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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 55 records · Page 3Linked to original sources

William Carlos Williams (1883-1963): physician-writer and "godfather of avant garde poetry".

William Carlos Williams, Pulitzer Prize-winning physician-writer, was born in Rutherford, New Jersey, where he practiced medicine until he was incapacitated by a stroke at age 68. After graduating from the University of Pennsylvania School of Medicine, Williams trained in New York City and Leipzig, Germany, settling in Rutherford in 1909. Doctor Williams revolutionized American poetry by rejecting traditional conventions of rhyme and meter, and he masterfully used "American" English-brusque, colloquial, and incisive-in his poetry. Williams is recognized as one of the most original poets of the 20th century. His medical life sometimes trivialized, Williams was a serious student of medicine and considered himself "in the front lines, in the trenches." He regarded art and medicine as "two parts of a whole," and the intimate doctor-patient interface proved a powerful inspiration for his writing. Dr Williams was a physician of immense integrity and dedication; he regarded allegiance to humanism as important as excellence in medical science. Prolific in various genre, Dr William Carlos Williams attained belated recognition in spite of astonishing productivity and originality. His stature and influence has steadily increased since his death in 1963, and Dr Williams is now considered "the most important literary doctor since Chekhov."

Famous Persons↗

The cytoadherence linked asexual gene family of Plasmodium falciparum: are there roles other than cytoadherence?

The binding of erythrocytes infected with Plasmodium falciparum to the endothelium lining the small blood vessels of the brain and other organs can mediate severe pathology. A region at the right end of chromosome 9 has been implicated in the binding of parasitised erythrocytes to the endothelial receptor CD36. A gene expressed in asexual erythrocytic stage parasites has been identified in this region and termed the cytoadherence linked asexual gene (clag). Antisense RNA production and targeted gene disruption of clag resulted in greatly reduced binding to CD36. Hybridisation to 3D7 chromosomes showed clag to be a part of a gene family of at least nine members. All members analysed so far have a conserved gene structure of at least nine exons, as well as putative transmembrane domains. The possible functions of the gene family are discussed.

Animals↗

An investigation of factors limiting aerobic capacity in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) has been shown to produce exercise limitation and breathlessness. The purpose of this study was to investigate factors which may be responsible for limiting aerobic capacity in patients with AS. Twenty patients with no other cardio-respiratory disease performed integrative cardiopulmonary exercise testing (CPET). The results were compared to 20 age and gender matched healthy controls. Variables that might influence exercise tolerance, including pulmonary function tests (body plethysmography), respiratory muscle strength (MIP, MEP) and endurance (Tlim), AS severity assessment including chest expansion (CE), thoracolumber movement (TL), wall tragus distance and peripheral muscle strength assessed by maximum voluntary contraction of the knee extensors (Qds), hand grip strength and lean body mass (LBM), were measured in the patients with AS and used as explanatory variables against the peak VO2 achieved during CPET. As subjects achieved a lower peak VO2 than controls (25.2 +/- 1.4 vs. 33.1 +/- 1.6 ml kg-1min-1, mean +/- SEM, P = 0.001). When compared with controls, ventilatory response (VE/VCO2) in AS was elevated (P = 0.01); however gas exchange indices, transcutaneous blood gases and breathing reserve were similar to controls. AS subjects developed a higher HR/VO2 response (P < 0.01) on exertion but without associated abnormalities in ECG, blood pressure response or anaerobic threshold. The AS group experienced a greater degree of leg fatigue (P < 0.01) than controls at peak exercise. Although the breathlessness scores (BS) were comparable to controls at peak exercise, the slopes of the relationship between BS and work rate (WR) [AS 0.054 (0.1), Controls 0.043 (0.06); P < 0.05] and BS and % predicted oxygen uptake [AS 0.084 (0.18), Controls 0.045 (0.06); P < 0.01] were steeper in the AS subjects. There was weak association between peak VO2 and vital capacity (r2% 12.0), MIP (11.8) but no association between Tlim, CE, Wall tragus distance or TL movement. The strongest association with aerobic capacity was between measurements of peripheral muscle strength (Qds; r = 0.75; hand grip; r = 0.47) accounting for 53% (P < 0.001) and 23.5% (P < 0.01) of the total variance in peak VO2, respectively. The addition of LBM to Qds in the regression model significantly improved the explained variance to 78.3% (P < 0.001). This study shows that peripheral muscle function is the most important determinant of exercise intolerance in AS patients suggesting that deconditioning is the main factor in the production of the reduced aerobic capacity.

Case-Control Studies↗

Transmission-blocking immunity to Plasmodium falciparum in malaria-immune individuals is associated with antibodies to the gamete surface protein Pfs230.

Malaria-immune human sera were tested for their ability to affect the infectivity of Plasmodium falciparum gametocytes to Anopheles stephensi mosquitoes. Transmission-reducing effects of the sera were associated with the presence of antibodies to the gamete surface protein, Pfs230. Enhancement of transmission, manifest as elevated numbers of oocysts relative to controls, was observed for a number of sera, but was not found to be associated with antibodies against Pfs230. These results confirm that Pfs230 is a possible candidate for inclusion in a transmission-blocking malaria vaccine.

Animals↗

TNFalpha*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans.

We have investigated the association between alleles of the genes for tumour necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease during malarial (Plasmodium falciparum) and other infections in the Sri Lankan population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicated infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-alpha and TNF-beta allelic types were identified using the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes and restriction enzyme digestion. The odds in favour of carrying the TNFalpha*2 allele, mainly of the heterozygous genotype (TNFalpha*1,*2), were two to three times greater among individuals with severe disease, of either malarial or other infectious origin, relative to healthy controls or to those with uncomplicated malarial infections. No significant risk was associated with either of the alleles of TNF-beta.

Alleles↗

Muscle pump and central command during recovery from exercise in humans.

We sought to determine the relative contributions of cessation of skeletal muscle pumping and withdrawal of central command to the rapid decrease in arterial pressure during recovery from exercise. Twelve healthy volunteers underwent three exercise sessions, each consisting of a warm-up, 3 min of cycling at 60% of maximal heart rate, and 5 min of one of the following recovery modes: seated (inactive), loadless pedaling (active), and passive cycling. Mean arterial pressure (MAP), cardiac output, thoracic impedance, and heart rate were measured. When measured 15 s after exercise, MAP decreased less (P < 0.05) during the active (-3 +/- 1 mmHg) and passive (-6 +/- 1 mmHg) recovery modes than during inactive (-18 +/- 2 mmHg) recovery. These differences in MAP persisted for the first 4 min of recovery from exercise. Significant maintenance of central blood volume (thoracic impedance), stroke volume, and cardiac output paralleled the maintenance of MAP during active and passive conditions during 5 min of recovery. These data indicate that engaging the skeletal muscle pump by loadless or passive pedaling helps maintain MAP during recovery from submaximal exercise. The lack of differences between loadless and passive pedaling suggests that cessation of central command is not as important.

Adult↗

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Animals↗

Murine dendritic cells transduced with an adenoviral vector expressing a defined tumor antigen can overcome anti-adenovirus neutralizing immunity and induce effective tumor regression.

In this study transduced dendritic cells (DCs) were used to enhance immunogenecity of a specific tumor antigen. Using a polyoma middle T (PyMT) transgenic mammary carcinoma model we found that injections of DCs transduced with an adenoviral (Ad) vector expressing PyMT (DCAd-PymT) led to potent specific anti-tumor immunity. Efficacy was not affected by neutralizing Abs (high or low titers) and naive animals did not produce detectable anti-Ad Abs following two injections of transduced DCs. Repeated injections of transduced DCs significantly improved therapeutic efficacy in mice with established lung metastases. These data emphasize the ability of Ad-infected DCs to: i) minimize anti-Ad Ab production, ii) overcome pre-existing anti-Ad humoral immunity, and iii) improve vaccination efficacy when injected more than once.

Adenoviridae↗

Epidemiological considerations for malaria reduction by transmission blocking vaccination.

Outside of the temperate regions, malaria transmission continues throughout much of the world in a distribution which is not very different to that of one hundred years ago. However, with the notable exception of Africa sub Sahara, the morbidity and mortality due to malaria has generally been reduced to very low levels by comparison with earlier times. In a broad sense the malaria problem today falls into two distinct compartments, 1) how to deal with the remaining problem of malaria in the affected areas outside of sub Saharan Africa and 2) how to manage the, currently, much greater problem of malaria-related morbidity and mortality in Africa sub Sahara. Malaria control campaigns of the past have always placed great emphasis on reducing malaria inoculation rates in the affected populations. This may seem entirely logical, and is, indeed, an absolute requirement where eradication of malaria from an endemic area is the goal. There can, nevertheless, be dangers as well as benefits associated with reducing malaria inoculation rates in previously endemic populations. I discuss here the epidemiological issues which should be taken into account in this respect. I then examine the role that vaccination to reduce malaria inoculation rates in endemic populations--malaria transmission blocking vaccination--could play in malaria control.

Adult↗

Economic evaluation of the cochlear implant.

OBJECTIVE: To examine the economic efficiency of current cochlear implant technology under Australian conditions in profoundly deaf adults, partially deafened adults, and children. METHODS: Cost-utility study, with weights based on judgments from persons experienced with the technology, and cost data from Australian sources. RESULTS: Quality-of-life improvements due to functional consequences of hearing improvement were greater than those due to amelioration of hearing disability. Costs in Australian dollars per QALY (15-year assessment) ranged from $5,070-$11,100 for children, $11,790-$38,150 for profoundly deaf adults, and $14,410-$41,000 for partially deaf adults. CONCLUSIONS: Results suggest cochlear implantation is acceptable value for money when compared with other health programs to which resources are committed in Australia.

Adult↗

A preliminary comparison of videofluoroscopy of swallow and pulse oximetry in the identification of aspiration in dysphagic patients.

Pulse oximetry has recently received attention in the dysphagia literature because of its possible contribution to the management of neurogenic dysphagia. The present study was devised to examine whether pulse oximetry could be exploited to determine episodes of aspiration in patients with known dysphagia of neurologic origin. To this end, pulse oximetry was undertaken in six patients undergoing videofluoroscopic study of swallow. Normal controls also underwent pulse oximetry during feeding. The results indicate that there is no clear-cut relationship between changes in arterial oxygenation and aspiration. However, some support is found for the association between altered arterial oxygenation and oral feeding in dysphagic individuals. Further research in both normals and compromised individuals is needed.

Adult↗

The mask of Thomas Mann (1875-1955): medical insights and last illness.

Thomas Mann, German novelist and essayist, was awarded the Nobel Prize for literature in 1929 for his masterpiece, The Buddenbrooks, aided by his much acclaimed The Magic Mountain, which depicts life in a tuberculosis sanitorium. One of the most medically perceptive writers of the century, Mann was obsessed by illness and disease and produced works that reflect penetrating observation of medicine. When Hitler seized power, Mann fled Germany and entered Switzerland in forced exile. Mann later moved to the United States, becoming an American citizen in 1944. He became embroiled in political turmoil during the red-baiting era; disenchanted with this country, he returned to Switzerland in 1952 and died in Zürich in 1955. This vignette lifts the veil revealing the Mann behind the mask, tormented by life-long homoerotic tendencies that were confirmed by his unexpurgated diaries, published in 1979. I interviewed Professor Christoph Hedinger, who performed the autopsy on Thomas Mann. Professor Hedinger's protocol formed the primary source material for this study and clarified the exact cause of the Nobelist's death. Magisterial, with robust self-regard, Thomas Mann led a life that lends itself as a great human interest story. He was a highly intelligent, complex person whose sexual inversion provides some insight into the person but is irrelevant in assessing his artistic achievements. Mann's defiant stance against the Nazis and his masterful contributions to world literature assure him an enduring and unassailable role in world history.

Famous Persons↗

Lyman A. Brewer III (1907-1988): surgeon-scientist, inspirational teacher, and humanist.

Dr. Lyman Augustus Brewer III, a distinguished, colorful thoracic surgeon and among the first to practice that specialty in the West, died on June 25, 1988, in Los Angeles, California, after a courageous battle with lymphoma. Dr. Brewer was a great humanist, innovative clinical surgeon, charismatic teacher, and surgical leader. In World War II, Lieutenant Colonel Brewer served in the Second Auxiliary Surgical Group in the Mediterranean and European theaters and helped define criteria that became the standard for the management of thoracic war injuries. Out of this experience he authored the classic paper, "The Wet Lung in War Casualties." Dr. Brewer's scientific contributions embraced the broad spectrum of thoracic surgical topics, including treatment of tuberculosis, classification of lung cancer, bronchial stump buttressing using the pericardial fat pad (Brewer fat pad), and management of esophageal perforation. Dr Brewer wrote seven books and more than 100 papers, and served as First Vice President of The American College of Surgeons and as President of the American Association for Thoracic Surgery, The Society of Thoracic Surgeons, and The Pacific Coast Surgical Association.

History, 20th Century↗

The measurement of the single-breath transfer factor for carbon monoxide and its components using the Morgan Transflow system.

In contrast to the standard single-breath transfer factor for carbon monoxide (TLCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume (VC) and membrane component (DM), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24-55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23-54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of TLCO were used to derive a mean value for DM and VC for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean TLCO (mmol min-1 kPa-1) (standard first 5.13 +/- 1.15, high-oxygen first 5.14 +/- 1.12; limits of agreement -0.57 to 0.59 for DM or for VC. The long or short protocol produced no significant differences between the means of TLCO (mmol min-1 kPa-1) (long 8.0 +/- 1.9, short 8.0 +/- 1.9; limits of agreement -0.5 to 0.5), DM or VC. This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.

Adult↗