Sheath structure in negative ion sources for fusion (invited).

In fusion negative ion sources, the negative ions are formed on the caesiated plasma grid predominantly by hydrogen atoms from the plasma. The space charge of the negative ions leaving the wall is not fully compensated by incoming positive ions and at high enough emission a virtual cathode is formed. This virtual cathode limits the flux of negative ions transported across the sheath to the plasma. A 1D collisionless model of the sheath is presented taking into account the virtual cathode. The model will be applied to examples of the ion source operation. Extension of the model to the bulk plasma shows good agreement with experimental data. A possible role for fast ions is discussed.

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.

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.

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.

Effect of hypophysectomy and growth hormone on immune development in the domestic fowl.

The effect of hypophysectomy and recombinant growth hormone (rcGH) treatment on the growth and development of the immune system was investigated in young chickens. Flow cytometric analysis of cell surface markers revealed no changes in the proportion of thymocytes expressing CT-1a, CD4, and/or CD8 among any of the treatment groups. In contrast, the proportion of both single positive CD4 and CD8 peripheral blood lymphocytes (PBL) was altered in hypox birds treated with rcGH compared to the vehicle-treated group. Specifically, rcGH treatment produced a decrease in the proportion of CD8+ cells and an increase in the percentage of CD4+ PBL. There was little change in the labeling intensity of PBL or thymocytes associated with any treatment; however, double positive (CD4+CD8+) thymocytes from hypophysectomized chicks that were not given rcGH had increased fluorescence relative to rcGH supplemented hypox chicks. As expected, hypophysectomy reduced body, skeletal, and thymic growth. Treatment of hypox chicks with rcGH enhanced body weight while thymic weights were somewhat increased. Skeletal growth was not significantly altered by rcGH. Bursal growth appeared refractory to either treatment. These studies support the conclusion that growth hormone influences thymic growth and the maturation of thymus-derived lymphocytes. These results also demonstrate a biological activity for chicken growth hormone derived through recombinant technology.

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.

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.

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.

The dying patient: a comparative study of nurse caregiver characteristics.

The nurse's interaction with the dying patient is thought to be influenced by death anxiety, attitudes toward death, and perceptions of control. Differences relative to these three variables between nurses who work on a continuous basis with the dying and those who rarely encounter a dying patient were examined. Using 3 paper and pencil questionnaires, data were collected from 105 nurses (32 palliative care nurses, 44 psychiatric nurses, 29 orthopedic nurses). Significant differences were found between the palliative care nurses and nonpalliative care nurses on attitudes toward death and on 3 of the 4 subscales that assessed death anxiety. Suggestions for future research include a systematic examination of the relationship of attitudes and feelings about death to patient care.

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.

[Not Available]. / Liquides IV et le mourant hospitalisé

The authors examined charts for evidence of the use of intravenous fluids in all patients who died from malignant disease occurring in a tertiary care teaching hospital during a 1-year period. Total lengths of stay and survival time after obtaining "do not resuscitate" orders were longer in those who died without intravenous fluids. More than two-thirds of patients with cancer who died in hospital did so with an intravenous line.

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.

Intravenous fluids and the hospitalized dying: a medical last rite?

The authors examined charts for evidence of the use of intravenous fluids in all patients who died from malignant disease occurring in a tertiary care teaching hospital during a one-year period. Of 106 patients who were identified, 86 received intravenous fluids within their last 30 days of life, and 73 died with an intravenous line running.Intravenous fluid use appeared to be independent of age, sex, language, presence of family members, primary tumour site, presence of metastases, duration of illness, and presence of a "no cardiopulmonary resuscitation" order. Total lengths of stay and survival time after obtaining "do not resuscitate" orders were longer in those who died without intravenous fluids. More than two-thirds of patients with cancer who died in hospital did so with an intravenous line.

Differential diagnosis of non-parkinsonian tremors.

Tremors present to the practitioner a problem that can be solved clinically. Attention to the circumstances under which the tremors occur permits their classification as resting, postural, and intentional types. Each type has a specific locus in the nervous system. The cause can be established by a careful history. Many tremors respond to treatment.

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.

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.

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)

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.

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.