Prospective validation of the Ocular Trauma Score as a prognostic model to predict vision survival in injured adult patients from a developing country.

PURPOSE: To assess the prognostic value of the Ocular Trauma Score (OTS) in patients with eye injury treated in a University Hospital in South America. METHODS: One hundred and ninety subjects who were victims of eye trauma with different degrees of severity were evaluated and treated accordingly. Initial OTS categories were calculated for each patient and compared to the final visual result by transforming the achieved best-corrected visual acuity (BCVA) after treatment into OTS values. RESULTS: OTS visual acuity showed good correlation with the final BCVA after treatment [Spearman's ρ = 0.857, 95 % confidence interval (CI) 0.813-0.891, P < 0.0001). No difference between the predicted BCVA and achieved BCVA was noticed (P < 0.0001, Chi-square test). CONCLUSION: The OTS provided useful information on outcomes treatment after eye trauma and can be used as a prognostic model to predict vision survival in injured adult patients from a developing country.

Use of tetrandrine to differentiate between mechanisms involved in silica-versus bleomycin-induced fibrosis.

Animals exposed to silica or bleomycin (BLM) develop pulmonary fibrosis. Tetrandrine (TT) has been shown to inhibit stimulant-induced macrophage respiratory burst and effectively reduce silica-induced lung injury. The present study employed TT as a probe to assess the differences in mechanisms involved in silica- and BLM-induced pulmonary responses. Rats received a single intratracheal instillation of silica (40 mg/rat, sacrificed 4 wk postexposure) or BLM (1 mg/kg or approximately 0.25 mg/rat, sacrificed up to 2 wk postexposure). TT was administered orally at 18 mg/kg, 3 times/wk for desired time periods beginning 5 d before silica or BLM exposure. Both the silica and BLM exposures resulted in a significant increase in lung weight, total protein, lactate dehydrogenase (LDH), and phospholipids (PL) content in the acellular fluid from the first lavage, and hydroxyproline content in the lung tissue. Alveolar macrophages (AM) isolated from rats exposed to silica or BLM exhibited significant increases in secretion of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta (TGF-beta). TT treatment significantly lowered the silica- or BLM-induced increase in lung weight, while marginally reducing the release of IL-1 and TNF-alpha by AM. TT, however, markedly inhibited the silica-induced increase in the acellular protein, LDH and PL, hydroxyproline content, and the production of TGF-beta by AM but had no marked effect on these same parameters in BLM-exposed rats. Histological examination of rats exposed to BLM for 14 d showed pulmonary inflammation and fibrosis. TT treatment had only a small effect on limiting the extent of these lesions and did not significantly affect their severity. In summary, data indicate that many inflammatory and fibrotic effects of in vivo silica exposure are substantially attenuated by TT, whereas the stimulation by BLM is only marginally affected by this drug. Since TT acts to attenuate AM-mediated reactions, these results suggest that AM may play a pivotal role in silica-induced fibrotic development and may be less involved in the pathogenesis of BLM-induced fibrosis.

Enhancement of nitric oxide production by pulmonary cells following silica exposure.

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.

The effects of chronic exercise on metabolic and reproductive functions in male rats.

Previous studies concerning the effects of swimming on various endocrine gland functions have been performed. Our study was thus designed to analyze the effects of chronic exercise (swimming) on the resting metabolic rates (RMR) of adult rats. Most of the protocols used a water temperature of 33 C. It is our contention that such a protocol is not exclusively an exercise stress, but also a hypothermic stress. The protocol of our study was designed in a way that hypothermic stress was not part of the exercise stress. Male rats were swam in 36 C water for 3 hours a day, 5 days a week for 4 months. RMR of the animals were determined 24 h after the next to last swim session. Plasma hormone levels and epididymal sperm concentrations were determined in animals sacrificed 24 h after the last swim period. Exercising animals had a RMR 16% greater than that of control animals (p < 0.02), yet total and free thyroxine and total and free triiodothyronine were not significantly elevated. Neither plasma testosterone nor epididymal sperm counts were significantly reduced in the exercising animals. It appears that chronic exercise produces an elevation in RMR which is unrelated to thyroid gland activity and does not suppress the hypothalamic-pituitary-gonadal axis.

Cushing'S syndrome attributable to topical use of lotrisone.

OBJECTIVE: To emphasize the potentially devastating consequences of topical application of corticosteroids. METHODS: A case report is presented of a previously healthy 38-year-old woman in whom florid Cushing's syndrome developed after prolonged use of Lotrisone. RESULTS: Four years of continuous topical administration of Lotrisone, a combination antifungal-corticosteroid product, led to the development of Cushing's syndrome. The cream had been applied to less than 10% of the total body surface area without use of occlusive dressings, and the patient had no evidence of liver dysfunction or systemic skin disorder. Laboratory studies revealed an unmeasurable corticotropin level, suppressed or unmeasurable cortisol levels, and suppressed or low-normal 24-hour urine collection values for 17-hydroxy-steroids, 17-ketosteroids, and urinary free cortisol, all of which confirm suppression of the hypothalamic-pituitary-adrenal axis. CONCLUSION: (1) Betamethasone dipropionate can lead to the development of Cushing's syndrome, even in the absence of enhancing factors. (2) Combination medications can lead to the unintentional use of component agents. (3) Availability of potent corticosteroids as over-the-counter medications allows for inappropriate duration of therapy and inadequate medical supervision.

Combined octreotide and insulin therapy in acromegaly.

OBJECTIVE: To describe an unusual treatment strategy for certain patients with both acromegaly and insulin-requiring diabetes. METHODS: We present a case history of a man with a pituitary adenoma and diabetes mellitus and chronicle his response to various treatment modalities. RESULTS: Acromegaly, a disease state with excess growth hormone (GH) and insulin-like growth factor-I, is associated with carbohydrate intolerance. Octreotide, a somatostatin analogue, is used in the treatment of acromegaly to lower GH levels. Despite effective lowering of GH levels, certain patients with acromegaly have persistent or even worsening carbohydrate intolerance and may require insulin therapy. Such a regimen would necessitate five or more injections per day. We describe a 51-year-old man who was diagnosed with a GH-producing pituitary adenoma in 1987. Despite transsphenoidal resection, frontal craniotomy, and radiation therapy, symptoms and increased levels of GH persisted. The patient was diagnosed with diabetes mellitus in August 1989 and treated with glipizide. Because of persistently increased GH levels, he was treated with octreotide. His glycohemoglobin level increased to 21% despite use of maximal doses of glipizide. The patient refused insulin therapy because of his objection to numerous daily injections. Despite adjustments in diet and exercise, glycemic control remained poor. As a trial, we thus attempted combining octreotide and regular insulin in the same syringe and administering the medications in a single subcutaneous injection. No precipitate formation was evident, and he had no adverse effects. Glucose control improved, and the glycohemoglobin level was lower but still elevated. GH levels remained at less than 5 ng/mL. His symptoms of acromegaly were unchanged, but his overall attitude and energy level improved. CONCLUSION: The efficacy of the individual components of this treatment was demonstrated in the combination of insulin and octreotide. The combined administration of insulin and octreotide has limited application in patients with acromegaly and insulin-requiring diabetes mellitus.

Fluoromicroscopic studies of bleomycin-induced intracellular oxidation in alveolar macrophages and its inhibition by taurine.

The mechanism of bleomycin-induced pulmonary fibrosis is not yet clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide more insight into the cellular oxidative property of bleomycin, we have developed a fluoromicroscopic method using 2',7'-dichlorofluorescin diacetate (DCFHDA) as an oxidative fluorescence probe to study the bleomycin-induced intracellular oxidation in rat AM and the inhibition of the oxidation by taurine, a compound known to inhibit the bleomycin-induced fibrosis. Bleomycin at 5 to 20 micrograms/ml has a moderate stimulatory effect (1.87- to 2.66-fold) on the secretion of superoxide anion. A high concentration of bleomycin (20 micrograms/ml), however, inhibits cell response to zymosan-induced secretion of superoxide anion. At 4 micrograms/ml, bleomycin has no effect on cell membrane integrity or morphology but results in a significant increase in intracellular oxidation. This oxidative process is Fe(2+)-dependent and is accompanied by an increase in intracellular calcium (35 nM). Both the intracellular oxidation and calcium rise induced by internalized bleomycin are inhibited by pretreatment of cells with varying concentrations of taurine (25, 125, and 187.5 microM). The inhibitory effect on intracellular oxidation was found to be 36, 57, and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical aspects of coal workers' pneumoconiosis and silicosis.

Coal workers' pneumoconiosis and silicosis are two important respiratory disorders that result from the inhalation of respirable particles in mining. This chapter focuses on the clinical aspects of these disorders, including their pathogenesis and pathology, and approaches to their evaluation and management.

Strategies for the treatment of pneumoconiosis.

Regulatory control of dust in the workplace has greatly reduced the development of pneumoconiosis, yet the prevention of silicosis and coal workers' pneumoconiosis has not been accomplished. Cases of pneumoconiosis continue to occur, and there is no proven way to affect the natural history of these progressive inflammatory and fibrotic processes. Although pneumoconiosis and silicosis are considered untreatable in Western countries, in China an aggressive search has been underway for therapeutic agents and clinical procedures to treat these diseases. The important aspects are reviewed for the tried therapies, including corticosteroids, aluminum citrate complex, PVNO, tetrandrine, xinin, and whole lung lavage.

Changes in psychotropic drug use in long-term residents of an ICF/MR facility.

Psychotropic drug use of 139 persons residing continuously over a 10-year period in an ICF/MR was monitored. Results indicate an ongoing decrease in psychotropic drug use, primarily antipsychotic agents, as well as the benefits of ongoing monitoring of individual drug usage. This monitoring can be utilized to minimize side effects of medication. Information obtained can be organized and utilized to improve care. Drug histories, when used with other data pertinent to targeted benefit to risk of medication.

Insulin, somatomedin-C, human chorionic gonadotropin, and forskolin enhance glucose oxidation by granulosa cells.

The long exposure times required to observe stimulatory effects of insulin on steroidogenesis and protein synthesis in granulosa cells suggested that these effects might be secondary to stimulation of another metabolic process. The present studies examined the effects of insulin, the insulin-like growth factor somatomedin-C (Sm-C), human chorionic gonadotropin (hCG), and forskolin, a compound that activates adenylyl cyclase independently of a receptor, on glucose metabolism. Granulosa cells from preovulatory porcine ovarian follicles were incubated at 37 degrees C in Dulbecco's phosphate-buffered saline supplemented with bovine serum albumin, vitamins, amino acids, and glucose (0.01-20 mM). Cells were incubated with [14C]glucose for up to 23 h with or without a prior 20-h preincubation. Oxidation of glucose, assessed by quantitation of 14CO2 produced, was dependent on time and concentration of glucose. Optimal glucose concentrations for glucose oxidation were 3 mM in the absence or presence of insulin and correlated well with the measured glucose concentrations in follicular fluid (3 mM). After a 20-h preincubation in the absence or presence of insulin (1 microM), the rates of CO2 production were 10.6 and 21.6 pmol/micrograms DNA/h for control and insulin-treated cells, respectively. Insulin had an EC50 of 164 nM. Sm-C and hCG were more potent stimulators than insulin with EC50s of 768 pM and 161 pM, respectively. The greater sensitivity of granulosa cells to Sm-C than to insulin supports the concept that insulin exerts its effect via reactivity with the Sm-C receptor. The effect of hCG may have been mediated by cyclic adenosine 3',5'-monophosphate (cAMP), since forskolin also enhanced 14CO2 production.(ABSTRACT TRUNCATED AT 250 WORDS)