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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 109 records · Page 6Linked to original sources

Anton P. Chekhov, MD (1860-1904): dual medical and literary careers.

This is a story of a physician who was one of the world's greatest short story writers. Anton Pavlovich Chekhov successfully performed dual careers of writing and practicing medicine during a short but productive life. Many biographers overlook Dr Chekhov's role, although his medical training and practice flowed over into his writing, influencing both his subject matter and his style. His stories and plays reveal the insights that Dr Chekhov discovered about the human psyche at work, thus delving into psychosomatic medicine nearly 50 years before its time. Despite orders to stop practicing medicine because of his own deteriorating health, Chekhov devoted himself further to the study of medicine, publishing a landmark study in social medicine that advocated reform of the Russian penal system. Meanwhile, his fictional works earned him the coveted Pushkin prize for the best literary work of the year in 1888. Shortly after celebrating his third wedding anniversary to actress Olga Knipper, Anton Chekhov died at age 44, victim of a nearly lifelong battle with tuberculosis.

Famous Persons↗

Respiratory dysfunction and white cell activation following cardiopulmonary bypass: comparison of membrane and bubble oxygenators.

OBJECTIVE: Cardiopulmonary bypass induces respiratory dysfunction postoperatively, with activation of both the complement system and white cells implicated. This study compared the effects of bubble and membrane oxygenators for cardiopulmonary bypass in terms of respiratory dysfunction and markers of white cell activation and endothelial damage. METHODS: Fifty patients undergoing cardiopulmonary bypass were randomly allocated either membrane or bubble oxygenation. Respiratory function was assessed serially by arterial oxygen tension and alveolar-arterial oxygen gradient. Complement activation was measured by serial sampling of serum C3a levels. White cell activation was assessed by serial measurement granulocyte elastase; other markers investigated were levels of thromboxane B2, von Willebrand factor and malondialdehyde. All sample measurements were made preoperatively, early and late during bypass, 4-6 h postoperatively and then on the 1st, 2nd and 6th postoperative day. All samples were corrected for haemodilution, and differences between groups tested non-parametrically. RESULTS: In both groups of patients there was a highly significant fall (P < 0.001) in arterial oxygen tension accompanied by a highly significant rise (P < 0.0001) in aleveolar-arterial oxygen gradient at 18 h compared to preoperative values persisting until 6 days postoperatively. Levels of C3a increased significantly in both groups at 10 min post bypass, increased further at 60 min peaking at 4-6 h post bypass. Granulocyte elastase serum levels increased significantly at 10 min postoperatively in both groups compared to control levels, remaining elevated till 48 h, but returning to control levels by 6 days. There was a small difference (P < 0.04) between the groups at 4-6 h only. Levels of von Willebrand factor increased significantly at 60 min post bypass in both groups, remaining elevated 6 days postoperatively. Levels of malondialdehyde increased at 10 min post bypass, remaining elevated until 6 days post bypass. Thromboxane levels showed no significant changes. For all markers measured, there were no significant differences between the groups other than those already indicated. CONCLUSIONS: This study demonstrated marked respiratory dysfunction, complement activation and white cell activation in patients undergoing cardiopulmonary bypass with either bubble or membrane oxygenators. There was marked variability in the response of individual patients with either oxygenation technique, but overall no significant differences between the groups.

Blood Gas Analysis↗

Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families.

The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Adult↗

A malaria parasite toxin associated with Plasmodium vivax paroxysms.

We have previously demonstrated a correlation between clinical paroxysms in Plasmodium vivax malarial infections and the appearance in patients' plasma of factors that kill blood stage parasites (gametocytes). This activity was, as previously shown, dependent on the presence in paroxysm plasma of tumour necrosis factor-alpha (TNF-alpha), which acts in conjunction with other 'complementary' factors. Here we have identified a parasite component which is essential for this activity and functions as a 'complementary' factor together with TNF, and a third component of unknown origin. The P. vivax parasite component present in paroxysm plasma can be substituted with a blood-stage schizont extract of either P. vivax or P. falciparum. This was demonstrated by restoring the parasite-killing activity to post-paroxysm plasma (from which it was absent) with the addition of the extracts together with TNF. The active materials in these extracts, however, are different from the natural components in P. vivax paroxysm plasma, i.e. while the schizont extracts are immunologically cross-reactive between species, the activity of the natural P. vivax toxin(s) in patients' plasma is neutralized only by the homologous antisera. Plasmodium falciparum infections have neither distinct paroxysms nor parasite-killing activity in plasma. The pronounced paroxysms of P. vivax infections may thus be due in part of a species-specific toxin(s).

Acute Disease↗

Past quit smoking assistance and doctors' advice for white and African-American smokers.

Data for 473 African-American and white smokers showed that whites were more likely than African Americans to use formal cessation programs to quit smoking, to report that their doctor told them to stop smoking, and to use nicotine replacement therapy. While physicians advised a high proportion of smokers of each race group to quit smoking and were quite aggressive in prescribing nicotine replacement therapy, they were deficient in providing necessary behavioral support to their patients.

Adult↗

A prospective study of six methods for detection of hepatic colorectal metastases.

Many techniques are available for the identification of patients with hepatic colorectal metastases. The accuracy and clinical relevance of transabdominal ultrasound (US), computed tomography (CT), static scintigraphy, dynamic scintigraphy (HPI), intraoperative ultrasound (IOUS) and manual palpation, in the detection of intrahepatic colorectal metastases were assessed in 73 consecutive patients presenting with colorectal carcinoma; 39 were male and 34 female with a mean age of 68 years (range 43-90 years). In 33 patients either intraoperative ultrasound or palpation were omitted owing to emergency presentation (n = 14) or subsequent non-operative management (n = 19). All six investigations were completed in 40 patients. Computed tomography and hepatic perfusion scintigraphy (HPI) were the most sensitive, detecting over 90% of lesions, the others identifying approximately 80% of lesions, Specificity in all methods, apart from dynamic scintigraphy, was over 80%. Contrast-enhanced CT would appear to remain the most accurate method available. However, if the prognostic ability of HPI is confirmed on subsequent follow-up, the accuracy of HPI will rise with time, whereas that of CT will fall. Intraoperative ultrasonography took time to perform and did not alter the management of any patient within the study. We suggest that its use is limited to those patients in whom resection is contemplated, where the vascular anatomical detail provided may be invaluable.

Adult↗

Write it now, or never!

Writers need knowledge and credentials to write, but one key to successful writing is to start writing now. Often the only difference between a published writer and a unpublished writer is simply that the published writer did the writing.

Denial, Psychological↗

Spontaneous regression in angiocentric T-cell lymphoma.

An 8-year-old boy presented with a 10-week history of ulcerating lesions which were histologically and immunocytochemically consistent with the diagnosis of angiocentric T-cell lymphoma. The disease was limited to the skin and resolved with no chemotherapy. Angiocentric T-cell lymphoma is commonly a disease with considerable morbidity and is often fatal. Epstein-Barr virus (EBV) could not be identified in involved tissue by immunostaining or by in situ hybridization. We consider whether the uncharacteristic absence of EBV in this case has prognostic significance.

Child↗

The influence of fat free mass on prediction of densitometric body composition by bioelectrical impedance analysis and by anthropometry.

OBJECTIVE: To examine the effect of varying size of fat free mass (FFM) on the precision and bias of body composition prediction by bioelectrical impedance analysis (BIA) from four equations of Segal et al (BIA-Segal), Gray et al (BIA-Gray, Lukaski et al (BIA-Lukaski) and those from a manufacturer (BIA-EZC), by body mass index (BMI), and by skinfold methods with reference to estimation by densitometry. SUBJECTS: 73 men and 77 women aged 17-71 years, were measured for height, weight, FFM, bioelectrical impedance and age. RESULTS: BIA-Segal gave the highest precision (men: R2 = 83%, women: R2 = 75%) and the least bias (men: slope = 0.88; women: slope = 0.81) of all BIA methods. There were poorer precision (R2 < or = 50%) and more bias (slope < 0.70) by BIA-Lukaski and BIA-EZC in both sexes, which were comparable to the simpler BMI method. The skinfold method gave R2 = 83% and slope = 0.84 in men and R2 = 61% and slope = 0.86 in women. Bland and Altman analysis showed BIA-Segal gave prediction of FFM within +/-6 kg of 95% confidence interval limit of agreement of that estimated by UWW in most subjects. Other BIA methods presented unacceptably large underestimates of up to 15-17 kg in FFM. CONCLUSIONS: The BIA-Segal provide the best predictions of the methods tested, but using BMI-or waist-specific equations may be more practical than the original BIA-Segal method, which BIA methods are affected by large FFM, and not better than anthropometric methods in predicting FFM.

Adolescent↗

Tour de force.

Explore the source record for details and available documents.

Cell Division↗

Cultural diversity process improves organizational community in urban teaching medical center.

An urban teaching facility with nearly 3,000 employees had communication problems associated with race, gender and other cultural differences. It also competed for health care dollars and faced possible reduction in federal funding. The medical center instituted mandatory training in cultural diversity and customer service-and integrated the training process with the hospital's overall quality improvement plan and marketing strategy. The integrated approach affected the bottom line-Hurley's patient base has increased, and the medical center operates in the black. Training in cultural diversity and customer service is an effective tool to improve employee communication and improve financial outlook.

Cultural Diversity↗

Abnormal excitatory neurotransmitter metabolism in schizophrenic brains.

BACKGROUND: Schizophrenia has been hypothesized to be caused by a hypofunction of glutamatergic neurons. Findings of reduced concentrations of glutamate in the cerebrospinal fluid of patients with schizophrenia and the ability of glutamate-receptor antagonists to cause psychotic symptoms lend support to this hypothesis. N-acetylaspartylglutamate (NAAG), a neuropeptide that is highly concentrated in glutamatergic neurons, antagonizes the effects of glutamate at N-methyl-D-aspartate receptors. Moreover, NAAG is cleaved to glutamate and N-acetylaspartate by a specific peptidase, N-acetyl-alpha-linked acidic dipeptidase (NAALADase). To test the glutamatergic hypothesis of schizophrenia, we studied the NAAG-related glutamatergic variables in postmortem brains from patients with schizophrenia, neuroleptic-treated controls, and normal individuals, with particular emphasis on the prefrontal cortex and hippocampus. METHOD: Different regions of frozen brain tissue from three different groups (patients with schizophrenia, neuroleptic-treated controls, and normal controls) were assayed to determine levels of NAAG, N-acetylaspartate, NAALADase, and several amino acids, including aspartate and glutamate. RESULTS: Our study demonstrates alterations in brain levels of aspartate, glutamate, and NAAG and in NAALADase activity. Levels of NAAG were increased and NAALADase activity and glutamate levels were decreased in the schizophrenic brains. Notably, the changes in NAAG level and NAALADase activity in schizophrenic brains were more selective than those for aspartate and glutamate. In neuroleptic-treated control brains, levels of aspartate, glutamate, and glycine were found to be increased. CONCLUSIONS: The changes in levels of aspartate, glutamate, NAAG, and NAALADase are prominent in the prefrontal and hippocampal regions, where previous neuropathological studies of schizophrenic brains demonstrate consistent changes. These findings support the hypothesis that schizophrenia results from a hypofunction of certain glutamatergic neuronal systems. They also suggest that the therapeutic efficacy of neuroleptics may be related to increased glutamatergic activity.

Adult↗

Plasmodium falciparum: parasites defective in early stages of gametocytogenesis.

Some molecular characteristics of Plasmodium falciparum lines which do not produce gametocytes are described. Parasites carrying a subtelomerically deleted chromosome 9 cannot form even the earliest forms of gametocytes, detectable with antibodies against the gametocyte-specific antigen Pfg27. In a parasite culture of clone HB3, in which both intact and deleted forms of chromosome 9 are present, full-length chromosome 9 molecules are retained mainly in gametocytes. These data suggest that the subtelomeric portion of chromosome 9 is required at an early stage of gametocytogenesis. Parasite subclones derived from gametocyte producing clone 3D7, which completely lost ability to produce gametocytes, are also described. Unlike the previous gametocyteless lines, these parasites stably maintain a full-length chromosome 9 and the ability to cytoadhere to C32 melanoma cells after prolonged asexual propagation. Their defect in sexual development is therefore genetically and functionally distinct from that of parasites carrying a deleted chromosome 9. Gametocyteless subclones derived from 3D7 do not produce any Pfg27 mRNA, while this gene is anomalously expressed in asexual stage parasites of two lines of a different genetic background, 1776sel8 and C10, one able and the other unable to produce gametocytes.

Animals↗

Linkage analysis of 26 Canadian breast and breast-ovarian cancer families.

We have examined 26 Canadian families with hereditary breast or ovarian cancer for linkage to markers flanking the BRCA1 gene on chromosome 17q12-q21. Of the 15 families that contain cases of ovarian cancer, 94% were estimated to be linked to BRCA1. In contrast, there was no overall evidence of linkage in the group of 10 families with breast cancer without ovarian cancer. A genetic recombinant in a breast-ovarian cancer family indicates a placement of BRCA1 telomeric to D17S776, and helps to define the region of assignment of the cancer susceptibility gene. Other cancers of interest that appeared in the BRCA1-linked families included primary peritoneal cancer, cancer of the fallopian tube, and malignant melanoma.

Adult↗

Predicted disulfide-bonded structures for three uniquely related proteins of Plasmodium falciparum, Pfs230, Pfs48/45 and Pf12.

Pfs230 is a surface protein of the gametes of Plasmodium falciparum and has been demonstrated to be a target of malaria transmission-blocking antibodies; it is an important candidate antigen for a transmission-blocking vaccine. The target epitopes of transmission-blocking antibodies against Pfs230 are almost all reduction sensitive suggesting that disulfide bonds are critical for folding the native molecule. Following the cloning of the Pfs230 gene attempts are now underway to express subunits of the protein for use in vaccine trials. It will be important to understand the disulfide-bond structure of the Pfs230 to achieve this goal. In this paper we present a model for this structure based on the observation that the Pfs230 molecule contains a series of regularly repeated cysteine-containing motifs. Four such motifs have been identified, together with a fifth cysteineless motif, which occur in the same relative order, with regular alternating omission of specific motifs, 14 times throughout the length of the protein. Each of the 14 sets of motifs contains an even number of cysteine residues (2, 4 or 6). We postulate that each set folds into a separate disulfide-bonded domain in which corresponding pairs of cysteines form an equivalent disulfide bond in every such domain. The postulated bonding arrangements in the different domains are mutually confirmatory throughout the sequence of Pfs230. We have identified two other malaria proteins, Pfs48/45 and Pf12, which share the same arrangements of motifs and conform to the same disulfide-bond structure proposed for Pfs230; no other proteins in the sequence data base share these characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum.

A gene encoding a novel cdc2-related protein kinase has been identified in Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to regions that are conserved in members of the cdc2 gene family. This gene, called Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA gene family, members of which are negative regulators of cell growth in vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific accumulation of mRNA in gametocytes.

Amino Acid Sequence↗

COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies.

We report the deduced protein sequence and preliminary characterization of Pfg377, a novel sexual stage antigen of Plasmodium falciparum. An initial cDNA clone (Pfg377-1) encoding the N-terminal 755 amino acids of Pfg377 was isolated by transfecting a 3D7 gametocyte cDNA library into COS7 cells and selecting using a pool of anti-Pfs230 monoclonal antibodies. The protein encoded by Pfg377-1 included an N-terminal hydrophobic signal sequence, but no apparent transmembrane anchor. Instead, the particular cDNA clone selected was fused in-frame at its 3' end with the coding sequence for the human decay acceleration factor membrane anchor, which had been deliberately placed downstream of the vector polylinker in order to attach potential fusion proteins onto the COS cell surface. Northern blots probed with the Pfg377-1 cDNA demonstrated cross-hybridization to a single approximately 9.5-kb transcript, which was present only in sexual stages, and not in a sexual stages. DNA hybridization was used to obtain a series of overlapping genomic clones which collectively yielded the complete DNA sequence for Pfg377. There are no introns within the gene, which contains a 9360-bp open reading frame and encodes a 377-kDa protein. The Pfg377 protein is highly hydrophilic, and has an essentially non-repetitive structure, with only four very limited regions of tandem repeats. The Pfg377 gene resides on chromosome 12, and immunoelectron microscopy with two different anti-Pfg377 polyclonal antisera raised against two separate recombinant sub-fragments of the protein both indicated that the antigen is located in electron-dense organelles of the gametocytes--the osmiophilic bodies--which are proposed to play a role in parasite emergence from the erythrocyte during gametocyte maturation in the Anopheles mosquito midgut. Although it was selected with anti-Pfs230 antibodies, comparison of the sub-cellular locations and protein sequences of Pfg377 and Pfs2 show them to be completely distinct antigens. We hypothesize that Pfg377-1 was initially isolated because it expresses an epitope which is recognized by (i.e., cross-reacts with) one of the anti-Pfs230 monoclonal antibodies used to select the original transfected COS cells.

Amino Acid Sequence↗