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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 379 records · Page 21Linked to original sources
PubMed1994

Pathophysiologic factors governing the variability of ischemic responses to treadmill and bicycle exercise.

Ischemic responses may vary considerably when patients with coronary artery disease (CAD) are tested serially, but the pathophysiologic mechanisms that govern this variability have not been well evaluated. We thus evaluated whether clinical, hemodynamic, physiologic, and anatomic factors influenced the variability in ischemic responses among 140 patients (mean age 54 +/- 11 years) subjected to both bicycle and treadmill exercise electrocardiography. Radionuclide ventriculography was obtained during bicycle exercise in each patient. The population included 77 patients with CAD, 21 patients with normal coronary arteriograms, and 42 patients with < 5% likelihood of CAD. Bicycle exercise evoked higher systolic blood pressure (p < 0.001) and double-product (p < 0.001) responses compared with treadmill exercise in the patients with CAD and in the normal subjects, and it evoked a lower frequency of chest pain (12% vs 41%, p < 0.001) in the 34 patients with CAD who had ST-segment depression during both exercise tests. There was a high frequency of variability in ischemic responses during treadmill versus bicycle exercise: 22 (39%) of the 56 CAD patients who had exercise-induced ST-segment depression manifested this response during one stress test only. This variability was strongly related to the functional and anatomic magnitude of disease. Ischemic variability decreased progressively as the response of left ventricular ejection fraction (LVEF) to exercise worsened progressively (p = 0.003 by analysis of variance), from 83% in those with an LVEF increase of > 10% with exercise to only 13% in those with an LVEF fall of > or = 5% with exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1994

Regiospecific reduction of polycyclic aromatic quinones by rabbit liver dihydrodiol dehydrogenases.

Dihydrodiol dehydrogenase (DDH) isoenzymes were purified from rabbit liver (Klein et al., Eur. J. Biochem., 205 (1992) 1155), and the major forms CF-1, CF-5 and CM-2 were tested for their substrate specificity with dihydrodiol and quinone metabolites of polycyclic aromatic hydrocarbons. CF-5, which was shown to correspond to aldehyde reductase in rabbit liver, was found to efficiently oxidize aromatic dihydrodiol metabolites (phenanthrene-1,2-dihydrodiol, benz[a]anthracene-3,4-dihydrodiol) while CF-1, corresponding to carbonyl reductase, and CM-2 were much less active. All three enzyme forms were found to reduce polycyclic K-region o-quinones of benz[a]anthracene, chrysene and benzo[a]pyrene. CF-1 was the least active, and CM-2 was the most active form with reaction velocities of > 10 mumol/min.mg protein. Among a range of synthetic quinones tested, benz[a]anthracene-8,9-quinone and benzo[a]pyrene 9,10-quinone were also good substrates for the three enzymes, as well as p-benzoquinone and naphthalene-1,4-quinone. The reduction of polycyclic o-quinones, but not of p-benzoquinone, by enzyme CM-2 was accompanied by the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the formation of catechol metabolites from dihydrodiols and o-quinones may be catalyzed by the same enzymes in rabbit liver, and the reaction rate of the enzymatic reduction is strongly dependent on the structural type of the polycyclic quinone.

Alcohol Oxidoreductases↗
PubMed1994

Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity.

OBJECTIVES: This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing. BACKGROUND: Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only approximately 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity. METHODS: We studied 45 men (mean age +/- SD 58 +/- 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise. RESULTS: During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality; the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 +/- 0.29 to 1.34 +/- 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 +/- 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 +/- 24.5 min) than in Group II (3.6 +/- 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise. CONCLUSIONS: Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Activities of Daily Living↗
PubMed1994

Maternal cocaine use without evidence of fetal exposure.

We report a case of lack of fetal exposure to cocaine and benzoylecgonine as evidenced by meconium and hair analysis, but exposure to nicotine and its metabolite cotinine, after extensive maternal use of cocaine and nicotine. These data suggest that the mode of maternal use of cocaine and individual differences in placental handling of the drug may protect some fetuses, and highlight the need to address interpatient variability.

Adult↗
PubMed1994

Urinary iron excretion depends on the mode of administration of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with homozygous beta-thalassemia.

OBJECTIVE: To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion. HYPOTHESIS: Sustained serum concentrations of L1 will cause more iron chelation than the same daily dose given in larger but less frequent amounts. PATIENTS AND METHODS: Ten patients with thalassemia with a mean age of 20.9 +/- 4.7 years (range, 13 to 27 years), who were receiving regular treatment with 75 to 100 mg/kg/day oral L1, received 75 mg/kg/day L1 orally in equally divided doses: every 6 hours for 3 days and every 12 hours for 3 days. The two study periods occurred 1 month apart immediately after the monthly blood transfusions. Urine was collected for two consecutive 24-hour periods during each of the different schedules. Serial blood samples were collected from six patients over a 6-hour period and analyzed for total L1 and the L1 glucuronide metabolite concentrations. RESULTS: The patient's mean hemoglobin levels (138.8 +/- 12.5 and 139.0 +/- 11.6 gm/L) and ferritin levels (2856.4 +/- 2207.8 and 2890.0 +/- 2264.4 micrograms/L) were similar during the every-6-hour and every-12-hour L1 administrations, respectively. There was significantly more urinary iron excretion when L1 was administered every 6 hours (0.59 +/- 0.29 mg/kg/day) versus every 12 hours (0.40 +/- 0.26 mg/kg/day; p = 0.0129). Calculated 24-hour area under the plasma concentration-time curve of L1 was similar during the every-6-hour (7023.9 +/- 2637.8 mg.min/L) and every-12-hour (7050.1 +/- 1668.8 mg.min/L) experiments. CONCLUSIONS: These data suggest that the sustained presence of L1 in the blood results in greater chelation of iron than that observed with larger, less frequent doses.

Administration, Oral↗
PubMed1994

A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Analgesic, respiratory, and pharmacokinetic effects.

BACKGROUND: A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. METHODS: TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant. RESULTS: There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml for more than 15 s) and episodes of slow respiratory rate (less than 8 breaths/min persisting for more than 5 min) and significantly increased requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl plasma concentration was higher in the TTSF-75 group than in the TTSF-50 group, the differences were not significant. Fentanyl plasma concentration decreased significantly 48 h after patch application. CONCLUSIONS: Application of TTSF patches 2 h preoperatively is associated with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.

Administration, Cutaneous↗
PubMed1994

Effects of extracorporeal membrane oxygenation on morphine pharmacokinetics in infants.

OBJECTIVES: To study the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics of morphine in infants. DESIGN: A prospective, comparative study of morphine pharmacokinetics during and after ECMO. SETTING: The pediatric intensive care unit at a children's hospital. PATIENTS: Seven infants, aged 1 day to 12 months, requiring ECMO. INTERVENTION: Infusion of morphine. MEASUREMENT AND MAIN RESULTS: Steady-state concentrations of morphine were used to generate a morphine clearance rate. Plasma clearance rate of morphine increased from 0.574 +/- 0.3 L/kg/hr to 1.058 +/- 0.727 L/kg/hr after discontinuation of ECMO (p < .01). Two infants experienced a clinical picture consistent with opioid withdrawal. CONCLUSION: Infants requiring morphine after ECMO may require higher dose rates to maintain adequate sedation.

Extracorporeal Membrane Oxygenation↗
PubMed1994

A method for simultaneous measurement of cocaine and nicotine in neonatal hair.

Maternal exposure to drugs and chemicals is increasingly being recognized as adversely affecting the developing fetus. To date, a very large number of fetuses have been exposed in utero to cocaine and cigarette smoke. Neonatal hair as a biological marker for fetal exposure in cocaine and nicotine has emerged as an excellent tool in correlating in utero exposure and outcome. However, a limiting factor is the sparsity of neonatal hair. We report on the first method that allows determination of both cocaine and nicotine as well as their metabolites in the same hair samples.

Cocaine↗
PubMed1994

Is 'silent' myocardial ischemia really as severe as symptomatic ischemia? The analytical effect of patient selection biases.

BACKGROUND: The clinical significance of exercise-induced chest pain remains controversial, as reflected by sharply discordant clinical results within the medical literature. Thus, we developed a prospective study to compare the functional significance of silent versus symptomatic ischemia and to evaluate whether patient selection biases influence this analysis. METHODS AND RESULTS: We evaluated 117 patients (mean age, 63 +/- 9 years) with ischemic ST-segment depression during treadmill testing. Each patient underwent Tl-201 myocardial perfusion single-photon emission computed tomography (SPECT) after exercise followed by 24-ambulatory ECG monitoring. Patients were divided into silent versus symptomatic cohorts and were compared for the degree of hemodynamic, exercise and ambulatory ECG, and thallium abnormalities during stress testing. Analyses were repeated as the patient population became increasingly restricted. Compared with the silent patients, patients with chest pain during exercise had a shorter exercise duration (P < .009), lower peak heart rate (P = .009) and double product (P = .005), lower heart rate threshold for ST depression (P < .05), more episodes of ambulatory ST-segment depression (P < .05), a higher frequency of ischemia abnormalities during Tl-201 SPECT (P = .02), and higher summed Tl reversibility scores (P = .002). As the population became increasingly restricted, the relative magnitude of differences in silent versus symptomatic cohorts diminished, whereas the absolute magnitude of ischemic abnormalities progressively increased in both cohorts. For example, within the restricted group having ischemia on both exercise and ambulatory ECG, 50% of the silent cohort had severe ischemia on Tl SPECT (five or more reversible defects) and more than one third demonstrated the ominous finding of transient left ventricular dilation after exercise. CONCLUSIONS: The induction of chest pain is associated with substantially more functional abnormalities when it is analyzed in a relatively "broad-spectrum" coronary artery disease population; by contrast, chest pain tends to lose its apparent value as a clinical test parameter when its analysis is restricted to coronary artery disease populations with a greater a priori likelihood of manifesting inducible ischemia. These findings may help resolve some of the previous discordant literature reports.

Angina Pectoris↗
PubMed1994

Personality test scores as predictors of alcoholism almost a decade later.

OBJECTIVE: Comparisons of alcoholic and control subjects have revealed potential differences on a variety of personality tests. However, these results are difficult to interpret because subgroups of alcoholic subjects with antisocial personality disorder were often included in the overall analyses, and because testing was usually carried out while alcoholic subjects were in withdrawal. This article evaluates whether individuals' personality test scores at approximately age 20 predict their risk of subsequent development of alcohol abuse or dependence by about age 30. METHOD: As part of a larger prospective study of sons of alcoholic and control subjects, subsets of up to 78 subjects (39 matched pairs) out of a sample of 223 men took various personality tests that included the Eysenck Personality Inventory, subtests of the MMPI, and evaluations of locus of control and anxiety. An average of more than 9 years later, the incidence of alcohol abuse or dependence in these 223 subjects was determined by structured interviews. RESULTS: The 55 men who subsequently went on to develop alcohol abuse or dependence did not differ on any of the personality tests from the 168 men who did not develop alcoholism. CONCLUSIONS: These data are consistent with prospective studies indicating that except for antisocial personality disorder, it is difficult to identify a reliable personality profile associated with an individual's risk of alcoholism.

Adolescent↗
PubMed1994

Acyclovir excretion in human breast milk.

OBJECTIVE: To measure acyclovir concentrations in the breast milk of a lactating woman using the drug for herpes zoster while nursing her 7-month-old infant. METHODS: The maternal dosage of acyclovir was 800 mg five times daily for seven days. Three random breast milk samples collected on the fifth and sixth days of therapy were analyzed for acyclovir concentrations with radioimmunoassay (RIA). RESULTS: Acyclovir concentrations in breast milk ranged from 18.5 mumol (4.16 micrograms/mL) to 25.8 mumol (5.81 micrograms/mL). An estimate of the infant's dosage ingested through nursing was 0.73 mg/kg/d, or approximately 1 percent of the maternal dose in milligrams/kilograms/day. The baby was nursed without any signs of adverse effects. CONCLUSIONS: Acyclovir was measured in clinically insignificant concentrations in the milk of a woman receiving large dosages for herpes zoster. Breast feeding continued without adverse effects to the nursing infant.

Acyclovir↗
PubMed1994

Origin of the North American house mouse.

The house mouse, Mus domesticus, was introduced to the American continent in the post-Columbian era. We have used mouse chromosome 17 DNA probes to trace the origin of the wild house mice on the East Coast of the United States. Of the four probes used, one in particular proved to be informative in this regard. The D17Tu20 probe defines a polymorphism at a locus telomeric of the H-2 complex. TaqI restriction enzyme digests of genomic DNA blotted and hybridized with the D17Tu20 probe revealed the existence of restriction fragments shared by mice from the Atlantic coast of England, France, and the United States but absent in all other tested populations sampled from different parts of the world. This unique polymorphic pattern apparently arose by the loss of two restriction sites in the population on the coast of Brittany. The mutations then presumably spread to England, and from there to the United States. Since the mutations are also present in mice from Florida, English (rather than Spanish) mouse populations may have been either the sole or the main source of immigrants to the eastern United States. This conclusion is also supported by data obtained with the other probes. Presence of the D17Tu20 mutations in some of the laboratory strains indicates that American wild mice contributed to the gene pool of the inbred strains. We postulate that the colonization of North America by English wild mice began in the second half of the seventeenth century.

Animals↗
PubMed1994

[Acute injury to the lateral ligament of the ankle joint in the athlete].

The ankle sprain is one of the most common injuries in sports. It is useful to classify the grade of injury clinically. Stress x-rays, stress ultrasound or radiographic examinations are not necessary. Based on the analysis of 24 controlled studies we conclude that functional treatment is sufficient. It does not lead to higher subjective or objective instability nor to a greater number of reinjuries. Functional treatment has no complications. Although controlled studies about the treatment of athletes are missing, but there is no reason for a different treatment in athletes.

Adolescent↗
PubMed1994

Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry.

A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study.

Aluminum↗
PubMed1994

Prevalence of fetal exposure to cocaine in Toronto, 1990-1991.

There has been an increasing use of cocaine in North America among women of reproductive age. The potential effects of cocaine on the fetus have raised serious concerns about the health of large numbers of children exposed in utero to the drug. Using neonatal hair and urine tests for benzoylegconine (BE), we quantified the incidence of fetal exposure to cocaine among 600 babies born in 3 nurseries in Toronto from 1990-91. A total of 37 babies (6.25%) tested positive for cocaine exposure by either hair test, urine test, or both. The hair test detected 33 cases and failed to identify 4 babies who had low urine concentrations of BE. The urine test failed to identify 76% of the cases. In downtown Toronto, the overall rate of fetal exposure to cocaine was 12.5% (25/200), significantly higher than in the 2 suburban nurseries (3%; 12/400). Babies are born with hair which has grown during the last trimester of pregnancy; hence, our analysis identifies women who have used cocaine long after they became aware of pregnancy. Our figures translate to more than 5,000 babies annually in the greater Toronto area who are cared for postnatally by mothers regularly using cocaine. Because history and urine testing during delivery fail to identify the majority of these cases, most of these children are not likely to receive the appropriate medical and social services and follow-up.

Adolescent↗