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Biomedical subjects

S Chan

Publications and source records attributed to S Chan.

At least 235 records · Page 13Linked to original sources

Antihypertensive therapy with prazosin in patients with left ventricular dysfunction. Improvement in cardiac performance and exercise tolerance.

Although the relationship between blood pressure and cardiac performance has been widely recognized, there are few published clinical observations concerning the effect of blood pressure control on cardiac function. We evaluated the effect of prazosin, an antihypertensive agent which also improves hemodynamic measurements in normotensive patients with heart failure, in 16 patients with moderate hypertension and reduced ejection fractions. Therapy with digoxin and diuretics was continued throughout the study, but other antihypertensive agents were withdrawn at least one week prior to the initiation of the study. Measurements of ejection fraction, cardiothoracic ratio and the duration of maximal treadmill exercise were made before and after two months of antihypertensive therapy with prazosin. On prazosin, blood pressure fell from a mean of 169/103 to 141/84. Excellent control was achieved in 13/16 patients and significant reductions were noted in the remaining three. Concomitantly, ejection fraction rose from .38 +/- .02 (SEM) to .43 +/- .03 (P less than .02), cardiothoracic ratio decreased from .55 +/- .02 to .53 +/- .02 (P less than .05) and exercise capacity increased from 9.2 +/- 0.9 to 11.9 +/- 1.1 minutes (P less than .005). Prazosin was well tolerated except in one patient who experienced worsening angina. These findings emphasize the importance of rigorous blood pressure control in hypertensive patients with left ventricular dysfunction and indicate that prazosin is effective in this setting.

Aged↗

The serum sodium concentration after surgical operation: precision permits predictions.

In view of previous conflicting reports, the distribution of a water overload was investigated in 6 healthy volunteers. The fall in serum sodium was predictable from prior measurement of total body water (tritium) confirming that the induced hyponatraemia was dilutional. Using a standard intravenous fluid regimen, a prospective study for 6 days on 50 patients undergoing major abdominal surgery established a confidence band for change in serum sodium concentration. This band not only enables precise prediction of whether observed sodium values in patients are "normal' for that point in their postoperative course, but also demonstrates that changes are more prolonged than was at first thought. Their dilutional nature following uncomplicated surgery is supported by linear relationships between serum osmolality and serum sodium (s-Osm = 1.86 [s-Na+] + 18:74; (P < 0.001) and between observed and calculated osmolality (Obs-Osm = 0.97 [Calc-Osm] + 15.11; P < 0.001). More detailed investigation of 14 patients by isotope dilution provided independent evidence of dilutional change. This conclusion is additionally supported by lesser changes in patients on a more restricted fluid regimen. As a practical confirmation of the utility of this approach, departures from the simple dilutional relationships were observed in 7 critically ill patients whose postoperative course was complicated. In this group osmolal "gags' of 20-50 mosmol/kg were identified. Current standard postoperative fluid regimens cause dilutional changes; these are predictable and provide a yardstick for use in management of both the healthy and the ill surgical patient.

Adult↗

Evaluation of a high-resolution electrophoresis system.

A high-resolution electrophoresis system (Panagel) is evaluated by comparing the results with Microzone electrophoresis and with quantitation of individual protein fractions by the radial immunodiffusion technic and by the SMA system. The high-resolution electrophoresis showed a higher percentage of gamma globulin and a lower percentage of albumin than the Microzone system, with the alpha-1, alpha-2, and beta globulins being similar in quantity. The eight protein fractions studied: albumin, alpha-1 antitrypsin, alpha-2 macroglobulin, haptoglobin, beta-lipoprotein, C3 complement, and gamma globulin, correlated very well with the corresponding components in the various methods used. The normal values of the protein fractions were determined.

Adult↗

Dose-response behavior on the isolated rat uterus of oxytocin analogs with modifications at binding sites.

The dose-response behavior on the in vitro rat uterus of analogs of oxytocin with modification at sites in the molecule which have been predicted to contribute to the binding of the peptide to the smooth muscle receptor have been studied. Dose-response curves of [7-(3,4-dehydroproline)]oxytocin, [7-glycine]oxytocin, [7-alanine]oxytocin, deamino-[7-glycine]oxytocin and [4-threonine,7-glycine]oxytocin were determined and compared with that of oxytocin. The authors found that neither the slope of the curves nor the maximal response obtained for any of the analogs differed significantly from the hormone. The uterotonic potencies of the analogs corresponded to the relative positions along the concentration axis of their dose-response curves and to their affinities as determined by their pD2 values. The authors tentatively concluded that differences in uterotonic potencies of these analogs are in fact the result of differences in their affinity for the uterine receptor. The experimental identification of position 7 of neurohypophyseal peptides as a hormone-receptor binding site corroborates such a proposed role for the side chain of this residue based on earlier conformation-activity considerations.

Animals↗

The use of laser capture microdissection (LCM) and quantitative polymerase chain reaction to define thyroid hormone receptor expression in human 'term' placenta.

UNLABELLED: Term 'villous' placenta consists of a heterogeneous mix of different cell types comprising the trophoblast layers, villous stroma and fetal blood vessels. The importance of using techniques which allow investigation of pure populations of cells has been increasingly recognised. We demonstrate the use of laser capture microdissection (LCM) in combination with quantitative RT-PCR (QPCR) to assess the relative expression of mRNAs encoding the major thyroid hormone receptor (TR) isoforms (alpha1, alpha2 and beta1) in trophoblasts (syncytiotrophoblast and cytotrophoblast layers) compared with stromal cells in human term placenta. Highly reproducible results for each gene were obtained for each placental sample studied (n = 6). There was significantly less mRNA encoding TRalpha1 (68%; p = 0.05) and TRbeta1 (40%; p = 0.03) in the trophoblast layer compared to the heterogeneous stromal cells. However, there was no significant difference in TRalpha2 mRNA expression between the two groups of cells. CONCLUSION: LCM with QPCR can precisely locate and accurately quantify mRNA expression in specific cell populations from placental tissue.

Adult↗

Evaluation of reproductive outcomes in women inadvertently exposed to hexachlorobenzene in southeastern Turkey in the 1950s.

In southeastern Turkey during the period of 1955-57, women were accidentally exposed to the fungicide hexachlorobenzene (HCB) after eating contaminated seed grain and developed porphyria cutanea tarda (PCT). While HCB has been shown to be a potent oocyte toxicant in primates and has been identified as an ovarian follicular fluid contaminant in women, its effect on human reproduction is poorly understood. This study was undertaken to evaluate the effects of HCB on women with a known high dose exposure. A retrospective controlled cohort comparison study of three groups was conducted. Group 1, those with confirmed PCT; Group 2, controls for the region and Group 3, controls for the country of Turkey, were followed-up after approximately 40 years (n=42/group). Blood samples were taken for analysis of serum HCB, estradiol, follicle-stimulating hormone (FSH) and inhibin. Frequency of HCB detection was greatest in Group 3, while number of cases with HCB values exceeding 1 ng/mL was significantly greater in Groups 1 and 2. There were no differences in the other biochemical measures. Interviews were completed for each patient regarding reproductive history (number of pregnancies, live births, spontaneous abortions, still births and sex of live babies). Multiple comparisons of the three groups, based on Fisher's test found the groups were inhomogeneous. When serum HCB was analyzed using correlated response logistic regression, there was a strong relationship between serum HCB levels and risk for spontaneous abortion but not sex ratio of children. The following findings were made. HCB is detectable and ubiquitous in serum samples from women in the country of Turkey with identified and unidentified exposure events. Spontaneous abortion risk is not restricted to women with identifiable exposure to HCB but to a surrogate marker of exposure (serum HCB sample). The risk of spontaneous abortion with HCB exposure requires further investigation.

Abortion, Spontaneous↗

Atrial septal aneurysm: a new classification in two hundred five adults.

Atrial septal aneurysm is a localized "saccular" deformity, generally at the level of the fossa ovalis, which protrudes to the right or the left atrium or both. For 39 months we prospectively analyzed 205 consecutive patients in whom atrial septal aneurysm was diagnosed echocardiographically. The direction and movement of atrial septal aneurysms were carefully studied in multiple views, and, according to our findings, we now propose a new classification: type 1R if the bulging is in the right atrium only, type 2L if the bulging is in the left atrium only, type 3RL if the major excursion bulges to the right atrium and the lesser excursion bulges toward the left, type 4LR if the maximal excursion of the atrial septal aneurysm is toward the left atrium with a lesser excursion toward the right atrium, type 5 if the atrial septal aneurysm movement is bidirectional and equidistant to both atria during the cardiorespiratory cycle. We found an incidence of 1.9%, a mean age of 63 years (25 to 97 years), a female/male ratio of 2:1, valvular regurgitation 74%, hypertension 64%, left ventricular hypertrophy 38%, coronary heart disease 32%, patent foramen ovale 32%, pulmonary hypertension 31%, stroke 20%, dysrhythmias 16%, valvular prolapse 15%, and atrial septal defect 3%. No differences were found between mobile and motionless types of atrial septal aneurysm. However, differences were found between predominantly left bulging or right bulging atrial septal aneurysm (134 versus 57 patients), as well as other variables. All types of atrial septal aneurysm have particular clinical or echocardiographic characteristics. The new classification is a complete, simple, and practical form. Atrial septal aneurysm is associated with congenital and acquired heart diseases but also can present as an isolated abnormality.

Adult↗

Spectral analysis of sudden bradycardia during intrathecal meperidine anesthesia.

BACKGROUND AND OBJECTIVES: Severe bradycardia occurring suddenly during spinal anesthesia, although rare, is potentially fatal. Bradycardias are more common after intrathecal meperidine. We report two such episodes occurring in elderly male patients undergoing transurethral surgery. METHODS: Subarachnoid block was provided using 50 mg meperidine. Autonomic function was assessed by measuring heart rate (HR) variability using R-R intervals from standard electrocardiographic recordings. Frequency-domain spectra were constructed from 512 heartbeats, and an autoregressive method was used to calculate spectral power. RESULTS: In both patients, bradycardia (HR <50 beats/min) occurred after about 10 minutes and was associated with severe hypotension and a 10- to 100-fold increase in spectral density in both the low (0.04-0.15 Hz), mainly sympathetic, and the high (0.15-0.40 Hz), mainly parasympathetic, frequency bands. These spectral increases were subsequently attenuated by intravenous atropine. Heart rate slowing was noted to be periodic, or oscillatory, in one patient. CONCLUSION: Sudden increases in vagal, or parasympathetic, activity probably accounted for bradycardia.

Adjuvants, Anesthesia↗

Versatile expression system for rapid and stable production of recombinant proteins.

Previously we reported the development of a novel expression system with Tat/TAR-oriP vectors and HKB11 cell line, which supports high level protein expression (Cho et al. Cytotechnology 2001, 37, 23-30). In the present study, we further demonstrated that HKB11 cells are suitable for high throughput expression (microgram scale) of genomic candidates in transient transfection system for in vitro evaluation of biological functions. HKB11 cells were also shown to support the production of milligram to gram quantities of protein drug candidates for in vivo evaluation of efficacy in various disease models. Stable HKB11 clones secreting high levels of a tissue factor (TF; 40-50 pg/c/d) and B-domain deleted recombinant factor VIII (BDDrFVIII; 5-10 microU/c/d) were derived under serum-free conditions. The specific productivity for these two proteins from the HKB11 cells was 10-fold greater than those from CHO cells derived under the similar conditions. In conclusion, we have demonstrated that the HKB11 cell line is well-suited for transient and long-term production of recombinant proteins.

Animals↗

Limbic system abnormalities associated with mesial temporal sclerosis: a model of chronic cerebral changes due to seizures.

In a landmark 1966 study, widespread cerebral abnormalities were discovered at histopathologic examination of autopsied brains from patients with long-standing temporal lobe epilepsy. In the brains diagnosed with mesial temporal sclerosis (MTS), these abnormalities involved not only the hippocampus but also other structures of the limbic system and medial temporal lobe. Many of these changes are evident at magnetic resonance imaging. Because many of these abnormalities are found within limbic structures along a known neuroanatomic pathway (the Papez circuit), they suggest a pattern of cerebral damage related to the physiologic interconnections between the hippocampus and associated limbic structures. It appears that limbic damage associated with MTS more often affects the structures most closely connected to the hippocampus along the Papez circuit. The frequency and widespread distribution of these cerebral abnormalities suggest that MTS is not limited to the medial temporal lobe but instead represents a limbic system disorder.

Amygdala↗

Establishment of a human somatic hybrid cell line for recombinant protein production.

Cell fusion techniques were used to derive mammalian host cell lines suitable for large-scale production of therapeutic proteins. Although the 293S cell line, of human embryonic kidney origin, is an excellent host cell for mammalian gene expression, these cells have a tendency to form large and tight aggregates in suspension cultures and bioreactors. To solve the problem of aggregation, 293S cells were fused to a human suspension cell line, 2B8 (a Burkitt's lymphoma derivative), using polyethylene glycol (PEG). The PEG-treated 293S and 2B8 cells were selected in a medium supplemented with hypoxanthine-aminopterin-thymidine and G418 (1 mg/ml) to eliminate nonfused cells. These hybrid clones, designated as HKB (hybrid of kidney and B cells), are negative for endogenous immunoglobulin expression. Most clones are readily adaptable to serum-free suspension culture under shaking conditions without forming large and tight aggregates. One clone, HKB11, was shown to support high-level expression of cytokines [interleukin (IL)-2 and IL-4], ICAM-1 and rFVIII in a side-by-side comparison with 293 and Chinese hamster ovary cells. The above-described characteristics of HKB cells indicate that HKB11 is a favorable cell host for the production of human therapeutic proteins.

Burkitt Lymphoma↗