A new clue to clavicular fracture in newborn infants?
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Biomedical subjects
Publications and source records attributed to M K Chung.
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Studies conducted in our laboratory have demonstrated that activated immune cells produce a soluble inhibitor(s) of cardiac myocyte contractile and cyclic AMP (cAMP) responses to beta-adrenergic stimulation. To examine the mechanism of this effect, metabolic assays were conducted on cultured rat cardiac myocytes incubated in the presence and absence of supernatants harvested from rat activated splenocyte cultures. Intracellular cAMP accumulation in response to isoproterenol was inhibited by up to 74% in a dose-dependent fashion by conditioned media containing soluble cytokines from activated immune cells. By use of myocyte cultures in which contaminating nonmyocyte proliferation was inhibited by nonlethal irradiation, this phenomenon was shown to be independent of mitogenic effects. Isobutylmethylxanthine, a phosphodiesterase inhibitor, did not ablate cytokine-induced inhibition of cAMP accumulation. Parameters of beta-adrenergic receptor binding and affinity were also unaffected. cAMP suppression was maintained after cholera toxin stimulation of cAMP production via stimulatory G protein ADP-ribosylation. cAMP inhibition was not apparent when cells were stimulated with forskolin, a direct adenylate cyclase activator. Importantly, pertussis toxin treatment significantly ablated cytokine-induced cAMP inhibition. Thus, interference with agonist-occupied beta-adrenergic receptor coupling to adenylate cyclase to produce cAMP and subsequent contractile responses is induced by a factor(s) elaborated by activated immune cells. This interference occurs at the level of signal transduction across the membrane, can be overridden by pertussis toxin, and may involve changes in the coupling of the stimulatory/inhibitory G proteins to adenylate cyclase. These results demonstrate a novel mechanism of cytokine-induced myocyte dysfunction and may have important pathophysiological ramifications in immune-mediated myocardial diseases.
Patients who presented with a chief complaint of headache in the outpatient family practice setting were found to have a high prevalence of depression (63%) by the Zung Self-Rating Depression Scale (SDS) index. A statistically significant relationship was found between the frequency of headaches (P = .03) with level of depression. In fact, 74% of patients with headaches recurring almost every day had a clinically significant depression diagnosed as defined by the Zung SDS score. The Zung SDS score also correlated with the length of time that the problem of headache existed (P less than .05). Item analysis of the individual 20-item depression score revealed that four questions accounted for 93% of the variance. This analysis suggests that shorter, more abbreviated screening questions could be developed and refined in the future for use by the busy clinician. Headache is an important marker for depression in the primary care setting. It can be inferred from this study that the clinician may need to focus more on treating the entity of depression than on treating just the symptom of headache.
Reversible congestive heart failure can accompany cardiac allograft rejection and inflammatory myocarditis, conditions associated with an immune cell infiltrate of the myocardium. To determine whether immune cell secretory products alter cardiac muscle metabolism without cytotoxicity, we cultured cardiac myocytes in the presence of culture supernatants from activated immune cells. We observed that these culture supernatants inhibit beta-adrenergic agonist-mediated increases in cultured cardiac myocyte contractility and intracellular cAMP accumulation. The myocyte contractile response to increased extracellular Ca2+ concentration is unaltered by prior exposure to these culture supernatants, as is the increase in myocyte intracellular cAMP concentration in response to stimulation with forskolin, a direct adenyl cyclase activator. Inhibition occurs in the absence of alteration in beta-adrenergic receptor density or ligand binding affinity. Suppressive activity is attributable to the macrophage-derived cytokines interleukin 1 and tumor necrosis factor. Thus, these observations describe a role for defined cytokines in regulating the hormonal responsiveness and function of contractile cells. The effects of interleukin 1 and tumor necrosis factor on intracellular cAMP accumulation may be a model for immune modulation of other cellular functions dependent upon cyclic nucleotide metabolism. The uncoupling of agonist-occupied receptors from adenyl cyclase suggests that beta-receptor or guanine nucleotide binding protein function is altered by the direct or indirect action of cytokines on cardiac muscle cells.
In the investigation of lower back stress, the muscle forces of the erector spinae and the rectus abdominis are often calculated using the two-dimensional biomechanical model. These muscle forces are used to estimate the compressive forces at L5/S1 disc. This paper presents a study of the muscle forces predicted by a two-dimensional biomechanical model during pushing and pulling and myoelectric activity from the corresponding muscles. The goal was to investigate whether a simple two muscle torso model would reasonably estimate the muscle actions in pushing and pulling tasks. Six subjects participated in the experiment. EMG (rms) value was used as an indicator of muscle forces. The results show high correlation between the predicted muscle forces and the measured root-mean-square EMG values in trunk pushing and pulling (r2 = 0.93) and hand pushing and pulling (r2 = 0.96) in an erect posture with hips braced but low in hand pushing and pulling using a free posture (r2 = 0.37).
We hypothesize that reversible depression of cardiac function in cardiac allograft rejection and lymphocytic myocarditis reflects down modulation of the beta-adrenergic receptor system by a soluble product of activated immune cells. Thus, exposure of cultured cardiac myocytes to mixed lymphocyte culture or activated splenocyte supernatants produces 70% inhibition of isoproterenol-stimulated cAMP concentrations (Ki = 5% supernatant) in the absence of gross cellular injury or control media effects. This cAMP suppressive factor is not dialyzable and is ammonium sulfate precipitable. Beta-adrenergic receptor density, binding constant and affinity states are unaffected. These results demonstrate the existence of a cytokine inhibitor of cAMP accumulation that may mediate, in part, depression of cardiac contractility observed when immune cells invade the myocardium.
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Quadriceps contracture in children can result from multiple intramuscular injections. We describe here seven patients with this complication. These patients were unable to completely flex the involved knee. At surgery, extensive fibrosis of the quadriceps muscle was found. Lengthening of the scar and contracted muscle and tendon restored a good deal of flexion. If long-term antibiotic treatment is anticipated, the intravenous route should be employed if possible.
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DW-116 is a newly developed fluoroquinolone antibacterial with a broad spectrum against both Gram-positive and Gram-negative bacteria. We have reported recently that DW-116 is embryotoxic and teratogenic in rats. The present study was conducted to investigate the teratogenicity of DW-116, together with maternal toxicity and developmental toxicity using New Zealand White rabbits. The test chemical was administered by gavage to pregnant rabbits from gestational day (GD) 6 through to GD 18 at dose levels of 0, 5, 19.5 and 76.1 mg kg(-1) day(-1). All does were subjected to caesarean section on day 28 of gestation and their foetuses were examined for external, visceral and skeletal abnormalities. In the 76.1 mg kg(-1) group, a minimal maternal toxicity, as evidenced by decreased body weight gain during treatment period, was observed in pregnant rabbits. Significant embryo-foetal toxicity, including increased number of foetal deaths and delayed foetal ossification, was seen. However, no treatment-related morphological changes were detected in foetal external, visceral and skeletal examinations. There were no adverse effects on either pregnant dams or embryo-foetal development at 19.5 and 5 mg kg(-1). It was concluded that administration of DW-116 during the major organogenetic period in rabbits produced decreased maternal body weight gain, increased number of foetal deaths and foetal developmental delay but no evidence of teratogenicity. The no-observed-adverse-effect levels (NOAELs) of DW-116 are considered to be 19.5 mg kg(-1) day(-1) for does and embryo-foetuses, respectively.
The increased embryotoxicity of pyrimethamine (PYM) with concomitant oral dosing of folic acid (FA) was examined in rats. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (PYM 1.2 mg/kg/day), FA (FA 50 mg/kg/day), PYM I+FA (1.2 and 50 mg/kg/day, respectively), PYM II (2.7 mg/kg/day), PYM II+FNA (2.7 and 12 mg/kg/day, respectively), and a vehicle control group. The agents were administered for 11 days from day 7 throughout 17 of gestation. PYM and FA were administered by gavage and FNA was administered intraperitoneally. Visceral and skeletal malformations were observed in the fetuses of both PYM I+FA and PYM II groups; these included dilatation of the lateral ventricle and fused ribs. No malformed fetuses were observed in the fetuses of the other four groups. External malformations were observed only in the fetuses of PYM II groups; these included cleft palate, cleft lips, and brachygnathia, among others. These results show that the concomitant gavage dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also confirmed.
DA-125 is a new anthracycline antitumor antibiotic derived from adriamycin. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin. The potential of DA-125 to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred twenty mated SD rats (sperm in vaginal lavage = day 0) were distributed among three treated groups and a control group. DA-125 was given at dose levels of 0, 0.1, 0.3, and 1.0 mg/kg/day administered intravenously to pregnant rats from days 7 to 17 of gestation. All dams were subjected to caesarean section on day 20 of gestation. At 1 mg/kg/day, reduced food intake, reduced body weight, and decreased spleen weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 11.9, 41.8, and 14.5%, respectively. Characteristic malformations included exencephaly, gastroschisis, cleft lip, dilatation of lateral and third ventricles, and fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3 mg/kg. The results show that DA-125 is teratogenic at a minimally maternally toxic dose in rats.
SKI 2053R, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. The potential of SKI 2053R to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred mated rats (sperm in vaginal lavage = Day 0) were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rats from Days 6 to 16 of gestation at dose levels of 0, 0.75, 1.5, and 3.0 mg/kg/d. All dams were subjected to caesarean section on Day 20 of gestation. At 3 mg/kg, reduced food intake, reduced body weight, and decreased liver weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of visceral and skeletal malformations occurred at an incidence of 18.5 and 6.0%, respectively. Characteristic malformations included dilated cerebral ventricle, anophthalmia, microphthalmia, fused or absent cervical arch, fused thoracic arch, fused thoracic centrum, and fused rib, among others. Delayed ossification of both sternebrae and metatarsals was also observed. There were no signs of maternal toxicity or embryotoxicity at 0.75 and 1.5 mg/kg. The results show that SKI 2053R is embryotoxic at a minimally maternally toxic dose in rats.
To assess the testicular cytotoxicity induced by DA-125, a new anthracycline anticancer agent, 50 male Sprague Dawley rats were randomly assigned to five groups, with 10 rats in each group, and were given different single intravenous doses of DA-125 at dose levels of 0, 6.25, 12.5, 25, and 50 mg/kg body weight. On Day 56 after treatment, all male rats were killed and necropsied. Parameters of testicular cytotoxicity included genital organ weights, testicular sperm head counts, epididymal sperm motility and morphology, repopulation index, epididymal index, and histopathologic examinations. At 25 and 50 mg/kg, the weights of testes, epididymides, and seminal vesicles were reduced dose-dependently, but prostate weight was not different among the groups. At 50 mg/kg, the number of testicular sperm heads was decreased. However, the motility and morphology of epididymal sperm were comparable to the control values. On histopathologic examination, atrophy of seminiferous tubules, loss or decrease of germ cells, formation of multinucleated giant cells, and/or vacuolization of Sertoli cells in the testis were observed at 25 and 50 mg/kg. In addition, decreased sperm content and increased degenerative germ cells in the ductus epididymis were also found. Some recovery of spermatogenesis was observed at 25 mg/kg, whereas a decline in the repopulation index was observed at 50 mg/kg, indicating that the surviving stem cells had become unable to produce differentiated germ cells to enter the spermatogenic pathway. There was no evidences of testicular cytotoxicity at 6.25 and 12.5 mg/kg. These results indicate that administration of a single dose of DA-12.5 (25 to 50 mg/kg) results in testicular damage in male Sprague-Dawley rats.
OBJECTIVES: We evaluated atrial transport function after the Maze procedure in long-term follow-up and compared left and right atrial function in Maze patients with that of healthy age-matched controls using echo Doppler techniques. BACKGROUND: The Maze procedure is designed to eliminate atrial fibrillation, restore normal sinus rhythm, and preserve atrial contraction. Initial data indicate that atrial transport function is restored in most patients undergoing the Maze procedure. The long-term echo Doppler evaluation of patients after the Maze procedure has not been well described. METHODS: We performed pulsed-wave Doppler and two-dimensional echocardiographic studies on 31 patients (24 men, mean age 53.8 years) who underwent the Maze procedure and who had a follow-up study greater than 3 months (mean 16.5 months) after the procedure. Measurements included peak left ventricular and right ventricular inflow A-wave velocity, maximum and minimum left atrial and right atrial areas, and fractional area change of the left and right atria. Results were compared with those obtained from 15 age-matched control subjects (11 men, mean age 53.8 years). RESULTS: Twenty-two patients (71%) had left atrial function shown by the presence of left ventricular inflow A-wave, and 25 patients (81%) had right atrial function shown by the presence of right ventricular inflow A-wave on Doppler echocardiography. The left ventricular inflow A-wave velocity was significantly lower than that of age-matched controls (37.5 +/- 15.5 versus 61.0 +/- 13.9 cm/sec; p < 0.001), whereas the right ventricular inflow A-wave velocity did not significantly differ between patients and control subjects (35.4 +/- 9.9 versus 35.3 +/- 4.9 cm/sec; p = Not significant). Although left and right atrial areas decreased significantly after the procedure, there was no significant change in the fractional area change which was smaller in Maze patients than control individuals. CONCLUSIONS: (1) In long-term follow-up of 16.5 months after the Maze procedure, left atrial systolic function was preserved in 71% of our patients and right atrial systolic function was preserved in 81%; (2) the left ventricular inflow peak A-wave velocity after Maze is considerably less than that in age-matched controls; and (3) left and right atrial sizes decreased after the procedure with no change in the fractional area change. These findings suggest that the Maze procedure is effective in restoring atrial function in the majority of patients; however, restored function is less than in control individuals.
Atrial flutter is a macroreentrant arrhythmia that is associated with cardiovascular and pulmonary disease. In the United States, 200,000 new cases of atrial flutter can be expected to develop every year with a male to female ratio of over 2:1. This arrhythmia is associated with atrial fibrillation in over half the cases. It is also associated with an increased risk of thromboembolic complications, but less than that is seen with atrial fibrillation. The most common form of atrial flutter involves a large reentrant circuit within the right atrium, encircling the tricuspid annulus. Other, less common forms of atrial flutter may involve other anatomic barriers, atriotomy scars, and infarcted areas of the atria. Treatment of atrial flutter often involves electrical cardioversion and/or antiarrhythmic medications. Type I and Type III antiarrhythmic drugs are often used to terminate or prevent recurrent episodes and Type II (beta-blockers) and Type IV (calcium channel blockers) can be used to control the ventricular rate during atrial flutter. However, antiarrhythmic drugs alone control atrial flutter in only 50% to 60% of patients. Since the early 1990s, radiofrequency catheter ablation has been used to interrupt the reentrant circuit and prevent recurrences of atrial flutter. Radiofrequency ablation is acutely successful in over 90% of cases and avoids the long-term toxicity seen with antiarrhythmic drugs. Advanced mapping techniques and newer methods of delivering the radiofrequency lesions are being used to delineate unusual forms of atrial flutter and to minimize fluoroscopic exposure during the procedure.
OBJECTIVES: To determine whether a modified technique for laparoscopic extracorporal oophorectomy is less complicated and safer than traditional laparoscopic oophorectomy. METHODS: Four obese patients in their second trimester underwent open laparoscopy for treatment of large ovarian cysts. A Cook Ob/Gyn special cyst aspirator with a 14-gauge aspirating needle was inserted into the abdomen to drain the ovary through a separate 10-mm port; the site of insertion depends on the location of the ovary. After the cyst was decompressed, the 10-mm incision was enlarged to 3 cm, and either extracorporal oophorectomy or cystectomy was performed. RESULTS: No complications occurred. Average blood loss was less than 15 cc; average carbon dioxide insufflation time was less than 20 minutes. Average operating time was 40 minutes, which was significantly less than traditional laparoscopic oophorectomy. The patients were discharged in less than 23 hours. Patient A had a 500-cc dermoid cyst, and subsequently had a normal vaginal delivery at term. Patient B had a 1600-cc cyst removed. She had a cesarian delivery due to cephalopelvic disproportion. Pathological analysis of the specimen identified the mass as a dermoid cyst and serous cystadenoma. Patient C had a 3200-cc ovarian cyst. Currently, she is in her 24th week of gestation. Patient D had a 700-cc simple ovarian cyst removed at her 16th week of gestation. CONCLUSIONS: Laparoscopic extracorporal oophorectomy requires significantly less CO2 insufflation time and a shorter operation time, hence, decreasing the adverse effects on the fetus. The enlarged second trimester uterus made traditional laparoscopy more complicated. Performing the procedure extracorporally decreased the possibility of operative complications.