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Biomedical subjects

M J Edwards

Publications and source records attributed to M J Edwards.

At least 271 records · Page 15Linked to original sources

Hemoglobin Yakina. II. High blood oxygen affinity associated with compensatory erythrocytosis and normal hemodynamics.

Erythrocytosis without clinical illness was noted in a man and his two daughters. Their blood contained approximately 62% hemoglobin A and 38% a new hemoglobin, designated hemoglobin Yakima. The oxygen affinity of whole blood from each subject was greatly increased and heme-heme interactions were impaired. At 37 degrees C and a plasma pH of 7.40, the oxygen pressure required to produce 50% saturation of hemoglobin with oxygen was only 12 mm Hg as compared with a normal of 26 mm Hg. The high oxygen affinity of this blood is attributed to the presence of hemoglobin Yakima; and the increased oxygen affinity was shown to be characteristic of the isolated abnormal hemoglobin. A Bohr effect was present in hemoglobin Yakima. Arterial oxygen pressure, oxygen consumption, and cardiac output at rest were normal. With respect to oxygen delivery to tissues, the increased hemoglobin concentration appears to be the major compensation for the marked displacement of the oxygen-hemoglobin equilibrium curve, although other factors may contribute. The finding of high normal quantities of erythropoietin in the urine is consistent with this degree of erythrocytosis.

Erythropoietin↗

Effect of prenatal heat stress on brain growth and serial discrimination reversal learning in the guinea pig.

Exposure of pregnant guinea pigs to an environmental temperature of 42 degrees C for 1 hr daily on Days 20-24 of gestation resulted in a significant reduction in the birthweight and brainweight of newborn offspring. These deficits persisted to early maturity and were still evident at 250 days of age following behavioral testing. Although some degree of postnatal neurogenesis and brain growth had occurred, this was not sufficient to compensate for the retarding influence of prenatal hyperthermia. Heat stress was also observed to seriously impair learning performance on the original discrimination task and this tendency persisted over the subsequent 4 reversals for both initial and perseverative errors. Impaired learning performance was related to reduction in brainweight. Animals with lower brainweights made significantly more initial, perseverative and total number of errors over the 5 problems. In addition, 12 of the 14 behaviorally tested stressed progeny had brainweights that were at least 2 standard deviations below the mean of the controls and as a result were classified as micrencephalic. Although heat stressed animals showed a significant reduction in the number of amacrine synapses in the inner plexiform layer of the retina, performance differences were not atrributed to changes in synaptic organisation of the retinal circuitry or to visual or other ophthalmic defects, but brain function. Animals with higher mean maternal poststressing core temperatures gave birth to progeny which had smaller whole and part wet-brainweights. Examination of the effect of poststressing core temperature on brainweight revealed that brain growth, independent of bodyweight, was retarded when this temperature elevated above 41.5 degrees C. This represented a rise of approximately 2.1 degrees C above normal and for each 1 degree C rise above this temperature, brainweight was reduced by 0.4227 g of the control value. Analysis of the atmospheric content of the incubator during stressing sessions ruled out the possibility that changes in level of oxygen and carbon dioxide may have contributed to the retarding influence on fetal development and learning ability in the guinea pig.

Animals↗

Lymphatic mapping and sentinel lymph node biopsy in the staging of melanoma.

In recent months, we have witnessed a 'paradigm shift' in the management of intermediate-thickness melanoma. The collective experience of the recent past confirms the validity of the 'sentinel' lymph node as being the initial draining site from a specific area of skin. Furthermore, the sentinel lymph node has been confirmed as the most likely site in the regional lymph node basin to harbor occult metastatic disease. Identification of sentinel lymph nodes by visual inspection and intraoperative gamma probe detection after the peritumoral injection of Lymphazurin blue dye and technetium sulfur colloid is a reliable new technique. Staging accuracy also has improved, allowing the precise identification of patients who benefit from avoiding the morbidity of radical lymphadenectomy. The importance of accurate staging has been heightened by data demonstrating effective adjuvant therapy with recombinant interferon-alpha 2B. Precisely defining patient subsets who benefit from adjuvant high-dose interferon-alpha 2B is the current focus of clinical trials designed to maximize the enhanced staging accuracy of the novel approach of sentinel lymph node biopsy.

Biopsy, Needle↗

Pulmonary fibrosis from amorphous silica dust, a product of silica vapor.

After prolonged occupation exposure to amorphous silica dust-a product of vaporized crystalline silica (quartz)-eleven out of forty workers showed reticular and/or nodular abnormalities in roentgenograms of the chest. From this group, we present three illustrative cases. These had widespread pulmonary disease with granulomatous nodules and fibrosis (documented histologically in two cases), but there was no demonstrable restrictive impairment of pulmonary function. We discuss the possible importance of this previously underestimated toxicity, especially in an industrial setting.

Dust↗

Effects of heat on embryos and foetuses.

OBJECTIVES: This paper reviews the effects of elevated maternal temperature on embryo and foetal development in experimental animals and in humans. CONCLUSIONS: Hyperthermia during pregnancy can cause embryonic death, abortion, growth retardation and developmental defects. Processes critical to embryonic development, such as cell proliferation, migration, differentiation and programmed cell death (apoptosis) are adversely affected by elevated maternal temperatures, showing some similarity to the effects of ionizing radiation. The development of the central nervous system is especially susceptible: a 2.5 degrees C elevation for 1 h during early neural tube closure in rats resulted in an increased incidence of cranio-facial defects, and a 'spike' temperature elevation of 2-2.5 degrees C in an exposure of 1 h during early neurogenesis in guinea pigs caused an increase in the incidence of microencephaly. However, in general, thresholds and dose-response relationships vary between species and even between different strains of the same species, depending on genotype. This precludes rigorous quantitative extrapolation to humans, although some general principles can be inferred. In humans, epidemiological studies suggest that an elevation of maternal body temperature by 2 degrees C for at least 24 h during fever can cause a range of developmental defects, but there is little information on thresholds for shorter exposures. Further experimental and epidemiological studies are recommended, focusing on stage-specific developmental effects in the central nervous system using a variety of sensitive assays.

Animals↗

Hyperthermic teratogenicity, thermal dose and diagnostic ultrasound during pregnancy: implications of new standards on tissue heating.

Hyperthermia is a recognized teratogen in mammalian laboratory animals and is a suspected teratogen for humans. The purpose of this synopsis is to reanalyse existing data on hyperthermia-induced teratogenic effects in experimental mammalian systems in terms of a thermal dose (temperature:time) concept, and then to illustrate the utility of this concept to human situations involving potential thermal increments to post-implantation embryos and foetuses. For example, the threshold temperature elevation for hyperthermia-induced teratogenic effects in experimental mammals is estimated (but not rigorously tested) to be approximately 1.5 degrees C above core values for exposures of long duration, possibly with a thermal dose of approximately 5 min duration or more at 4 degrees C. This level of tissue temperature increment is within the capability of some modern diagnostic ultrasound (DUS) devices sold within the USA and abroad. Epidemiological studies have not indicated any hazard from the use of DUS, but such studies are limited in sensitivity and were conducted with DUS devices whose acoustic outputs were relatively low compared to those presently available. After a regulatory change that allowed for substantially increased acoustic outputs, modern DUS devices were mandated to provide the user with on-screen information (the Thermal Index, or 'TI') about ultrasound-induced temperature increments in the target tissue. The TI is generally accurate to within a factor of 2, but the factor may be as high as 6 in certain obstetric settings. Thus, informed use of and attention to the TI is strongly advised, with this admonition gaining increased emphasis if the present regulations regarding allowable acoustic outputs of DUS devices were to be further relaxed or eliminated.

Animals↗

Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence.

Giant cell tumor of the tendon sheath (GCTTS), tenosynovial giant cell tumor (TGCT), and pigmented villo-nodular synovitis (PVNS) are the common names for a group of rare proliferative disorders that involve synovial joints and tendon sheaths. Considerable confusion exists about the surgical treatment and diagnosis of these disorders. This review evaluates the presentation, surgical therapy and recurrence of these three proliferative disorders. We retrospectively reviewed the clinical data from all cases of GCTTS, TGCT, and PVNS from 1985 to 1997. A total of 35 patients were identified: GCTTS (n=8), TGCT (n=1), and PVNS (n=26), there were 18 men and 17 women. The median age was 48 years (range 6-84 years). The most common site of involvement was the knee (15), followed by wrist (7), elbow (4), and hip (4). Seven patients had extra-articular involvement, and 19 were found incidentally at operations for other reasons. Among the 4 patients who developed recurrent disease, 2 had extra-articular disease at the time of their original diagnosis. None died, and none required major amputation. One patient was treated with adjuvant radiotherapy following resection of a recurrence. It is important to distinguish between focal and diffuse forms of synovial involvement. If focal, simple surgical excision is appropriate. If diffuse, complete synovectomy is indicated for disease confined to the joint, and resection of all gross disease is indicated for extra-articular disease. Radical resection with negative margins is not necessary in most instances. In rare aggressive cases, local recurrence may necessitate more extensive resection and radiation therapy.

Female↗