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Biomedical subjects

L Becker

Publications and source records attributed to L Becker.

At least 109 records · Page 6Linked to original sources

An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia.

In 1989, our medical center used continuous quality improvement concepts in the creation of a Nosocomial Pneumonia Prevention Team whose aim was to significantly reduce nosocomial ventilator-associated pneumonia. The team included representatives from nursing, respiratory therapy, pulmonary medicine, internal medicine, anesthesiology, education and training, and infection control. Because the majority of mechanically ventilated patients were located in the intensive care unit, this unit became the focus of the prevention efforts. Team meetings were held regularly, with all representatives brainstorming barriers, possible interventions, methods of outcome measurement, and frequency of evaluation. Policies and procedures were reviewed, surveillance was increased, handwashing practices were surveyed, periodic feedback to staff was begun, and an educational program was developed and presented. During 1990, we observed a 57% reduction in ventilator-associated pneumonia from the baseline years, 1987 and 1988. Statistical comparison of proportions by z test indicated a p value less than 0.05. Fifteen cases of nosocomial ventilator-associated pneumonia were prevented and a cost saving of $105,000 was realized. Performance of traditional surveillance for outliers, coupled with literature-based thresholds, can lead to tolerance of inordinately high endemic rates. Infection control programs can significantly reduce endemic rates of nosocomial ventilator-associated pneumonia through continuous quality improvement methods and multidisciplinary interventions, with standard infection control procedures used for improvement.

California↗

Synthesis of C60H2 by rhodium-catalyzed hydrogenation of C60.

Reduction of C60 with rhodium(0) on alumina and hydrogen in deuterated benzene (C6D6) at ambient temperature and pressure yields a mixture of hydrogenated compounds; C60H2 has been characterized as the major product in 14% yield based on 1H NMR.

Benzene↗

Microdialysis of the pontine reticular formation reveals inhibition of acetylcholine release by morphine.

BACKGROUND: Systemically administered morphine inhibits rapid eye movement (REM) sleep; however, the neuronal mechanisms through which morphine disrupts REM sleep remain poorly understood. Recently, the authors have shown that morphine-mediated REM sleep inhibition is localized to a specific region of the pontine reticular formation: the gigantocellular tegmental field (FTG). Because cholinergic neurotransmission in the FTG is known to play a role in REM sleep generation, the present study examined the hypothesis that systemically administered morphine would cause decreased acetylcholine release in the FTG. METHODS: Microdialysis probes were stereotaxically positioned in the FTG of six barbiturate-anesthetized cats to measure acetylcholine release. Cholinergic input to the FTG arises from the laterodorsal (LDT) and pedunculopontine tegmental (PPT) brain stem nuclei. By electrically stimulating the LDT and PPT, it was possible to measure stimulation-evoked acetylcholine release in the FTG. Morphine sulfate (MSO4) was administered intravenously (500 micrograms.kg-1). High performance liquid chromatography with electrochemical detection was used to measure stimulation-evoked acetylcholine release in the FTG before and after the systemic administration of morphine sulfate. RESULTS: Acetylcholine release in the pontine FTG was depressed significantly (P < 0.01) by systemic morphine sulfate. Acetylcholine release without electrical stimulation of the LDT and PPT averaged 0.6 +/- 0.18 (mean +/- SD) pmol/10 min of dialysis. Before morphine sulfate was administered, electrical stimulation of cholinergic LDT and PPT neurons increased acetylcholine release within the FTG to 1.9 +/- 0.76 pmol/10 min. After morphine sulfate was administered, there was a 37% decrease in acetylcholine release within the FTG to average values of 1.2 +/- 0.63 pmol/10 min. There was no significant effect of morphine sulfate on spontaneous acetylcholine release in the absence of LDT and PPT stimulation. CONCLUSIONS: Because FTG levels of acetylcholine release increase during REM sleep, the present results are consistent with the hypothesis that diminished acetylcholine release in the pontine FTG comprises one mechanism by which morphine inhibits REM sleep.

Acetylcholine↗

Primary leptomeningeal melanoma: an unusually aggressive tumor in childhood.

Primary malignant melanoma of the leptomeninges of the central nervous system is a rare and aggressive tumor in children. We report our experience from 1964 to 1990 with this tumor in eight children. The mean age at diagnosis was 4.9 years (range, 1.3 to 13 yr). Five children presented with signs and symptoms of raised intracranial pressure from hydrocephalus secondary to tumoral obliteration of the basal cisterns, but the time from the initial symptomatology to diagnosis was frequently delayed. Three patients in this series had hairy nevi in association with their leptomeningeal melanoma. Cerebrospinal fluid (CSF) analysis typically showed raised opening pressures, decreased glucose, and increased protein concentrations. Malignant melanoma cells were found in the CSF in three patients. Confirmatory radiographic examinations included air encephalography, myelography, and computed tomographic and magnetic resonance scanning. Four patients were treated with lumboperitoneal shunts, and one patient was treated with a ventriculoperitoneal shunt for hydrocephalus. Two patients underwent craniotomies and subtotal excisions of their tumors. In seven patients, a definitive diagnosis of leptomeningeal melanoma was made by pathological examination of tissues sent at surgery or at post mortem. In one case, the diagnosis was established by a detailed cytological analysis of the CSF. Four children died of fulminant disease and tumor spread before treatment could be instituted. The four children who received treatment had a combination of radiation therapy and chemotherapy. One child received intrathecal methotrexate. The two children with the longest survivals (2 and 3 yr, respectively) received cisplatinum and dimethyltriazenoimidazole carboxamide in addition to craniospinal irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The long-term outcome after surgical treatment of dorsally exophytic brain-stem gliomas.

Dorsally exophytic brain-stem gliomas represent a distinctive subgroup of pediatric brain-stem neoplasms that are amenable to radical excision because of their benign histology and growth characteristics. However, their attachment to the floor of the fourth ventricle invariably precludes complete tumor excision. The long-term behavior of the residual tumor remains a subject of concern. To address this issue, the authors reviewed their experience with 18 dorsally exophytic brain-stem gliomas treated between 1974 and 1990. At operation, the tumors filled the fourth ventricle, fungating out of a broad-based area of the dorsal brain stem. The exophytic tumor was resected, but no attempt was made to remove tumor from the brain stem. Histological examination showed that 16 of the tumors were grade I or II astrocytomas, one was a ganglioglioma, and one was an otherwise benign-appearing glioma with several foci of anaplasia that was classified as a grade III astrocytoma. The latter patient was one of only two in the series to receive postoperative radiation therapy; both cases so treated have no evidence of disease on follow-up imaging studies 61 and 135 months postoperatively. One other child who had stable disease postoperatively died of shunt malfunction 18 months after tumor excision. Serial radiographic studies in the other 15 patients have shown no evidence of disease in three, stable residual disease in eight, and tumor enlargement 12, 28, 40, and 84 months postoperatively in four (median follow-up period 113 months). Each of the four patients with tumor regrowth underwent repeat tumor excision. Two of these children received perioperative radiation therapy at the time of disease progression and both showed reduction in tumor volume 28 and 65 months after their second operation. In contrast, both patients who did not receive radiotherapy at the time of disease progression had further tumor enlargement 48 and 84 months after their second operation and underwent a third tumor resection; one received postoperative radiation therapy and has no evidence of disease 58 months after his third operation and the other child has stable disease 27 months postoperatively. Histological examination of tumor specimens obtained at second and third operations showed no change from the appearance of the tumor on the initial resection. The authors conclude that the majority of dorsally exophytic brain-stem gliomas can be managed successfully with subtotal excision and, if necessary, cerebrospinal fluid diversion. The small percentage of tumors in this series that showed recurrent growth remained benign histologically.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma.

Data have been analysed for 327 patients with advanced renal cell carcinoma receiving a continuous infusion of recombinant interleukin 2 (rIL-2) alone (225 patients) or rIL-2 plus lymphokine activated killer (LAK) cells (102) on a normal oncology ward. Eligibility criteria were uniform across protocols, all patients having advanced progressive disease, but with an ambulatory performance status. The baseline characteristics of patients receiving rIL-2 alone did not differ significantly from those receiving LAK, with the exception that the LAK treated patients had a better performance status. Despite similar treatment intensity, toxicity was more severe in the patients receiving LAK. The addition of LAK did not lead to higher response rates or to prolonged response duration, progression-free survival or survival. This review confirms the activity of rIL-2 for the treatment of advanced renal cell carcinoma and demonstrates that the addition of LAK cells does not lead to increased efficacy.

Adult↗

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.

Aged↗

Maturational and aging effects on guanine nucleotide binding protein immunoreactivity in human brain.

Age-related changes in transmembrane signal transduction have been reported for a number of hormonal receptors in human tissues. Guanine nucleotide binding proteins (G-proteins) are major regulatory components in the signal transduction processes for numerous receptors. Developmental changes in the abundance of specific G-protein alpha subunits, especially for Go, have already been shown in rat brain and in neuronal cell lines. In this study, immunoblotting analyses were performed with specific rabbit polyclonal antisera to Gs alpha, Gi alpha, Go alpha, and G beta subunits to estimate semi-quantitatively these G-protein subunits in samples of parietal cortex obtained postmortem from 18 subjects free of neurologic or psychiatric disease whose ages ranged from 3 days to 92 years. The Gs and Gi alpha subunit immunoreactivities were correlated significantly and inversely with age. The Gi alpha immunoreactivity declined markedly (46%) after the age of 40. As other G-protein subunit concentrations showed no age-dependent changes, the observed relationship between Gs and Gi alpha subunits and age is not likely due to cell loss occurring with advancing age. Of particular interest, the ratio of 52 to 45 kDa Gs alpha subunit immunoreactivities was significantly higher in infants than that found for adult parietal cortex. Given that changes in G-protein subunit abundance directly affect receptor-G-protein-effector functionality and response, these age-related alterations may be of importance in cerebral dysfunction and the development of neuropsychiatric disease in the later years of life.

Adolescent↗

Effect of rimantadine on the immune response to influenza A infections.

The effects of rimantadine on lymphocyte responses to mitogens CON-A and PHA, natural killer cell activity, and the development of serum and local antibodies were studied during an epidemic outbreak of influenza A (H3N2). Twenty-three families consisting of 38 adults and 46 children had a member who developed a flu-like illness and were randomly assigned to receive placebo or rimantadine either as treatment or post exposure prophylaxis. Nasal washings for virus isolation and IgG and IgA determination were collected on days 1, 5, and 10 of illness. Blood samples for immunologic studies were obtained on days 1 and 5 of clinical illness and on day 21. No differences in lymphocyte responses to CON-A and PHA or in natural-killer cell activity were noted between placebo and rimantadine groups. The development of neutralizing antibodies to influenza H3N2 was also not affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in the rimantadine group compared to the placebo group (0/9 vs. 6/9, P less than 0.005). The findings indicate that rimantadine had no adverse affect on the systemic immune system. However, local immune response was diminished in individuals taking rimantadine possibly due to the presence of less immunogen resulting from reduction of virus in secretions of individuals taking antivirals.

Antibody Formation↗

Growth and development of the brain in Down syndrome.

The brain of a child with Down syndrome develops differently from a normal one, attaining a form reduced in size and altered in configuration. Directly related to the mental retardation are neuronal modifications manifest as alterations of cortical lamination, reduced dendritic ramifications, and diminished synaptic formation. However, selected cholinergic marker enzymes such as choline acetyl transferase and acetyl cholinesterase have shown no alterations in young children with Down syndrome. The pace of the neuronal transformations is related to stage of maturation. With early growth and development, the normal dendritic tree continuously expands. In Down syndrome, at 4 months of age, the neurons show a relatively expanded dendritic tree, but during the first year the dendrites stop growing and become atrophic relative to control neurons. Accompanying these neuronal irregularities are subtle alterations of other cell types: astrocyte, oligodendrogliocyte, microglia, and endothelial cell. In early infancy, one of the astrocytic markers, GFAP, is not altered, but there is greater expression of S-100 protein in the temporal lobe in Down syndrome. Oligodendrogliocyte dysfunction is reflected in delayed myelination in pathways of frontal and temporal lobes. Microglia appear more prominent in Down syndrome. A minority of children with Down syndrome have vascular dysplasias and focal calcification of basal ganglia. In young children, expression of beta-amyloid in Down syndrome is no different than in normal children but disappears after age two, only to reappear in adults. As some of these studies suggest, the identification of genes on chromosome 21 and the determination of the gene product allow the production of specific antibodies and, through immunohistochemical techniques, the identification of the expression of these proteins in both normal development and Down syndrome. Specifically, the localization and appearance in development of proteins such as the beta-subunit of S-100, beta-amyloid (A4 protein), superoxide dismutase, and OK-2 are providing the means for better understanding the morphogenesis of the cellular and eventually molecular basis for the mental retardation in Down syndrome.

Acetylcholinesterase↗

Two frameshift mutations in the cystic fibrosis gene.

Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We have identified in exon 7 two frameshift mutations, one caused by a two-nucleotide insertion and the other caused by a one-nucleotide deletion; these mutations--CF1154insTC and CF1213delT, respectively, are predicted to shift the reading frame of the protein and to introduce UAA(ochre) termination codons at residues 369 and 368.

Adolescent↗

An unusual case of craniofacial fibrous dysplasia presenting in early infancy.

Fibrous dysplasia (FD) of bone is one of the most frequently encountered anomalies of skeletal development. It may involve one or more bones and, particularly when polyostotic, is sometimes associated with abnormal skin pigmentation and endocrine abnormalities. FD occurs mainly in large limb bones, ribs, and craniofacial bones in older children and young adults. Usually craniofacial involvement is detected because of local swelling or asymmetry of the face or head. Neurological symptoms, primarily due to involvement of the foramina, have been reported but are not common. Infantile fibrous dysplasia of the craniofacial region has rarely been reported.

Angiography↗