lost amplitude and duration. These results are consistent with the theory that the source-to-sink ratio determines the safety factor for wave propagation and wave block near the core. With decreasing source-to-sink ratio, TAP progressively decreases in amplitude and duration. In the center of the core, the cells, while excitable, remain quiescent near their resting potential. This decrease reflects a progressive decrease in the source-to-sink ratio. TAP vanishes in the core where cells remain quiescent near their resting potential. Functional and meandering reentrant wavefronts are compatible with the spiral mechanism of reentry where block at the rotating point is provided by the steep curvature of the wave tip.
Animals↗
Clinical profiles in adult diabetic ketoacidotic patients in a tertiary referral medical center in southern Taiwan.
Diabetic ketoacidosis (DKA) is not rare among adults. We retrospectively analyzed the precipitating factors, diabetic history, clinical features, and outcomes of adult DKA patients treated at a tertiary referral medical center in southern Taiwan between January 1994 and May 1996. Seventy-eight patients, aged from 18 to 80 years (median 47), had 87 episodes of DKA (44 males had 49 episodes; 34 females had 38 episodes). Twenty-two episodes occurred in patients with no history of diabetes mellitus (age 18-77 yr, median 40.5). The most common precipitating factor was infection (53 episodes), especially in patients aged more than 40 years. Fifteen patients died during the 87 episodes, giving a case fatality rate of 17%; DKA was precipitated by cerebrovascular accidents in two of the 15 patients and by infection in 13. Among the 53 episodes precipitated by infection, multiple logistic regression analysis showed that old age, requirement for endotracheal intubation, and low body temperature on arrival were associated with fatality. Of the 63 patients who were discharged, 39 required insulin therapy; plasma glucose was well-controlled by oral hypoglycemic agents or diet in only eight (age 29-75 yr, median 57; hemoglobin A1c 5.1-7.8%, median 6.6). The high rate of previously undiagnosed diabetes in adult DKA patients indicates a deficiency in early recognition of, and timely therapy for, diabetes in southern Taiwan.
Adult↗
Early outcome of extremely low birth weight infants in Taiwan.
We retrospectively evaluated the outcome and the risk factors for mortality among extremely low birth weight (ELBW) infants born at National Taiwan University Hospital. The records of all live-born infants with body birth weight of less than 1,000 g from January 1, 1993, to December 31, 1996, were evaluated. Infants with major anomalies or whose parents refused resuscitation were excluded from the analysis. There were 81 ELBW infants (0.59%) among a total of 13,835 live births during the study period, and 73 cases were enrolled for study. The mean gestational age (GA) was 27.2 (range, 24-34) weeks. Sixty-six percent of the ELBW infants were born by cesarean delivery. Respiratory distress syndrome occurred in 64% of infants and exogenous surfactant therapy was given to 47%, while intermittent mandatory ventilation was given to 85%. Symptomatic patent ductus arteriosus occurred in 34% of infants, septicemia in 30%, chronic lung disease in 48%, grade III to IV intraventricular hemorrhage in 27%, stage III to V retinopathy of prematurity in 33%, and necrotizing enterocolitis in 8%. Neonatal survival was 74%, survival to discharge was 60%, and intact survival was 50%. The survival rate was 40% for infants with a birth body of weight less than or equal to 750 g, and 68% for those with a birth body weight of greater than 750 g. While survival was 27% for infants with a GA of less than 26 weeks, it was 75% for those with a GA of greater than or equal to 26 weeks. The survival rate improved year by year for those with a GA less than 28 weeks. Cox regression analysis of survival showed that Apgar score at 1 minute (p = 0.0063), pulmonary hypertension (p = 0.012), and severe intraventricular hemorrhage (p = 0.0031) were the most important factors associated with mortality. Though the outcome of ELBW infants in our institute seems poorer than in some more developed countries, it is improving. The prognosis for ELBW infants of 24 to 25 weeks' GA remains guarded under our present care.
Female↗
Clinical study of failure in continuous spinal anesthesia with bupivacaine.
BACKGROUND: Continuous spinal anesthesia (CSA) has been considered to be better in temporal and dose flexibility, as well as hemodynamic stability than single dose spinal anesthesia. However, the failure of spinal anesthesia is not a rare experience for anesthesiologists. Here we present our experience in solving the problem and discuss the possible causes for the failure. METHODS: 236 cases were studied retrospectively from January to December in 1996. All were over 65 years old, ASA III, scheduled for transurethral procedures or orthopedic operation. CSA was performed with 0.2% bupivacaine. Failed CSA was confirmed by positive pin-prick test at T10 dermatome(umbilicus) 30 minutes after 20 mg bupivacaine was injected. For failed cases, 5 mL 1% lidocaine was injected intrathecally for rescue. The failure rate, sensory and motor blockade, success rate by changing to lidocaine and its dosage were recorded. RESULTS: Eleven of 236 cases (4.7%) were considered spinal failure since the initial 20 mg bupivacaine could not provide adequate T10 anesthesia in 30 minutes. Addition of 5 mL 1% lidocaine produced a profound sensory and motor blockade in 9 cases, while further lidocaine injection was required in two cases. The success rate by rescuing lidocaine was 100% with an average lidocaine consumption by 52.5 +/- 4.5 mg. DISCUSSION: Factors contributed to failure spinal anesthesia including failure of technique, errors of judgment, maldistribution and failure of local anesthetic itself. However, we thought that change of pH value of local anesthetic in CSF may play a great part in these failed CSAs. Despite the reasons for failure, we demonstrate that failure of continuous spinal anesthesia by 0.2% bupivacaine can be readily resolved by 1% lidocaine.
Aged↗
Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.
We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route.
Action Potentials↗
New observations on the development of the gonadotropin-releasing hormone system in the mouse.
In ongoing efforts to study the ontogeny of gonadotropin-releasing hormone (GnRH) neurons, we serendipitously observed that increasing times of incubation in antibodies enhanced signal detection. Here, we describe significant differences in the early migration pattern, population dynamics, and growth cone morphology from published reports. The first immunoreactive GnRH cells were detected in the mouse at E10.75 (7.6 +/- 2.8 cells; morning after mating = E0.5), prior to the closure of the olfactory placode. Although half of these cells were in the medial wall of the olfactory pit, the other half had already initiated their migration, and approximately one quarter had reached the telencephalic vesicle. Although the migratory pattern of the GnRH cells after E11.00 was identical to that described previously, these earliest migrating cells traveled singly rather than in cords, with some reaching the presumptive preoptic area (posterior to the ganglionic eminence) by E11.75. The number of GnRH cells increased significantly (p < 0.05) to 777 +/- 183 at E11.75 and peaked at 1949.6 +/- 161.6 (p < 0.05) at E12.75. The adult population was approximately 800 cells distributed between the central nervous system (CNS) and the nasal region. Hence, the population of GnRH neurons during early development is much larger than previously appreciated; mechanisms for its decline are discussed. Neuritic extensions on the earliest GnRH neurons are short (30-50 microm) and blunt and may represent the leading edge of the moving cell. By E12.75, GnRH axons in the CNS had a ribboned or beaded morphology and increasingly more complex growth cones were noted from this time until the day of birth. The most complex growth cones were associated with apparent choice points along the axons' trajectory. By E13.75, GnRH axons were seen at the presumptive median eminence in all animals, and it was at this stage that the axons began to branch profusely. Branching, as well as the presence of growth cones, continued post-natally. These results provide further insights into the pathfinding mechanisms of GnRH cells and axons.
Animals↗
What nature's knockout teaches us about GnRH activity: hypogonadal mice and neuronal grafts.
The hypogonadal mouse is one of "nature's knockouts," bearing a specific deletion in the gene for gonadotropin-releasing hormone (GnRH), with the result that no GnRH peptide is detectable in the brain. The lack of reproductive development after birth provides an animal model that has proved fruitful in clarifying the role of GnRH in reproductive behavior and physiology. Behavioral studies with hypogonadal mice convincingly demonstrate that although GnRH may facilitate the appearance of sexual behavior, this peptide is not essential for either male or female sexual behavior in the mouse. Administration of GnRH to hypogonadal mice with regimens mimicking GnRH pulsatility initiates reproductive development. Surprisingly, continuous exposure to GnRH stimulates remarkable ovarian and uterine growth and increased FSH release, although pituitary content of LH and FSH remains unchanged. In contrast, when brain grafts of normal fetal preoptic area (POA), containing GnRH cells, are implanted in the third ventricle of adult hypogonadal mice, both pituitary and plasma gonadotropin levels increase. Grafted GnRH neurons innervate the median eminence of the host and support pulsatile LH secretion in the majority of animals with graft-associated gonadal development. Studies of hypogonadal mice with POA grafts demonstrate that distinct components of reproductive function are dissociable: hosts may demonstrate reflex but not spontaneous ovulation; others may show positive but not negative feedback. Activation of grafted GnRH cells in response to sensory input to the host, as revealed in Fos expression studies, is an example of the integration of the graft with the host brain that underlies such capabilities. A goal of these studies is to elucidate the specific connectivity underlying discrete aspects of reproductive function.
Animals↗
Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells.
In the present study, the effect of GHRP-2 on GH release was evaluated in rat primary pituitary cells, and the results were compared with those elicited by GHRP-6. In the rat system, GHRP-2, like GHRP-6, acts synergistically with GRF to release GH. Co-administration of GHRP-2 and GHRP-6 at maximal concentrations had no further effect on GH release than either one alone. The GHRP's were able to desensitize cells to each other, but not to GRF. The effect of GHRP-2 was inhibited by Peptide Antagonist, but was not affected by a GRF antagonist. In conclusion, GHRP-2 was found to stimulate GH release from rat pituitary cells via the same receptor and mechanism as GHRP-6, despite the structural difference between the peptides.
Animals↗
Endopeptidase EC 3.4.24.15 presence in the rat median eminence and hypophysial portal blood and its modulation of the luteinizing hormone surge.
The endopeptidase EC 3.4.24.15 (EP24.15) is a zinc metalloendopeptidase that is widely distributed in a variety of tissues, including the testes, pituitary and the central nervous system. Among its numerous roles in metabolizing and processing biologically-active peptides, the enzyme degrades gonadotropin-releasing hormone (GnRH) by cleaving the central Tyr5-Gly6 bond. The aim of the present studies was to determine whether EP24.15 can modulate the concentrations of GnRH within the hypothalamo-hypophysial portal blood and thereby play a physiological role in reproduction. Our data suggest the presence of immunoreactive EP24.15 in the perivascular space of the median eminence and that this enzyme is secreted into portal blood. We have also shown a physiological role for this enzyme in that an inhibition of its activity with a specific inhibitor augmented the steroid-induced LH increase in ovariectomized rats. The present results suggest that secretory and post-secretory mechanisms are important in shaping the GnRH signal from the central nervous system; GnRH metabolism by EP24.15 may be one such mechanism.
Animals↗
Accessory atrioventricular pathways with only antegrade conduction in patients with symptomatic Wolff-Parkinson-White syndrome. Clinical features, electrophysiological characteristics and response to radiofrequency catheter ablation.
Information about accessory pathways conducting only in the antegrade direction is limited. The purposes of the present study were to prospectively investigate the clinical features, electrophysiological characteristics, effects of radiofrequency catheter ablation and recurrent atrial fibrillation after successful ablation in patients with accessory pathways conducting only in the antegrade direction, and to compare them with those who had pathways capable of bidirectional conduction in a consecutive series of 759 patients. Electrophysiological studies and radiofrequency catheter ablation were performed in 33 study patients with antegrade-only accessory pathways and in 377 patients with bidirectional accessory pathways for comparison. The patients with accessory pathways conducting only in the antegrade direction were older (47 +/- 16 vs 40 +/- 16 years, P = 0.037) and had a higher incidence of atrial fibrillation (100% vs 27.1%, P < 0.001) as well as related syncope (33.3% vs 10.1%, P = 0.001). The study patients also had more accessory pathways located in the posterior septum and a higher incidence of retrograde atrioventricular nodal conduction. The biophysical variables, success and complication rates of radiofrequency ablation were similar in both groups. During the follow-up period of 32 +/- 12 months, symptomatic atrial fibrillation after successful ablation did not recur in 79% and 81% of patients with unidirectional and bidirectional accessory pathways, respectively. Furthermore, old age and cardiovascular diseases were independent predictors of recurrent atrial fibrillation after radiofrequency ablation. In conclusion, this study showed that atrial fibrillation with preexcitation was the usual presentation in patients who had symptomatic Wolff-Parkinson White syndrome with an antegrade-only accessory pathway, and might be related to antegrade conduction of the accessory pathway. Therefore elimination of antegrade-only and bidirectional pathways by radiofrequency ablation could prevent the recurrence of symptomatic atrial fibrillation in younger patients without cardiac disease.
Adult↗
Mumps infection complicated by transient hyperinsulinemic hypoglycemia.
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Child↗
Meandering and unstable reentrant wave fronts induced by acetylcholine in isolated canine right atrium.
The mechanism(s) by which acetylcholine (ACh) increases atrial vulnerability to reentry and maintains its activity for longer durations remains poorly defined. In the present study we used high-resolution activation maps to test the hypothesis that ACh promotes meandering of atrial reentrant wave fronts, resulting in breakup and the generation of new wave fronts that sustain the activity. Reentry was induced in 11 isolated canine right atrial tissues (3.8 x 3.2 cm) by a premature point stimulus (S2) before and after superfusion with ACh (15 x 10(-6) M). Endocardial isochronal activation maps were constructed with the use of 509 bipolar electrodes (1.6-mm spatial resolution), and the dynamics of the activation wave fronts were visualized with animation. A vulnerable period was found during which an S2 current strength > 4.4 +/- 2.5 mA [lower limit of vulnerability (LLV)] and < 26 +/- 13 mA [upper limit of vulnerability (ULV)] induced a single stationary reentrant wave front that lasted 3 +/- 2.5 s with a period of 159 +/- 17 ms (16 episodes). AC shortened the refractory period from 100 +/- 12 to 59 +/- 9 ms (P < 0.001) and increased vulnerability to reentry induction by simultaneous decrease in the LLV (0.7 +/- 0.2 mA, P < 0.001) and an increase in the ULV (82 +/- 24 mA, P < 0.01). ACh accelerated the rate (period of 110 +/- 16 ms, P < 0.001) and converted the stationary reentrant wave front to a nonstationary (meandering) reentrant wave front showing polymorphic electrograms, i.e., "fibrillation-like" activity (22 episodes). Rapid meandering of the reentry tip led to wave front breakup (18 episodes) and the generation of new wave fronts (19 episodes). These wave front dynamics also led to sustained (76 +/- 224 s, P < 0.001) fibrillation-like electrograms. We conclude that ACh increases the ULV and promotes meandering of a single reentrant wave front, leading to breakup and the generation of new wave fronts. Single meandering and complex wave front dynamics cause fibrillation-like activity and sustain the activity for longer duration.
Acetylcholine↗
Effect of thyroid hormone on urinary excretion of epidermal growth factor.
Thyroid hormones were demonstrated to upregulate the synthesis of epidermal growth factor (EGF) mRNA and proEGF in the kidneys in vivo. This prospective study was performed to examine the extent of the hypothyroid state in modulating EGF excretion in the urine (U-EGF; n = 23). Patients with thyroid cancer were serially followed up from the euthyroid status, which was retained by thyroxine supplement after thyroidectomy, to the hypothyroidism in preparing for 131I whole body scanning. Paired thyroid function panel, including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and U-EGF levels were measured on a weekly basis. Logarithmically transformed values of U-EGF were inversely correlated with TSH serum levels (p = 0.0000), but positively associated with T4 levels (p = 0.0005). No apparent correlation was observed with the T3 serum content, age and gender of the patients (p > 0.1, respectively). If the interval of measurement was taken into consideration, serum TSH was the most significant factor in association with U-EGF (p = 0.0003). Our data indicate that excretion of EGF in human urine depends substantially upon thyroid hormone support.
Adult↗
Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome.
To determine the efficacy of cortisol and its metabolite, cortisone, measured simultaneously by high performance liquid chromatography (HPLC) in the diagnosis of Cushing's syndrome, we retrospectively reviewed the histories of 29 surgically proven Cushing's syndrome patients (20 Cushing's disease, 5 ectopic ACTH syndrome, and 4 adrenal Cushing's syndrome) and 6 patients with exogenous Cushing's syndrome. These 35 patients had urinary free cortisol determined by both HPLC and competitive binding methods. The efficacy of the HPLC assay using cortisol alone was equivalent to that of the competitive binding assay; 22 of 29 (76%) patients had increased cortisol. Cortisone also aided in the diagnosis; 25 of 29 (86%) had increased cortisone. Twenty-seven of the 29 (93%) patients had either both cortisone and cortisol (n = 19) or at least 1 of the 2 (n = 8) increased. All 6 patients with exogenous Cushing's syndrome had suppressed urinary free cortisol, cortisone, and the presence of prednisone and prednisolone. In the competitive binding assay, all exogenous Cushing's patients had falsely increased cortisol results. In conclusion, urinary free cortisol plus cortisone determined simultaneously by HPLC added a new dimension to the diagnosis of Cushing's syndrome. It should be considered when exogenous Cushing's syndrome is suspected or when only one urinary cortisol test is allowed to be ordered.
ACTH Syndrome, Ectopic↗