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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 595 records · Page 33Linked to original sources

Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients.

The localization of cortical sites essential for language was assessed by stimulation mapping in the left, dominant hemispheres of 117 patients. Sites were related to language when stimulation at a current below the threshold for afterdischarge evoked repeated statistically significant errors in object naming. The language center was highly localized in many patients to form several mosaics of 1 to 2 sq cm, usually one in the frontal and one or more in the temporoparietal lobe. The area of individual mosaics, and the total area related to language was usually much smaller than the traditional Broca-Wernicke areas. There was substantial individual variability in the exact location of language function, some of which correlated with the patient's sex and verbal intelligence. These features were present for patients as young as 4 years and as old as 80 years, and for those with lesions acquired in early life or adulthood. These findings indicate a need for revision of the classical model of language localization. The combination of discrete localization in individual patients but substantial individual variability between patients also has major clinical implications for cortical resections of the dominant hemisphere, for it means that language cannot be reliably localized on anatomic criteria alone. A maximal resection with minimal risk of postoperative aphasia requires individual localization of language with a technique like stimulation mapping.

Adolescent↗

Uniform elimination pattern for glibenclamide in healthy Caucasian males.

It has been shown, that the elimination rate of intravenously administered tolbutamide shows considerable interindividual variation, due to strong genetic influence. These pharmacogenetic differences in the metabolic clearance rate of tolbutamide may result in drug failure in fast-eliminators, and it may cause an increased incidence of side effects in slow-eliminators. It is not known whether different "pharmacogenetics" exist for other sulfonylurea drugs. Therefore, we have injected glibenclamide (0.02 mg/kg body weight) intravenously in 52 male, normal weight, healthy volunteers. Serum glibenclamide levels were followed for up to 24 h. The terminal phase half-life of glibenclamide was 2.46 +/- 0.67 h (mean +/- SD), total drug clearance was 48.7 +/- 11.0 ml.min-1 and the slow disposition phase rate constant was 0.30 +/- 0.08 h-1. From the individual data of each subject frequency histograms were developed for these and other kinetic parameters and tested with a Kolmogoroff-Smirnoff-test for unimodal normal distribution. There was no significant (p greater than 0.05) deviation from the unimodal normal distribution for these parameters. In contrast to the pharmacogenetics of tolbutamide metabolism the present data indicate that glibenclamide follows an uniform elimination pattern in healthy caucasian males.

Adolescent↗

Role of gamma globulin.

The introduction of preparations of immune serum globulin that are safe for intravenous use (IVIG) has made possible safe and effective prophylactic treatment for patients with a variety of humoral immunodeficiencies. These include not only primary agammaglobulinemia and common variable hypogammaglobulinemia but also the antibody deficiencies that accompany chronic lymphocytic leukemia (CLL) and multiple myeloma, as well as the hypogamma-globulinemia found in very low birth weight newborns who have not received adequate transplacental IgG from their mothers. In contrast, trials to date have not shown efficacy of IVIG in preventing sepsis in burn patients. The ease of administration and efficacy of IVIG in preventing respiratory symptoms in hypogammaglobulinemic patients has suggested that many other patients presenting with sinusitis and asthma, recurrent bronchitis, and other chronic chest symptoms might also benefit from IVIG and that they should be worked up for IgG subclass or specific antibody deficiencies. Side effects of IVIG administration are generally minor and may be prevented by slow administration and/or pretreatment with aspirin or Benadryl. The only contraindication to IVIG treatment is anaphylactic sensitivity to IgA, which is extremely rare. IVIG is thus an effective and safe form of prophylaxis that can reduce the incidence of pneumonia and other respiratory infections in patients with antibody deficiency as a predisposing factor.

Adult↗

[Clinical experiences with late mothers and their wished for children].

By way of introduction, this article considers the growth of the desire for a child and problems of counter-transference among older, but in terms of motherhood younger parents. The discussion concerns disturbance of the mother-child relationship among 34 child psychiatry patients whose mothers were between 37 and 44 years of age when they were born. The article expresses the view that late motherhood, beginning shortly before the end of the reproductive phase, is related to a particular problem of inner maturation among late mothers. With the birth of a child, late mothers enter into a state of sustained partial regression that endangers active adjustment and the maternal care of the child during all developmental phases. The mother's need to be more or less mothered herself by her child is a sign of the mother's difficulties in detaching herself from her own mother. As a result of the causal disturbance in the process of maturation toward a maternal identity, problems in the relationship between both late and minority-age mothers reveal many similarities, though there are also fundamental differences between the two.

Adolescent↗

Coronary care in New York City hospitals.

New York City, with six medical schools and an elaborate emergency medical system, would appear to be a locale with optimal resources for coronary care. To assess coronary care facilities and practices, a comprehensive questionnaire was prepared by a multidisciplinary committee and submitted to 72 hospitals. Seventy-nine percent (57/72) responded, including all medical school affiliated hospitals and 41 of the 45 with more than 300 beds. Twenty-nine percent (16/55) did not have a coronary care unit separate from a general intensive care unit. Thirty-three percent (18/55) of coronary care units were designed before 1970. Although 85% (46/54) of the coronary care units had a 1:2 registered nurse per patient ratio during days, only 43% (23/54) maintained this ratio at night. Central monitoring was available in all hospitals, but only 40% (21/52) indicated 24-hour continuous monitor observation. Forty-five percent (25/55) had cardiac catheterization facilities, and 43% (24/56) had an intra-aortic balloon available. Forty-six percent (26/57) of coronary care units transferred post-myocardial infarction patients to non-monitored general beds. Fifty-eight percent (31/53) offered dietary counseling to patients, and 33% (18/54) had an inpatient cardiac rehabilitation program. Thus, New York City hospitals demonstrate a marked variability in coronary care unit facilities and practices and a substantial number of hospitals deviate from published recommendations for coronary care units.

Coronary Care Units↗

[Injuries to the upper tibial epiphysis. Apropos of 20 cases].

The authors report 20 cases of injuries involving the proximal tibial epiphysis (16 avulsion fractures of the tibial tubercle, 4 epiphyseal fractures), occurring in adolescents engaged in athletics, in 3/4 of the cases. Sixteen displaced fractures needed open reduction and internal fixation with screw(s). Leg shortening (12 mm) occurred in a 14 year-old male with a displaced fracture of both the tibial tubercle and proximal epiphysis, in which premature ossification had taken place; fixation with Kirschner wires would have been the treatment of choice before closure of the tibial epiphysis. At follow-up, function was acceptable in all cases; all the patients had returned to full daily activity and no further surgical procedures were needed. Long-term knee laxity became obvious in one patient, however, with repeated fracture of the tibial tubercle. Associated ligamentous and meniscal tears should therefore be sought on early clinical examination and confirmed by arthroscopy or arthrotomy after surgical fixation.

Adolescent↗

Evaluation of a structured treatment and teaching programme on non-insulin-dependent diabetes.

A structured treatment and teaching programme for non-insulin-treated non-insulin-dependent (type 2) diabetes was evaluated prospectively in general practice. The four group sessions were mainly conducted by paramedical personnel. 65 patients from five general practices were assessed at the start of the programme and 50 (mean age 65 years, diabetes duration 7 years) completed the 1 year follow-up (intervention group). The control group consisted of 49 patients (mean age 63 years, diabetes duration 7 years) from three other general practices without the programme. In the intervention group the percentage of patients receiving sulfonylureas fell from 68% at the start of the study to 38% after 1 year (mean difference 30%, 95% confidence interval [CI] 16-44%); the mean weight loss was 2.7 kg (95% CI 1.6-3.8 kg), and non-fasting triglycerides were reduced by 0.77 mmol/1 (95% CI 0.35-1.19 mmol/l); and glycosylated haemoglobin remained unchanged (7.1% of total haemoglobin). In the control group none of these indices was changed during the study year, and 10% of patients started insulin treatment. The structured treatment and teaching programme improved the overall quality of patient care in elderly non-insulin-dependent diabetic patients treated by general practitioners.

Aged↗

Functional differences between the 40 kDa and 50 to 70 kDa IgG Fc receptors on human neutrophils revealed by elastase treatment and antireceptor antibodies.

Most previous studies of IgG FcR on neutrophils (PMN) have focused on a single FcR of Mr = 50 to 70 kDa, which is recognized by mAb 3G8 and anti-Leu-11a. In the course of studying the effects of extracellular proteases on PMN receptor expression and function, we found that treatment with human leukocyte elastase reduced the expression of this FcR on the PMN surface by as much as 85% in flow cytometric studies, but did not inhibit ingestion of IgG-coated particles or O2- production induced by multivalent IgG complexes, and caused only a 35% decrease in IC binding to PMN. Since a second FcR with Mr = 40 kDa recognized by mAb IV-3, recently has been identified on PMN, we sought to determine if this FcR was resistant to elastase and thus accounted for the elastase stability of IgG-mediated PMN functions. Elastase treatment that reduced 3G8 binding by 85% caused no decrease in binding of mAb IV-3. For non-elastase-treated PMN, mAb IV-3 against the 40 kDa FcR caused as much as 79 +/- 7% inhibition of IgG-induced O2- production, whereas mAb 3G8 against the 50 to 70 kDa FcR caused only 32 +/- 5% inhibition. In contrast, for IC-binding, mAb IV-3 caused only 15 +/- 6% inhibition, whereas mAb 3G8 caused as much as 80 +/- 9% inhibition, a reversal of their relative effects on O2- production. In parallel studies with elastase-treated PMN, mAb IV-3 actually blocked more IC binding than did mAb 3G8, 55 +/- 4% vs 40 +/- 6%, respectively, presumably because most of the 50 to 70 kDa FcR molecules had been cleaved. The effect of the two mAb together in blocking IC binding was additive, whereas for blocking of O2- production, mAb 3G8 added little or nothing to the effect of mAb IV-3 alone. Direct 125I-labeled Ab binding studies with intact PMN revealed seven times as many 50 to 70 kDa as 40kDa FcR, 110,200 +/- 9600 and 15,100 +/- 700 sites/cell, respectively. Our findings suggest that the elastase-resistant 40 kDa FcR is primarily responsible for IgG-mediated activation of human PMN, whereas the elastase-sensitive 50 to 70 kDa FcR predominates in IC binding, by virtue of its numerical superiority, but does not directly activate the cell. The latter may serve to hold IgG-coated microorganisms or other multivalent IC in place at the PMN surface, enhancing contact with the 40 kDa FcR and thus facilitating cell activation in a cooperative manner.

Adult↗

Intracellular degradation of the complement C3b/C4b receptor in the absence of ligand.

Human neutrophils (PMN) respond to various soluble stimuli by translocating intracellular complement C3b/C4b receptors (CR1) to the cell surface. Ligand-independent internalization of surface CR1 has been demonstrated previously, but the fate of total cellular CR1 during PMN stimulation has not been determined. In order to study the fate of CR1 during neutrophil activation, we have employed a unique approach for the quantitative analysis of intracellular antigens which allows simultaneous measurement of total cellular and surface membrane antigen pools. Stimulation of isolated PMN with N-formyl-Met-Leu-Phe or ionomycin resulted in a mean 7-fold increase in surface CR1 expression within 15 min. Total cellular CR1 decreased by as much as 45% within 15 min, with loss continuing for up to 1 h. Inclusion of NH4Cl during PMN stimulation inhibited the loss of total CR1 without affecting surface CR1 expression. Addition of phenylmethylsulfonyl fluoride inhibited loss of total CR1 and enhanced the stimulus-induced increases in surface CR1. These data suggest that intracellular degradation of CR1 occurs during stimulation of PMN and may involve proteolysis in an acidic intracellular compartment. Since our experiments were done with isolated PMN in the absence of serum and complement components, this degradation occurred in the absence of C3b, the ligand for CR1. To our knowledge, ligand-independent degradation of a cell surface receptor has not been previously detected.

Cell Separation↗

In vivo and in vitro investigations on biological effects of aromatic bis-(2-chloroethyl)amino-bisphosphonic acids, new agents proposed for chemotherapy of bone tumors: cytostatic activity in rat osteosarcoma; toxicity and genotoxicity in liver and bone marrow; mutagenicity in S. typhimurium.

Two new aromatic bis-(2-chloroethyl)-amino derivatives (BCMP and BAD) which are linked to osteotropic bisphosphonates were investigated for their therapeutical efficacy in rat osteosarcoma. Furthermore their genotoxic potential in vitro was determined in S. typhimurium and in mammalian cells. Finally, parameters for toxicity and genotoxicity were determined in liver and bone marrow cells following in vivo treatment. It was shown that BAD was of higher therapeutic effectiveness than BCMP. Both compounds induced approximately a two fold increase of his+ revertants in S. typhimurium TA1535 following metabolic activation by subcellular liver fractions. Both compounds also induced amplification of SV40 DNA in SV40 transformed cells (CO631). This endpoint may be of importance for acquired resistancy of cells during therapy. DNA-single strand breaks were induced by BCMP but not by BAD in liver cells and CO631 cell line. Following in vivo treatment BCMP was of higher genotoxic activity in liver cells than BAD. In comparison, genotoxicity of both compounds was much lower in bone marrow cells than in liver cells. BCMP was again more potent than BAD in inducing DNA single strand breaks, whereas BAD was more toxic. The higher therapeutic efficacy of BAD together with its lower genotoxic properties makes this compound superior to BCMP as a candidate for applied chemotherapy in humans.

Animals↗

Different numbers of maternal and paternal siblings of cystic fibrosis patients.

When 458 parents of children suffering from cystic fibrosis (CF) from all over the German Democratic Republic were interviewed to determine the number of their siblings, it was found that the maternal families had a total of 1369 children and the paternal, 1220. While the fathers of CF patients tended to originate from families with one or two children, more mothers than fathers came from families with three to twelve children (P = 0.01). The average number of children in the maternal families was 2.99; in the paternal families, only 2.66. To rule out any methodological errors, sibs of mothers and fathers of various control groups were studied. We found that the number of siblings in these groups was balanced. The differences in our findings are probably due to CF heterozygosity. The underlying mechanism is unknown.

Adult↗

The effects of thermal biofeedback and autogenic training of cardiovascular reactivity: the joint USSR-USA Behavioral Hypertension Treatment Project.

Cardiovascular reactivity (heart rate, systolic, and diastolic BP) to mental arithmetic and cold pressor were measured before and after treatment as part of the cross-cultural (USSR and USA) evaluation of thermal biofeedback and autogenic training (in comparison with self-relaxation) as treatments for mild hypertension in unmedicated males. There were no statistically reliable decreases in cardiovascular reactivity from before to after treatment. However, downward shifts in basal levels of systolic and diastolic BP at post-treatment led treated patients to have lower stress-induced levels of BP.

Adult↗

Improved localization of infratentorial ependymoma by magnetic resonance imaging: implications for radiation treatment planning.

Ependymomas of the posterior fossa extend into the upper cervical spinal cord in approximately one-third of cases. Unfortunately, the posterior fossa and upper cervical cord region is often poorly seen on computed tomography (CT), making radiotherapy planning difficult. We report five cases of posterior fossa ependymoma with extension into the cervical cord where magnetic resonance imaging (MRI) demonstrated the caudal extent of tumor more clearly than CT. The extent of tumor depicted by MRI in each case correlated well with the operative findings. Higher doses of radiotherapy to the entire tumor volume are associated with improved survival in infratentorial ependymoma; however, the radiation tolerance of the cervical spinal cord is close to the dose necessary to control posterior fossa ependymoma, making limitation of radiation field volumes important. MRI may provide a method of precisely defining caudal tumor extent of posterior fossa ependymomas so that limited volume, high dose radiotherapy can be more safely administered to these patients.

Brain Neoplasms↗