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OBJECTIVES: Mental health difficulties are often exacerbated during the perinatal period. Policy and guidelines are increasingly being used to enhance the quality of healthcare. We conducted a literature review of published research relating to pregnancy and breastfeeding in mental health policy. METHODS: Relevant terms were searched in Medline, CINAHL, APA PsycINFO and EMBASE for articles published in English from 1970 until 2020. Only papers that referenced policy, guidance, legislation or standards were included. While a systematic approach was used, the nature of the results necessitated a narrative review. RESULTS: Initially, 262 papers were identified, 44 met the inclusion criteria. Reproductive health is given sparse consideration in research relating to mental health policy. Despite this, some key areas emerged. These included: the need for proactive preconception psychoeducation, proactive screening of mothers of infants and young children for perinatal mental health issues, enhanced prescribing practice for women of child-bearing age, enhanced monitoring during pregnancy, development of safe modification of coercive practices should they need to be employed in emergency circumstances and targeted measures to reduce substance misuse. Themes that arose relating to breastfeeding and bonding are also described. CONCLUSIONS: Female reproductive health is often ignored in research relating to mental health policy, guidelines and standards. These tools need to be harnessed to promote good healthcare. Reproductive health should be included in the care plan of all mental health patients. These topics need to be integrated into existing relevant policies and not isolated to a separate policy.
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Lactancia Materna , Atención a la Salud , Embarazo , Lactante , Humanos , Femenino , Preescolar , Salud Mental , Política de SaludRESUMEN
Aims Irish decision-making capacity legislation is due to fundamentally change from 2022, with the commencement of the Assisted Decision-Making (Capacity) Act 2015, removing 'best interests' decision-making and replacing it with a 'will and preference' basis. This study aimed to investigate awareness amongst doctors regarding this Act, and specific knowledge relating to capacity assessment and advanced healthcare directives. Methods The study utilised a cross-sectional anonymised self-report questionnaire within a second tier hospital located in a rural part of Ireland. Results Only 2% of doctors had received any formal training on the Act, 25% were unsure of their role and 45% were unsure of a patient's role in decision-making. 37% believed that best interests was retained in decision-making. 50% were unaware of their obligations in assessing capacity, 23% were unable to assess capacity correctly and 47% were unsure of any consultative obligations in decision-making. 90% were unaware of what constituted a valid Advanced Healthcare Directive. Conclusion Further training is urgently required if the Act is to be successfully implemented in 2022.
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Toma de Decisiones , Médicos , Directivas Anticipadas , Estudios Transversales , Atención a la Salud , HumanosRESUMEN
Suicide is a relatively common event in those seeking psychiatric care. However, its impact is nonetheless traumatic and devastating for those involved in the care of the patient. Community mental health teams (CMHTs) address every aspect of a patient's life, which creates a unique relationship between the team and the patient. Patient suicide can have serious, detrimental effects on individual team members, on the functioning of the team itself and on the care of other patients in the aftermath of such an event. In spite of this, there are limited protocols to guide CMHTs in this situation. This article seeks to emphasise the impact of patient suicide on CMHTs as a specific entity. It highlights the need for more research in this area, in order to direct the formation of more coherent local and national guidelines.
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Salud Mental , Suicidio , Humanos , PsicoterapiaRESUMEN
OBJECTIVES: Women of childbearing age often experience mental health problems, receive psychotropic medication and are admitted to mental health units. Approximately 40% of pregnancies are unplanned and many women experience perinatal mental health problems. It is therefore vital that consideration is given to reproductive health in mental health policy. We aimed to evaluate the consideration of pregnancy and breastfeeding in the policies of an inpatient mental health service. METHODS: The policies of a regional inpatient psychiatric unit were independently reviewed by two researchers. Policies that had implications for pregnancy and breastfeeding for patients were identified. Whether or not these policies considered pregnancy and breastfeeding and the detail of this consideration was evaluated. RESULTS: One hundred and thirteen policies were evaluated. Forty had implications for pregnancy but only 10 of these mentioned pregnancy and only 3 in detail. Only 3 of the 28 policies that had relevance to breastfeeding mothers mentioned it and none discussed it in detail. Key areas of omission included prescribing, seclusion and restraint and cultural and religious considerations. CONCLUSION: Pregnancy and breastfeeding were almost entirely absent in the ward policies of our inpatient unit. Their consideration in the acute setting is vital. An individual or group of individuals should be responsible for ensuring that reproductive health is considered in all policies as well as in a larger specific policy suitable for referencing. The rights of the reproductive woman should be comprehensively considered in inpatient mental health care policy.
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Aim To describe an uncommon side effect of sudden withdrawal of Clozapine. Method This case describes the occurrence of catatonia following the sudden discontinuation of long term Clozapine therapy. Results Symptoms resolved with treatment with benzodiazepines and IV fluids. Discussion In conclusion, catatonia can occur on sudden discontinuation of Clozapine therapy. Caution should be exercised when reducing or discontinuing this medication.
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Antipsicóticos/efectos adversos , Catatonia/inducido químicamente , Clozapina/efectos adversos , Síndrome de Abstinencia a Sustancias/etiología , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/tratamiento farmacológicoRESUMEN
Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.
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Anticuerpos Monoclonales/química , Anticuerpos Neutralizantes/química , Linfocitos B/inmunología , Calostro/inmunología , Anticuerpos Anti-VIH/química , Proteína gp120 de Envoltorio del VIH/antagonistas & inhibidores , Inmunoglobulina G/química , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Neutralizantes/aislamiento & purificación , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Linfocitos B/patología , Linfocitos B/virología , Lactancia Materna , Calostro/citología , Calostro/virología , Reacciones Cruzadas , Células Dendríticas/inmunología , Células Dendríticas/patología , Células Dendríticas/virología , Resistencia a la Enfermedad/inmunología , Células Epiteliales/inmunología , Células Epiteliales/patología , Células Epiteliales/virología , Femenino , Microbioma Gastrointestinal/inmunología , Anticuerpos Anti-VIH/biosíntesis , Anticuerpos Anti-VIH/aislamiento & purificación , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/aislamiento & purificación , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Leche Humana/química , Leche Humana/inmunología , Leche Humana/virología , Embarazo , Simbiosis/inmunologíaRESUMEN
A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(â¼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.
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Linfocitos B/inmunología , Linfocitos B/metabolismo , Calostro/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/genética , Infecciones por VIH/inmunología , VIH-1/inmunología , Lactancia , Negro o Afroamericano , Formación de Anticuerpos/inmunología , Linfocitos B/citología , Recuento de Linfocito CD4 , Evolución Clonal , Calostro/citología , Regiones Determinantes de Complementariedad/genética , Epítopos de Linfocito B/inmunología , Femenino , Anticuerpos Anti-VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , Infecciones por VIH/sangre , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Memoria Inmunológica , Inmunofenotipificación , Transmisión Vertical de Enfermedad Infecciosa , Tasa de Mutación , Fenotipo , Hipermutación Somática de Inmunoglobulina , Carga ViralRESUMEN
PURPOSE: Conventional calculation methods of patient release criteria for compliance with NRC regulations are based on the assumption that both patient and bystander are each a single point in space. This study was intended to assess the patient-specific external radiation exposure to a bystander interacting with the patient following radionuclide therapy with 131I. METHODS: 131I-sodium iodide treatment for hyperthyroidism and thyroid cancer and 131I-tositumomab treatment of non-Hodgkin's lymphoma were considered. 131I distribution provided by the patient SPECT image was rendered on the SPECT-fused CT images. The CT images were then imported to a Monte Carlo based simulation code, MCNPX 2.7, as a source phantom. For a target phantom, we employed the adult male hybrid phantom developed at the University of Florida and National Cancer Institute. A single orientation - patient and a bystander facing one another at 1.0 m - was considered. S factors (dose per unit cumulative activity (A)) for each organ in a bystander was obtained from the MC calculations and effective dose (EDE) per A was calculated based on tissue-weighted individual organ doses. The results were compared with the calculations using UF/NCI adult hybrid source/target phantoms and the revised adult ORNL stylized source/target phantoms. RESULTS: EDE per A of the stylized phantom was 1.5% higher than that of the hybrid phantom for uniform source localization in the thyroid. However, EDE per A of the hybrid phantom was 20% less than that of stylized phantoms for a torso source. The difference is attributed to the realistic shape of the frontal body comparing to the simple ellipsoidal trunk of the stylized phantom. CONCLUSIONS: Based on the realistic hybrid phantoms and accurate MC radiation transport calculation tools, patient specific dosimetry for a bystander is feasible. S factors will be calculated using the patient CT image with 131I bio-distributions and hybrid phantoms.
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Athletes (n = 345) invited to the annual combine conducted by the National Hockey League (NHL) prior to the entry draft were administered tests to measure upper body strength, lower body power, aerobic and anaerobic energy systems, and body composition. Their common variance was extracted using factor analysis from which an overall composite index was derived. A score on this index in the 90th percentile is associated with 72% and 60% probability of playing in the NHL within 4 years after the draft for defensemen and forwards, respectively. These findings demonstrate that by taking into account the shared variance on standard tests of fitness, it is possible to use the athlete's results to gauge his potential for playing in the NHL.
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Hockey/fisiología , Aptitud Física/fisiología , Umbral Anaerobio/fisiología , Rendimiento Atlético/fisiología , Fuerza de la Mano/fisiología , Humanos , Fuerza Muscular/fisiología , Valor Predictivo de las Pruebas , Entrenamiento de Fuerza , Levantamiento de Peso/fisiologíaRESUMEN
A case of a urethral diverticulum following the insertion of a tension-free vaginal tape (TVT) is presented. The patient was a woman with stress urinary incontinence who underwent surgery to correct intrinsic sphincter deficiency. Three cases of urethral diverticula have been published thus far as complications of TVT insertions, but this is the first complication associated with intrinsic sphincter deficiency. The high pressures in the proximal urethra that result from positioning the TVT in the middle urethra, especially when obstruction co-exists with an open bladder neck, can be a predisposing factor for this complication. The possibility of a urethral diverticulum when postvoid incontinence occurs after the insertion of a TVT should be carefully evaluated.
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Divertículo/cirugía , Cabestrillo Suburetral/efectos adversos , Incontinencia Urinaria de Esfuerzo/cirugía , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Uretra/cirugía , Enfermedades Uretrales/cirugía , Vejiga Urinaria/patología , Vejiga Urinaria/cirugíaRESUMEN
The primary purpose of this study was to determine the fitness variables with the highest capability for predicting hockey playing potential at the elite level as determined by entry draft selection order. We also examined the differences associated with the predictive abilities of the test components among playing positions. The secondary purpose of this study was to update the physiological profile of contemporary hockey players including positional differences. Fitness test results conducted by our laboratory at the National Hockey League Entry Draft combine were compared with draft selection order on a total of 853 players. Regression models revealed peak anaerobic power output to be important for higher draft round selection in all positions; however, the degree of importance of this measurement varied with playing position. The body index, which is a composite score of height, lean mass, and muscular development, was similarly important in all models, with differing influence by position. Removal of the goalies' data increased predictive capacity, suggesting that talent identification using physical fitness testing of this sort may be more appropriate for skating players. Standing long jump was identified as a significant predictor variable for forwards and defense and could be a useful surrogate for assessing overall hockey potential. Significant differences exist between the physiological profiles of current players based on playing position. There are also positional differences in the relative importance of anthropometric and fitness measures of off-ice hockey tests in relation to draft order. Physical fitness measures and anthropometric data are valuable in helping predict hockey playing potential. Emphasis on anthropometry should be used when comparing elite-level forwards, whereas peak anaerobic power and fatigue rate are more useful for differentiating between defense.
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Rendimiento Atlético , Hockey/fisiología , Aptitud Física/fisiología , Adolescente , Adulto , Análisis de Varianza , Antropometría , Humanos , Masculino , Análisis de RegresiónRESUMEN
OBJECTIVE: To analyze and report the current data on the treatment of both neurogenic and idiopathic detrusor overactivity with Botulinum toxin. METHODS: Literature review using Pub-Med and Medline from 1990 until June 30, 2006. RESULTS: Case series of patients with neurogenic detrusor dysfunction (NDD) and idiopathic detrusor overactivity (IDO) range from 15 to 200 patients with follow up from 12 to 36 weeks post-treatment. Significant improvements in cystometric bladder capacity, reflex volume at first urge to void, and bladder compliance are seen in nearly all patients. Approximately 50% of NDD patients achieved urinary continence and almost all had improvement in bladder control up to 36 weeks following treatment. Patients with IDO with urgency alone or with incontinence also had urodynamic as well as symptom improvement. Approximately 75% of patients with IDO and incontinence are dry at 12 weeks post-treatment. Urgency disappears on average in two thirds of patients. Quality of life scores also shows significant improvement for all groups. CONCLUSION: Botulinum toxin-A has emerged as a promising option for the treatment of neurogenic and refractory idiopathic detrusor overactivity. Studies to date have shown that not only is this treatment effective at decreasing urinary symptoms and incontinence, as well as improving potentially dangerous urodynamic measures, but it is also minimally invasive, reversible and safe. Questions over proper dosing and dilution, number of injection sites, and re-injection rates remain to be answered.
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Toxinas Botulínicas/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Incontinencia Urinaria/tratamiento farmacológico , Femenino , Humanos , Calidad de Vida , Resultado del TratamientoRESUMEN
Carcinogenic potential of the thiazolidinedione antidiabetic troglitazone was assessed in 104-week studies in mice and rats. Mice were given 50, 400, or 800 mg/kg, male rats 100, 400, or 800 mg/kg, and female rats 25, 50, or 200 mg/kg. Vehicle and placebo controls were included. Survival was significantly decreased in both sexes of both species at high doses, but was adequate for valid evaluation of carcinogenicity. Hypertrophy and hyperplasia of brown adipose tissue was observed in both species at all doses, and fatty change and hypocellularity of bone marrow was noted in mice at all doses and in female rats at 50 and 200 mg/kg. Hepatocellular vacuolation was observed in mice at 400 and 800 mg/kg, and centrilobular hepatocellular hypertrophy occurred in rats at > or = 200 mg/kg. Ventricular dilatation, myocardial fibrosis, and atrial myocyte karyomegaly in male rats at 400 and 800 mg/kg and female rats at all doses were morphologically similar to spontaneous lesions, but incidence and severity were increased compared with controls. In mice, the incidence of hemangiosarcoma was increased in females at 400 mg/kg and in both sexes at 800 mg/kg. The incidence of hepatocellular carcinoma was increased in female mice at 800 mg/kg. Troglitazone exposure [AUC((0-24))] at the lowest dose associated with increased tumor incidence in mice was 16 times human therapeutic exposure at 400 mg daily. No tumors of any type were increased in rats at exposures up to 47 times therapeutic exposure.
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Carcinógenos/toxicidad , Cromanos/toxicidad , Hipoglucemiantes/toxicidad , Tiazoles/toxicidad , Tiazolidinedionas , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/patología , Administración Oral , Animales , Área Bajo la Curva , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Pruebas de Carcinogenicidad , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Cromanos/administración & dosificación , Cromanos/farmacocinética , Relación Dosis-Respuesta a Droga , Corazón/efectos de los fármacos , Hemangiosarcoma/inducido químicamente , Hemangiosarcoma/patología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Longevidad/efectos de los fármacos , Ratones , Miocardio/patología , Ratas , Ratas Wistar , Especificidad de la Especie , Análisis de Supervivencia , Tiazoles/administración & dosificación , Tiazoles/farmacocinética , TroglitazonaRESUMEN
Immunomodulatory oligosaccharides found on helminths also are found in human milk, and both helminths and milk have been shown to be immunosuppressive. We have been examining the immunomodulatory capabilities of two oligosaccharides expressed in milk and on helminth parasites, lacto-N-fucopentaose III and lacto-N-neotetraose (LNnT). In an attempt to dissect mechanisms that lead to Th2 polarization and immune suppression, we examined the early response in mice to the glycoconjugate LNnT-Dextran (LNnT-Dex). We found that injection of LNnT-Dex expanded a cell population, phenotypically defined as Gr1(+)/CD11b(+)/F4/80(+), as early as 2 h after injection. Examination of spontaneous cytokine production showed that this Gr1(+)/F4/80(+) population of cells spontaneously produced low levels of proinflammatory cytokines, but higher levels of IL-10 and TGF-beta ex vivo, compared to peritoneal cells from mice injected with Dex. Gr1(+) cells adoptively suppressed naive CD4(+) T cell proliferation in vitro in response to anti-CD3/CD28 Ab stimulation. Suppression of naive CD4(+) cells involved cell contact and was dependent on IFN-gamma and NO, with a discrete role played by IL-10. Coculture of naive CD4(+)T cells with Gr1(+) suppressor cells did not lead to CD4(+) T cell apoptosis, although it did imprint on naive CD4(+) T cells a response characterized by lower levels of IFN-gamma, coincident with increased IL-13 production. Our results suggest that both human milk and helminth parasites may share a ligand-specific mechanism involved in the generation of anti-inflammatory mediators that suppress Th1-type and inflammatory responses.
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Amino Azúcares/farmacología , Linfocitos T CD4-Positivos/inmunología , Citocinas/biosíntesis , Helmintiasis/inmunología , Inmunosupresores/farmacología , Activación de Linfocitos , Oligosacáridos/farmacología , Polisacáridos/farmacología , Animales , Antígenos CD28/fisiología , Comunicación Celular , Femenino , Antígeno de Macrófago-1/análisis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Óxido Nítrico/fisiologíaRESUMEN
Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (<20 h) expansion of the Gr1(+) subpopulation of F4/80(+)/CD11b(+) peritoneal cells, comprising up to 75% of F4/80(+)/CD11b(+) peritoneal cells compared with 18% in uninjected or dextran-injected mice. Functionally, these cells suppressed anti-CD3- and anti-CD28-induced proliferation of naive CD4(+) T cells. LNFPIII-dextran also expanded functional Gr1(+) suppressor macrophages in SCID mice, demonstrating that expansion and function of suppressor cells did not require T cells. Suppression in both BALB/c and SCID mice was NO and IFN-gamma dependent, as addition of inhibitors of inducible NO synthase (N(G)-monomethyl-L-arginine), as well as anti-IFN-gamma Abs, restored the ability of CD4(+) T cells to proliferate in vitro. Depletion of the F4/80(+) subset of Gr1(+) cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1(+) suppressor macrophage population in the peritoneal cavities of otherwise naive mice. These Gr1(+) cells suppress proliferation of naive CD4(+) T cells in an NO-dependent mechanism, and may play a regulatory role in the switching of Th1- to Th2-type responses.
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Amino Azúcares/inmunología , Antígenos Helmínticos/inmunología , Linfocitos T CD4-Positivos/inmunología , Inmunosupresores/inmunología , Macrófagos Peritoneales/inmunología , Polisacáridos/inmunología , Schistosoma mansoni/inmunología , Animales , Antígenos de Diferenciación , Antígenos CD28 , Complejo CD3 , División Celular , Interferón gamma/metabolismo , Activación de Linfocitos , Macrófagos Peritoneales/citología , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Óxido Nítrico/metabolismo , Transducción de SeñalRESUMEN
PURPOSE: We determined the actuarial revision rate for artificial urinary sphincters implanted in patients who were incontinent after radical prostatectomy. MATERIALS AND METHODS: We reviewed the records of 70 consecutive patients who were incontinent after radical prostatectomy and who underwent primary artificial urinary sphincter implantation at the University of Michigan between 1984 and 1999. Questionnaires were mailed to all patients with an indwelling device, and telephone calls were placed to those who did not respond to the mailing. Information about surgical revision and current continence status was obtained from chart review and questionnaire response. The Kaplan-Meier curves for actuarial freedom from operative revision were constructed. RESULTS: Of the 66 patients with available postoperative data 24 (36%) required reoperation at a mean followup of 41 months. The 5-year actuarial rate for freedom from any operative revision was 50%, and the corresponding rate for cuff revision was 60%. A single operative revision did not predispose the patient to further revision. Questionnaire data indicated a continence rate of 80% (range 0 to 2 pads). CONCLUSIONS: Approximately half of the patients who were incontinent after radical prostatectomy may expect to undergo operative revision within 5 years after artificial urinary sphincter implantation. Despite this high reoperation rate, an excellent level of continence is maintained.
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Prostatectomía/efectos adversos , Incontinencia Urinaria/etiología , Incontinencia Urinaria/cirugía , Esfínter Urinario Artificial , Análisis Actuarial , Anciano , Estudios de Seguimiento , Humanos , Masculino , Reoperación/estadística & datos numéricosRESUMEN
The contribution of the bone marrow to in vivo erythropoietin (EPO) elimination was evaluated by determining EPO pharmacokinetic (PK) parameters in five adult sheep in a paired manner before and after chemotherapy-induced marrow ablation. After busulfan-induced bone marrow ablation, EPO PK demonstrated progressive decreases in plasma clearance (CL), elimination half-life [t1/2(beta)], and volume of distribution at steady state (Vss) with concomitant increases in mean residence time (MRT). Eight days after beginning busulfan treatment, there were no further changes in CL, t1/2(beta), MRT, and Vss. Only 20% of baseline CL remained by day 8. The volume of distribution (Vc) and distribution half-life [t1/2(alpha)], in contrast, remained unchanged from baseline. White blood cell counts and reticulocytes gradually declined after the start of marrow ablation. Examination of bone marrow core biopsy samples obtained on day 10 revealed less than 10% of baseline marrow cellularity. No colony-forming unit erythroid (CFU-E) colonies were found after 6 days of incubation for bone marrow aspirates drawn at days 8 and 13 following busulfan treatment, whereas pre-busulfan aspirates yielded 29 CFU-E colonies per 10(5) cells in CFU-E cultures. Treatment of a sheep with 5-fluorouracil showed changes in PK parameters that were similar to the results from treatment with busulfan. The present study indicates that the bone marrow significantly contributes to the elimination of EPO in vivo.
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Antineoplásicos Alquilantes/farmacología , Médula Ósea/metabolismo , Busulfano/farmacología , Eritropoyetina/farmacocinética , Animales , Antimetabolitos Antineoplásicos/farmacología , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Fluorouracilo/farmacología , Semivida , Radioisótopos de Yodo , Proteínas Recombinantes , OvinosRESUMEN
A selective nonpeptide endothelin A (ETA) receptor antagonist, CI-1020, was administered to beagle dogs intravenously (i.v.) for 4 hours to 4 weeks. One animal/sex received CI-1020 at 1 mg/kg/hr intravenously for 4, 8, or 24 hours to investigate onset of arteriopathy. Control animals (1/sex) received the vehicle only. To determine reversibility of arteriopathy, 8 dogs/sex were given CI-1020 at 1 mg/kg/hr for 4 days. Two dogs/sex were sacrificed 1, 3, 8, and 29 days following cessation of infusion. Lesion development with prolonged exposure was investigated in 1 male dog. It was given CI-1020 by i.v. bolus at 120 mg/kg/day for 4 weeks and Monastral blue dye was administered i.v. to facilitate localization of vascular lesions. Coronary blood flow was determined in 4 dogs infused with CI-1020 at 0.3, 3, and 30 mg/kg for one hour at each dose. Macroscopically, hemorrhage or blue discoloration of Monastral blue was noted in the extramural coronary arteries along the coronary groove and atrium. Histologically, the earliest coronary changes were noted in animals sacrificed after 24 hours of treatment and characterized by medial hemorrhage and necrosis with a few infiltrating neutrophils. In the reversibility study, incidence and severity of arteriopathy was dependent on time of sacrifice following cessation of infusion. Acute necrotizing inflammation of arteries was present in all animals (n = 4) on day 1 postinfusion, whereas on day 8 postinfusion, lesions characterized by medial small pockets of trapped red cells, cell debris, and adventitial thickening were seen in 1 dog/sex. By day 29 postinfusion, coronary arteries were similar to controls. In the dog given daily i.v. bolus injections of CI-1020 for 4 weeks, arterial inflammatory lesions varied from acute to chronic, although most lesions were considered chronic active. Monastral blue pigments were noted in the wall of most arteries with chronic or chronic active lesions. Acute lesions were similar to those noted in day 1 postinfusion of the reversibility study. Medial smooth muscle necrosis and/or fibrosis with mixed inflammatory cell infiltrates characterized chronic or chronic active lesions. Smooth muscle proliferation and migration into the intima were also noted. There were no significant changes in coronary blood flow, coronary vascular resistance, or mean arterial blood pressure following CI-1020 infusion for 3 hours. In the 24-hour infusion study, plasma endothelin 1 (ET-1) levels were mildly elevated (1.5-4 fold) during CI-1020 infusion when compared to either pretest or control values. These results indicate that administration of endothelin antagonist (CI-1020) to dogs was associated with development of coronary arteriopathy, which was completely resolved within 29 days following cessation of treatment. With prolonged (4-week) CI-1020 treatment, arterial lesions at varying stages of development (acute, chronic active, chronic) were seen, suggesting that tolerance to treatment (up to 4 weeks) does not occur.
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Enfermedad Coronaria/inducido químicamente , Vasos Coronarios/efectos de los fármacos , Dioxoles/toxicidad , Antagonistas de los Receptores de Endotelina , Actinas/análisis , Animales , Arterias/efectos de los fármacos , Arterias/patología , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Enfermedad Coronaria/patología , Vasos Coronarios/patología , Dioxoles/administración & dosificación , Perros , Relación Dosis-Respuesta a Droga , Femenino , Corazón/efectos de los fármacos , Hemorragia/inducido químicamente , Hemorragia/patología , Técnicas para Inmunoenzimas , Inyecciones Intravenosas , Masculino , Miocardio/química , Miocardio/patología , Receptor de Endotelina A , Factores de Tiempo , Túnica Media/efectos de los fármacos , Túnica Media/patologíaRESUMEN
PURPOSE: Many surgical procedures to improve outlet resistance in children with neuropathic bladders are obstructive and increase the detrusor leak point pressure. In contrast, fascial slings are designed to achieve continence by increasing the Valsalva or stress leak point pressure without altering the detrusor leak point pressure. We evaluate the effectiveness of fascial slings in achieving continence in pediatric patients with neuropathic bladder. MATERIALS AND METHODS: From October 1994 until February 1999, 10 females and 8 males with neuropathic bladder secondary to myelodysplasia or traumatic spinal cord injury underwent fascial sling procedures. Mean patient age was 14 years (range 8 to 18) and all were incontinent despite aggressive medical management. Urodynamic evaluation was performed preoperatively and postoperatively. Specific urodynamic measurements included detrusor leak point pressure, stress leak point pressure and detrusor compliance. Compliance was only compared in the 12 nonaugmented cases. RESULTS: With a mean followup of 21.2 months (range 6 to 57), preoperative and postoperative urodynamics revealed little change in mean detrusor leak point pressure (23.2 versus 23.22 cm. H2O) but a substantial increase in mean stress leak point pressure (41.6 versus 64.5 cm. H2O). Mean compliance was unchanged in the nonaugmented group (22.00 versus 26.78 ml/cm. H2O). Four patients (22.22%) remained wet after surgery, of whom 2 were successfully treated with a repeat sling procedure and 1 with collagen injection for an overall continence rate of 94.44%. CONCLUSIONS: Fascial slings can be effectively used in pediatric patients for neuropathic incontinence. Furthermore, stress urinary incontinence is corrected by increasing the Valsalva or stress leak point pressure with preservation of the detrusor leak point pressure. Preservation of detrusor leak point pressure is particularly advantageous because other forms of bladder outlet procedures achieve continence at the expense of increasing detrusor pressures, thus placing the upper tracts at risk for damage.