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Biomedical subjects

G Hart

Publications and source records attributed to G Hart.

At least 181 records · Page 10Linked to original sources

Calculation of percentage of hormone independent transplantable cells in experimental mammary tumors.

Some cancer types (e.g. breast cancers) are known to consist of mixed populations of cells which respond to hormones, and cells that do not. A theoretical model is proposed to investigate the proportion of these different cell types in experimental tumors. The model exploits the fact that when grafts are treated with hormones, both cell types form an outgrowth, whereas in the absence of hormones only the autonomous cell types can grow. Method 1 consists of serially transplanting the tumor to be investigated in castrated mice that are not treated with hormones, and comparing the growth rates of two consecutive transplant generations. Method 2 involves comparing the growth of the tumor in hormone treated and untreated castrated mice. The merits and limitation of each of these two methods are discussed.

Animals↗

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy.

A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with greater than 65 Gy, the two year local control was 35%. If treated with less than 65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was less than 100 cm2, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.

Adenocarcinoma↗

Diagnosis clusters: a new tool for analyzing the content of ambulatory medical care.

A clustering method for the analysis of ambulatory morbidity data is presented. This approach reduces spurious variations resulting from idiosyncratic diagnosis labeling and coding habits of physicians and facilitates the analysis of the content of ambulatory medical care through the use of aggregate morbidity data. The clusters provide a tool that allows for the comparison of the content of practice based on different factors such as provider training, practice organization, and patient characteristics. Ninety-two diagnosis clusters were derived using the 1977 and 1978 National Ambulatory Medical Care Survey (NAMCS). These clusters incorporate 86 per cent of all ambulatory visits to office-based physicians in the contiguous United States. The clusters were constructed based on the consensus of a group of clinicians including both generalists, as well as selected subspecialists representing the spectrum of ambulatory medical practice. The diagnosis clusters presented are compatible with the International Classification of Diseases (ICDA-8 and ICD-9-CM) and the International Classifications of Health Problems in Primary Care (ICHPPC and ICHPPC-2). Several applications demonstrating the utility of the method are presented, and directions for future applications are suggested.

Ambulatory Care↗

The effects of low concentrations of cardiotonic steroids on membrane currents and tension in sheep Purkinje fibres.

1. Simultaneous measurements of voltage-clamp currents and tension were made in shortened sheep Purkinje fibres exposed to various concentrations of strophanthidin, ouabain and digoxin.2. In 5.4 mM-K moderate doses (mean 2.4 x 10(-7)M) of the drugs produced an inward shift of the current-voltage relationship at very negative potentials, consistent with an increase in cleft K concentration (Cohen, Daut & Noble, 1976b), which was always accompanied by an increase in tension. This change, which has been attributed to Na-K pump inhibition, was often better correlated with an increase in voltage-dependent tonic tension than in twitch tension.3. Exposure to dihydro-ouabain gave a monotonic increase in tension but a delayed increase in inward current. This suggests (cf. Lee, Kang, Sokol & Lee, 1980) that minor changes in pump activity may not always change the current-voltage relationship.4. Low concentrations of strophanthidin (5 x 10(-9) to 5 x 10(-7) M) produced an outward current shift at very negative potentials, this change becoming smaller with a more rapid onset and reversing on increasing the dose. This change is attributed to pump stimulation.5. The outward current shift was often associated with a negative inotropic effect, which always reversed either spontaneously or on removal of the drug.6. The alternative response at a narrower dose range (1 x 10(-8) to 2 x 10(-7) M) was an increase in twitch (not tonic) tension, termed the low-dose positive inotropic effect.7. After a low concentration of cardiotonic steroid had given an early negative inotropic effect the bulk Ca concentration was reduced and the drug re-applied. The low-dose positive inotropic mechanism was then observed.8. Outward current shifts and negative inotropy were also obtained with low concentrations of the clinically used glycosides digoxin and ouabain.9. Low concentrations of strophanthidin applied to externally stimulated sheep ventricular trabeculae produced negative inotropy with lengthening of the action potential duration. Positive inotropy and action potential shortening occurred with higher doses.10. A computer model of ionic currents and distributions in Purkinje fibres satisfactorily reproduced the changes in membrane currents and ionic gradients observed with cardiotonic steroids. The only perturbations capable of explaining our results were Na pump stimulation and inhibition.11. It is concluded that cardiotonic steroids possess two inotropic mechanisms. The first is a low-dose positive inotropic mechanism causally unrelated to changes in sodium pump activity and possibly a direct release of a membrane-associated calcium fraction. Should this mechanism be unavailable then net pump stimulation at low doses will produce negative inotropy. The second mechanism is the well known Na-lag process.

Animals↗

The kinetics and temperature dependence of the pace-maker current if in sheep Purkinje fibres.

The kinetic properties of the if channel in shortened sheep Purkinje fibres were investigated using a two-micro-electrode voltage-clamp technique in the presence of Ba2+, Mn2+ and tetrodotoxin (TTX). The time course of the hyperpolarization-activated if currents (DiFrancesco, 1981 b) at potentials within the activation range was found to depend on whether the channel was switching 'on' or 'off'. At potentials positive to the half-activation point if decay was faster than if onset; at potentials negative to the half-activation point if onset was faster than if decay. The time courses of if onset and decay become similar only at potentials close to the centre of the activation range. If a single exponential was fitted to the time course of if switching, the time constant (tau y) was found to vary as a function of potential from approximately 50 msec to several seconds. The tau y - voltage relation is an extremely steep bell-shaped distribution. Reducing external Na+ (range 140-17.5 mM) did not alter the voltage dependence of the if time course. Increasing external K+ (range 5-60 mM) shifted the if time constants and activation curve by similar amounts in a depolarizing direction. The temperature dependence of if was investigated over the range 27.5-41 degrees C. Cooling reversibly slowed the time course of if activation with a Q10 of 3.13 (S.D. +/- 0.85, n = 62). A reversible reduction in the slope of the fully-activated current-voltage relation was observed on cooling, the Q10 being 1.35 (S.D. +/- 0.07), and was usually accompanied by a small depolarizing shift of the half-activation point and the reversal potential Ef. It is concluded that the if time course shows a marked potential dependence and does not obey Hodgkin-Huxley kinetics. Its temperature dependence resembles that of if in the sino-atrial node (DiFrancesco & Ojeda, 1980).

Animals↗

Normal ranges of T4 screening values in low birthweight infants.

Thyroxine (T4) screening values in infants of low birthweight in relation to birthweight and gestational age are reported. There were 86 healthy infants of low birthweight (group 1), and 29 preterm infants with respiratory distress syndrome (group 2). All the group 2 infants and 36% of those in group 1 had a T4 screening value below the cut-off point (-2.1 SD). In group 1 there was a significant increase in T4 with birthweight at a given gestational age, as well as with gestational age at a given birthweight. In group 2 there was also a significant increase in T4 values in relation to birthweight and gestational age, but it could not be ascertained whether this increase existed at a given gestational age or birthweight. A statistical model giving normal ranges of T4 for both groups of infants is presented, which, if applied to low birthweight infants, makes it possible to estimate the effect of low birthweight on T4 screening values, provided the birthweight and gestational age are known. In this manner the sensitivity of screening for congenital hypothyroidism is enhanced and the recall rate reduced.

Birth Weight↗

Predictive value of serologic tests.

An analysis of serologic tests for treponemal disease performed in Australian aboriginal communities is used to illustrate factors influencing the predictive value positive of serologic tests. Simple extrapolation of predictive value estimates, from prevalence, sensitivity, and specificity data, is complicated by variation of specificity between strata of a population, and the weighting of true positive and false positive results produced by the criteria for selecting individuals for testing. The predictive value positive of a particular test is greatest when it is used for incident cases suspected of having a disease, but lower when the same test is used to screen a whole population unless longitudinal data are available to exclude individuals with past disease. Preferential testing of individuals without active disease may produce very low predictive values. Empirical estimation of the predictive value of tests provides objective guidelines for decision making and enables increased predictability by modification of testing criteria.

Adolescent↗

The role of treponemal tests in therapeutic decision making.

As part of process evaluation of a syphilis control program, the predictability of serologic tests was assessed by reviewing the primary care case records (containing serology findings on 5,643 sera) of all individuals in six aboriginal communities. The direct relationship of predictability to positivity of treponemal test was influenced by the Venereal Disease Research Laboratory (VDRL) titre and when results were stratified by this variable, an inverse association of predictive value with levels of positivity of treponemal test was demonstrated. The predictive values positive of the FTA-ABS-IgM test for untreated disease was 0.31 for VDRL titres of 1:4 and increased to 0.84 for VDRL titres exceeding 1:16. The predictive value of treponemal tests would be increased by more restrictive criteria for their performance, and optimum interpretation demands concurrent assessment of VDRL titre, and clinical and epidemiological background of the individual patient. This type of evaluation on individual control programs is encouraged because the quantitative findings will vary with disease prevalence, testing criteria, and the individual laboratory testing performance.

Decision Making↗

Estradiol and progesterone in human breast cancer cytosols and their relationship to receptor incidence.

Plasma and breast cancer cytosol estradiol and progesterone levels were determined in pre and postmenopausal women and correlated with tumor estrogen and progesterone receptor incidence and content. There was no statistical correlation between plasma estradiol levels and estrogen or progesterone receptor incidence or content in premenopausal patients. Similarly, no correlation was apparent between plasma estradiol and progesterone levels, and tumor cytosol steroid concentration in either pre or postmenopausal women. In contrast to these observations, a significant inverse relationship developed between plasma progesterone levels and progesterone receptor incidence in premenopausal patients. An increase in tumor progesterone concentration in pre and postmenopausal patients was also significantly, and inversely related to receptor incidence. Our observations suggest that an increase in plasma progesterone and a decrease in tumor estrogen: progesterone ratio is significantly correlated with a decrease in estrogen and progesterone receptor incidence in pre- and postmenopausal patients.

Adult↗

Radiotherapy of lymph node metastases in patients with squamous cell carcinoma of the head and neck region.

The results of radiotherapy alone in 233 patients with lymph node metastases of squamous cell carcinoma in the head and neck region were examined. It appeared that the recurrence rate in the neck was mainly related to: localization of the primary tumor; the recurrence of the primary tumor; the radiation dose; and the presence of a residual palpable tumor mass in the neck 6 weeks after radiation. The optimum radiation dose was about 2000 ret. An isoeffect curve was calculated, which differed only slightly with the nominal standard dose (NSD) formula. Elective irradiation of the contralateral neck appeared to diminish the outgrowth of neck node metastases at the side. Changes in the radiation treatment in the last treatment period, such as a higher radiation dose and a larger treatment area, resulted in a lower recurrence rate for the neck node metastases, and also in a higher survival rate.

Aged↗

Molluscicidal steroid glycoalkaloids possessing stereoisomeric spirosolane structures.

Both the steroidal glycoalkaloid mixture obtained from Solanum mammosum fruits (solasonine 1 and solamargine 2) and the stereoisomeric glycosidic alkaloid tomatine 3 are toxic at 10 and 25 ppm to Lymnaea cubensis and Biomphalaria glabratus, respectively. Their aglycones solasodine 4 and tomatidine 5 obtained by hydrolysis of the glycosides showed no toxicity to either mollusk under the test conditions used. Preliminary structure-activity correlations indicate that the molluscicidal properties depend on the type of aglycones and on the glycoside bond. A common molecular structure in molluscicidal spirosolane and spirostane glycosides is recognized.

Alkaloids↗

Syphilis control in populations previously exposed to yaws.

Application of an epidemiologic strategy, involving repeated annual screening, public relations activities and treatment to selected groups, for syphilis control in four communities is described. The predictive value of the VDRL screening test was influenced by the titre of the test and the age and location of individuals on whom it was performed. The predictive value of 1:8 VDRL titres (for active syphilis) varied from zero in individuals over 50 years of age, in one community to 0.96 in individuals 10-29 years old in another. Reduction in transmission of infection was closely related to the degree of screening coverage of the community and adjacent communities with which intercourse occurred.

Adolescent↗

Syncope caused by cough-induced complete atrioventricular block.

Cough syncope is a well-recognized syndrome in which loss of consciousness follows a bout of prolonged coughing. The pathophysiology of this syndrome has been attributed to lowered cerebral perfusion pressure consequent on an increased intrathoracic pressure, which lowers cardiac output (by a Valsalva mechanism) and impairs cerebral venous return. We report a case of cough-induced syncope in which ECG monitoring showed that coughing produced paroxysmal atrioventricular block with ventricular asystole. Such a case has not previously been documented.

Adie Syndrome↗

Problems facing aboriginal health workers in a community health service.

The length of service and reason for resignation of Aboriginal health workers recruited from 1976 to 1978 are discussed. Resignation rates in the first and second years of employment were 46% and 22.4%, respectively. Resignation was often the final outcome of intolerable personal conflicts with family, community and workmates, compounded by confusion and diversity of opinion over job roles.

Australia↗

Mammary tumorigenicities of three chemically induced mouse kidney cell lines in syngeneic female hosts.

Three chemically induced, mammary tumour virus (MMTV) and leukemia virus (MuLV) producing, baby mouse kidney (BMK) cell lines derived from respectively strains BALB/c (-/HeA and -/CrglA) and C57BL/LiA were investigated for their mammary tumour (MT) evoking potentials in syngeneic female hosts. An i.p. inoculated virus-enriched fraction from A3 cells (BALB/c/HeA) had a similar oncogenic effect as i.p. and s.c. inoculated whole A3 cells. The average MT ages were reduced in all 3 groups. Cell lines BBM (BALB/c/CrglA) and BB (C57BL/LiA) were tested as i.p. inoculated whole cells. Again, the average MT age was reduced in thus treated BALB/c/Crgl females. In the case of C57BL/LiA the percentage of animals with MT was strongly increased in the BB cell inoculated group (1 MT in control group). Bioassay results corrected for intercurrent death cases (including leukosis) were statistically significant. It is concluded that the endogenous MMTV variants of the 3 mouse (sub-)strains are virulent MT evoking viruses in autologous hosts when they are induced.

Animals↗

The hard sell for savings. Interview by Sally Burningham.

The NHS might seem to present an opportunity to purchase, store and distribute on a national basis but it is, in reality, a series of largely autonomous local services. According to Graham Hart, DHSS controller of supply, in most parts of the country supplies are held in 'a variety of small, local stores unsuited to their purpose'.

Computers↗