RESUMEN
Rocky Mountain Kaiser Permanente has taken aggressive steps to ensure optimal treatment of all modifiable cardiac risk factors, especially low-density lipoprotein (LDL) cholesterol, in patients with coronary artery disease. In this article, we are presenting (1) the basic rationale for our approach, (2) the critical steps translating philosophy into practice, and (3) justification for all health plans to pursue a similar course. The continuum of physician-directed disease management systems that have evolved in our region-one administered by cardiology nurses in the perihospitalization period and the other by pharmacists in the long-term, outpatient setting-is then detailed. Although the relatively short duration that our comprehensive systems have been in place precludes any assessment of their impact on cardiac death, coronary artery disease events, or coronary artery disease procedure rates, the improvements in intermediate surrogate outcomes are promising. Virtually all surveyed patients participating in our management systems have been "very" or "extremely" satisfied with their experience. The LDL-cholesterol screening rate in the approximately 2,500 participants in the programs to date has reached 97%. Of these patients, 84% have LDL cholesterol <130 mg/dL and 48% <100 mg/dL, and only 15% of those few with LDL cholesterol >130 mg/dL (2.5% overall) are currently not receiving lipid-lowering therapy. The proportions of patients on aspirin/antiplatelet and beta-blocker therapy after myocardial infarction are 97% and 92%, respectively. The lipid-screening and treatment rates, especially, represent significant improvement from our own baseline, and compare favorably with outcomes from other practice settings. In conclusion, health maintenance organizations have tremendous incentive and the unique opportunity and ability to develop systems to better manage large numbers of individuals with coronary artery disease.
Asunto(s)
LDL-Colesterol/sangre , Enfermedad Coronaria/complicaciones , Sistemas Prepagos de Salud/organización & administración , Hiperlipidemias/tratamiento farmacológico , Programas Controlados de Atención en Salud/organización & administración , Colorado , Enfermedad Coronaria/sangre , Enfermedad Coronaria/terapia , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Hipolipemiantes/uso terapéutico , Satisfacción del PacienteRESUMEN
The diagnosis of hemochromatosis requires liver biopsy and the quantification of hepatic iron. Magnetic resonance imaging (MRI) of the liver shows a characteristic decrease in tissue signal intensity in iron overload states, but its role in the diagnosis of hemochromatosis has not been fully delineated. Forty-three patients (31 men and 12 women) were referred for the evaluation of hemochromatosis based upon a fasting transferrin saturation > 55% and/or a serum ferritin > 400 ng/ml in males or > 300 ng/ml in females. Each patient prospectively underwent MRI of the liver prior to percutaneous liver biopsy and quantitative hepatic iron determination. Homozygous hemochromatosis was diagnosed in 10 patients based upon an hepatic iron/age index > or = 2. MRI was performed with a 1.5 Tesla system using standard spin-echo sequences (T1; TR = 300-500 ms, TE = 13-17 ms, PD; TR = 2,000-2,600 ms, TE = 30 ms). Signal intensity values were blindly determined for regions of interest in liver and skeletal muscle at T1 and proton density. Ratios of liver to muscle (LM) for T1 and proton density (PD) calculated from these values showed a significant correlation with quantitative iron by multiple regression analysis. The LMPD ratio provided the best correlation with hepatic iron (r = -0.6946; p < 0.001). Linear regression analysis also provides an equation that can be used to predict hepatic iron based upon the LMPD ratio; micrograms/g of hepatic iron = (-5,174 x LMPD) + 9,932. All patients with LMPD ratios of > 0.5 had hepatic iron/age indices of < 2.0, thereby excluding homozygous hemochromatosis. These results suggest that LMPD ratios derived from MRI of the liver can accurately predict hepatic iron content. These ratios can be clinically useful in the evaluation of hemochromatosis among patients who either refuse or have contraindications to liver biopsy.
Asunto(s)
Hemocromatosis/diagnóstico , Hierro/análisis , Hígado/química , Hígado/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Biopsia , Femenino , Hemocromatosis/genética , Hemocromatosis/patología , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: To determine the prevalence of celiac disease in a cohort of patients with insulin-dependent diabetes mellitus and to describe the clinical characteristics of patients with coexistent disease. DESIGN: Prospective cohort study. SETTING: U.S. Army medical center. PATIENTS: 47 patients with insulin-dependent diabetes mellitus. MEASUREMENTS: Antiendomysial antibody testing was used to screen for celiac disease. The diagnosis of celiac disease required histologic evidence of villous atrophy and crypt hyperplasia and a positive antiendomysial antibody test result. In patients identified as having coexistent disease, complete blood counts, multiphasic biochemical testing, D-xylose absorption testing, and bone mineral density estimates were done. RESULTS: 3 of 47 patients with insulin-dependent diabetes mellitus (6.4%; 95% CI, 1.4% to 17.5%) had positive antiendomysial antibody test results and small-bowel biopsy specimens consistent with celiac disease. The 95% CI lies entirely above the estimated prevalence of celiac disease expected in the general U.S. population, which ranges from 0.02% to 0.1%. Mean bone mineral densities were 0.8 and 1.1 SD below age-, ethnicity-, and sex-matched controls in each of the 2 antiendomysial antibody-positive patients tested. Small bowel absorption was abnormal in 1 of the 2 patients tested by D-xylose. Anemia and hypoalbuminemia were not detected in any of the patients with coexistent disease. Only 1 of the 3 patients had symptoms of diarrhea. All patients were at or above their ideal body weights. CONCLUSIONS: Celiac disease appears to be more common among patients with insulin-dependent diabetes mellitus than in the general U.S. population (p less than 0.001). Two of the three patients with coexistent disease in this study had subclinical or latent celiac disease.
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Enfermedad Celíaca/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Adulto , Atrofia , Autoanticuerpos/análisis , Densidad Ósea , Enfermedad Celíaca/diagnóstico , Femenino , Humanos , Hiperplasia , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Miofibrillas/inmunología , Estudios ProspectivosRESUMEN
OBJECTIVE: To test the effectiveness of pentoxifylline as a therapy for diabetic impotence. RESEARCH DESIGN AND METHODS: A 3-month placebo-controlled double-blind treatment study was conducted at a single center. Therapeutic response was assessed subjectively by serial self-appraisals of erectile function and objectively by nocturnal penile tumescence (NPT) monitoring. RESULTS: This cohort of impotent diabetic men displayed substantial neurological and penile vascular dysfunction. Age, body mass index, duration of diabetes, duration of impotence, glycemic control, mode of therapy for non-insulin-dependent diabetes, mean testosterone, mean prolactin, and penile brachial indexes were similar in the treatment (n = 34) and placebo groups (n = 26). NPT monitoring revealed infrequent erectile events, diminished average rigidity, and decreased tumescence. Pentoxifylline did not alter overall glycemic control and did not improve neurological, vascular, or erectile function. In fact, a slight decrease in average percent rigidity from 22 +/- 3 to 17 +/- 2% (mean +/- SE, P < 0.05) was observed in the pentoxifylline-treated group. Although eight (24%) pentoxifylline-treated and five (19%) placebo-treated men reported benefit, no objective improvement was observed in nocturnal tumescence. CONCLUSIONS: Pentoxifylline is not an effective treatment for diabetic erectile dysfunction.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Disfunción Eréctil/tratamiento farmacológico , Erección Peniana/efectos de los fármacos , Pentoxifilina/uso terapéutico , Vasodilatadores/uso terapéutico , Anciano , Análisis de Varianza , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Disfunción Eréctil/fisiopatología , Frecuencia Cardíaca , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Placebos , Prevalencia , Sístole , Factores de TiempoRESUMEN
Clinically relevant HP dysfunction occurs infrequently in the course of HIV infection and AIDS, and is usually due to destruction or infiltration of the region by opportunistic infections. However, more subtle defects occur with much greater frequency. Since these impairments, especially in the gonadotrophic and corticotrophic axes, are observed in HIV patients before the development of ARC or AIDS, direct involvement of the hypothalamus or pituitary by the neurotropic HIV virus or by other HIV-mediated factors is possible. Further investigation of hypothalamic and pituitary hormones by provocative means, in addition to assessment of the pulsatile secretion of these hormones, at all stages of HIV infection will be needed to clarify the role of the virus in these individuals.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Hipotálamo/fisiopatología , Hipófisis/fisiopatología , Humanos , Sistema Hipófiso-Suprarrenal/fisiopatología , Glándula Tiroides/fisiopatología , Vasopresinas/fisiologíaRESUMEN
PURPOSE: To examine the potential relationship between gout and hypothyroidism. PATIENTS AND METHODS: Fifty-four consecutive patients with a diagnosis of monosodium urate crystal-proven gouty arthritis on joint aspiration were prospectively evaluated for hypothyroidism with an ultrasensitive thyroid-stimulating hormone (TSH) assay. Twenty-five patients with a diagnosis of monosodium urate crystal-proven gout were retrospectively identified from a population of 137 patients receiving uric acid-lowering medications. These patients were also screened for hypothyroidism. Age, race, sex, and weight matched patients with noninflammatory rheumatic diseases and no history of gout served as controls. Hypothyroidism was diagnosed when a TSH was greater than 6.0 microU/mL or if a history of hypothyroidism requiring replacement therapy was documented. RESULTS: The prevalence of hypothyroidism in the prospective group was significantly increased compared to controls (P < 0.05). Overall 15% of these patients, 25% of women and 12% of the men, had hypothyroidism. These rates were 2.5 times greater in women and 6 times greater in men than found in the controls. The mean TSH of the prospective gouty patients was also significantly greater than those levels found in control patients (5.2 +/- 12 versus 1.8 +/- 1.1 microU/mL, P < 0.05, chi-square), even when all abnormally elevated TSH values were excluded from analysis. The prevalence of hypothyroidism in the retrospective group was even higher: 20% overall, 40% in women and 15% in men. CONCLUSIONS: The prevalence of hypothyroidism is significantly increased in patients with aspirate-proven gouty arthritis. Screening for hypothyroidism with an ultrasensitive thyroid-stimulating hormone assay should be considered in all patients presenting with gouty arthritis and those with a history of recurrent gouty flares.
Asunto(s)
Artritis Gotosa/complicaciones , Hipotiroidismo/epidemiología , Anciano , Femenino , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Tirotropina/sangreRESUMEN
We describe, for the first time, a patient with both symptomatic acromegaly and Chiari-I malformation. These conditions could coexist by chance alone, but the probability of both presenting simultaneously in a previously healthy man seem quite remote. Alternatively, acromegaly through associated bony and soft tissue enlargement could lead to the development of symptoms from Chiari-I malformation in this patient.
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Acromegalia/complicaciones , Acromegalia/fisiopatología , Encéfalo/anomalías , Neoplasias Hipofisarias/cirugía , Adulto , Terapia Combinada , Hormona del Crecimiento/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Octreótido/uso terapéutico , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/radioterapiaRESUMEN
BACKGROUND: Although use of histamine H2 antagonists for chronic treatment of primary hyperparathyroidism (PHP) is ineffective, pretreatment with cimetidine has been reported to reduce the incidence of postoperative hypocalcemia in patients with PHP undergoing neck exploratory operation. The current investigation was conducted to determine the validity of this assertion. METHODS: In a randomized, double-blind, placebo-controlled trial, 20 patients with PHP were treated with either cimetidine or placebo for 10 to 14 days before neck exploratory operation. Clinical outcome and biochemical indexes before and after drug treatment in both groups were compared. RESULTS: Cimetidine treatment resulted in a modest increase in preoperative parathyroid hormone level but did not affect any other parameter, including serum calcium level or renal tubular reabsorption of phosphate. Intraoperative time was similar in both groups. Mean postoperative calcium nadir was identical regardless of therapy (8.3 mg/dl), and seven (70%) patients from each group had at least one serum calcium measurement less than 8.5 mg/dl. CONCLUSIONS: Cimetidine treatment before neck exploratory operation for PHP does not diminish the frequency or severity of postoperative hypocalcemia.
Asunto(s)
Cimetidina/uso terapéutico , Hiperparatiroidismo/cirugía , Hipocalcemia/prevención & control , Complicaciones Posoperatorias/prevención & control , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the discriminating ability of various specific endocrine studies on patient outcome from the intensive care unit (ICU). DESIGN: Prospective cohort study of patients requiring intensive care. SETTING: Adult medical and coronary care units in a military referral hospital. PATIENTS: A total of 61 consecutive patients requiring intensive care over a 5-month period and 20 control subjects. INTERVENTIONS: Patients were evaluated within 24 hrs of ICU admission (day 1) with determination of the following variables: serum triiodothyronine, thyroxine, triiodothyronine resin uptake, thyrotropin, luteinizing hormone, follicle-stimulating hormone, testosterone, basal cortisol, adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and Acute Physiology and Chronic Health Evaluation (APACHE II) score. A total of 24 hrs later (day 2), the same battery of tests was repeated with the exception of the adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and APACHE II score. Individual variables were compared between survivors and nonsurvivors. MEASUREMENTS AND MAIN RESULTS: The best discriminators of patient outcome in descending order were the basal serum cortisol and triiodothyronine concentrations obtained on day 2 and the APACHE II score with predictive abilities of 81%, 74%, and 70%, respectively. No combination of variables was superior to the day 2 basal cortisol concentration for discrimination of outcome. CONCLUSIONS: The basal cortisol and triiodothyronine concentrations obtained from blood samples collected within 48 hrs of ICU admission appear to be better discriminators of patient outcome than the APACHE II score.
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Enfermedad Crítica/mortalidad , Hormonas/sangre , Unidades de Cuidados Intensivos , Evaluación de Resultado en la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colorado , Enfermedad Crítica/terapia , Femenino , Hospitales con 300 a 499 Camas , Hospitales Militares , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Triyodotironina/sangreRESUMEN
Glucocorticoids are known inhibitors of prostaglandin production. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are promoters of natriuresis and renin release. Excessive prostaglandin production, therefore, might contribute to the altered sodium balance and renin release observed in primary adrenal insufficiency. To test this hypothesis, sodium balance and prostaglandin production were measured in adrenalectomized rats and in animals receiving prostaglandin inhibitors or replacement dexamethasone. Compared to sham-operated controls, adrenalectomized rats had decreased two-day sodium balance and elevated plasma renin concentration (PRC), renal PGE2 production, and renal 6-ketoprostaglandin F1 alpha (6kPGF1 alpha, the nonenzymatic metabolite of PGI2); however, no appreciable change in aortic 6kPGF1 alpha production was observed. Dexamethasone given to adrenalectomized rats normalized PRC but had no effect on sodium balance or prostaglandin production. Likewise, prostaglandin inhibitors did not alter the sodium balance or decrease the PRC post adrenalectomy. These data confirm renal prostaglandin production is increased in adrenalectomized rats, but suggest that the elevation is not due directly to glucocorticoid deficiency. Further, PRC levels in adrenal insufficiency do not appear to be prostaglandin mediated. In conclusion, excessive renal prostaglandin production does not contribute to altered sodium balance or increased PRC in adrenalectomized rats.
Asunto(s)
Glándulas Suprarrenales/fisiología , Dexametasona/uso terapéutico , Dinoprostona/farmacología , Epoprostenol/farmacología , Renina/sangre , Sodio/metabolismo , Adrenalectomía , Animales , Aspirina/farmacología , Dinoprostona/antagonistas & inhibidores , Epoprostenol/antagonistas & inhibidores , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Indometacina/farmacología , Masculino , Prostaglandinas/biosíntesis , Ratas , Ratas Sprague-DawleyRESUMEN
Mutations in the insulin gene can impair the bioactivity of the insulin molecule. Previously, two classes of mutations have been identified: 1) those that impair posttranslational processing of proinsulin to insulin, and 2) those that alter the structure of the insulin molecule, thereby reducing the affinity of the molecule for the insulin receptor. We have investigated two apparently unrelated patients, both of which have mutations that inhibit the conversion of proinsulin to insulin. By directly sequencing genomic DNA amplified by polymerase chain reaction, we have demonstrated that both patients are heterozygous for the same point mutation converting codon 65 from an arginine (CGT) to a histidine (CAT) codon. Because Arg65 is one of the two dibasic amino acids at the site of proteolytic cleavage between the insulin A-chain and C-peptide, this mutation explains the impairment in the cleavage of proinsulin to insulin. Interestingly, the same His65 mutation has been identified in the insulin gene of a Japanese kindred with familial hyperproinsulinemia. Thus, this mutation has occurred in three apparently unrelated kindreds from two different racial groups. This observation is consistent with the hypothesis that the dinucleotide sequence CpG, the first two nucleotides in the arginine (CGT) codon, is a "hot spot" for mutations.
Asunto(s)
Arginina , ADN/análisis , Histidina , Insulina/genética , Proinsulina/sangre , Proinsulina/genética , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , Glucemia/análisis , Codón , Exones , Amplificación de Genes , Genes , Humanos , Hiperinsulinismo/genética , Hiperinsulinismo/metabolismo , Insulina/biosíntesis , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Hibridación de Ácido Nucleico , Péptido Hidrolasas , Reacción en Cadena de la Polimerasa , Proinsulina/metabolismoRESUMEN
Adrenal, gonadal, and thyroid function were assessed in 40 asymptomatic subjects in whom infection with the human immunodeficiency virus (HIV) had recently been documented. None of the patients had historical or clinical evidence of endocrine dysfunction. Their mean serum hormone levels were also within the expected ranges, but several differences were noted compared to those of seronegative controls. Basal cortisol, basal aldosterone, and ACTH-stimulated cortisol were significantly lower in the HIV group. One subject (2.5%) had a subnormal cortisol response, and two (5%) had abnormal aldosterone responses to ACTH. PRA tended to be higher, and serum angiotensin-converting enzyme levels somewhat lower in the HIV group. Serum free testosterone was markedly elevated in the HIV patients and was associated with an exaggerated LH response to GnRH, but PRL, estradiol, and basal and peak GnRH-stimulated FSH did not differ between groups. Three subjects (8%) had subclinical hypothyroidism. Serum thyroid hormone levels were normal, but basal T3 was lower in the HIV group compared to control values. While of little immediate clinical importance, many subtle endocrine aberrations are evident very early in the course of HIV infection. These findings obtained in HIV-seropositive subjects without infections or tumors and who were not receiving medical therapy suggest an effect of HIV on each of the endocrine systems examined.