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Biomedical subjects

K Kulig

Publications and source records attributed to K Kulig.

At least 37 records · Page 2Linked to original sources

Search for new antiarrhythmic and hypotensive compounds. Synthesis, antiarrhythmic, antihypertensive, and alpha-adrenoceptor blocking activity of novel 1-[(2-hydroxy-3-amino)]-propylpyrrolidin-2-one derivatives.

A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl])propyl]-pyrrolidin-2- one (MG-1) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for alpha 1- and alpha 2-adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for alpha 1- and alpha 2-adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.

Adrenergic alpha-Antagonists↗

Predictors of coronary artery disease in patients with cocaine-associated myocardial infarction. Cocaine-Associated Myocardial Infarction (CAMI) Study Group.

PURPOSE: To identify clinical criteria predictive of underlying coronary artery disease in patients with cocaine-associated myocardial infarction. PATIENTS AND METHODS: Using a retrospective cross-sectional study design at 29 acute care hospitals, we identified 70 patients with cocaine-associated myocardial infarction who had a determination of the presence or absence of coronary artery disease. Clinical characteristics of patients with coronary artery disease (> 50% stenosis on cardiac catheterization or reversible ischemia on stress test) were compared with patients without coronary artery disease (< 50% stenosis on cardiac catheterization). RESULTS: Compared with patients without coronary artery disease (n = 21), patients with coronary artery disease (n = 49) were older (42 versus 31 years; P < 0.001), had more traditional cardiac risk factors (2.3 versus 1.5; P < 0.001), more frequent history of hypertension (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.4 to 20.4); more frequent family history of myocardial infarction (OR, 4.4; 95% CI, 1.3 to 15.1), more bradydysrhythmias (OR, 8.0; 95% CI, 1.0 to 65.5), and more likely to have an inferior infarct location (P = 0.04). CONCLUSION: Age, number of cardiac risk factors, location of myocardial infarction, and bradydysrhythmias predict underlying coronary artery disease in patients with cocaine-associated myocardial infarction. If validated, this knowledge may be used to develop a medically appropriate, cost-effective evaluation strategy for patients following cocaine-associated myocardial infarction.

Adult↗

Acute medical costs of fluoxetine versus tricyclic antidepressants. A prospective multicentre study of antidepressant drug overdoses.

Despite demonstrated differences in toxicity profiles between tricyclic antidepressants (TCAs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), no studies have examined hospital costs associated with acute antidepressant overdoses. Given the high incidence of such overdoses, it is important to examine treatment patterns and associated costs. This prospective, multicentre cohort study compared the hospital and physician costs associated with TCA and fluoxetine drug overdoses. Over a 30-month period, 622 consecutive patients with a fluoxetine or TCA overdose presented to the emergency departments, or were admitted to intensive care or medical units, of 9 participating medical centres across the US. Inclusion criteria were: ingestion of a single antidepressant (fluoxetine or a TCA), without clinically significant co-ingestants; laboratory confirmation of the overdose; and retrievable hospital bills. Patients were followed until discharge from the emergency department or hospital. Hospital and physician charges were collected from billing data. Hospital charges were adjusted using Health Care Financing Administration cost: charge ratios to estimate costs; physician charges were adjusted to estimate costs. Patient demographic and clinical data were prospectively gathered during the course of medical treatment. Clinical data recorded included level of consciousness, cardiopulmonary complications, vital sign or ECG abnormalities, agitation, seizures, CNS depression and death. 136 patients (121 with TCA overdose and 15 with fluoxetine overdose), representing 21.8% of the 622 patients entered, met the inclusion criteria. Mean length of stay varied from 0.73 [+/-standard error of the mean (SEM) 0.33] days for fluoxetine overdose patients to 3.59 (+/-SEM 0.48) days for TCA overdose patients (p = 0.038). Mean hospital costs were $US668 for patients with a fluoxetine overdose compared with $US4691 for those with a TCA overdose (p < 0.0001). No significant differences were observed between the TCA and fluoxetine overdose groups with regard to physician costs. Median hospital and physician costs increased from $US3029 to $US4396 from the first 15-month period of the study to the second 15-month period of the study for the TCA overdose group, but decreased from $US881 to $US396 for the fluoxetine overdose group. Patients with fluoxetine overdoses had lower hospital and total medical costs compared with patients with TCA overdoses. There was some evidence supporting a reduction in the medical costs of treating fluoxetine overdoses over the 30-month study period.

Adult↗

Urine toxicology screens in drivers suspected of driving while impaired from drugs.

OBJECTIVE: Police departments, in conjunction with the National Highway Traffic Safety Administration, have developed a standardized evaluation aimed at identifying drivers impaired by drugs other than ethanol. These evaluations are performed by specially trained police officers known as Drug Recognition Experts. METHODS: We retrospectively reviewed the evaluations of 242 drivers detained for driving while impaired in the City and County of Denver from January 1, 1988 to June 30, 1990. RESULTS: All drivers had urine toxicology screens performed, which were positive for a mean 1.2 +/- 0.9 SD (range zero to four) for drugs having the potential for causing driving impairment. The 193/242 urine screens (79.8%) testing positive showed the following drugs: cannabis 162 (66.9%), stimulants (including cocaine metabolites) 80 (33.1%), depressants (benzodiazepines and barbiturates) 24 (9.9%), narcotics 12 (5.0%), inhalants (toluene) 1 (0.4%), hallucinogens (LSD) 1 (0.4%), and other 3 (1.2%). Drug Recognition Experts, based on their initial evaluation, were able to predict correctly some or all of the drugs found on the urine screens in 178/242 (73.6%) of cases. Overall agreement between the Drug Recognition Experts opinions and urine screen results had a kappa value (p < 0.05) of 0.41. CONCLUSIONS: There was a high rate (79.8%) of positive urine toxicology screens in drivers suspected of nonethanol drug impairment. In most cases, Drug Recognition Experts were able to reliably predict the results of these screens.

Adolescent↗

Nerve growth factor production by lymphocytes.

Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium from clones or lines positive for NGF mRNA was capable of inducing p140 tyrosine kinase autophosphorylation in 3T3 fibroblasts transfected with cDNA encoding for the tyrosine kinase family NGF receptor. We conclude that lymphocytes synthesize and secrete NGF either as a para-autocrine factor acting on the immune system itself, or as a factor for the maintenance of peripheral neurons.

3T3 Cells↗

Methamphetamine toxicity prevented by activated charcoal in a mouse model.

STUDY OBJECTIVE: To determine the effectiveness of activated charcoal in preventing toxicity from oral methamphetamine HCI. DESIGN: Randomized, prospective, nonblinded, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: CD-1 male mice. INTERVENTIONS: Mice were given 100 mg/kg methamphetamine HCI (lethal dose 60) in water by oral gavage. Within 1 minute of methamphetamine administration, mice received either 1 g/kg activated charcoal or an equivalent volume of water as control. MEASUREMENTS AND MAIN RESULTS: Mice were observed for time to onset of symptoms (piloerection, agitation, and tremor) and mortality at 1, 24, and 48 hours. Activated charcoal delayed onset of symptoms (5.53 +/- 1.25 minutes versus 4.27 +/- 1.22 minutes, P < .002) and decreased mortality compared to controls at 1 hour (1 of 20 versus 10 of 20, P < .003) and 24 hours (five of 20 versus 12 of 20, P < .05). There was no difference between groups in mortality at 48 hours. CONCLUSION: A single dose of activated charcoal given after oral methamphetamine delayed onset of toxicity and decreased early mortality in mice. There was no effect on overall mortality.

Animals↗

Acute zinc chloride ingestion in a child: local and systemic effects.

A 16-month-old boy ingested liquid zinc chloride/ammonium chloride soldering flux. He developed severe local burns, metabolic acidosis, hepatic damage, hyperamylasemia, lethargy, and hypertension. Peak measured plasma zinc was 1,199 micrograms/dL. Because of persistent signs of systemic toxicity, he was chelated with dimercaprol (BAL) and EDTA. Although clinical improvement was noted coincident with the initiation of chelation, there was no apparent increase in urinary zinc excretion. Scarring in the gastric antrum necessitated an antrectomy. The child recovered without other apparent complications.

Acidosis↗

Inhibition of activation-induced changes in the structure of the T cell interleukin-7 receptor by cyclosporin A and FK506.

We have recently shown that activation of T cells causes structural changes in the interleukin-7 receptor (IL-7R) (Foxwell et al. Int. Immunol. 1992, 4: 277). Unactivated cells expressed a receptor characterized as a cross-linked protein of 107-kDa whereas activated cells had reduced levels of this 107-kDa complex and now express a major cross-linked product of 93 kDa. These changes in receptor expression were concomitant with the acquisition of IL-7 growth responsiveness by activated T cells. In this study, the effect of the potent immunosuppressive agents cyclosporin A and FK506 on the activation-induced responsiveness to IL-7-driven proliferation and the concomitant changes in receptor structure have been investigated. Cyclosporin A and FK506 suppressed the expression of the 93-kDa complex and the loss of the 107-kDa complex on activated cells. The presence of exogenous IL-7 inhibited the effects of the drugs on IL-7R structure, allowing expression of the 93-kDa complex. Expression of the 93-kDa complex could also be induced either by ionomycin or phorbol esters. As observed for other T cell activation parameters, only those which induced a calcium signal (ionomycin) but not protein kinase C (phorbol esters) were sensitive to the drugs. In all studies, the expression of the 93-kDa complex correlated with the ability of cells to proliferate to IL-7, and thus these results further support the hypothesis that the 93-kDa form of the IL-7R is required to transmit the cytokine's growth signal. Moreover, these data suggest that activation-induced transcriptional events are required for the expression of the 93-kDa complex and the down-regulation of the 107-kDa complex. As reported for IL-2R and IL-4R, our data also show that the expression of another T cell growth factor receptor is sensitive to the effects of cyclosporin A and FK506. These observations also have important implications for reported cyclosporin A effects on the thymus where IL-7 can act as a growth factor for thymocytes.

Cells, Cultured↗

Prevention of toxicity from oral cocaine by activated charcoal in mice.

STUDY OBJECTIVE: To study the effectiveness of activated charcoal in preventing toxicity after an enterally administered cocaine hydrochloride overdose in mice. DESIGN: A prospective, randomized, controlled animal laboratory investigation. INTERVENTIONS: Fasted mice were given aqueous cocaine hydrochloride (0.8% final concentration) 100 mg/kg body weight orally by gavage tube. One minute later, animals received one of three treatments by gavage: 1 g activated charcoal/kg body weight, 2 g activated charcoal/kg body weight, or an equivolume of water (control). All treatments consisted of 20 mL/kg body weight of an activated charcoal slurry with water. MEASUREMENTS: After 24-hour observation, proportions of seizures and deaths between each group were compared using Pearson chi 2 test followed by Fisher's exact test (P < .017 for significance after Bonferroni's correction). MAIN RESULTS: There were 20 seizures and 16 deaths in the control group (20 mice). There were four seizures (P = .0004) and one death (P = .0004) in the 1-g activated charcoal/kg group (ten mice) and five seizures (P = .0018) and three deaths (P = .015) in the 2-g activated charcoal/kg group (ten mice). CONCLUSION: In this mouse model, activated charcoal decreased the incidence of seizures and death after an enteral cocaine hydrochloride overdose.

Administration, Oral↗

Lithium absorption prevented by sodium polystyrene sulfonate in volunteers.

STUDY OBJECTIVE: To determine if sodium polystyrene sulfonate prevents absorption of lithium in human beings. DESIGN: Prospective, crossover study. TYPE OF PARTICIPANTS: Healthy volunteers age 22 to 34 years (three women and three men). INTERVENTIONS: After an eight-hour fast, subjects ingested 0.5 mEq/kg (18.5 mg/kg) lithium carbonate. One hour later, they ingested either 857 mg/kg sodium polystyrene sulfonate in 4 mL water/g sodium polystyrene sulfonate (experimental) or an equal volume of water without sodium polystyrene sulfonate (control). MEASUREMENTS AND MAIN RESULTS: Serum lithium levels were drawn zero, one, two, three, four, six, eight, ten, 12, and 24 hours after lithium ingestion. The sodium polystyrene sulfonate group had a smaller mean area under the serum concentration curve (11.6 +/- 1.0 mEq/L.hr versus 13.6 +/- 1.5 mEq/L.hr, P < .001) and lower mean highest measured lithium level (0.85 +/- 0.11 mEq/L versus 1.05 +/- 0.10 mEq/L, P < .05) compared with the control group. There was no significant difference in 24-hour urine lithium excretion or in serum sodium and potassium levels. CONCLUSION: Sodium polystyrene sulfonate administration decreased absorption of lithium after a lithium carbonate overdose. Sodium polystyrene sulfonate may be useful clinically for gastric decontamination after lithium overdoses.

Absorption↗

Exchange transfusion and multidose activated charcoal following vancomycin overdose.

The inadvertent administration of a concentrated vancomycin solution to a 47 day-old premature male twin resulted in extremely high vancomycin levels and altered renal function. A 1.5 volume exchange transfusion did not change the measured vancomycin level. Multiple doses of oral activated charcoal, 1 g/kg, were administered beginning 5 h after the exchange transfusion. A calculated half-life of vancomycin before the exchange transfusion was 35 h. The half-life after the exchange transfusion and during charcoal administration was calculated to be 12 h. The only apparent adverse effect of this vancomycin overdose was reversible nephrotoxicity. The infant's hearing, tested by brainstem auditory responses, was normal. The higher volume of distribution of vancomycin in infants may preclude removing significant amounts of this drug by exchange transfusion. Gastrointestinal dialysis with activated charcoal warrants consideration in cases of vancomycin overdose in neonates.

Charcoal↗

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Adult↗