Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2-) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min-1 kg-1). 2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy. 3. O2- generation by isolated monocytes was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2- production was significantly (P = 0.008) higher for non-survivors (31.3 +/- 8.8 nmol 30 min-1 10(-6) cells; n = 4) than for survivors (6.2 +/- 2.3 nmol 30 min-1 10(-6) cells; n = 7). 4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2- production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2- production with opsonized zymosan. 5. These results suggest that (1) increased O2- production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2- production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.
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PMID:Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep. 166 89

Two Hampshire-Landrace crossbred pigs were found to contain developmental stages of Caryospora bigenetica following oral inoculation with 1 x 10(8) oocysts. One pig was given intramuscular injections of methylprednisolone acetate. Both pigs displayed clinical signs of dermal coccidiosis from 3 to 10 days after inoculation, including swollen jowls and hocks, bilateral ocular discharges, generalized erythema, and lethargy. Meronts and gamonts were observed histologically in numerous tissues including jowl, ear, footpad, tongue, and lung at 10 days postinoculation. The present study is the first report of C. bigenetica infections in swine.
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PMID:Experimental Caryospora bigenetica (Apicomplexa: Eimeriidae) infections in swine (Sus scrofa). 173 58

Seventy-four post-menopausal women with metastatic breast cancer were treated with a combination hormonal regimen consisting of tamoxifen, aminoglutethimide danazol and medroxyprogesterone acetate (POND). 72% of the patients had received no previous treatment. The overall response rate (complete and partial remission) was 43.5% with a median response duration of 19 months and a median survival of 27 months. The most common sites of response were in regional nodes and local chest wall disease. The major side-effects were those expected from the individual agents: nausea, lethargy, rash and oedema.
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PMID:Combination of tamoxifen, aminoglutethimide, danazol and medroxyprogesterone acetate in advanced breast cancer. 214 4

Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.
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PMID:Activity of datelliptium acetate (NSC 311152; SR 95156A) against solid tumors of mice. 217 44

Primary hypoadrenocorticism was diagnosed in ten young to middle-aged cats of mixed breeding. Five of the cats were male, and five were female. Historic signs included lethargy (n = 10), anorexia (n = 10), weight loss (n = 9), vomiting (n = 4), and polyuria (n = 3). Dehydration (n = 9), hypothermia (n = 8), prolonged capillary refill time (n = 5), weak pulse (n = 5), collapse (n = 3), and sinus bradycardia (n = 2) were found on physical examination. Results of initial laboratory tests revealed anemia (n = 3), absolute lymphocytosis (n = 2), absolute eosinophilia (n = 1), and azotemia and hyperphosphatemia (n = 10). Serum electrolyte changes included hyponatremia (n = 10), hyperkalemia (n = 9), hypochloremia (n = 9), and hypercalcemia (n = 1). The diagnosis of primary adrenocortical insufficiency was established on the basis of results of adrenocorticotropic hormone (ACTH) stimulation tests (n = 10) and endogenous plasma ACTH determinations (n = 7). Initial therapy for hypoadrenocorticism included intravenous administration of 0.9% saline and dexamethasone and intramuscular administration of desoxycorticosterone acetate in oil. Three cats were euthanatized shortly after diagnosis because of poor clinical response. Results of necropsy examination were unremarkable except for complete destruction of both adrenal cortices. Seven cats were treated chronically with oral prednisone or intramuscular methylprednisolone acetate for glucocorticoid supplementation and with oral fludrocortisone acetate or intramuscular injections of repository desoxycorticosterone pivalate for mineralocorticoid replacement. One cat died after 47 days of therapy from unknown causes; the other six cats are still alive and well after 3 to 70 months of treatment.
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PMID:Primary hypoadrenocorticism in ten cats. 246 93

The effectiveness of aminoglutethimide as an adrenal inhibitor has been well-documented by decreases in plasma testosterone and delta 4 levels, which fall significantly following the drug in previously orchiectomized patients. The use of cortisone or cortisol along with aminoglutethimide complicates the interpretation of the role of aminoglutethimide in effecting clinical responses. However, since physiologic replacement doses were used in most cases, a significant role for cortisone in effecting a clinical response is unlikely. Aminoglutethimide does have side-effects including rash and lethargy. It requires administration of replacement doses of cortisone and sometimes mineralocorticoid as well since it inhibits adrenal steroid synthesis in all pathways. Peripheral adrenal androgen inhibitors, such as flutamide, Megace, cyproterone acetate or 5 alpha-reductase inhibitors, in the future may be equally effective and simpler to administer than aminoglutethimide but objective and adequate numbers of studies using acceptable objective criteria must be done in order to adequately compare these drugs to aminoglutethimide. There appears to be approximately a 33% response rate (partial objective regression and objectively stable) following blockade of adrenal androgens in patients in relapse after castration. Blockade of adrenal androgen is certainly more tolerable and has many fewer side-effects than the alternative of chemotherapy which does not give response rates in most cases that are significantly different from those noted with aminoglutethimide. Murray's paper, combined with prior studies by Drago et al., goes a long way in establishing adrenal androgen blockade with that drug as the next step to be taken in patients following relapse from prior castration (medical or surgical). The most important question revolves around the timing of adrenal androgen blockade. As stated by Murray, will adrenal androgen blockade provide better survival if given earlier following relapse? The answer is not known yet. The answer may come from the work of Labrie [1], Geller and Albert [2] and others, who suggest that total survival in prostate cancer may be improved with blockade of adrenal androgens not after relapse following castration, but with panandrogen blockade at the time of initial therapy for prostate cancer.
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PMID:Adrenal androgen blockade in relapsed prostate cancer. 293 57

A 52-year-old man with myxedema was evaluated for anterior chest pain that was considered to be compatible with myocardial ischemia. The night after admission he developed extreme bradycardia, hypotension, and apneic episodes lasting up to 25 s. Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema. Alveolar hypoventilation caused by decreased sensitivity to carbon dioxide, inadequate central neural drive, peripheral muscle force, and obesity all may have contributed to the apnea. Chest pain has not recurred, and results of electrocardiography have remained normal following full thyroid hormone replacement. The early recognition of myxedema causing sleep apnea will allow specific treatment to avoid the cardiovascular risks related to prolonged apnea and will help avoid confusion with other etiologies of cardiovascular abnormalities.
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PMID:Extreme bradycardia during sleep apnea caused by myxedema. 363 55

Phorbol esters, in particular 12-O-tetradecanoyl-phorbol-13-acetate (TPA), have been shown to have profound effects on most biological systems including tumor promotion. Presented here are studies on the acute toxic effects of TPA, and the effects of phorbol esters on the in vivo and in vitro, T cell-dependent, antigen-specific antibody response in the mouse. The LD50 of a single i.v. dose of TPA in the mouse was 309 micrograms/kg. Acute toxic effects included lethargy, hypothermia and enlarged, hemorrhagic spleens at the higher doses. TPA was shown to be a potent inhibitor of the in vivo primary antibody response as measured by the IgM antibody-forming cell (AFC) response to sheep red blood cells (sRBC). The ED50 of a cumulative i.v. dose was 145 micrograms/kg administered the day before and the day of immunization (72.5 micrograms/kg/day). A cumulative dose of 500 micrograms/kg (250 micrograms/kg/day) resulted in a 100% suppression of the response. This in vivo exposure to TPA did not alter B cell/T cell ratio in the spleen. Phorbol ester analogs inactive in other biological systems were also inactive in the in vivo AFC response. The in vitro AFC assay was used to determine what cell type was being affected by TPA. Separation of the adherent spleen cells into B and T cell populations was done using nylon wool columns and anti-theta plus complement treatment. Experiments with these cell populations indicated that TPA produced suppression of the response due to an effect on the nylon wool adherent cell population.
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PMID:Suppression of the antibody response by phorbol esters in the mouse is due to an effect on the nylon wool adherent cell population. 387 72

Both hyperammonemia and blood-brain barrier (BBB) breakdown have been implicated in the evolution of hepatic encephalopathy. To define a possible relationship, Swiss Albino mice were subjected to sublethal encephalopathic doses of ammonium acetate; the integrity of the BBB was determined grossly with Evans blue and quantitatively with [14C]-alpha-aminoisobutyrate (AIB). Some animals were injected with a dose of ammonium acetate sufficient to maintain coma for 1 hr (AC group). One group, termed stuporous (AS), received only enough ammonium acetate to interfere with grooming and exploratory activity; this dosage was insufficient to completely block the righting response, which was absent in the AC group. When compared to that of controls (CON) receiving normal saline instead of ammonium acetate, cerebral tissue from the AC group was stained blue and contained nearly double the amount of AIB; AS group brain tissue was unstained and the AIB content did not differ significantly from normal. Some of the AC group were pretreated with drugs known to retard BBB breakdown; one set received dexamethasone (AC-DXMN), another the ornithine decarboxylase inhibitor difluoromethyl ornithine (AC-DFMO), and a third L-ornithine (AC-ORN). Brain tissue from the AC-ORN group stained blue and AIB content did not differ significantly from that of the untreated AC group. Cerebral tissue of the AC-DXMN pretreatment group stained light blue; AIB content was significantly lower than in the AC group and greater than the CON group. The AC-DFMO brains were unstained and AIB content was significantly lower than in the AC group but did not differ significantly from CON. These results indicate that hyperammonemia may induce BBB breakdown but that the disruption of barrier integrity is not antecedent to the development of coma, although it seems to coincide with coma in time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disruption of the blood-brain barrier in hyperammonemic coma and the pharmacologic effects of dexamethasone and difluoromethyl ornithine. 393 Jul 57

Thirteen cats with diabetes mellitus were evaluated. Clinical signs included polydipsia, polyuria, polyphagia, lethargy, and weight loss. Results of physical examination included obesity, hepatomegaly, mild seborrhea sicca, muscle wasting, and dehydration. One cat walked plantigrade and was suspected of having a diabetic neuropathy. Persistent hyperglycemia, glucosuria, high liver enzyme activities, hypercholesterolemia, hyperproteinemia, and low electrolyte concentrations were the common laboratory findings. In 3 cats diabetes mellitus developed after megestrol acetate therapy; 2 of these cats required only temporary insulin treatment. In a 3rd cat, which had no history of receiving diabetogenic drug therapy, remission of diabetes mellitus also was observed. Serum insulin and plasma glucose concentrations were determined in 6 cats after administration of an intermediate-acting insulin (isophane insulin) and in 3 cats after administration of a long-acting insulin (protamine zinc insulin). The insulin concentration peaked 2 to 6 hours after the injection of intermediate-acting insulin and 6 to 12 hours after the injection of long-acting insulin. The lowest glucose concentration was recorded 4 to 8 hours after injection of intermediate-acting insulin, and 6 to 12 hours after injection of long-acting insulin. It was concluded that, although insulin therapy must be adjusted to the individual, the diabetic cat usually requires twice-daily administration of isophane insulin; however, the protamine zinc insulin can be given once daily for satisfactory control.
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PMID:Insulin therapy in cats with diabetes mellitus. 629 64


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