RESUMEN
Inflammation plays a crucial role in neurodegenerative diseases, but the irritants responsible for this response remain largely unknown. This report addressed the hypothesis that hypochlorous acid reacts with dopamine to produce melanic precipitates that promote cerebral inflammation. Spectrophotometric studies demonstrated that nM amounts of HOCl and dopamine react within seconds. A second-order rate constant for the reaction of HOCl and dopamine of 2.5 × 10(4)M(-1)s(-1) was obtained by measuring loss of dopaminergic fluorescence due to HOCl. Gravimetric measurements, electron microscopy, elemental analysis, and a novel use of flow cytometry confirmed that the major product of this reaction is a precipitate with an average diameter of 1.5 µm. Flow cytometry was also used to demonstrate the preferential reaction of HOCl with dopamine rather than albumin. Engulfment of the chlorodopamine particulates by phagocytes in vitro caused these cells to release TNFα and die. Intrastriatal administration of 10(6) particles also increased the content of TNFα in the brain and led to a 50% loss of the dopaminergic neurons in the nigra. These studies indicate that HOCl and dopamine react quickly and preferentially with each other to produce particles that promote inflammation and neuronal death in the brain.
Asunto(s)
Química Encefálica , Encéfalo/metabolismo , Inflamación/metabolismo , Melaninas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Línea Celular Tumoral , Dopamina/análogos & derivados , Dopamina/química , Dopamina/metabolismo , Dopamina/farmacología , Halogenación , Humanos , Ácido Hipocloroso/química , Ácido Hipocloroso/metabolismo , Inmunohistoquímica , Masculino , Ratones Endogámicos C57BL , Microscopía Electrónica , Fagocitos/efectos de los fármacos , Fagocitos/metabolismo , Fagocitos/ultraestructura , Fagocitosis , Espectrofotometría , Factor de Necrosis Tumoral alfa/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
OBJECTIVES: To compare the efficacy and safety of ciprofloxacin (CIP) oral suspension to trimethoprim/sulfamethoxazole (TMP/SMX) oral suspension among older women with acute urinary tract infections (UTIs). DESIGN: Prospective, randomized, open-label, multicenter study of older women (age 65 and older). SETTING: Community and nursing home. PARTICIPANTS: A total of 261 older women were evaluable for safety. Of these, 172 (86 community, 86 nursing home) were evaluable for clinical and bacteriological efficacy. INTERVENTION: Patients were randomized to a 10-day regimen of either CIP (250 mg/5 mL twice daily) or TMP/SMX (160/800 mg/20 mL twice daily). MEASUREMENTS: Clinical response 4 to 10 days posttherapy. RESULTS: For the efficacy-valid population, posttherapy clinical resolution was statistically superior following CIP (97%) versus TMP/SMX (85%) (95% CI=2.0-21.3; P= .009). Eradication of pretreatment bacterial isolates posttherapy was also higher following CIP (95%) versus TMP/SMX (84%) (95% CI=2.7-21.3; P= .019). For the intent-to-treat population, posttherapy clinical resolution was significantly higher in the CIP group (96%) than in the TMP/SMX group (87%) (95% CI=0.2-16.7; P= .025). Safety was assessed in the intent-to-treat population and the incidence of drug-related adverse events were significantly lower following CIP (17%) than following TMP/SMX (27%) (P= .047). Premature discontinuation due to these events was also less prevalent with CIP than with TMP/SMX (2% vs 11%, respectively) (P= .004). CONCLUSION: CIP suspension showed higher clinical success and bacteriological eradication rates than did TMP/SMX for both community-based and nursing home-residing older women with acute UTIs. Furthermore, CIP suspension was associated with significantly lower rates of adverse events and premature discontinuations compared with TMP/SMX suspension.
Asunto(s)
Antiinfecciosos Urinarios/efectos adversos , Antiinfecciosos/administración & dosificación , Ciprofloxacina/administración & dosificación , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Infecciones Urinarias/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Antiinfecciosos Urinarios/uso terapéutico , Ciprofloxacina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Casas de Salud , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Suspensiones , Factores de Tiempo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Urinary tract infection (UTI) is a common problem that is distressing for patients and costly for the healthcare system. UTIs commonly affect young, sexually active women; the elderly; and patients who have predisposing factors, such as catheterization. Recurrent infections are likely to occur in all these patients groups. Patients who are pregnant or have predisposing factors are at increased risk for complications related to untreated UTIs, such as long-term renal damage. Given these risks and the public health burden associated with the condition, it is important that clinicians have up-to-date information regarding the classification, symptoms, pathogenesis, and empiric treatment of UTIs.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/fisiopatología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/fisiopatología , Factores de Edad , Aminoglicósidos/uso terapéutico , Antiinfecciosos Urinarios/uso terapéutico , Infecciones Bacterianas/epidemiología , Farmacorresistencia Bacteriana , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Masculino , Embarazo , Prevalencia , Recurrencia , Factores Sexuales , Infecciones Urinarias/epidemiología , beta-Lactamas/uso terapéuticoAsunto(s)
Antibacterianos/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Adulto , Anciano , Aminoglicósidos/uso terapéutico , Antiinfecciosos Urinarios/uso terapéutico , Diagnóstico Diferencial , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Posmenopausia , Premenopausia , Enfermedades de Transmisión Sexual/diagnóstico , Infecciones Urinarias/diagnóstico , beta-Lactamas/uso terapéuticoRESUMEN
In November 1996, 11 lots of one U.S. manufacturer's 1996-97 trivalent influenza vaccine were voluntarily recalled because of decreasing potency of the A/Nanchang/933/95 (H3N2) component. Because the elderly are at high risk of developing influenza-related complications, we assessed the postvaccination antibody titers of nursing home residents who received recalled vaccine and assessed the antibody response to revaccination. Blood samples were collected 3 weeks after vaccination from 86 residents at three nursing homes who received recalled vaccine and 86 residents at three other nursing homes who received a different manufacturer's vaccine. Medical records were reviewed. Residents of one nursing home were later revaccinated. Blood samples were collected on the day of revaccination and again in 3 weeks. Serum was tested by hemagglutination inhibition for antibody to all three components of the 1996-97 influenza vaccine. The geometric mean antibody titer (GMT) (33 vs 55; p=0.01) and the percentage of residents with an antibody titer > or = 1:40 (52 vs 67%; p=0.04) to the A/Nanchang/933/95 component were lower among residents who received recalled vaccine compared to those who received non-recalled vaccine, but had similar GMTs against the other two vaccine components. After revaccination, the GMT to A/Nanchang/933/95 increased from 24 on the day of revaccination to 39 (p=0.01) in residents from one nursing home. Therefore, vaccination with the recalled vaccine was associated with lower postvaccination antibody titers to A/Nanchang/933/95, but not against the other two vaccine components. Revaccination was moderately effective in increasing antibody titers. With annual changes in influenza vaccine strains, routine post-release stability testing of influenza vaccine should continue.
Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la Influenza/inmunología , Anciano , Anciano de 80 o más Años , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Masculino , Casas de Salud , Factores de Tiempo , VacunaciónRESUMEN
There have been few studies of hypertension in nursing home patients. To assess the prevalence, demographic characteristics, comorbidity and drug therapy in hypertensive nursing home patients compared with those who are normotensive, we reviewed all medical charts of patients in three nursing home facilities. Of the 804 patients, 355 (44.2%) have hypertension. Calcium channel blockers were the most frequently prescribed anti-hypertensive (30.3%) and together with diuretics (28.4%) and ACE inhibitors (27.7%) account for more than 85%. Hypertensive patients take more cardiac, hypoglycaemic, and analgesic drugs (P = <0.001, <0.001, and 0.004, respectively) than those who are normotensive. Overall patients take an average of 8.68 medications daily. In hypertensive patients, the average number of comorbid conditions (excluding hypertension) is 5.02 compared with 3.23 in normotensive patients. Hypertension is significantly associated with diabetes, heart disease, cerebrovascular disease, neoplasms, endocrine disorders, gastrointestinal diseases, psychiatric disorders, dementia, other central nervous system diseases, skin problems, blood diseases and inversely with hip fracture. Blood pressure control (<140/90 mm Hg) is achieved in 88.8%, is not related to age and is significantly more frequent in males than females (91.8% vs 82.6% P = 0.025). The problem of hypertension in nursing home patients is complex and has received insufficient study. Since studies demonstrating benefit from anti-hypertensive therapy in the elderly excluded the very elderly and those with significant comorbid conditions, additional research is needed.
Asunto(s)
Hipertensión/tratamiento farmacológico , Casas de Salud , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , MasculinoRESUMEN
BACKGROUND: Pharmacologic treatment of hypertension reduces risks of stroke, congestive heart failure, renal failure, and mortality, but whether medications, once begun, need to be continued for life is uncertain. METHODS: Several search strategies on MEDLINE using key words "medication," "withdrawal," "discontinuance," and "therapy" in several combinations, nested within "hypertension," were not productive. Accordingly, articles known to the authors and citations within them were reviewed. A survey of a random sample of members of the New York Academy of Family Practice was conducted to ascertain current practice of practicing physicians. RESULTS: Eighteen studies of antihypertensive medication withdrawal were located and all were reviewed. In 12 trials average success rates of 40.3 percent after 1 year of follow-up and 27.7 percent after 2 years were achieved. In six studies limited to elderly patients, an average success rate of 26.2 percent was obtained for periods of 2 or more years. The trials, however, were heterogeneous in design, patient selection criteria, and follow-up. The survey of family physicians indicated that 79.1 percent attempt withdrawal of antihypertensive medications in hypertensive patients whose blood pressure is controlled and who are without symptoms from medication. CONCLUSIONS: We conclude that successful withdrawal of antihypertensive medications can have substantial benefits with few or no adverse consequences and might be successful in about one third of patients. Additional research is required to substantiate rates of successful medication withdrawal, to define the best method of withdrawing medications, and to delineate characteristics of patients in whom withdrawal is most likely to succeed.
Asunto(s)
Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/etiología , Adulto , Anciano , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Medicina Familiar y Comunitaria , Femenino , Estudios de Seguimiento , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana EdadRESUMEN
A well coordinated plan that includes a mechanism for surveillance, rapid antigen detection testing and viral culture, infection control techniques and chemoprophylaxis is effective for aborting outbreaks of influenza A in the nursing home. Amantadine has been better studied in this situation, and experience with rimantadine is limited. The safety and efficacy of our dose guidelines for nursing home residents need to be studied and directly compared with rimantadine dose guidelines. Except for chemoprophylaxis, these guidelines can be applied to outbreaks of influenza B as well.
Asunto(s)
Brotes de Enfermedades/prevención & control , Hogares para Ancianos , Gripe Humana/prevención & control , Casas de Salud , Anciano , Amantadina/uso terapéutico , Guías como Asunto , Humanos , Gripe Humana/diagnóstico , Gripe Humana/epidemiologíaRESUMEN
The effect of plasma protein binding changes on drug clearance is an important concept in clinical pharmacology. In a hypoalbuminemic patient receiving acetazolamide, albumin infusion (50 g) increased acetazolamide plasma protein binding towards normal as the serum albumin concentration rose (r = 0.91, P < .001). The ratio of acetazolamide renal plasma clearance to creatinine clearance decreased as serum albumin levels increased (r = 0.78, P < .05) and the unbound drug fraction fell (r = 0.88, P < .01), but clearance ratios based on unbound plasma acetazolamide levels did not change. Albumin infusion resulted in a nonparallel decline over time between plasma and unbound plasma acetazolamide concentrations. These data demonstrate that, over the range of observed serum albumin concentrations, acetazolamide renal plasma clearance is sensitive to changes in plasma protein binding. Furthermore, our findings emphasize the importance of measuring unbound drug levels when protein binding changes occur during the course of drug disposition studies. Finally, this methodology allows for the fascile assessment of the effects of plasma protein binding changes on renal drug clearance.
Asunto(s)
Acetazolamida/sangre , Proteínas Sanguíneas/metabolismo , Riñón/metabolismo , Anciano , Anciano de 80 o más Años , Humanos , Infusiones Intravenosas , Masculino , Tasa de Depuración Metabólica , Unión Proteica , Albúmina Sérica/administración & dosificaciónRESUMEN
Presence of cytomegalovirus (CMV) specific immunoglobulin M (IgM) is generally considered strong evidence of current or recent CMV infection. Sera from 110 elderly individuals (age range 61-100 years) were compared with sera from 87 younger individuals (age range 16-47 years). Prevalence of CMV IgM was found to be 30% in the older group (mean age 83 years) and only 6% in the younger group (mean age 29 years). In spite of increased CMV antibody levels, none of the elderly individuals were symptomatic. Viral cultures of urine from 72 elderly individuals were negative for CMV. These results suggest that the presence of CMV-specific IgM must be interpreted with caution in an elderly population.
Asunto(s)
Anticuerpos Antivirales/sangre , Citomegalovirus/inmunología , Inmunoglobulina M/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Citomegalovirus/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Humanos , Persona de Mediana EdadRESUMEN
Elderly glaucoma patients are often treated with acetazolamide, a carbonic anhydrase inhibitor with clearance dependent on renal function. A high incidence of metabolic acidosis and other adverse effects have been noted among these patients but the reasons for this have not been explained. We hypothesized that commonly used doses of acetazolamide among the elderly result in excessive blood concentrations and that these concentrations are related to acid-base disturbances. We measured steady-state acetazolamide levels in plasma, plasma ultrafiltrate (unbound), and erythrocytes among 12 elderly subjects (79.2 +/- 7.6 years old). Mean plasma (18.9 +/- 10.9 micrograms/mL) and ultrafiltrate concentrations (1.0 +/- 0.7 microgram/mL) exceeded the therapeutic range (plasma 5-10 micrograms/mL; ultrafiltrate 0.25-0.50 microgram/mL) for glaucoma control by two fold and were elevated in 75% of subjects. Plasma and ultrafiltrate acetazolamide levels significantly correlated with the dose adjusted for creatinine clearance (r = 0.91, P less than 0.001; r = 0.89, P less than 0.001, respectively). Acidotic subjects (serum total carbon dioxide less than or equal to 22 mEq/L) tended to have higher plasma, ultrafiltrate, and erythrocyte acetazolamide levels compared with nonacidotic subjects. Serum total carbon dioxide levels were significantly correlated with erythrocyte acetazolamide concentrations (r = -0.75, P = 0.03). The ratio of erythrocyte acetazolamide concentration to creatinine clearance separated acidotic from nonacidotic subjects (P less than 0.01). These findings suggest that some of the adverse effects of acetazolamide can be avoided by reducing the dose to compensate for age-related reductions in renal drug clearance.
Asunto(s)
Acetazolamida/sangre , Acidosis/inducido químicamente , Riñón/fisiopatología , Acetazolamida/farmacocinética , Acidosis/fisiopatología , Anciano , Anciano de 80 o más Años , Dióxido de Carbono/sangre , Creatinina/sangre , Electrólitos/metabolismo , Femenino , Humanos , Pruebas de Función Renal , Masculino , UltrafiltraciónRESUMEN
This report describes an adverse reaction to iodinated glycerol, an organic form of iodine prescribed as a mucolytic-expectorant. In a patient with a previous history of severe potassium iodide-induced hypothyroidism, administration of iodinated glycerol resulted in mild subclinical hypothyroidism. There is one report in the literature of goiter resulting from iodinated glycerol and physicians should be aware of the potential for hypothyroidism with this agent. Iodinated glycerol should be added to the list of iodine-containing organic compounds that interfere with thyroid function.
Asunto(s)
Glicerol/efectos adversos , Hipotiroidismo/inducido químicamente , Yodo/efectos adversos , Anciano , Femenino , Humanos , Yoduro de Potasio/efectos adversos , Hormonas Tiroideas/sangreRESUMEN
Two elderly patients, who were chronically receiving aspirin, developed lethargy, incontinence, and confusion after dosing with acetazolamide. Unbound plasma acetazolamide concentrations were elevated and plasma protein binding was reduced, suggesting an interaction with aspirin. In vitro studies demonstrated a concentration-dependent effect of salicylate on acetazolamide binding to serum proteins. At a therapeutic serum acetazolamide level of 8.0 micrograms/ml, the unbound percentage of acetazolamide in serum was 3.3% and increased to 11.0% and 30.0%, with serum salicylate levels of 200 and 386 micrograms/ml, respectively. Furthermore, the apparent association constant of acetazolamide for binding to serum proteins was decreased by 58% and 86% of its control value at these respective salicylate concentrations. The maximal binding capacity of serum for acetazolamide was not affected by salicylate. Pharmacokinetic studies in four volunteers showed that the plasma protein binding and renal clearance of acetazolamide were significantly reduced during chronic salicylate dosing. Salicylate appears to competitively inhibit the plasma protein binding of acetazolamide and simultaneously to inhibit acetazolamide renal tubular secretion. Caution is advised when acetazolamide and salicylate are used concurrently.
Asunto(s)
Acetazolamida/metabolismo , Salicilatos/metabolismo , Acetazolamida/efectos adversos , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Aspirina/metabolismo , Proteínas Sanguíneas/metabolismo , Interacciones Farmacológicas , Femenino , Humanos , Cinética , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Salicilatos/efectos adversos , Ácido SalicílicoRESUMEN
Influenza vaccine may inhibit hepatic metabolism of drugs and has been reported to prolong the prothrombin time in patients receiving warfarin by affecting the coagulation pathway. In a group of seven elderly residents of a long-term care facility who were receiving warfarin, prolongation of the prothrombin and partial thromboplastin times could not be shown up to 5 weeks after vaccination against influenza. The results were similar in nine elderly subjects who were not receiving warfarin.
Asunto(s)
Vacunas contra la Influenza/efectos adversos , Warfarina/uso terapéutico , Anciano , Humanos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Factores de TiempoRESUMEN
Steady state theophylline concentrations were prospectively measured in 13 elderly institutionalized individuals following influenza vaccination. Vaccine-mediated increase in concentrations could not be identified. In seven individuals receiving warfarin, no change in prothrombin or partial thromboplastin times occurred following vaccination. No adverse drug reactions were observed. The following year 14 individuals receiving theophylline and 12 receiving warfarin were vaccinated without adverse drug reactions noticed. These data fail to support previous reports of influenza vaccine inhibition of theophylline metabolism or vaccine-enhanced anticoagulation and are consistent with recent reports on younger subjects.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Vacunas contra la Influenza/farmacología , Teofilina/sangre , Warfarina/farmacología , Anciano , Análisis de Varianza , Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Femenino , Humanos , Vacunas contra la Influenza/efectos adversos , Institucionalización , Masculino , Tiempo de Tromboplastina Parcial , Estudios Prospectivos , Tiempo de ProtrombinaRESUMEN
A railroad accident in Somerville, Massachusetts, led to spillage of phosphorus trichloride liquid. Attempted clean-up with water led to the liberation of phosphorus trichloride, phosphoric acid, hydrochloric acid, and phosphorus oxides. Seventeen people exposed to this mixture were studied. Patients experienced eye irritation, lacrimination, nausea, vomiting, and dyspnea. Six patients had transient elevation of lactic dehydrogenase. Although all patients had normal chest roentgenographic findings, pulmonary function tests showed statistically significant decreases in vital capacity (p = 0.02), maximal breathing capacity (p = 0.02), forced expiratory volume in one second (p = 0.02), and maximal expiratory flow rate at 25 percent of vital capacity (p = 0.05) in those closest to the accident site. Further, patients exposed for less than one and a half hours had significantly greater maximal expiratory flow rates at 25 percent of vital capacity when compared with patients who had been exposed longer (p = 0.02). In seven patients, repeated pulmonary function tests one month later showed improvement, suggesting strongly that the acute effects may have been due to phosphorus trichloride toxicity.