RESUMEN
This review addresses the range of operations suggested to be of contemporary value in the treatment of constipation with critical evaluation of efficacy data, complications, patient selection, controversies and areas for future research.
Asunto(s)
Estreñimiento/cirugía , Niño , Colectomía , Estimulación Eléctrica , Enema , Humanos , Íleon/cirugía , Plexo Lumbosacro/fisiología , Recto/inervación , Recto/cirugíaRESUMEN
Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia. We studied FC in controls (n = 25), Alzheimer's disease (n = 25) and FTLD (n = 25). A neutral stimulus (coloured square on a computer screen) was repeatedly paired with a 1 s burst of 100 db white noise. Change in skin conductance response to the neutral stimulus was used to measure conditioning. Physiological-anatomical correlations were examined using voxel-based morphometry (VBM). Both patient groups showed impaired acquisition of conditioned responses. However, the basis for this deficit appeared to differ between groups. In Alzheimer's disease, impaired FC occurred despite normal electrodermal responses to the aversive stimulus. In contrast, FTLD patients showed reduced skin conductance responses to the aversive stimulus, which contributed significantly to their FC deficit. VBM identified correlations with physiological reactivity in the amygdala, anterior cingulate cortex, orbitofrontal cortex and insula. These data indicate that Alzheimer's disease and FTLD both show abnormalities in emotional learning, but they suggest that in FTLD this is associated with a deficit in basic electrodermal response to aversive stimuli, consistent with the emotional blunting described with this disorder. Deficits in responses to aversive stimuli could contribute to both the behavioural and cognitive features of FTLD and Alzheimer's disease. Further study of FC in humans and animal models of dementia could provide a valuable window into these symptoms.
Asunto(s)
Enfermedad de Alzheimer/psicología , Condicionamiento Psicológico , Demencia/psicología , Miedo , Estimulación Acústica , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Respuesta Galvánica de la Piel , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Estimulación Luminosa , Distribución AleatoriaRESUMEN
STUDY DESIGN: Retrospective clinical study with 1-year follow-up. OBJECTIVES: Treatment of faecal incontinence by permanent sacral nerve stimulation (SNS) in patients suffering from cauda equina syndrome (CES). SETTING: Klosterneuburg, Austria. BACKGROUND AND PURPOSE: A flaccid paresis of the sphincter ani muscle and the pelvic floor combined with faecal incontinence can occur in patients suffering from CES as a result of a trauma in the region of the lumbar spine. If the incontinence cannot be managed by the use of laxatives or anal tampons, the patient is restricted in his/her quality of life. Thus, it was our aim to improve sphincter function and anal sensitivity to achieve voluntary rectal defaecation. MATERIALS AND METHODS: The functional integrity of at least one sacral root (S2-S4) was determined through percutaneous nerve evaluation (PNE). Following this analysis, a period of external temporary SNS was performed to evaluate the functional effect. If there was a decrease in the number of episodes of faecal incontinence during this evaluation period, a neurostimulation device (InterStim; Medtronic) was implanted. PATIENTS: A total of 11 patients suffering from flaccid paresis of the anal sphincter muscle and faecal incontinence caused by CES underwent PNE, which was successful in 8 patients. Two of these patients were eliminated from the procedure at the end of the temporary SNS period, one patient refused the permanent implantation. Therefore, five patients proceeded to permanent implantation, which led to an improved continence in all the cases. DISCUSSION: In the synopsis of the preoperative proctologic and neurological findings, successful electric stimulation of the sacral roots can be expected in incomplete CES. In the case of flaccid paresis of the anal sphincter muscles caused by an incomplete CES, permanent SNS offers a promising option for the treatment of faecal incontinence. .
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Polirradiculopatía/terapia , Sacro/lesiones , Fracturas de la Columna Vertebral/complicaciones , Raíces Nerviosas Espinales/lesiones , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados/tendencias , Incontinencia Fecal/etiología , Incontinencia Fecal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/fisiología , Hipotonía Muscular/etiología , Hipotonía Muscular/fisiopatología , Hipotonía Muscular/terapia , Músculo Esquelético/inervación , Músculo Esquelético/fisiopatología , Diafragma Pélvico/inervación , Diafragma Pélvico/fisiopatología , Polirradiculopatía/etiología , Polirradiculopatía/fisiopatología , Estudios Retrospectivos , Raíces Nerviosas Espinales/fisiopatología , Resultado del TratamientoRESUMEN
PURPOSE: Constipation is frequently a multifactorial disease. This study was designed to evaluate the potential effects of sacral nerve stimulation for patients suffering from severe chronic constipation. METHODS: Nineteen patients suffering from pathologic colonic transit time or rectal outlet obstruction were included. Only patients with severe rectal outlet obstruction who needed digital manipulation for defecation or patients suffering from pathologic colonic transit constipation with less than two bowel movements per week were regarded as candidates. A temporary stimulation lead was implanted into the sacral foramen that showed the best muscular response. After an evaluation period, the stimulation electrode was removed. An improvement in constipation (more than 2 bowel movements per week or defecation without digital manipulation, respectively) during the test stimulation, as well as a recurrence of prestimulation constipation symptoms during the following surveillance period of three weeks were prerequisites for implanting the permanent sacral nerve stimulating system. RESULTS: All of the patients showed a positive motor response to acute needle stimulation. After the evaluation period, eight patients (42 percent) reported an improvement of constipation, and permanent systems were implanted successfully. During the median follow-up of 11 (range, 2-20) months, a significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (baseline: median: 23, range, 18-27; 12 months after implantation: median, 8, range, 4-13). After successful sacral nerve stimulation, patients also showed a significant improvement in their quality of life. CONCLUSIONS: Patients suffering from severe constipation are a new challenge for sacral nerve stimulation but further research on pelvic floor function is needed.
Asunto(s)
Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estreñimiento/fisiopatología , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Sacral nerve stimulation (SNS) has emerged as a promising technique for the treatment of faecal incontinence. This study assessed the outcome of SNS in a cohort of patients with incontinence of neurological aetiology. METHODS: Thirty-six patients were included in a trial of SNS. Twenty-nine subsequently had a permanent implant. Evaluation consisted of a continence diary, anal manometry, saline retention testing and quality of life assessment. RESULTS: After a median follow-up of 35 (range 3-71) months, 28 patients showed a marked improvement in or complete recovery of continence. Incontinence to solid or liquid stool decreased from a median of 7 (range 4-15) to 2 (range 0-5) episodes in 21 days (P = 0.002). Saline retention time increased from a median of 2 (range 0-5) to 7 (range 2-15) min (P = 0.002). Maximum resting and squeeze anal canal pressures increased compared with preoperative values. Quality of life on all scales among patients who received a permanent implant increased at 12 and 24 months after operation. CONCLUSION: SNS is of value in selected patients with neurogenic faecal incontinence.
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Electrodos Implantados , Incontinencia Fecal/terapia , Plexo Lumbosacro , Calidad de Vida , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: This study examined the use of sacral nerve stimulation (SNS) to treat faecal incontinence in patients with partial spinal injury. METHODS: Patients selected for SNS had experienced more than one episode of faecal incontinence per week to liquid or solid stool for more than 1 year and had failed maximal conservative treatment. All patients had an intact external anal sphincter. RESULTS: Temporary SNS was performed in 13 patients (median age 58.5 (range 39-73) years). The spinal insults were disc prolapse (six), trauma (four), spinal stenosis (one) or occurred during neurosurgery (two). Twelve patients (eight women and four men) had successful temporary stimulation and proceeded to permanent implantation. The median follow-up time was 12 (range 6-24) months. The mean(s.d.) number of episodes of incontinence decreased from 9.33(7.64) per week at baseline to 2.39(3.69) at last follow-up (P = 0.012). The number of days per week with incontinence and staining decreased significantly (both P < 0.001). Ability to defer defaecation improved from a median of not being able to defer (range 0-1 min) to being able to defer for 5-15 (range 0 to over 15) min (P = 0.022). CONCLUSION: SNS can benefit patients with faecal incontinence following partial spinal injury.
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Plexo Lumbosacro , Traumatismos Vertebrales/complicaciones , Adulto , Anciano , Terapia por Estimulación Eléctrica/efectos adversos , Electrodos Implantados , Incontinencia Fecal/etiología , Femenino , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/terapia , Masculino , Persona de Mediana Edad , Dolor/etiología , Estudios Prospectivos , Calidad de Vida , Traumatismos Vertebrales/terapiaRESUMEN
Digitalis-like compounds (DLC) are steroidal hormones that are synthesized in, and released from, the adrenal gland, whose regulation may be directed by the hypothalamic-pituitary-adrenal (HPA) axis. Increasing evidence points to antitumour properties of these compounds and we hypothesized that the establishment of tumours in athymic nude mice may be facilitated by an abnormal synthesis or secretion of DLC. To explore this hypothesis, DLC concentrations were determined in the plasma, and in adrenal and hypothalamic tissues of nude compared to normal mice under basal conditions, and 30 min after a stress stimulus (i.p. injection of 100 micro l saline) with or without additional adrenocorticotropic hormone (ACTH) 1 micro g/per animal. Simultaneously, plasma corticosterone and serum adrenocorticotropic hormone (ACTH) concentrations were analysed. The basal DLC concentrations were similar in the plasma and the hypothalamus of both strains, whereas the basal adrenal DLC concentration was significantly lower in the nude mice compared to normal mice. The stress stimulus induced in normal mice a significant increase in DLC concentrations in the adrenal gland, the plasma and the hypothalamus. However, in nude mice, it caused an increase only in the adrenal gland and the hypothalamus, whereas the plasma DLC concentration was not affected. In both strains, the administration of ACTH in addition to injection stress did not provoke a further increase in DLC concentrations while inducing a significant increase in plasma corticosterone concentration. Regardless of the applied stimulus, the nude mice expressed significant lower DLC concentrations in the adrenal gland and the plasma compared to normal mice. The low basal adrenal DLC concentration in nude mice and their impaired DLC response towards stress- and ACTH stimulation both support an involvement of DLC in tumorigenesis.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Glicósidos Cardíacos/sangre , Corticosterona/sangre , Hipotálamo/metabolismo , Estrés Fisiológico/sangre , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/fisiología , Animales , Glicósidos Digitálicos/sangre , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Neuroinmunomodulación/fisiología , Sistema Hipófiso-Suprarrenal/metabolismo , Especificidad de la Especie , Estrés Fisiológico/fisiopatologíaRESUMEN
Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to -19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individual's changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Estrógenos Conjugados (USP)/administración & dosificación , Estrógenos/administración & dosificación , Terapia de Reemplazo de Hormonas , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fosfatasa Alcalina/sangre , Biomarcadores , Huesos/efectos de los fármacos , Huesos/metabolismo , Colágeno/sangre , Colágeno Tipo I , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Péptidos/sangreRESUMEN
Anal incontinence is estimated to be present in approximately 2% of the total population. However, the incidence of this disorder increases with age, affecting up to 11% of men and 26% of women after the age of 50 years. In general, the causes of long-standing fecal incontinence may be divided into anorectal or congenital malformations, perineal trauma (due to surgery or accident), pudendal nerve lesions with or without muscular injury, and low-motor neuron lesions. Classical surgical treatment includes direct repair of the circumscribed gap in the anal sphincter, the so-called overlapping sphincteroplasty or anal repair. In the short term, this method was shown to be very effective in improving continence. Surgical repair of a diffuse weakness of the pelvic floor by application of the postanal repair method has led to more controversial results. While the short-term results are frequently beneficial, full continence is rarely achieved in the long run, especially in patients with imparied pudendal nerve function. All currently used surgical methods focus on the direct mechanical approach to the pelvic floor muscles and/or the anal sphincter. Therefore, the response to this kind of therapy is limited by the presence of a simultaneously existing neurogenic lesion (pudendal nerve damage), as well as by the magnitude and intensity of muscular injury. These problems have been addressed by the development of new methods that focus on the replacement of large muscular defects (Dynamic Graciloplasty) and the treatment of neurogenic causes of fecal incontinence (Sacral Nerve Stimulation-SNS).
Asunto(s)
Incontinencia Fecal/terapia , Terapia por Estimulación Eléctrica , Incontinencia Fecal/etiología , Incontinencia Fecal/cirugía , HumanosRESUMEN
BACKGROUND & AIMS: Sacral nerve stimulation is a proven therapeutic option for the treatment of some forms of urinary incontinence. Very recently, preliminary reports have given evidence for its efficacy in fecal incontinence (FI) too. METHODS: Since November 1998, 20 patients have been treated for severe FI. The cause of FI was mainly neurologic (n = 15), and was idiopathic in 5 patients. After temporary (subchronic) external stimulation over a period of 10-14 days, patients whose continence status improved underwent implantation of a permanent quadripolar lead and a subcutaneously implanted pulse generator. RESULTS: Acute (needle) testing revealed a positive pelvic floor response in 16 patients who underwent subsequent permanent implantation. The median number of incontinence episodes decreased from 6 episodes (3-15/21 days) to 2 (0-5/21 days). The time period of retention of a volume of saline causing an urge until definitive defecation was 2 minutes (range, 0-5 minutes) preoperatively and increased to 7.5 minutes (2-15 minutes) postoperatively. Results of preoperative and postoperative (3 months) anal manometry showed a statistically significant increase in maximal resting and squeeze pressures. CONCLUSIONS: Sacral nerve stimulation seems to be a new and promising modality for patients with certain types of FI in whom conventional treatment options have failed to achieve an improvement.
Asunto(s)
Terapia por Estimulación Eléctrica , Incontinencia Fecal/terapia , Plexo Hipogástrico/fisiología , Recto/inervación , Adolescente , Adulto , Anciano , Defecación , Incontinencia Fecal/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Manometría , Persona de Mediana Edad , Complicaciones Posoperatorias , Recto/fisiología , Sacro , Resultado del TratamientoRESUMEN
The in vivo efficacy of the echinocandin antifungal caspofungin acetate (caspofungin; MK-0991) was evaluated in models of disseminated aspergillosis and candidiasis in mice with cyclophosphamide (CY)-induced immunosuppression. Caspofungin is a 1, 3-beta-D-glucan synthesis inhibitor efficacious against a number of clinically relevant fungi including Aspergillus and Candida species. Models of CY-induced transient or chronic leukopenia were used with once daily administration of therapy initiated 24 h after microbial challenge. Caspofungin was effective in treating disseminated aspergillosis in mice that were transiently leukopenic (significant prolongation of survival at doses of > or =0.125 mg/kg of body weight and a 50% protective dose [PD(50)] of 0.245 mg/kg/day at 28 days after challenge) or chronically leukopenic (50 to 100% survival at doses of > or =0.5 mg/kg and PD(50)s ranging from 0.173 to 0.400 mg/kg/day). Caspofungin was effective in the treatment and sterilization of Candida infections in mice with transient leukopenia with a 99% effective dose based on reduction in log(10) CFU of Candida albicans/gram of kidneys of 0.119 mg/kg and 80 to 100% of the caspofungin-treated mice having sterile kidneys at caspofungin doses from 0.25 to 2.0 mg/kg. In Candida-infected mice with chronic leukopenia, caspofungin was effective at all dose levels tested (0.25 to 1.0 mg/kg), with the log(10) CFU of C. albicans/gram of kidneys of caspofungin-treated mice being significantly lower (>99% reduction) than that of sham-treated mice from day 4 to day 28 after challenge. Also, 70 to 100% of the caspofungin-treated, chronic leukopenic mice had sterile kidneys at caspofungin doses of 0.5 to 1.0 mg/kg from day 8 to 28 after challenge. Sterilization of Candida infections by caspofungin in the absence of host leukocytes provides compelling in vivo evidence for fungicidal activity against C. albicans. Further human clinical trials with caspofungin against serious fungal infections are in progress.
Asunto(s)
Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Ciclofosfamida/farmacología , Péptidos Cíclicos , Péptidos , Animales , Aspergilosis/transmisión , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Candidiasis/transmisión , Caspofungina , Modelos Animales de Enfermedad , Equinocandinas , Femenino , Huésped Inmunocomprometido , Terapia de Inmunosupresión , Lipopéptidos , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Resultado del TratamientoRESUMEN
Using functional MRI we compared the patterns of activation in an effortful word retrieval task (stem completion) performed both silently and aloud. The silent and overt conditions showed expected differences in activation magnitude in regions such as primary motor cortex. Some regions, such as frontal operculum and dorsolateral frontal cortex, showed similar activation magnitude across conditions. Thalamus was more active on the left in both conditions and showed a symmetric drop in activity in the silent compared with the overt condition. Putamen was also more active in the overt condition and showed a larger decrease in activity on the right than on the left in the silent compared with the overt condition. Thus it appears that silent and overt performance of this task engage the thalamus and putamen in different ways.
Asunto(s)
Encéfalo/anatomía & histología , Vocabulario , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Putamen/fisiología , Tálamo/fisiologíaAsunto(s)
Canal Anal/cirugía , Incontinencia Fecal/terapia , Canal Anal/diagnóstico por imagen , Canal Anal/inervación , Terapia por Estimulación Eléctrica , Incontinencia Fecal/diagnóstico , Motilidad Gastrointestinal , Humanos , Imagen por Resonancia Magnética , Manometría , Prótesis e Implantes , UltrasonografíaRESUMEN
BACKGROUND: The influence of blood transfusions in the risk of postoperative infection remains controversial. We examined the association between autologous (AB) and homologous (HB) blood transfusions with postoperative infection in elective surgery. METHODS: The medical records of 991 Medicare patients aged > or =65 years submitted to hysterectomy and hip and knee replacement were reviewed. Logistic regression analysis was used to control for age, comorbidity, year, and type of procedure. RESULTS: Overall, 451 (46%) patients required transfusions. AB was given to 324 (72%), HB to 94 (21%); 33 (7%) patients received both. Forty-two patients (4%) developed postoperative infections. The infection rate was not different among patients receiving HB (7%), AB (5%), AB+HB (0), and nontransfused patients (4%); P = 0.18). After adjustment for confounders, HB and AB remained not associated with infections. CONCLUSION: In elective surgery with small volume transfusion, neither AB nor HB transfusions were associated with an increased risk of postoperative infections.
Asunto(s)
Transfusión de Sangre Autóloga , Procedimientos Quirúrgicos Electivos , Infecciones/epidemiología , Complicaciones Posoperatorias/prevención & control , Anciano , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Transfusión de Sangre Autóloga/estadística & datos numéricos , Colorado/epidemiología , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Femenino , Humanos , Histerectomía/estadística & datos numéricos , Modelos Logísticos , Masculino , Medicare/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Estados UnidosRESUMEN
Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy.
Asunto(s)
Alendronato/uso terapéutico , Densidad Ósea/efectos de los fármacos , Resorción Ósea/tratamiento farmacológico , Anciano , Alendronato/administración & dosificación , Fosfatasa Alcalina/sangre , Aminoácidos/orina , Biomarcadores/sangre , Biomarcadores/orina , Resorción Ósea/sangre , Resorción Ósea/orina , Calcio de la Dieta/administración & dosificación , Calcio de la Dieta/farmacología , Colágeno/orina , Colágeno Tipo I , Método Doble Ciego , Femenino , Fémur/efectos de los fármacos , Humanos , Osteocalcina/sangre , Péptidos/orina , Radio (Anatomía)/efectos de los fármacos , Columna Vertebral/efectos de los fármacos , Vitamina D/farmacologíaRESUMEN
BACKGROUND: Controlled muscle fiber conversion by electrostimulation makes transformation of fast twitching type II muscle fibers to slow twitching type I fibers possible, which gives skeletal muscles the capacity for tetanic contraction. This phenomenon has been recently applied in the so-called "dynamic graciloplasty" to restore function of an insufficient or excised anal sphincter. This paper describes our results with this method in patients with fecal incontinence or following an abdomino-perineal resection (APR) of the anorectum. METHODS: From April 1992 through April 1997, 28 patients (12 women and 16 men) were treated by dynamic graciloplasty. The median age was 53.5 years (range 16 to 79). Indications were as follows: APR + synchronous restoration of the excised sphincter by graciloplasty (n = 12); total anorectal reconstruction (TAR) following APR in the past (n = 6); Patients with acquired fecal incontinence (n = 4); and Congenital atresia (n = 6). Muscle transposition, implantation of stimulation electrodes and pulse generator were done as a single-stage procedure, the "neosphincter" was wrapped in a modified technique (split-sling technique). Muscle transformation was performed by controlled neuromuscular stimulation during 8 weeks (from 1992 to 1995) and 4 weeks (since 1996), respectively. RESULTS: No postoperative mortality (90 days) was observed in either group. In our early experience, rectal injury occurred in 4 patients as the most prominent complication. Evaluation of the functional outcome showed the best results in patients operated either for congenital of acquired incontinence who achieved a continence for solids and liquids or solids alone, respectively (1 or 2 according to Williams' score) in 90%, while patients following APR showed a satisfying outcome (continence for solids and liquids, solids alone or with occasional episodes for liquids) in only 55.5%. In patients following APR, defecation disorders turned out to be the most prominent functional problem and had to be treated by enemas. CONCLUSION: In this series, we have been able to perform dynamic graciloplasty as a one-stage procedure using a modified muscle wrap (split-sling-technique) thus reducing the time period until continence could be achieved to 7 weeks. We found the appropriate tension of the muscle wrap essential to prevent direct injury to the rectum as it was seen in our early experience. For this reason, we have introduced a modified device to perform intraoperative anal manometry and to measure pressures created by the neosphincter objectively.
Asunto(s)
Canal Anal/fisiopatología , Canal Anal/cirugía , Terapia por Estimulación Eléctrica , Incontinencia Fecal/terapia , Músculo Esquelético/trasplante , Neoplasias del Recto/cirugía , Adolescente , Adulto , Anciano , Incontinencia Fecal/etiología , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Masculino , Manometría , Persona de Mediana Edad , Complicaciones Posoperatorias , Neoplasias del Recto/complicaciones , Neoplasias del Recto/fisiopatología , Procedimientos Quirúrgicos Operativos/métodos , Resultado del TratamientoRESUMEN
Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.
Asunto(s)
Hepatopatías/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Silimarina/uso terapéutico , Humanos , FitoterapiaRESUMEN
The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated in mouse models of disseminated candidiasis, aspergillosis, and cryptococcosis. The echinocandins are potent inhibitors of 1,3-beta-D-glucan synthase. Two models of disseminated candidiasis were used. In a Candida albicans mouse survival model with both DBA/2N and CD-1 mice, estimates of the 50% effective doses (ED50s) of MK-0991 were 0.04 and 0.10 mg/kg of body weight/dose at 21 days after challenge, respectively. In a C. albicans target organ assay (TOA) with DBA/2N mice, MK-0991 at levels of > or =0.09 mg/kg/dose significantly reduced the numbers of C. albicans CFU/g of kidneys compared to the numbers in the kidneys of control mice from 1 to 28 days after challenge. Even when given as a single intraperitoneal dose either 30 min or 24 h after challenge, MK-0991 was effective and significantly reduced the numbers of C. albicans CFU/g of kidney compared to those in the controls. MK-0991 was >300-fold less active when it was administered orally than when it was administered parenterally. MK-0991 was efficacious in mouse TOAs against other C. albicans strains and Candida species including Candida tropicalis, Candida (Torulopsis) glabrata, Candida lusitaniae, Candida parapsilosis, and Candida krusei. MK-0991 was ineffective against disseminated Cryptococcus neoformans infections. In the model of disseminated aspergillosis in mice, MK-0991 at doses of > or =0.02 mg/kg/dose significantly prolonged the survival of DBA/2N mice, with estimates of the ED50 and ED90 of MK-0991 being 0.03 and 0.12 mg/kg/dose, respectively, at 28 days after challenge. MK-0991 is a potent, parenterally administered therapeutic agent against disseminated candidiasis and aspergillosis that warrants further investigation in human clinical trials.
Asunto(s)
Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Criptococosis/tratamiento farmacológico , Péptidos Cíclicos , Péptidos , Administración Oral , Animales , Caspofungina , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Equinocandinas , Femenino , Inyecciones Intraperitoneales , Enfermedades Renales/tratamiento farmacológico , Lipopéptidos , Ratones , Ratones Endogámicos DBARESUMEN
Patients who underwent potential curative surgery for colonic adenocarcinoma were enrolled in a prospectively randomised, controlled clinical trial of combined intraperitoneal (i.p.) plus systemic intravenous (i.v.) chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant treatment approach, specifically addressing the risk of peritoneal and hepatic recurrence, could improve disease-free and overall survival. Between May 1988 and December 1990, 121 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned for observation (which was considered standard care until the NIH consensus conference) or adjuvant chemotherapy with LV (200 mg/m2) plus 5-FU (350 mg/m2), both given i.v. (days 1-4) and i.p. (days 1 and 3) every 4 weeks for a total of six courses. After a median follow-up time of 4.6 years, a comparative analysis between the two groups of patients suggested both an improvement in disease-free survival (75% versus 58%; P = 0.06) and a survival advantage (78% versus 63%; P = 0.05) in favour of adjuvant chemotherapy. The sites of recurrence were also different, i.e. local regional and intrahepatic tumour recurrences were observed in only 6/58 (10%) and 5/58 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%) observed patients. The overall benefit of adjuvant therapy appeared to be greatest in patients with stage III colon cancer. Treatment-associated toxicity was infrequent and generally mild with only 5% experiencing severe (WHO grade 3) adverse reactions. Interim results of this adjuvant trial suggest that combined i.p. plus systemic i.v. chemotherapy with 5-FU and LV represents a potentially effective adjuvant regimen in stage II/III colon cancer.