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Biomedical subjects

L Kramer

Publications and source records attributed to L Kramer.

At least 91 records · Page 5Linked to original sources
PubMed1998

Electrocardiographic consequences of a peripatetic lifestyle in gray wolves (Canis lupus).

Cardiac chamber enlargement and hypertrophy are normal physiologic responses to repetitive endurance exercise activity in human beings and domestic dogs. Whether similar changes occur in wild animals as a consequence of increased activity is unknown. We found that free-ranging gray wolves (Canis lupus, n = 11), the archetypical endurance athlete, have electrocardiographic evidence of cardiac chamber enlargement and hypertrophy relative to sedentary captive gray wolves (n = 20), as demonstrated by significant increases in QRS duration, QT interval, and QT interval corrected for heart rate, a tendency towards increased Q, R, and S wave voltages in all leads, and a significant decrease in heart rate. We conclude that exercise activity level and therefore lifestyle affects physiologic variables in wild animals. An immediate consequence of this finding is that physiologic measurements obtained from a captive wild-animal population with reduced exercise activity level may not accurately reflect the normal physiologic state for free-ranging members of the same species.

Adaptation, Physiological↗
PubMed1998

Neuroimaging, physical, and developmental findings after inflicted and noninflicted traumatic brain injury in young children.

OBJECTIVE: To characterize neuroimaging, physical, neurobehavioral, and developmental findings in children with inflicted and noninflicted traumatic brain injury (TBI) and to identify characteristic features of inflicted TBI. METHODS AND PATIENTS: Forty children, 0 to 6 years of age, hospitalized for TBI who had no documented history of previous brain injury were enrolled in a prospective longitudinal study. TBI was categorized as either inflicted (n = 20) or noninflicted (n = 20) based on the assessment of hospital and county protective services. Glasgow Coma Scale scores and neonatal history were comparable in both groups. OUTCOME MEASURES: Acute computed tomography/magnetic resonance imaging studies and physical findings were evaluated. Glasgow Outcome Scale scores, cognitive development, and motor functioning were assessed an average of 1.3 months after TBI. chi2 analyses assessed differences in the distribution of findings in the inflicted and noninflicted TBI groups. RESULTS: Signs of preexisting brain injury, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly, were present in 45% of children with inflicted TBI and in none of the children with noninflicted TBI. Subdural hematomas and seizures occurred significantly more often in children with inflicted TBI. Intraparenchymal hemorrhage, edema, skull fractures, and cephalohematomas were similar in both groups. Retinal hemorrhage was only identified in the inflicted TBI group. Glasgow Outcome Scale scores indicated a significantly less favorable outcome after inflicted than noninflicted TBI. Mental deficiency was present in 45% of the inflicted and 5% of the noninflicted TBI groups. CONCLUSIONS: Characteristic features of inflicted TBI included acute computed tomography/magnetic resonance imaging findings of preexisting brain injury, extraaxial hemorrhages, seizures, retinal hemorrhages, and significantly impaired cognitive function without prolonged impairment of consciousness.

Brain Damage, Chronic↗
PubMed1998

Previous episodes of hypoglycemic coma are not associated with permanent cognitive brain dysfunction in IDDM patients on intensive insulin treatment.

Intensive insulin treatment of IDDM is associated with increased frequency of hypoglycemic coma. The extent of possible cerebral sequelae after recovery is still unknown. We studied the impact of previous hypoglycemic coma on neurophysiological measures of cognitive brain function in 108 patients with adult-onset IDDM receiving intensive insulin treatment. In the study, 55 IDDM patients (age 38 +/- 14 years, mean +/- SD) who had a history of > or =1 (median 3, range 1-35) comatose hypoglycemic event were compared with 53 IDDM patients (age 34 +/- 12 years) with no history of hypoglycemic events using P300 event-related potentials and psychometric tests (the Mini-Mental State Exam and trailmaking test, part A). Findings on these patients were compared with those from 108 matched healthy control subjects. No difference was observed in P300 latencies and psychometric tests between patients with and without a history of hypoglycemic coma (P300 latency, 346 vs. 342 ms; trailmaking test, 31 vs. 30 s; Mini-Mental State Exam, 29.5 vs. 29.6; NS). In diabetic patients, however, P300 latencies were delayed compared with those of healthy control subjects (344 vs. 332 ms; P < 0.001) and were correlated to diabetes duration but not to total hypoglycemic episodes. Scores on the Mini-Mental State Exam (29.5 vs. 29.6; P = 0.59) and trailmaking test (31 vs. 28 s; P = 0.10) were not different between patients and control subjects. In conclusion, previous episodes of hypoglycemic coma are not associated with permanent impairment of cognitive brain function in patients with adult-onset IDDM receiving intensive insulin treatment compared with patients without such episodes. Cognitive brain function, however, is subclinically impaired in relation to duration of diabetes.

Adult↗
PubMed1998

Serum biochemistry of captive and free-ranging gray wolves (Canis lupus).

Normal serum biochemistry values are frequently obtained from studies of captive sedentary (zoo) or free-ranging (wild) animals. It is frequently assumed that values obtained from these two populations are directly referable to each other. We tested this assumption using 20 captive gray wolves (Canis lupus) in Minnesota, USA, and 11 free-ranging gray wolves in Alaska, USA. Free-ranging wolves had significantly (P < 0.05) lower sodium, chloride, and creatinine concentrations and significantly higher potassium and blood urea nitrogen (BUN) concentrations; BUN to creatinine ratios; and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities relative to captive wolves. Corticosteroid-induced alkaline phosphatase activity (a marker of stress in domestic dogs) was detected in 3 of 11 free-ranging wolves and in 0 of 20 captive wolves (P = 0.037). This study provides clear evidence that serum biochemical differences can exist between captive and free-ranging populations of one species. Accordingly, evaluation of the health status of an animal should incorporate an understanding of the potential confounding effect that nutrition, activity level, and environmental stress could have on the factor(s) being measured.

Animals↗
PubMed1998

Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?

BACKGROUND: The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports. METHODS: Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS: A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.

Adult↗
PubMed1998

[The effect of chemotherapy on bone metabolism in patients with non-small cell lung cancer].

UNLABELLED: In this study the influence of chemotherapy on bone metabolism in patients with III stage of non-small cell lung cancer has been evaluated. 30 patients (men) in average age 57.1 years were enrolled to this trial. The trial carried out on 2 groups of patients: group A consisted of 30 patients with NSCLC, group B of 15 patients without neoplastic process. In all participants bone scintigraphy was done and the following biochemical markers were measured: osteocalcin concentration, alkaline phosphatase's bone fraction, twenty-four-hour calcium and hydroxyproline urine excretion. In patients after two courses of chemotherapy (mitomycin, cisplatin, vinblastine) statistically significant reduction of serum concentration of osteocalcin, alkaline phosphatase, also reduction of calcium and hydroxyproline urine excretion have been observed. Scintigraphic examination of bones showed statistically significant decrease in resorption of isotope (MDP 99mTc) in patients after chemotherapy (p < 0.05). CONCLUSIONS: The study shows positive influence of chemotherapy on bone metabolism in patients with NSCLC. Patients treated with chemotherapy have bone metastases less frequently.

Adult↗
PubMed1997

[Intestinal lavage solution for orthograde intestinal irrigation].

Gut lavage by ingestion of large volumes of electrolyte solutions has been shown to be an effective method of cleansing the colon before colonoscopy, barium enema or surgery. Absorption of water and electrolytes, which might be hazardous to patients who are unable to readily excrete an additional sodium and/or water load, is prevented by addition of non-absorbable substances to the solutions, but systematic studies are lacking. We have evaluated the influence of three solutions for gut lavage with different electrolyte composition (sodium concentration 67 mmol/l and 125 mmol/l) and addition of different non-absorbable substances (mannitol and polyethylene glycol [PEG]) on water and electrolyte homeostasis and subjective tolerance, both in healthy volunteers and in patients before endoscopy of the colon. In a randomized, blind study 6 liters of the three solutions were administered via a nasogastric tube to 6 healthy volunteers during 4 hours (i.e. 1.5 l/h). Body weight, serum concentrations of sodium, potassium and of phosphate were measured before infusion of the solution and after the last rhythmic rectal effluent. No significant changes were observed in any of the studied parameters and the incidence of side effects (nausea, abdominal cramps) was comparable. In an additional clinical double blind study, 26 patients before diagnostic colonoscopy were asked to drink 4 liters of the gut lavage solutions as quickly as possible in order to clean out the colon. The time for drinking was significantly shorter in patients using the mannitol and low sodium solution (204 +/- 70 minutes) than in patients drinking the solution with polyethylene glycol and a high sodium concentration (387 +/- 137 minutes). There was a tendency to a longer drinking period in patients ingesting the solution with polyethylene glycol and low sodium (306 +/- 106 minutes). Thus, the acceptance for solutions containing polyethylenglycol and high sodium concentration is reduced because of low palatibility. Again no influence on serum electrolyte concentrations or body weight could be observed in any patient, the spectrum of side effects was similar and the cleansing effect of all three solutions was adequate. In conclusion solutions for gut lavage containing a balanced electrolyte concentration and nonresorbable substances such as mannitol or polythylenglycol are equivalent. However, solutions containing mannitol and a low sodium concentration are better tolerated by the patients but the use of mannitol is limited because of the risk of releasing explosive gases during interventional endoscopy. To enhance the acceptance and palatibility of solutions for gut lavage containing polethylenglycol the addition of flavoured substances is recommended.

Adult↗
PubMed1997

Detection of subclinical brain dysfunction by sensory evoked potentials in patients with severe diabetic ketoacidosis.

OBJECTIVE: Subclinical brain dysfunction is a potentially deleterious complication of diabetic ketoacidosis but is rarely recognized. Thus, we investigated the diagnostic value of sensory evoked potentials for detecting subclinical brain dysfunction in patients with diabetic ketoacidosis. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital. PATIENTS: 5 neurologically asymptomatic patients (Glasgow Coma Scale score 15, slight drowsiness; aged 20 to 66 years) with an established diagnosis of severe diabetic ketoacidosis were studied. MEASUREMENTS AND RESULTS: Short- and long-latency sensory evoked potentials were recorded within 2 h of initiation of therapy for ketoacidosis and 7 days after normalization of ketoacidosis, respectively. Two hours after starting therapy, sensory evoked potential peak latencies were prolonged in all five patients compared to age-matched healthy subjects [cervical N 13 to cortical N 20 interpeak latency of short-latency evoked potentials (mean) 5.8 vs 5.3 ms, p < 0.05; N 35 peak latency 40 vs 34 ms, p < 0.05; N 70 peak latency of long-latency evoked potentials 102 vs 76 ms, p < 0.01]. In all five patients, cervical N 13 to cortical N 20 interpeak latency and N 35 and N 70 peak latency reverted to normal 7 days after recovery from diabetic ketoacidosis. CONCLUSIONS: Our study indicates that the recording of sensory evoked potentials is a sensitive method of detecting subclinical brain dysfunction in patients with severe diabetic ketoacidosis. Since sensory evoked potentials were significantly prolonged in all five patients, this strongly suggests that subclinical brain dysfunction occurs more frequently than is generally recognized.

Adult↗
PubMed1997

Modulation of host cell activation during feline immunodeficiency virus (FIV) infection.

The authors describe the mitogenic effect of feline immunodeficiency virus (FIV) infection (1) in vitro, on feline resting peripheral blood lymphocytes (PBL), and (2) in vivo, in experimentally infected cats. Infected PBL were more readily recruited than non-infected PBL, into the G1 phase of the cell cycle and showed increased expression of the specific cell-cycle markers p53 and p56. In-vivo lymphocyte activation following FIV infection was demonstrated by increased germinal centre activity in infected lymph nodes, together with a high expression of CD30, a B-cell activation marker. These results suggest that early events in FIV infection include modulation of host cell activation. Possible implications for pathogenesis are discussed.

Animals↗
PubMed1997

Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin.

BACKGROUND/AIMS: A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease. To examine whether it is useful to detect presymptomatic patients with Wilson's disease, serum ceruloplasmin was determined by radial immunodiffusion (normal: 20-60 mg/dl) in all patients (n = 2867) admitted for evaluation of a liver disease in 1993 and 1994. METHODS: Patients with levels lower than 20 mg/dl were further evaluated by determination of serum copper concentration, urine copper excretion and ophthalmological examination. If possible, a liver biopsy was performed and the hepatic copper content was determined by flame atomic absorption spectroscopy. RESULTS: Seventeen patients had serum ceruloplasmin levels < 20 mg/dl. One had asymptomatic Wilson's disease (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients Wilson's disease was excluded. Based on elevated hepatic copper concentration, there were considered as heterozygous carriers of the WD gene. The remaining patients had various liver diseases (acute viral hepatitis in three, chronic hepatitis in two, drug-induced liver disease in three, alcoholic induced liver disease in two) or malabsorption (n = 3). CONCLUSIONS: The positive predictive value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying presymptomatic Wilson's disease, screening by determination of serum ceruloplasmin in unselected patients with clinical or laboratory evidence of liver disease is neither feasible nor cost effective.

Adult↗
PubMed1997

Oxidative protein damage and degradation in lymphocytes from patients infected with human immunodeficiency virus.

It has been proposed that oxidative stress is the common mediator of apoptotic cell death in AIDS. However, mechanistic relationships between oxidative damage and cell death are far from clear. It is reported here that the mitogenic activation of T lymphocytes from human immunodeficiency virus-positive subjects involves perturbation of redox balance, as indicated by the increase in hydroethydine intracellular oxidation and manganese superoxide dismutase adaptive induction. Principal molecular targets of oxidative injury are cellular proteins whose content in carbonyl groups increases together with a dramatic increase in degradation of newly synthesized proteins catalyzed by the ATP- and ubiquitin-dependent proteolytic system. The major consequence of this metabolic anomaly is the decrease in protein cell mass leading to cells that are smaller than normal at lethal mitosis.

Adult↗
PubMed1996

Modulation of protein kinase C activity and calcium-sensitive isoform expression in human myeloid leukemia cells by bryostatin 1: relationship to differentiation and ara-C-induced apoptosis.

Previous studies have shown that pretreatment of human myeloid leukemia cells (HL-60) with the protein kinase C (PKC) activator bryostatin 1 potentiates ara-C-induced apoptosis. To test the hypothesis that this capacity stems from down-regulation of PKC activity and/or Ca2+-dependent (group-I; cPKC) isoform expression, comparisons were made between the effects of this agent and the stage-2 tumor promoter mezerein under conditions favoring either cellular differentiation or drug-induced apoptosis. Twenty-four-hour pretreatment of HL-60 cells with 10 nM bryostatin 1, which does not induce differentiation in this cell line, led to a profound reduction in membrane and cytosolic PKC activity, decreased expression of cPKC isoforms (alpha, betaI, betaII, gamma), and a marked increase in ara-C induced apoptosis. In contrast, 10 nM mezerein, which induces HL-60 cell differentiation, was less effective in down-regulating membrane and cytosolic PKC activity as well as alpha, betaI, and gamma cPKC isoform expression, and failed to potentiate ara-C-related apoptosis. The effects of bryostatin 1 were dominant to those of mezerein, in that the combination resulted in down-regulation of PKC activity and expression and potentiation of ara-C-induced apoptosis, but not cellular maturation. However, coadministration of the Ca2+ ionophore A23187 (250 nM) restored bryostatin 1's differentiating ability while antagonizing its capacity to augment apoptosis, despite failing to reverse bryostatin 1-induced down-regulation of PKC activity and cPKC isoform expression. Furthermore, pretreatment of differentiation-responsive monocytic leukemia cells (U937) with bryostatin 1 substantially reduced PKC activity and cPKC isoform expression, but exerted minimal effects on ara-C-related apoptosis. In contrast, exposure of U937 cells to bryostatin 1 after ara-C dramatically increased apoptosis, a phenomenon that did not occur in differentiation-unresponsive HL-60 cells. Collectively, these observations indicate that down-regulation of total assayable PKC activity and cPKC expression by bryostatin 1 are insufficient, by themselves, to account for potentiation of leukemic cell apoptosis, at least under conditions in which differentiation occurs. They also provide further evidence that a reciprocal and highly schedule-dependent relationship exists between leukemic cell differentiation and drug-induced apoptosis.

Antimetabolites, Antineoplastic↗
PubMed1996

Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation.

BACKGROUND: The effects of cardiac transplantation on cognitive brain function are uncertain. METHODS AND RESULTS: We measured cognitive brain function and quality of life in out-of-hospital cardiac transplant candidates (n = 55; ejection fraction, 19.9%; age, 54.8 years [means]). After transplantation, the patients were serially reevaluated at 4 months (n = 25) and at 12 months (n = 19). Brain function was measured objectively by cognitive P300 evoked potentials. Additionally, standard psychometric tests (Trail Making Test A, Mini-Mental State Examination, and Profile of Mood State test) were performed. Cognitive P300 evoked potentials were impaired in cardiac transplant candidates (359 ms, recorded at vertex) compared with 55 age- and sex-matched healthy subjects (345 ms, P < .01). Trail Making Test A was also abnormal (45 versus 31 seconds in 55 healthy subjects, P < .01). After transplantation, P300 measures were normalized at 4 months (345 ms, P < .05 versus before transplantation) but declined again at 12 months (352 ms, P = NS versus before transplantation). Stepwise multiple regression analysis revealed that cumulative cyclosporine dosage was the only predictor of individual cognitive brain function 4 months (753 mg/kg body wt, P < .05) and 12 months (2006 mg/kg body wt, P < .01) after transplantation, respectively. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate that cognitive brain function is significantly impaired in patients suffering from stable end-stage heart failure. Successful cardiac transplantation is effective to fully normalize impaired brain function. Subsequent relative long-term decline of cognitive brain function after successful cardiac transplantation is strongly suggested to be related to cumulative cyclosporine neurotoxicity.

Affect↗
PubMed1996

Detection of nontraumatic comatose patients with no benefit of intensive care treatment by recording of sensory evoked potentials.

OBJECTIVES: To determine the predictive ability of sensory evoked potential recordings in nontraumatic comatose patients. To evaluate the hypothesis that patients with bilateral absent cortical responses ultimately die despite long-term intensive care treatment. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Four hundred forty-one adult nontraumatic comatose patients (unarousable unresponsiveness to external stimulation, Glasgow Coma Score < or = 7) from various causes. Six hundred seventy-six sensory evoked potential measurements were performed within 7 days after onset of coma. MAIN OUTCOME MEASURES: Death or survival to hospital discharge. RESULTS: Eighty-six patients (20%) had a bilateral loss of the cortical evoked potential N20 peak. Despite long-term intensive care treatment, all died without awakening from coma (mortality rate, 100%; 95% confidence interval, 96-100). The mean stay at the ICU after evoked potential measurement until death was 8.1 days (697 patient days). The overall cost of ICU management for these 86 patients accounted for approximately $1,324,300. In the remaining 355 comatose patients with preserved cortical N20 peak, 148 (42%) survived and 207 (58%) died. In this latter group of patients, cervicomedullary N13 to cortical N20 conduction time was prolonged in nonsurvivors (mean +/- SD, 6.7 +/- 1.3 milliseconds) compared with that in survivors (mean +/- SD, 6.4 +/- 1.2 milliseconds, P < .05) and healthy controls (mean +/- SD, 5.5 +/- 0.4 milliseconds, P < .05). Although this difference is statistically significant, a preserved N20 peak is not useful to discriminate whether the individual patient will survive (N13-N20 conduction time of > 7 milliseconds had a positive predictive value of correct prediction of death of 0.67). CONCLUSIONS: Recording of sensory evoked potentials identifies a subgroup of adult nontraumatic comatose patients with a mortality rate of 100% in our sample. In these patients, advanced intensive care treatment should be withdrawn to provide limited ICU resources for patients with higher probability of favorable outcome. We emphasize that these results are not applicable to comatose patients following closed head trauma and particularly not to children.

Adolescent↗