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Biomedical subjects

L Kramer

Publications and source records attributed to L Kramer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Liver penetration by a duodenal ulcer in a young woman.

Liver penetration is a rare but serious complication of peptic ulcer disease. We report a case of a 33-year-old woman who took large doses of nonsteroidal antiinflammatory drugs and developed a giant duodenal ulcer that penetrated into her liver. The diagnosis was based on histologic examination of endoscopic biopsies. She was initially treated with a proton pump inhibitor, but, within 5 weeks, she developed a symptomatic postbulbar stricture that required surgical correction. We also review 11 other reported cases of endoscopically and histologically diagnosed peptic ulcer penetration into the liver.

Adult↗
PubMed2001

Aerosolized iloprost therapy could not replace long-term IV epoprostenol (prostacyclin) administration in severe pulmonary hypertension.

OBJECTIVES: To switch patients with severe pulmonary hypertension and previous life-threatening catheter-related complications from long-term IV epoprostenol therapy to aerosolized iloprost therapy. DESIGN: Open, uncontrolled trial. SETTING: Medical ICU of a university hospital. PATIENTS: Two patients with primary pulmonary hypertension and one patient with pulmonary hypertension after surgical closure of atrial septal defect (mean pulmonary artery pressure > or =50 mm Hg). All were classified as New York Heart Association class II under treatment with continuous IV epoprostenol for 4 years. INTERVENTIONS: Stepwise reduction of IV epoprostenol (1 ng/kg/min steps every 3 to 10 h) during repeated inhalations of aerosolized iloprost (150 to 300 microg/d with 6 to 18 inhalations/d). Continuous pulmonary and systemic arterial monitoring were performed. RESULTS: Aerosolized iloprost reduced pulmonary artery pressure by 49%, 49%, and 45%, respectively, and increased cardiac output by 70%, 75%, and 41% in the three patients. The effect lasted for 20 min and was similar at different doses of IV epoprostenol. Persistent treatment change to inhaled iloprost could not be achieved because all patients developed signs of right heart failure. After termination of iloprost inhalations, return to standard epoprostenol therapy led to clinical and hemodynamic restoration. CONCLUSIONS: Although aerosolized iloprost demonstrated short-term hemodynamic effects, it could not be utilized as alternative chronic vasodilator in patients with severe pulmonary hypertension.

Administration, Inhalation↗
PubMed2001

Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells.

Interactions between the purine analogue 2-fluoroadenine 9-beta-D-arabinofuranoside (F-ara-A) and the kinase inhibitor UCN-01 have been examined in human leukemia cells (U937 and HL-60) with respect to induction of mitochondrial damage, caspase activation, apoptosis, and loss of clonogenic survival. Simultaneous or subsequent exposure of F-ara-A-treated cells (2 microM) to UCN-01 (100 nM) resulted in a marked potentiation of apoptosis, manifested by loss of mitochondrial membrane potential (delta psi(m)), cleavage/activation of procaspase-9 and procaspase-3, DNA fragmentation, and degradation of poly-ADP(ribosyl) polymerase. Coadministration of UCN-01 with F-ara-A was also associated with diminished phosphorylation of the cdc25 phosphatase. In contrast, exposure of cells to the sequence UCN-01, followed by F-ara-A, resulted in only a modest increase in apoptotic cells. The ability of UCN-01 to potentiate F-ara-A-mediated lethality was not mimicked by the selective PKC inhibitor bisindolylmaleimide, nor did treatment of cells with UCN-01 enhance formation of F-ara-ATP or increase incorporation of [3H]F-ara-A into DNA. Enhanced apoptosis in cells exposed sequentially or simultaneously to F-ara-A and UCN-01 was accompanied by a substantial reduction in colony formation (e.g., to 0.01% of control values). Cotreatment with UCN-01 also increased F-ara-A-mediated apoptosis and loss of delta psi(m) in U937 cells ectopically expressing Bcl-2, although not to the same extent as that observed in empty-vector controls. Finally, simultaneous exposure (24 h) of malignant B lymphocytes from the pleural effusion of a patient with indolent non-Hodgkin's lymphoma to F-ara-A and UCN-01 ex vivo resulted in a striking increase in apoptosis, as determined by terminal deoxynucleotidyltransferase-mediated nick end labeling assay. These findings indicate that UCN-01 increases F-ara-A-induced mitochondrial damage and apoptosis in human leukemia cells in a sequence-dependent manner, and that these events occur in at least some primary human lymphoma cells.

Alkaloids↗
PubMed2001

A controlled study of sorbent suspension dialysis in chronic liver disease and hepatic encephalopathy.

To investigate the role of extracorporeal detoxification in cirrhotic patients with advanced hepatic encephalopathy not responding to medical treatment, 20 patients were randomized to receive six hours of additional sorbent dialysis or ongoing standardized medical treatment. Following treatment, the clinical stage of encephalopathy remained unchanged in both groups. Abnormal sensory evoked potentials improved following sorbent dialysis (N70 latency, 128 ms before versus 110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8 ms, P<0.01) indicating improvement in important aspects of cerebral function. In contrast, brain function remained unchanged following medical treatment (N70 latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2 ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly after sorbent dialysis but not after medical treatment. Biocompatibility of sorbent dialysis was limited and clinical complications occurred in a proportion of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis did not ameliorate the clinical stage of HE but improved neurophysiologic function in cirrhotic patients who had not responded to conventional medical treatment.

Adult↗
PubMed2000

Patterns formed by spiral pairs in oscillatory media.

We investigate by numerical simulations the dynamics of spiral pairs which are found in oscillatory and excitable media as described by the complex Ginzburg-Landau equation. Our simulations include two spiral pairs which approach each other and interact. The spirals typically exchange partners and form new pairs. This type of interaction gives rise to some patterns: a right-angle scattering pattern, a rotating state coming out of two traveling pairs, and a symmetric spiral lattice. The scenarios are compared to other conservative and dissipative systems where scattering at right angles is also observed.

Journal Article↗
PubMed2000

Structural basis for the activation of 20S proteasomes by 11S regulators.

Most of the non-lysosomal proteolysis that occurs in eukaryotic cells is performed by a nonspecific and abundant barrel-shaped complex called the 20S proteasome. Substrates access the active sites, which are sequestered in an internal chamber, by traversing a narrow opening (alpha-annulus) that is blocked in the unliganded 20S proteasome by amino-terminal sequences of alpha-subunits. Peptide products probably exit the 20S proteasome through the same opening. 11S regulators (also called PA26 (ref. 4), PA28 (ref. 5) and REG) are heptamers that stimulate 20S proteasome peptidase activity in vitro and may facilitate product release in vivo. Here we report the co-crystal structure of yeast 20S proteasome with the 11S regulator from Trypanosoma brucei (PA26). PA26 carboxy-terminal tails provide binding affinity by inserting into pockets on the 20S proteasome, and PA26 activation loops induce conformational changes in alpha-subunits that open the gate separating the proteasome interior from the intracellular environment. The reduction in processivity expected for an open conformation of the exit gate may explain the role of 11S regulators in the production of ligands for major histocompatibility complex class I molecules.

Amino Acid Sequence↗
PubMed2000

Outpatient urine culture: does collection technique matter?

BACKGROUND: Dysuria is one of the most common presenting complaints of young women, and urinalysis is one of the most common laboratory tests performed. Despite the fact that the midstream clean-catch technique is commonly used for urine collection, contaminated urine cultures occur with distressing regularity. The midstream clean-catch technique is time-consuming to explain, frequently not performed correctly by patients, costly for supplies, often embarrassing for patients and staff, and of unproven benefit. Therefore, we designed a study to compare various methods of obtaining specimens for culture from acutely dysuric young women. METHODS: A total of 242 consecutive female patients who presented with symptoms suggestive of a urinary tract infection were randomized into 3 groups. The first group (n = 77) was instructed to urinate into a clean container. No cleansing was done, and the specimen was not obtained midstream. The second group (n = 84) was instructed to collect a midstream urine sample with perineal cleansing and spreading of the labia. In an attempt to decrease contamination from the vagina, the third group (n = 81) was given the same instructions as group 2, with the addition of using a vaginal tampon. Contamination rates were calculated for all 3 groups. RESULTS: Contamination rates for the 3 groups were nearly identical (29%, 32%, and 31%, respectively). Comparing the no-cleansing group with the combined cleansing, midstream groups also showed no difference in contamination rates (28.6% and 31.5%, respectively, with P =.65). CONCLUSIONS: In young, outpatient women with symptoms suggestive of a urinary tract infection, the midstream clean-catch technique does not decrease contamination rates.

Adolescent↗
PubMed2000

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Adolescent↗
PubMed2000

Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.

Adolescent↗
PubMed2000

Director precession and nonlinear waves in nematic liquid crystals under elliptic shear

Elliptic shear applied to a homeotropically oriented nematic above the electric bend Freedericks transition (FT) generates slow precession of the director. The character of the accompanying nonlinear waves changes from diffusive phase waves to dispersive ones exhibiting spirals and spatiotemporal chaos as the FT is approached from above. An exact solution of the flow alignment equations captures the observed precession and predicts its reversal for non-flow-aligning materials. The FT transforms into a Hopf bifurcation opening the way to understand the wave phenomena.

Journal Article↗
PubMed2000

Partial pressure of ammonia versus ammonia in hepatic encephalopathy.

Ammonia is considered the major pathogenetic factor of cerebral dysfunction in hepatic failure. The correlation between total plasma ammonia and the severity of hepatic encephalopathy (HE), however, is variable. Because ammonia that is present in gaseous form readily enters the brain, the correlation with the grade of HE of the pH-dependent partial pressure of gaseous ammonia (pNH(3)) could be better than that of total arterial ammonia levels. To test this hypothesis, 56 cirrhotic patients with acute episodes of clinical HE (median age, 54 years; range, 21-75) were studied by clinical examination and by long-latency median-nerve sensory-evoked potentials (SEPs) N70 peak, an objective and sensitive electrophysiological measure of HE. pNH(3) was calculated from arterial blood according to published methods. The clinical grade of HE correlated (P <.001) with both pNH(3) and total ammonia, but correlation was stronger with pNH(3) (r =.79 vs.69, P =.01). A similar correlation was found for N70 peak latency (r =.71 with pNH(3) vs.64 with total ammonia, respectively, P =.08). In summary, arterial pNH(3) correlates more closely than total ammonia with the degree of clinical and electrophysiological abnormalities in HE. These findings support the ammonia hypothesis of HE and suggest that pNH(3) might be superior to total ammonia in the pathophysiological evaluation of HE.

Adult↗
PubMed2000

Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury.

Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0-6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n = 31) or noninflicted (n = 29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after non-inflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.

Brain Edema↗
PubMed2000

Normothermic cardiopulmonary bypass is beneficial for cognitive brain function after coronary artery bypass grafting--a prospective randomized trial.

BACKGROUND: Hypothermic and normothermic cardiopulmonary bypass (CPB) have resulted in apparently contradictionary cardiac and neurologic outcome. Cerebrovascular risk and cognitive dysfunction associated with normothermic CPB still remain uncertain. MATERIALS AND METHODS: In a prospective randomized study, we measured the effects of mildly hypothermic (32 degrees C, n=72) vs. normothermic (37 degrees C, n=72) CPB on cognitive brain function. All patients received elective coronary artery bypass grafting (mean age 62.1+/-6.3 years, mean ejection fraction 60.4+/-13%). Cognitive brain function was objectively measured by cognitive P300 auditory-evoked potentials before surgery, 1 week and 4 months after surgery, respectively. Additionally, standard psychometric tests ('trailmaking test A', 'mini-mental state') were performed and clinical outcome was monitored. RESULTS: Patients, operated with mild hypothermia, showed a marked impairment of cognitive brain function. As compared with before surgery (370+/-45 ms), P300 evoked potentials were prolonged at 1 week (385+/-37 ms; P<0.001) and even at 4 months (378+/-34 ms, P<0.001) after surgery, respectively. In contrast, patients operated with normothermic CPB, did not show an impairment of P300 peak latencies (before surgery 369+/-36 ms, 1 week after surgery 376+/-38 ms, n.s.; 4 months after surgery 371+/-32 ms, n.s.). Group comparison revealed a trend towards prolonged P300 peak latencies in the patient group undergoing mildly hypothermic CPB (P=0.0634) 1 week after surgery. Four months postoperatively, no difference between the two groups could be shown (P=n.s.) Trailmaking test A and mini mental state test failed to discriminate any difference. Five patients died (mild hypothermia n=3, normothermia n=2) postoperatively (cardiac related n=3, sepsis n=2). None of the patients experienced major adverse cerebrovascular events. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate, that subclinical impairment of cognitive brain function is more pronounced in patients undergoing mildly hypothermic CPB as compared with normothermic CPB for CABG.

Brain↗
PubMed2000

Biocompatibility of a cuprophane charcoal-based detoxification device in cirrhotic patients with hepatic encephalopathy.

Extracorporeal detoxification has been proposed to treat patients with hepatic encephalopathy (HE) not responding to standard therapy. To investigate the biocompatibility of a cuprophane charcoal-based detoxification device, a prospective, randomized, controlled study was performed. Of 41 consecutive patients with cirrhosis and HE grade II or III who did not improve with conventional treatment, 20 patients (median age, 56 years; range, 33 to 71 years; 13 men) were randomly assigned to either ongoing conventional treatment or one additional 6-hour treatment with a sorbent suspension dialysis system. Main outcome parameters were physiological function and blood parameters of biocompatibility. In the 10 patients undergoing combined conventional and sorbent suspension dialysis treatment, blood pressure remained unchanged and body temperature and heart rate increased (P: < 0.01). Platelet count decreased (medians, from 75 to 26 g/L; P: < 0.001) and international normalized ratio increased after combined treatment (2.0 to 2.2; P: < 0.001). Three patients developed bleeding complications during treatment or shortly after. Treated patients showed increases in levels of plasma elastase (104 to 586 microg/L; P: = 0.001), tumor necrosis factor-alpha (5.4 to 7.5 pg/mL; P: = 0.04), and interleukin-6 (118 to 139 pg/mL; P: = 0.04), but not interferon-gamma and E-selectin. No changes were observed in the 10 patients treated conventionally. In conclusion, despite technical refinements compared with charcoal hemoperfusion, biocompatibility of sorbent suspension dialysis is still very limited. Clinical complications were apparently caused by blood-membrane interactions and disseminated intravascular coagulation. We suggest further developments in design and appropriate strategies of anticoagulation to improve the biocompatibility of artificial liver support.

Adult↗
PubMed2000

Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine.

BACKGROUND: The effects of food restriction on energy metabolism have been under investigation for more than a century. Data obtained are conflicting and research has failed to provide conclusive results. OBJECTIVE: The objective of this study was to test the hypothesis that in lean subjects under normal living conditions, short-term starvation leads to an increase in serum concentrations of catecholamines and thus to an increase in resting energy expenditure. DESIGN: Resting energy expenditure, measured by indirect calorimetry, and hormone and substrate concentrations were measured in 11 healthy, lean subjects on days 1, 2, 3, and 4 of an 84-h starvation period. RESULTS: Resting energy expenditure increased significantly from 3.97 +/- 0.9 kJ/min on day 1 to 4.53 +/- 0.9 kJ/min on day 3 (P < 0.05). The increase in resting energy expenditure was associated with an increase in the norepinephrine concentration from 1716. +/- 574 pmol/L on day 1 to 3728 +/- 1636 pmol/L on day 4 (P < 0.05). Serum glucose decreased from 4.9 +/- 0.5 to 3.5 +/- 0.5 mmol/L (P < 0.05), whereas insulin did not change significantly. CONCLUSIONS: Resting energy expenditure increases in early starvation, accompanied by an increase in plasma norepinephrine. This increase in norepinephrine seems to be due to a decline in serum glucose and may be the initial signal for metabolic changes in early starvation.

3-Hydroxybutyric Acid↗
PubMed2000

Case study: a patient's survival.

Presentation of a case study involving a female patient, in her 20s, undergoing routine surgery for removal of atrial myxoma leading to a heart transplant. This case study will show the progression from postcardiotomy failure, the emergent use of the extracorporeal membrane oxygenator device, the insertion of the HeartMate device, and the final return to the operating room for a heart transplant. The case study will examine the physiologic demands on the patient, as well as the psychological effects from the various life-saving devices.

Adult↗