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Biomedical subjects

D B King

Publications and source records attributed to D B King.

At least 19 recordsLinked to original sources
PubMed1999

Parkinson's disease--levodopa complications.

Parkinson's disease is a readily recognized clinical syndrome, characterized by resting tremor, rigidity, bradykinesia and loss of postural reflexes. The introduction of levodopa transformed our management of this disease. As our experience has increased the long term side effects of levodopa have become more apparent. Levodopa complications comprise: wearing off, motor fluctuations, and psychiatric complications. The complexity of these clinical phenomena has been worked out with time and is now well-recognized. A number of management strategies can ameliorate these long-term complications. This article reviews the current management of late-stage Parkinson's disease.

Antiparkinson Agents↗
PubMed1998

Initial control of chemotherapy-induced nausea and vomiting in patient quality of life.

The side effects commonly experienced by patients receiving chemotherapy for the treatment of cancer can challenge many aspects of daily life. Nausea and vomiting, the most common side effects reported by patients, affect the ability to continue with usual life activities and, thus have a pronounced impact on quality of life. This paper reviews studies of the impact of nausea and emesis on quality of life, and highlights the importance of prevention of these side effects by presenting new data on how persistent uncontrolled nausea and vomiting can be. The Morrow Assessment of Nausea and Emesis (MANE) was used to collect information on symptoms experienced by consecutive patients starting chemotherapy between September 1987 and December 1995 at any of 18 geographically diverse member sites of the University of Rochester Cancer Center Community Clinical Oncology Program. Data from 1,413 patients were collected after each of four successive chemotherapy treatments. Reported incidences of posttreatment nausea and posttreatment vomiting after the first treatment were 59.4% and 28.6%, respectively. Occurrence of nausea/vomiting at the first treatment was a strong predictor of nausea/vomiting at later treatments. Of the 839 patients reporting initial nausea, 763 (90.9%) reported nausea at at least one subsequent treatment, and approximately 59% reported nausea after all three subsequent treatments. Fewer than half (45.6%) of the patients who had no nausea at the first treatment developed it later. The majority (72.0%) of patients reporting vomiting at the first treatment also reported subsequent vomiting, 30.7% of whom experienced emesis at all remaining treatments. Conversely, 76.2% of patients who were emesis-free at the first treatment remained so for all later treatments. These findings show a continuing need for further progress in controlling nausea and vomiting, and demonstrate the importance of aggressive nausea/vomiting control at the first treatment. In addition, more emphasis on controlling chemotherapy-induced nausea after its initial occurrence is necessary.

Antineoplastic Agents↗
PubMed1997

The thyroid hormone, 3,5,3'-triiodothyronine, is a negative modulator of domestic fowl (Gallus gallus domesticus) adrenal steroidogenic function.

Previous work with chickens (Gallus gallus domesticus) suggests a relationship between depressed thyroid hormone status and enhanced adrenal steroidogenic function. In addition, in hypophysectomized chickens, replacement of the thyroid hormone, 3,5,3'-triiodothyronine (T3), maintains chicken adrenal steroidogenic cell sensitivity to adrenocorticotropin (ACTH) but decreases steroidogenic capacity further than that due to hypophysectomy alone. The present in vivo and in vitro studies were conducted to determine the influence of thyroid status and T3 per se on avian adrenal steroidogenic function. Chicks (1 day old) were thyroidectomized using combined surgical and chemical (6-propyl-2-thiouracil) treatments and were administered a replacement dose of T3 (0, 1.5, 4.5, 15, and 45 microg/kg body wt/day) for 5 weeks. Whereas thyroidectomy (TX) decreased adrenal weight (-20%), it increased relative adrenal weight (mg/100 g body weight) (+171%), trunk plasma corticosterone (+880%), and aldosterone (+124%). In addition, TX increased basal, maximal ACTH-induced, maximal 8-bromo-cyclic AMP-induced, and maximal 25-hydroxycholesterol-supported corticosterone production (+520, +93, +124, and +195%, respectively) and aldosterone production (+578, +288, +280, and +275%, respectively) by isolated adrenal steroidogenic cells. T3, in a dose-dependent manner, reversed the effects of TX on these in vivo and in vitro parameters of adrenal steroidogenic function. Restoration of most of these parameters to those in the sham-treated control was attained with 4.5-15 microg/kg body wt/day. Although some of the effects of TX and T3 replacement on adrenal steroidogenic function may have been mediated through changes in circulating levels of ACTH, other data suggest a direct effect on adrenal steroidogenic cell function. Adrenal steroidogenic cells from sham-treated and TX birds were preincubated (0, 4, and 12 hr) with various concentrations of T3 (0, 0.3, 3, and 30 nM), washed, and then incubated for an additional 2 hr in medium containing the same respective concentrations of T3, with or without a maximal steroidogenic concentration of ACTH (100 nM). T3 had no acute effects on TX-dependent enhancement of adrenal steroidogenic cell function (2-hr incubation). However, with preincubation (4 and 12 hr), T3 inhibited basal and maximal ACTH-induced corticosterone production in a dose-dependent manner. This concentration-dependent, direct effect of T3 was not observed with cells from sham-treated birds. In addition, the ostensibly inactive thyroid hormone metabolite, 3,3',5'-triiodothyronine [reverse T3; 30 nM], was without effect. Taken collectively, these studies indicate that T3 is a direct negative modulator of avian adrenal steroidogenic function.

Adrenal Cortex Hormones↗
PubMed1993

Differential effects of methimazole and dexamethasone in avian muscular dystrophy.

We showed previously that thyroid antagonists and glucocorticoids partially alleviated the impaired righting ability and abnormally high levels of plasma creatine kinase activity in genetically dystrophic chicks. The goals of the present study were: (1) to ascertain whether the beneficial effects of methimazole (MMI; thyroid antagonist) on muscle function and plasma creatine kinase (CK) activity in dystrophic chickens are correlated with significant reduction in plasma triiodothyronine (T3) and thyroxine (T4); (2) to assess whether the MMI-induced thyroid changes are accompanied by increased plasma corticosterone level and/or changes in muscle glucocorticoid receptors which might account partially for the beneficial effects of MMI; and (3) to determine if plasma T3 and T4 are reduced in dexamethasone (DEX) treated dystrophic chickens which might account at least partially for the beneficial effects of DEX (a potent glucocorticoid) on avian dystrophy. The data show that beneficial effects of MMI are associated with reduced plasma levels of thyroid hormones and increased circulating levels of corticosterone. In addition, DEX actually increases plasma T3 levels. These differential effects indicate that reduced plasma thyroid hormone levels do not represent a common mechanism of beneficial drug effects in avian muscular dystrophy. On the other hand, elevated plasma glucocorticoid levels accompany the beneficial effects of both severe hypothyroidism and DEX treatment. The data also show that MMI induces down-regulation of muscle cytosolic glucocorticoid receptors which are higher than normal in dystrophic muscles.

Animals↗
PubMed1992

Effect of triiodothyronine on the expression of T cell markers and immune function in thyroidectomized White Leghorn chickens.

Hypothyroid K-strain chickens were produced by neonatal thyroidectomy and treatment with 6-propyl-2-thiouracil. Thyroidectomized birds were given 0, 1.5, 4.5, 15, or 45 micrograms/kg body wt of triiodothyronine (T3) by daily injection. At 5 weeks of age, thymocytes were prepared for flow cytometric analysis of CT-1a, CD3, CD4, and CD8 expression. Sham-operated birds had the smallest proportion of CT-1a+ cells and the brightest CT-1a+ cells. Unsupplemented thyroidectomized birds presented an inverse picture, while T3-treated thyroidectomized birds were intermediate. Fewer and less brightly labeled CD3+, CD4+, and CD8+ cells were associated with sham-operated birds or with higher levels of T3 replacement. Low levels (1.5 microgram/kg body wt) or no T3 treatment produced a greater proportion of positive, highly fluorescent cells. The ratios of CD4+ to CD8+ thymocytes were increased (P less than or equal to 0.05) by T3 supplementation. Functionally, thyroidectomy produced a decrease in mitogen-stimulated proliferation of peripheral blood lymphocytes. This effect was ameliorated by T3 supplementation. Further, thyroidectomy produced an elevation of plasma growth hormone concentrations. These results suggest that thyroid factors and alterations of thymic status significantly affect the generation of specific thymus-derived lymphocyte populations and their functional capabilities, perhaps due to changes in the thymic microenvironment. These alterations may have important consequences for the development of immunocompetence and disease resistance in chickens.

Animals↗
PubMed1992

The place of the dopaminergic agonists in the treatment of Parkinson's disease: the view from the trenches.

The use of the dopamine receptor agonists in Parkinson's disease has a compelling logic. These agents are supposed to act independently of the dying cells of the substantia nigra directly on the cells of the striatum. Early clinical trials in advanced disease were only mildly impressive. Later they were found to be beneficial in early disease but their effectiveness waned. Their ultimate failure may reflect the fact that the majority of current agents do not stimulate D1 and D2 receptors in a physiologic ratio. The drugs may act presynaptically and with the eventual loss of the anatomic relationships between nigra and striatum the drugs fail. There is, however, a rationale to their current use. When used along with L-Dopa in early disease the development of late-stage fluctuations are reduced with the same anti-parkinsonian benefits. Merging this concept with the demonstrated effect of selegiline in slowing the course of the disease, the current practice of triple therapy with selegiline, L-Dopa and a dopamine receptor agonist emerges.

Dopamine Agents↗
PubMed1991

Thyroidal involvement in the expression of avian muscular dystrophy.

We showed previously that propylthiouracil (PTU), a thyroid inhibitor, could alleviate several major signs of hereditary muscular dystrophy in chickens. The goals of the present investigation were to: (1) determine whether a nearly athyroid condition (achieved within two days after hatching by surgical thyroidectomy plus PTU) during an 11-day period beneficially affects the dystrophic condition when followed by triiodothyronine (T3) replacement to 33 days of age; (2) determine the beneficial effects on the expression of avian dystrophy when the thyroidectomized-PTU-treated chickens received a wide range of moderate to low T3 replacement doses beginning by two days after thyroidectomy; and (3) examine the thyroid hormone receptor system in dystrophic muscle for a possible abnormality. Thyroid deprivation increased muscle function (righting ability) and reduced plasma creatine kinase activity in dystrophic chickens. The major thyroid-related abnormality in dystrophic pectoralis muscles was an increased maximum binding capacity of solubilized nuclear T3 receptors.

Animals↗
PubMed1990

Animal research in psychology: declining or thriving?

From Dialog's PsychINFO database the number of studies with 6 species reported in the Psychological Abstracts was calculated for each year from 1967 to 1988. Also, the number of studies with an additional 11 species were calculated for each year from 1973 to 1988. A hand search in the Journal of the Experimental Analysis of Behavior and Learning and Motivation was also conducted to explore trends in studies on 12 species from 1970 to 1987. The numbers of studies on many species (e.g., baboons, bats, chimpanzees, dolphins, gerbils, guinea pigs, gorillas, hamsters, lemurs, mice, pigeons, rats, seals, and snakes) have remained stable. There has, however, been a steady decline in the numbers of studies on selected species (e.g., cats, dogs, and rabbits). Possible reasons for changing trends in studies on selected species include: increased costs, the cognitive emphasis in psychology, and arguably, animal rights activism.

Animal Welfare↗
PubMed1988

A double-blind study of bromocriptine and L-dopa in de novo Parkinson's disease. Short-term results.

The first phase of a longitudinal multicenter study comparing bromocriptine and L-dopa (as Sinemet) as de novo therapy for Parkinson's disease using a double-blind randomized design has recently been completed. Over a period of 5.5 months, bromocriptine and L-dopa were equipotent in reducing functional and neurological disability. These observations complement and extend earlier studies and suggest a role for bromocriptine as de novo therapy of Parkinson's disease.

Aged↗
PubMed1987

Amyotrophic lateral sclerosis in Nova Scotia.

A study of ALS incidence in Nova Scotia for a ten year period was carried out with the cooperation of neurologists, neurosurgeons, physiatrists and major medical hospitals. Over a ten year period 161 cases occurred, an incidence of 1.95 per 100,000 population in a province with a population of 825,000. There was an increase in incidence over the ten year period, with an incidence for the first five years of study of 1.50 per 100,000, and 2.40 per 100,000 for the latter five years. The peak incidence in 1981-1982 was 2.66 per 100,000. Although this is the highest incidence in community studies of ALS (excepting the unusual circumstances in Guam), it may reflect the realistic incidence of ALS rather than an unusual focus, as ascertainment was likely greater than in many other studies. The more significant finding is the suggestion of an increasing incidence, as noted in other studies in the U.S., England and Israel.

Adult↗
PubMed1987

Treatment of paramyotonia congenita with acetazolamide.

Treatment of paramyotonia congenita with acetazolamide has been shown to reduce myotonic symptoms but severe weakness has developed in some patients leading to a recommendation not to use the drug in this disorder. We studied a patient with the characteristic clinical and electrophysiological profile of paramyotonia congenita. Myotonia was effectively treated with a very low dose of acetazolamide and no weakness developed. We conclude that acetazolamide can be a safe and effective medication in paramyotonia congenita.

Acetazolamide↗
PubMed1987

Thyroidal influence on nuclear accumulation and DNA replication in skeletal muscles of young chickens.

Regulation of DNA accumulation may be a particularly important aspect of the regulation of skeletal muscle growth. Since thyroid hormones influence the growth of chicken skeletal muscle, including DNA accumulation, we ascertained whether triiodothyronine (T3) affects the accumulation of nuclei within muscle fibers and 3H-thymidine uptake into nuclei within the basal lamina and muscle total DNA. The number of nuclei and the diameter of pectoralis muscle fiber segments freed of adhering connective tissue were reduced markedly in cockerels treated with propylthiouracil (PTU) during the first month after hatching. T3 replacement for 1 week increased the number of nuclei per unit length of isolated fiber section by as much as 54%, compared to the value for birds receiving PTU alone, without affecting fiber diameter. There was also a 24% increase in the number of nuclei beneath the basal lamina of fiber cross sections near the origin of anterior latissimus dorsi (ALD) muscles within 48 hr after initiating T3 replacement in 25-day-old, PTU-treated cockerels. The incorporation of 3H-thymidine into nuclei beneath the basal lamina of ALD fiber cross sections was increased approximately two-fold at 24 hr after administering T3 to 8-day-old thyroidectomized (Tx) cockerels. Thymidine (-3H) incorporation into total DNA of ALD muscles incubated in vitro for 1 hr was also markedly enhanced as early as 6-12 hour after T3 administration to Tx chicks during the first week after hatching. Data from this study suggest that T3 enhances DNA replication and the accumulation of nuclei within the basal lamina of muscle fibers of thyroid-deprived chicks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of mammalian growth hormone and prolactin on the growth of hypophysectomized chickens.

Body weight gain and shank-toe growth during a 26-day treatment period following hypophysectomy were 55 and 46%, respectively, of control values, but the body weight gain was unaffected and bone growth only slightly reduced when the hypophysectomized chickens were fed a low dose of corticosterone (5 ppm). Bovine growth hormone (0.5 mg GH/kg body wt/day for 18 days) enhanced body weight gain and shank-toe length increase (an estimate of bone growth) by 46 and 33%, respectively, compared to the growth of hypophysectomized chickens receiving only corticosterone. These same endpoints were increased approximately 24% after ovine growth hormone treatment in hypophysectomized chickens not receiving corticosterone. Body weight gain during 18 days of treatment with bovine prolactin (0.5 mg PRL/kg/day) was 27% greater than the value for corticosterone-treated hypophysectomized chickens, but bone growth was unaffected. The mammalian GH preparations increased heart weight of the hypophysectomized chickens (25-29%), but pectoralis muscle weight was unaffected. GH treatment enhanced thymal weights by 71% in corticosterone-treated hypophysectomized chickens, and by 93% in hypophysectomized animals not receiving corticosterone. GH had no significant effect on bursal weights, and PRL had no effect on either of these lymphoid organ weights in corticosterone-treated hypophysectomized chickens. GH increased liver and adipose tissue weights considerably more than the large increases that followed treatment of hypophysectomized chickens with corticosterone alone (69 and 126% greater, respectively), but had no effect on these endpoints in hypophysectomized chickens not receiving corticosterone. PRL also greatly increased liver and adipose tissue weights in corticosterone-treated hypophysectomized chickens (79 and 75%, respectively). These results provide evidence that mammalian GH enhances body weight gain, bone growth, and the growth of several organs in the hypophysectomized chicken. Mammalian PRL increased body weight gain, liver weight, and adipose tissue weight in corticosterone-treated hypophysectomized chickens, but did not influence bone growth or the weights of the heart, pectoralis, thymi, or bursa.

Adipose Tissue↗
PubMed1986

Effect of chicken growth hormone, triiodothyronine and hypophysectomy in growing domestic fowl.

Hypophysectomy in growing chicks was followed by reduced body and skeletal (shank-toe length) growth. In addition decreases were observed in tibia length and weight (although the proximal growth plate often contained more cartilage and was less uniform in its thickness), the plasma concentrations of immunoreactive-Somatomedin C (IR-SmC) and free fatty acids and weight for the heart, liver, pectoralis, thymus, and bursa Fabricus. The effect of triiodothyronine (T3) and purified chicken growth hormone (GH) on body and other growth was examined in hypophysectomized chicks. Body and skeletal growth (as estimated by respectively the increases in body weight and shank toe length in 24 days) were increased by the administration of T3 (either as injections or in the diet). T3 also increased tibia weight and length and returned the proximal growth plate thickness to that found in intact controls. Similarly T3 administration was followed by increases in the weights of the heart, liver, thymus, and bursa Fabricus. However plasma concentrations of IR-SmC were unaffected by T3 treatment. Chicken GH at a dose of 100 micrograms/kg stimulated aspects of growth somewhat with injections of chicken GH being followed by a slight increase in tibia length and a substantial increase in thymus weight. Chicken GH also increased plasma concentrations of IR-SmC and free fatty acids. Combination T3 and chicken GH treatment did not cause greater growth than observed with T3 alone. An exception to this being the greater weight of the bursa Fabricus in the chicks receiving T3 and GH than T3 alone. Intact male chicks which received injections of chicken GH (10 micrograms) between 1 and 14 day old had slightly greater body weight at 31, 38 and 44 days old relative to vehicle injected chicks.

Aging↗
PubMed1985

Adrenocortical cell function in the hypophysectomized domestic fowl: effects of growth hormone and 3,5,3'-triiodothyronine replacement.

The control of adrenocortical function in the domestic fowl (Gallus domesticus) was investigated using adrenocortical cells isolated from hypophysectomized (hypox) and intact cockerels and from hypox cockerels injected with T3, purified chicken GH (cGH), and T3 plus cGH. Corticosterone in plasma and cell incubations was measured by RIA. Cellular responses to varying concentrations of steroidogenic agents were fitted and statistically analyzed by computer. Hypophysectomy reduced the basal plasma corticosterone (B) concentration to 53% of the value in intact birds and eliminated a stress response. Although hypophysectomy reduced adrenal weight by 20%, it did not change relative adrenal weight (milligrams per 100 g BW). However, replacement with cGH increased relative adrenal weight by 24%, whereas replacement with T3 or T3 plus cGH reduced relative adrenal weight by 16%. In the absence of steroidogenic agents, there were no detectable differences in B production by adrenocortical cells isolated from various experimental groups. However, with a maximal steroidogenic concentration of ACTH, B production by isolated adrenocortical cells from hypox birds was 61% of that by cells from intact birds. The ED50 of ACTH for cells from hypox cockerels was 2.7 times greater than that of cells from intact cockerels, thus indicating a loss of cell sensitivity to ACTH after hypophysectomy (the greater the ED50, the lesser the cell sensitivity). Although cGH replacement increased maximal B production (Bmax) induced by ACTH to 329% that by cells from hypox cockerels, it increased the ACTH ED50 3.6 times, thus decreasing cell sensitivity more than hypophysectomy alone. In contrast to cGH, T3 replacement maintained the cell sensitivity to ACTH at the level of cells from intact birds, but lowered Bmax to 54% that of cells from hypox cockerels. The combination of cGH and T3 administered to hypox cockerels both maintained cell sensitivity to ACTH and raised the Bmax to 358% that of cells from hypox animals. These treatments also affected 8-bromo-cAMP-induced Bmax and pregnenolone-supported Bmax, but did not significantly alter the ED50 of these agents.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Plasma concentrations of somatomedin-C in hypophysectomized, dwarf and intact growing domestic fowl as determined by heterologous radioimmunoassay.

The application of a human somatomedin-C radioimmunoassay for the determination of somatomedin-C in chicken plasma has been examined. Parallel inhibition of binding of 125I-labelled somatomedin-C to antisera raised against somatomedin-C was observed with acid-treated human and chicken plasma. The concentration of immunoreactive (IR)-somatomedin-C in the plasma of the domestic fowl appears to be GH dependent. Plasma concentrations of IR-somatomedin-C were reduced after hypophysectomy and partially restored by replacement therapy with chicken GH. The age/development pattern of circulating concentrations of IR-somatomedin-C has been determined in normal and dwarf strains of domestic fowl. Increases in the plasma concentration of IR-somatomedin-C were observed between 1 and 6 weeks of age in control male domestic fowl of either heavy (broiler type) or light (White Leghorn) strains. Thereafter, the plasma concentrations of IR-somatomedin-C remained constant in the heavy strain birds but declined in White Leghorn chicks. Plasma concentrations of IR-somatomedin-C were reduced in sex-linked dwarf chickens, in both light and heavy strains of fowl, but were unaffected in autosomal dwarf chickens.

Animals↗
PubMed1984

Thyroidal influence on body growth.

This review of thyroid influence on body growth in poultry is organized around the following parameters of growth: increase in body weight and skeletal size, muscle growth, and growth of cartilage and bone. The greatest effect of goitrogens on growth of embryos occurs during late embryogenesis at a time when normal thyroid hormone levels are increasing. Posthatching growth is reduced in severely hypothyroid animals, and body weight gain is affected more than bone growth. Thyroid hormone replacement restores body growth of thyroidectomized chickens, but supplemental hormone in normal animals has no beneficial effect on growth. Excessive T3 (fed at 1 ppm) is detrimental to growth and feed efficiency. No clear correlation between thyroid hormone concentration and growth rate of normal chickens has been identified. Growth depression in sex-linked dwarf birds is at least partially reversed by supplemental T3. Muscle growth is reduced in goitrogen-treated chickens and the growth reduction is reversed by supplemental thyroxine. Total DNA accumulation is reduced in hypothyroid chickens, but muscle mass relative to DNA content is normal following long-term treatment; this suggests some regulation of muscle mass relative to DNA content. T3 increases the number of muscle fiber nuclei in hypothyroid chickens and the uptake of 3H-thymidine into nuclei within the basal lamina. T3 directly stimulates growth and maturation of embryonic chick cartilage and enhances the in vitro action of somatomedins on cartilage growth. There is little information concerning the role of the thyroid in posthatching cartilage and bone growth in poultry.

Animals↗