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Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 253 records · Page 14Linked to original sources

Relation between cerebral oxygen delivery and neuronal cell damage in fetal sheep near term.

Asphyxia is one of the major causes for fetal brain damage. Although the quality of life of the so affected children is mostly very limited, the pathogenesis of hypoxic fetal brain damage is poorly understood. Particularly, there is a lack of studies, in which cerebral oxygen delivery is directly correlated to the extent of neuronal cell damage in the same brain specimens. Therefore, we measured cerebral oxygen delivery before (- 1 h), during (+3 min & +27 min) and after (+10 min, +4 h, +72 h) 30 min of ischaemia in 5 chronically catheterized normoxemic fetal sheep at 129 +/- 1 days gestation (term is at 147 days) using the microsphere method. In contrast to previous studies (Williams et al. 1990), we arrested carotid arterial blood flow above the lingual artery for 30 min during surgery. Seventy-two hours later the fetal brains were fixed in vivo under barbiturate anaesthesia of both the fetus and the ewe. After cerebral blood flow analysis neuronal cell damage was assessed with light microscopy in 43 specimens of the fetal brain after cresyl violet/fuchsin staining using a scoring system. After arrest of carotid arterial blood flow cerebral blood flow was reduced by 80%. Neuronal cell damage was focussed on the cerebral cortex. Almost no damage could be detected in deeper parts of the brain. In the cerebrum there was threshold oxygen delivery of 3 ml O2/100 g tissue/min, below which neuronal damage occurred. However, there was no correlation between cerebral oxygen delivery and neuronal cell damage in specimens of the cerebrum, in which oxygen delivery was less than 3 ml O2/100 g tissue/min, suggesting selective vulnerability. Therefore, in addition to the reduction in cerebral oxygen delivery, other variables, e.g. neurotransmitter release, receptor pattern or oxygen radicals, may be involved in the development of brain damage.

Analysis of Variance↗

Large daily fluctuations in plasma tyrosine in treated patients with phenylketonuria.

In patients with phenylketonuria (PKU), extra tyrosine supplementation is advocated in addition to tyrosine-enriched amino acid mixtures. PKU patients have low fasting plasma tyrosine concentrations, but little is known about tyrosine fluctuations during the day. Plasma tyrosine concentrations were studied in 12 PKU patients in response to a test without breakfast and to three tests with different tyrosine contents in breakfast and lunch: 0%/30%, 25%/30%, 50%/10%, and 75%/10% tests, reflecting the protein consumption at breakfast and lunch, respectively. Prolonged fasting resulted in a small decrease in the already low overnight fasting plasma tyrosine concentrations. Breakfast and lunch with 25% and 30% of the daily tyrosine intake resulted in both lower than normal and higher than normal tyrosine concentrations. The 50%/10% and 75%/10% tests resulted in excessively high plasma tyrosine concentrations in most patients. Therefore, both lower than normal and higher than normal postprandial plasma tyrosine concentrations were found in treated PKU patients, even if the daily tyrosine intake was distributed evenly. When there was a large fractional tyrosine intake from one meal, very high plasma tyrosine concentrations were found. Therefore, strict control of plasma tyrosine is necessary if tyrosine supplementation is considered in addition to the tyrosine-enriched amino acid mixtures.

Adolescent↗

Effects of two different enalapril dosages on clinical, haemodynamic and neurohumoral response of patients with severe congestive heart failure.

Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 'high' in comparison to continued 'low' angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/- 1.1 years; 69 men, 14 women) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included. After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide, right heart catheterization at rest and exercise was performed. All patients presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35 mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P = 0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P = 0.01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.

Angiotensin-Converting Enzyme Inhibitors↗

Dynamic test to diagnose loose uncemented femoral total hip components.

A new computed tomographic rotation study was developed to determine the stability of uncemented femoral components after total hip arthroplasty. The computed tomographic rotation study measures femoral component version with the leg in maximum external and internal rotation. The component is considered rotationally unstable, and thus loose, if these angles differ by more than 2 degrees. The results of the computed tomographic rotation study were confirmed with intraoperative inspection in 50 patients: 13 patients (Group A) with definite radiographic loosening, 22 patients (Group B) with equivocal radiographic loosening, and 15 patients (Group C) with documented stability. The results of the computed tomographic rotation study agreed with intraoperative findings for all patients in Groups A and C, and 20 of 22 patients in Group B (1 false negative and 1 false positive). Statistical analysis of Group B showed that the computed tomographic rotation study had a sensitivity of 91.6% and a specificity of 90.0%. The positive predictive value was 91.6%. These results indicate that the computed tomographic rotation study can supplement equivocal radiographic findings in assessing loosening of an uncemented femoral component.

Biomechanical Phenomena↗

Differential effects of exercise training intensity on blood pressure and cardiovascular responses to stress in borderline hypertensive humans.

BACKGROUND: Psychologic stress has been associated with the development of hypertension. Aerobic exercise training appears to decrease cardiovascular responses to psychologic stress. OBJECTIVE: To determine the efficacy of low-intensity and moderate-intensity exercise training in reducing blood pressure and cardiovascular responses to stress. DESIGN: We sought to compare the cardiovascular responses to a psychologic stressor, the Stroop Color Word Task (Stroop), before and after 12 weeks of low-intensity (about 45% maximal oxygen uptake) and moderate-intensity (about 75% maximal oxygen uptake) aerobic exercise training. METHODS: Eighteen borderline hypertensive subjects (resting blood pressure 139 +/- 9/92 +/- 9 mmHg) were divided randomly into three groups: control (no exercise), low-intensity exercise (40-50% maximal oxygen uptake), and moderate-intensity exercise (70-80% maximal oxygen uptake). Training groups exercised three times per week at the prescribed exercise intensity. Heart rate and blood pressure were recorded during the Stroop before, and after 4 and 8 weeks of exercise training. RESULTS: In the low-intensity exercise group, exercise training attenuated mean blood pressure, systolic blood pressure, and diastolic blood pressure responses to the Stroop and decreased resting blood pressure. The moderate-intensity exercise group demonstrated a reduced diastolic blood pressure response to the Stroop. CONCLUSIONS: These results suggest that, in borderline hypertensive humans, 12 weeks of aerobic exercise training attenuates the cardiovascular responses to the Stroop. Furthermore, low-intensity exercise training appears to be a more effective stimulus than moderate-intensity exercise training in reducing resting blood pressure and blood pressure responses to stress.

Adult↗

Clinical and imaging features of pulmonary strongyloidiasis.

We evaluated 20 patients with pulmonary strongyloidiasis for risk factors, clinical and imaging manifestations, complications, treatment, and outcome. Eighteen (90%) had risk factors for strongyloidiasis including steroid use, age greater than 65, chronic lung disease, use of histamine blockers, or chronic debilitating illness. Pulmonary signs and symptoms, including cough, shortness of breath, wheezing, and hemoptysis, were present in 19 (95%); adult respiratory distress syndrome (ARDS) developed in 9 (45%). Pulmonary infiltrates occurred in 18 (90%). Gastrointestinal signs and symptoms were also common. Peripheral blood eosinophilia occurred in 15 (75%). Twelve (60%) had secondary infection, and 3 (15%) had bacterial lung abscesses. All were treated with thiabendazole, 25 mg/kg twice daily; on average, patients without ARDS were treated for 3 days, versus 7 days for those with ARDS. Seventy percent responded to therapy; 30% died. Preexisting chronic lung disease and ARDS were statistically significant predictors of a poor prognosis.

Adolescent↗

The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products.

Thymopoietins (Tmpos) are a group of ubiquitously expressed nuclear proteins, with sequence homology to lamina-associated polypeptide 2 (LAP2). Here we report the isolation and characterization of seven mouse Tmpo mRNA transcripts named Tmpo alpha, beta, beta', gamma, epsilon, delta, and zeta. The alpha, beta, and gamma Tmpo cDNA clones are the mouse homologs of the previously characterized human alpha, beta, and gamma TMPOs, respectively, whereas Tmpo epsilon, delta, and zeta are novel cDNAs. Additionally, the mouse Tmpo gene was cloned and characterized. It is a single-copy gene organized in 10 exons spanning approximately 22 kb, which encodes all of the described Tmpo cDNA sequences, located in the central region of mouse chromosome 10. The almost identical genomic organization between the human and mouse genes, and the novel alternatively spliced mouse transcripts, led us to reanalyze the human TMPO gene. The human beta-specific domain was found to be encoded by 3 exons designated 6a, 6b, and 6c and not by a single exon as described previously. These findings suggest that there may be more human transcripts than currently recognized. The possible involvement of the new growing family of Tmpo proteins in nuclear architecture and cell cycle control is discussed.

Alternative Splicing↗

Effects of hypoxia and hypercapnia on patterns of sleep-associated apnea in elephant seal pups.

This project examined the effects of alterations in respiratory drive on the occurrence of sleep apnea in Northern elephant seal pups (Mirounga angustirostris). Sleep pattern was unaffected by levels of hypoxia (approximately 13%) or hypercapnia (approximately 6%) that doubled respiratory frequency during slow-wave sleep (SWS). During sleep in air, short periods of continuous breathing (mean length = approximately 2.6 min) alternated with periods of apnea (mean length = approximately 6.1 min). Under hypoxic or hypercapnic conditions, the frequency of occurrence of apneas was reduced primarily due to the occurrence of some sleep episodes without periods of apnea. In episodes in which apneas did occur, they began later in the sleep episodes, but their length and the length of the periods of eupnea were not significantly altered. During each period of eupnea, however, the instantaneous respiratory rate and the total number of breaths increased. Breathing during sleep was restricted to SWS, never occurring during rapid eye movement (REM) sleep, regardless of the respired gas mixture. If the levels of hypoxia and hypercapnia were raised further, all episodes of apnea during sleep could be eliminated together with all episodes of REM sleep. One interpretation of the data is that the threshold for altering breathing during eupnea (instantaneous breathing frequency and number of breaths per episode of eupnea) is lower than that for altering the lengths of the periods of apnea and eupnea and that the muscle atonia associated with REM sleep extends to all respiratory muscles.

Animals↗

Molecular cytogenetics of t(12;21) (p13;q22).

The translocation t(12;21)(p13;q22) is a frequent nonrandom rearrangement of B-cell lineage childhood acute lymphoblastic leukemia (ALL) which fuses the TEL and AML1 genes, normally localized to 12p13 and 21q22, respectively. The crucial chimeric gene, TEL-AML1, is transcribed from the der(21) and encodes the 336 NH2 aminoacics of TEL fused to the majority of the AML1 protein. The t(12;21) is very often associated with loss of the normal, untranslocated TEL allele. These various aspects are presented here.

Burkitt Lymphoma↗

Deletion of the short arm of chromosome 12 is a secondary event in acute lymphoblastic leukemia with t(12;21).

Translocation t(12;21) has been described as a nonrandom event in acute lymphoblastic leukemia (ALL) in patients with deletion of the short arm of chromosome 12, using fluorescence in situ hybridization techniques. Extensive FISH experiments were performed in order to re-examine the short arm of chromosome 12 in three children with ALL, previously shown to have t(12;21). It was shown that the t(12;21) is undetectable by routine R-banding technique and that the translocated 12 looks like a cytogenetically normal chromosome 12 in the three patients. Partial 12p deletion involving the TEL locus was shown to be interstitial in one patient with 12p- by using cosmid and YAC probes. In the second patient, the 12p- chromosome was secondary to the translocation since it was observed in about one half of the metaphases analyzed with FISH. In the third patient, the region of TEL usually rearranged in the t(12;21) displayed a germline pattern by Southern blotting, at diagnosis and in relapse. A few metaphases showed associated 12p- by standard cytogenetics, only in relapse. Thus we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in patients with this subtype of ALL and occurs on the 12p- chromosome. These data question the status of tumor suppressor gene hypothesized for TEL.

Blotting, Southern↗

Phenylketonuria: plasma phenylalanine responses to different distributions of the daily phenylalanine allowance over the day.

OBJECTIVE: To achieve smooth control of plasma phenylalanine concentrations in phenylketonuric patients, it is advocated to divide the daily intake of natural protein and amino acid supplements equally over the meals. However, this may be quite an encumbrance for the patient. We, therefore, investigated whether a breakfast with an unequal daily distribution results in an undue rise in the plasma phenylalanine concentration. DESIGN: Plasma phenylalanine concentrations were measured in seven patients with phenylketonuria in response to three tests with breakfast and lunch, representing an equally or unequally divided daily distribution of the individually tailored phenylalanine intake. Breakfast contained 25%, 50%, or 75%, whereas lunch contained 30% or 10% of the individual daily phenylalanine allowance, respectively. RESULTS: Plasma phenylalanine concentrations showed postprandial increases of up to 26% above baseline. Generally, phenylalanine returned to baseline during the test and remained within the target range if baseline phenylalanine was within that range. Two patients having values in the upper target range showed a rise just above the target range for 60 minutes on an unequal daily distribution of phenylalanine. In another patient treated similarly, plasma phenylalanine did not return to baseline during the test. CONCLUSIONS: Unequal distributions of the daily phenylalanine allowance are justified, provided that the patient is in good clinical condition, adjusted to the diet adequately, and the daily allowance is not exceeded. At this time, however, we cannot recommend this unequal daily distribution for daily practice.

Adolescent↗

Isochromosome 7q and trisomy 8 are consistent primary, non-random chromosomal abnormalities associated with hepatosplenic T gamma/delta lymphoma.

Four patients with hepatosplenic T gamma/delta lymphoma, a rare but distinct entity of peripheral T cell lymphoma, are reported on. In each case, cytogenetic studies showed the presence of an Isochromosome 7q and a trisomy 8. A few chromosome studies have previously been reported in this lymphoma subtype but comparison with these published cases confirms that isochromosome 7q and trisomy 8 are primary, non-random chromosomal abnormalities in hepatosplenic T gamma/delta lymphoma.

Adolescent↗

Translocation t(10;11) involving the MLL gene in acute myeloid leukemia. Importance of fluorescence in situ hybridization (FISH) analysis.

Fluorescence in situ hybridization analysis in an infant with acute monocytic leukemia revealed a complex translocation, t(10;11;4) (p12; q23;q26). Southern blot analysis confirmed the existence of rearrangement of the MLL gene. The frequent occurrence of complex translocations involving 10p12 and 11q23 is discussed in function of the opposite orientation of the AF10 and MLL genes on 10p and 11q. The importance of FISH analysis in t(10; 11) is emphasized.

Chromosomes, Human, Pair 10↗

Faconi anemia and bone marrow clonal chromosome abnormalities.

Clonal chromosome abnormalities were detected in bone marrow cells of 20 patients with Fanconi anemia investigated at various stages of the disease. Two presented with acute leukemia, six with myelodysplastic syndrome, and 12 had minor or no morphological abnormalities of hematopoietic cells. Abnormalities of chromosome 7 were detected in nine patients (monosomy, isochromosome, or other structural rearrangement), and chromosome 1 was rearranged in four. The types and the significance of clonal chromosome abnormalities which may be present without apparent evolution toward acute leukemia or myelodysplastic syndrome in Fanconi anemia patients are discussed.

Adolescent↗