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Biomedical subjects

R Maynard

Publications and source records attributed to R Maynard.

17 recordsLinked to original sources
PubMed1998

Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression.

Pancreatic adenocarcinoma develops from histologically identifiable intraductal lesions that undergo a series of architectural, cytological, and genetic changes. Limited genetic evidence recently suggested that the p16 gene plays a role in the progression of these "duct lesions." Duct lesions were identified in pancreata from 33 pancreaticoduodenectomies performed for infiltrating adenocarcinoma. All of these infiltrating adenocarcinomas were previously shown to contain alterations in the p16 gene or its promoter. Monoclonal and polyclonal anti-p16 antibodies were used for histological immunodetection. One hundred twenty-six duct lesions were identified. Nine (30%) of 30 flat, 4 (27%) of 15 papillary, 37 (55%) of 67 papillary with atypia, and 10 (71%) of 14 carcinoma in situ duct lesions showed loss of p16 expression. These included 30% of the flat lesions versus 53% of the nonflat lesions and 29% of the nonatypical lesions versus 58% of the atypical lesions. For both comparisons, the differences were statistically significant (P = 0.036 and P = 0.003, respectively). Loss of p16 expression occurs more frequently, but not exclusively, in higher-grade duct lesions. These data support the hypothesis that pancreatic duct lesions are neoplastic and that they represent the precursors of infiltrating adenocarcinoma. Immunohistochemical detection of p16 provides a new technology to study the genetic alterations in and stages of progression of large numbers of morphologically defined pancreatic duct lesions.

Adenocarcinoma↗
PubMed1997

Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas.

The Rb/p16 tumor-suppressive pathway is abrogated frequently in human tumors, either through inactivation of the Rb or p16INK4a/CDKN2/MTS1 tumor-suppressor proteins, or through alteration or overexpression of the cyclin D1 or cyclin-dependent kinase 4 oncoproteins. We reported previously that the p16 gene was genetically inactivated in 82% of pancreatic carcinomas. Nearly half of these inactivations were by intragenic mutation of p16, and the remainder were by homozygous deletion of the gene. Here, we analyzed pancreatic carcinomas for additional mechanisms by which the Rb/p16 pathway might be inactivated. Transcriptional silencing of the p16 gene in association with methylation of its 5'-CpG island was examined by methylation-specific PCR in 18 pancreatic carcinomas. Nine of these were known to harbor an intragenic mutation in p16, and nine had a wild-type p16 coding sequence. Seven of the 18 tumors were hypermethylated, and all 7 were p16 wild-type (P = 0.001). Complete silencing of transcription from methylated wild-type gene sequences was demonstrated. Immunohistochemical analysis revealed normal expression levels of the Rb protein in all carcinomas studied. None of the carcinomas had genomic amplification of the cyclin D1 or CDK4 genes, and none had mutation of the p16-binding domain of CDK4. An additional p16 mutation was identified. In total, the Rb/p16 pathway was abrogated in 49 of the 50 carcinomas (98%) studied, all through inactivation of the p16 gene. Similar results were obtained in an independently analyzed series of 19 pancreatic carcinomas. These data demonstrate the central role of the Rb/p16 pathway in the development of pancreatic carcinoma.

Carrier Proteins↗
PubMed1993

Cerebral hemodynamics during cardiopulmonary bypass in children using near-infrared spectroscopy.

We describe a new noninvasive method using near-infrared spectroscopy for monitoring cerebral hemodynamics during cardiopulmonary bypass in children. All patients were undergoing open heart operations for repair of congenital heart defects. Standardized anesthesia, an alpha-stat method of blood gas management, and nonpulsatile flow were used in all cases. All measurements during bypass were made after steady-state conditions had been reached. Cerebral blood flow was measured on 13 occasions in 4 children, aged between 4 and 10 months (median, 5 months). Values of 15.9 to 53.5 mL x 100 g-1 x min-1 were obtained. Cerebral blood volume was measured in 1 patient, aged 4 months. Volumes of 4.3 to 8.0 mL x 100 g-1 were obtained on bypass at full pump flow (2.4 L.min-1 x m-2). On bypass at half flow, the volume increased to 14.7 mL x 100 g-1. Change in cerebral blood volume with changing carbon dioxide tension (CBVR) was measured in 13 patients aged from 1 to 90 months (median, 13.5 months). Preoperatively, CBVR was 0.12 +/- 0.07 mL x 100 g-1 x kPa-1 and was independent of mean arterial pressure, which remained between 40 and 80 mm Hg in all cases. During hypothermic bypass (25 degrees C), CBVR was significantly reduced to 0.05 +/- 0.02 mL x 100 g-1 x kPa-1. In addition, there were three values at mean arterial pressure of lower than 40 mm Hg in which CBVR was negative (-0.04 +/- 0.01 mL x 100 g-1 x kPa-1). We conclude that near-infrared spectroscopy is useful for the noninvasive investigation of cerebral hemodynamics during cardiopulmonary bypass.

Carbon Dioxide↗
PubMed1992

Effect of rapid thoracic compression on the cerebral blood flow-velocity patterns of small infants.

We measured the middle cerebral artery (MCA) flow-velocities of 12 small infants (mean weight, 2,882 +/- 602 g) before, during, and after the rapid thoracic compression (RTC) maneuvers of partial forced expiratory flow-volume studies. Cerebral flow-velocities were measured using transcranial Doppler ultrasonography. RTC increased MCA end diastolic flow-velocities and Pourcelot indices of all infants (P less than 0.001). These values returned to baseline immediately after the release of chest compression. We also measured the MCA flow-velocities of several preterm infants during their normal daily activities. The changes in flow-velocity patterns observed during normal daily life were similar to those observed during RTC. These findings demonstrate that RTC produces real, but likely not pathologic, changes in cerebral blood flow-velocities.

Blood Flow Velocity↗
PubMed1984

[Brain stem AEP in toxic comas. Correlation with brain stem reflexes].

24 deep toxic comas with respiratory assistance were studied by brain-stem reflex and BAEP. Laboratory analysis showed several simultaneous toxics (phenobarbital, benzodiazepines, tricyclic antidepressants...). Three groups of patients were defined: Twelve patients with normal BAEP and with relatively preserved brain-stem reflex (oculocephalic and oculovestibular are often disturbed but photomotor is present). Eleven patients with delayed BAEP and with more disturbed brain-stem reflex (photomotor is missing 3 times). In 2 cases (one of which is mentioned above in group B) brain-stem reflex and BAEP disappear and these patients die. Cerebral anoxia is associated here with toxics. Causes of delayed latencies (group B) are discussed (hypothermia, toxics). BAEP seems important in diagnosis and prognosis of toxic coma.

Adult↗
PubMed1983

[Seizures in the newborn infant; value of polygraphy].

Recordings were made from 20 newborns during seizures in their first days of life, using a polygraphic study enabling observation of electro-clinical seizures, electric seizures, and seizures with no EEG transfer. The interictal EEG as well as the duration of status epilepticus are discussed. An estimation of the prognosis from the EEG clinical criteria is envisaged. CT scans and ultrasound scans were performed in serious cases of neonatal distress responsible for status epilepticus; these showed diffused or localized oedema of the white matter, either isolated or associated with intracranial hemorrhagic lesions.

Electroencephalography↗
PubMed1982

A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection.

Four hundred fifty volunteers participated in a placebo-controlled, double-blind, randomized trial of the prophylactic effects of rimantadine and amantadine during an outbreak of influenza A. The subjects received drugs orally at a dose of 100 mg twice a day for six weeks. Influenza-like illness occurred in 41 per cent of the subjects receiving placebo but in only 14 per cent of those receiving rimantadine and 9 per cent of these receiving amantadine (P less than 0.001 for either drug vs. placebo). Laboratory-documented influenza occurred in 21 per cent of placebo recipients, 3 per cent of rimantadine recipients, and 2 per cent of amantadine recipients (P less than 0.001). These findings represent efficacy rates of 85 per cent for rimantadine and 91 per cent for amantadine, as compared with placebo. More recipients of amantadine (13 per cent) than recipients of rimantadine (6 per cent; P less than 0.05) or placebo (4 per cent; P less than 0.01) withdrew from the study because of central-nervous-system side effects. On the basis of this study, rimantadine appears to be the drug of choice for the prophylaxis of influenza A.

Adamantane↗
PubMed1970

[Amnesic ictus].

Explore the source record for details and available documents.

Age Factors↗
PubMedDate not supplied

[EEG and clinical study of 107 patients with acute severe traumatic comas (author's transl)].

The authors describe the EEG recordings of 107 patients with acute severe cranial trauma and signs of axial lesions. The initial EEG included: sleep patterns, alternating tracings, alpha band tracings which were either nonreactive pseudo-alpha or modulated alpha often reactive, and diffuse slow wave tracings. They found no particular tracing corresponding to a precise level of rostrocaudal destructuration, but some associations were seen more frequently. EEG sleep patterns and alternating tracings were never observed in brain stem lesions, the activity recorded being of low voltage, rigid, and non-reactive. The presence of spontaneous fluctuations (with sleep rhythms in some cases) and reactivity in other levels (mesodiencephalic junction, diencephalic and cortical-subcortical) are good prognostic signs. Focalised EEG signs are seen especially in the more rostral levels.

Brain Injuries↗