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1.
Radiol Case Rep ; 19(6): 2483-2486, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38577129

RESUMEN

A 51-year-old woman presented to her local emergency department with acute onset right-sided flank pain and nausea. Her blood results on admission were largely unremarkable aside from leucocytosis and neutrophilia. Two days after admission, she developed the following: stage 3 AKI with oliguria, anaemia, thrombocytopenia, and acute derangement of liver function tests. A computed tomography of the kidney ureter bladder demonstrated a right-sided 4 mm obstructing vesicoureteric junction stone with associated hydronephrosis and hydroureter. She was transferred to a tertiary care centre; gram negative sepsis was confirmed with a Proteus on blood culture and laboratory findings were in keeping with DIC. She was treated with Tazobactam/Piperacillin and intravenous fluids. In addition, further imaging showed improving right-sided hydronephrosis and left renal cortical necrosis. The aetiology of this presentation was sepsis complicated by disseminated intravascular coagulation. The coagulopathy likely contributed to the unilateral renal cortical necrosis. Cortical necrosis usually affects both kidneys, and is typically a complication of sepsis, shock, or obstetrical trauma. To our knowledge, there are only 2 reported cases of unilateral renal cortical necrosis and contralateral hydronephrosis with renal colic and septic shock. Potential pathogenetic mechanisms are discussed.

2.
Cancers (Basel) ; 16(6)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38539462

RESUMEN

BACKGROUND: Vasomotor symptoms (VMSs) associated with menopause represent a significant challenge for many patients after cancer treatment, particularly if conventional menopausal hormone therapy (MHT) is contraindicated. METHODS: The Menopause after Cancer (MAC) Study (NCT04766229) was a single-arm phase II trial examining the impact of a composite intervention consisting of (1) the use of non-hormonal pharmacotherapy to manage VMS, (2) digital cognitive behavioral therapy for insomnia (dCBT-I) using Sleepio (Big Health), (3) self-management strategies for VMS delivered via the myPatientSpace mobile application and (4) nomination of an additional support person/partner on quality of life (QoL) in women with moderate-to-severe VMS after cancer. The primary outcome was a change in cancer-specific global QoL assessed by the EORTC QLC C-30 v3 at 6 months. Secondary outcomes included the frequency of VMS, the bother/interference of VMS and insomnia symptoms. RESULTS: In total, 204 women (82% previous breast cancer) with a median age of 49 years (range 28-66) were recruited. A total of 120 women completed the protocol. Global QoL scores increased from 62.2 (95%CI 58.6-65.4) to 70.4 (95%CI 67.1-73.8) at 6 months (p < 0.001) in the intention to treatment (ITT) cohort (n = 204) and from 62 (95%CI 58.6-65.4) to 70.4 (95%CI 67.1-73.8) at 6 months (p < 0.001) in the per-protocol (PP) cohort (n = 120). At least 50% reductions were noticed in the frequency of VMS as well as the degree of bother/interference of VMS at six months. The prevalence of insomnia reduced from 93.1% at the baseline to 45.2% at 6 months (p < 0.001). The Sleep Condition Indicator increased from 8.5 (SEM 0.4) to 17.3 (SEM 0.5) (p < 0.0005) in the ITT cohort and 7.9 (SEM 0.4) to 17.3 (SEM 0.5) (p < 0.001) in the PP cohort. CONCLUSIONS: A targeted composite intervention improves the quality of life for cancer patients with frequent and bothersome vasomotor symptoms with additional benefits on frequency, the bother/interference of VMS and insomnia symptoms.

3.
Trials ; 24(1): 89, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747246

RESUMEN

BACKGROUND: A cancer diagnosis is a known precipitant of psychological distress, with fear of recurrence being a well-documented distressing consequence of cancer. Cancer recurrence often results in an additional psychological burden, which may exacerbate as a result of the COVID-19 pandemic. METHODS: This is a single-centre, prospective, randomised controlled trial. Patients identified as having experienced cancer recurrence since March 2020 (the onset of the COVID-19 pandemic in Ireland) will be screened for participation. Eligible, consenting candidates who score 4 or higher on the Distress Thermometer will be enrolled in the study. Participants will be randomly allocated to receive either a 6-week, group-based, online, compassion-focussed therapy and breathing pattern retraining intervention or the control arm. Those in the control arm will all be offered the group intervention after the 18-week study period. The primary outcome is the Distress Thermometer score at 18 weeks post-baseline though secondary outcomes will include measures of mood, traumatic distress and mental adjustment to cancer. DISCUSSION: To our knowledge, this protocol describes the first RCT which directly examines the effect of a group-based psychological intervention on Irish patients experiencing cancer recurrence in the context of COVID-19. The outcome of this trial is likely to be twofold: It will determine if the psychological intervention achieves its primary objective of distress amelioration 3 months post-intervention and to establish the feasibility of delivering this intervention in a virtual format. TRIAL REGISTRATION: ClinicalTrials.gov NCT05518591. Registered on 25 August 2022. All items from the World Health Organization Trial Registration Data set have been included.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Pandemias , Empatía , Estudios Prospectivos , Neoplasias/terapia , Respiración , Resultado del Tratamiento
4.
Ir J Med Sci ; 192(1): 45-55, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35141870

RESUMEN

BACKGROUND: Menopause may cause a constellation of symptoms that affect quality of life. Many women will have menopause induced or exacerbated by treatment for cancer whether that be through surgery, chemotherapy, radiotherapy, or anti-endocrine therapy. As treatments advance, the number of people living with and beyond a cancer diagnosis is set to increase over the coming years meaning more people will be dealing with the after effects of cancer and its treatment. AIMS: This review aims to summarise available data to guide clinicians treating women with menopausal symptoms after the common cancer diagnoses encountered in Ireland. The use of menopausal hormone therapy is discussed as well as non-hormonal and non-pharmacological options. CONCLUSIONS: Managing menopausal symptoms is an important consideration for all physicians involved in the care of people living with and beyond a cancer diagnosis. High-quality data may not be available to guide treatment decisions, and, thus, it is essential to take into account the impact of the symptoms on quality of life as well as the likelihood of recurrence in each individual case.


Asunto(s)
Neoplasias , Calidad de Vida , Femenino , Humanos , Irlanda , Menopausia , Neoplasias/tratamiento farmacológico
6.
HRB Open Res ; 5: 80, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37251362

RESUMEN

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease. There is a need for interoperable national registries to enable reporting of real-world long-term outcomes and their predictors in AAV. Methods: The Irish National Rare Kidney Disease (RKD) registry was founded in 2012. To date, 842 patients with various forms of vasculitis have been recruited across eight nephrology, rheumatology and immunology centres. We focus here on patient- and disease- characteristics, treatment and outcomes of the 397 prospectively recruited patients with AAV. Results: Median age was 64 years (IQR 55-73), 57.9% were male, 58.9% had microscopic polyangiitis and 85.9% had renal impairment. Cumulative one- and five-year patient survival was 94% and 77% respectively. Median follow-up was 33.5 months (IQR 10.7-52.7). After controlling for age, baseline renal dysfunction (p = 0.04) and the burden of adverse events (p <0.001) were independent predictors of death overall. End-stage-kidney-disease (ESKD) occurred in 73 (18.4%) patients; one- and five-year renal survival was 85% and 79% respectively. Baseline severity of renal insufficiency (p = 0.02), urine soluble CD163 (usCD163) (p = 0.002) and "sclerotic" Berden histological class (p = 0.001) were key determinants of ESKD risk. Conclusions: Long-term outcomes of Irish AAV patients are comparable to other reported series. Our results emphasise the need for personalisation of immunosuppression, to limit treatment toxicity, particularly in those with advanced age and renal insufficiency. Baseline usCD163 is a potential biomarker for ESKD prediction and should be validated in a large independent cohort.

7.
Contemp Clin Trials Commun ; 24: 100865, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34869938

RESUMEN

AIMS: This study will aim to assess if a composite intervention which involves a specific evidence-based intervention for management of insomnia and non-hormonal pharmacotherapy to manage vasomotor symptoms (VMS) of menopause can improve quality of life for patients experiencing troublesome VMS after cancer who are not eligible for standard systemic menopausal hormone therapy (MHT). Participants will be asked to nominate a partner or companion to support them during this process as an additional form of support. BACKGROUND: The menopause transition and its symptoms represent a significant challenge for many patients after cancer treatment, particularly those for whom conventional MHT is contraindicated. These symptoms include hot flushes, night sweats, urogenital symptoms as well as mood and sleep disturbance. These symptoms can exacerbate the consequences of cancer and its treatment. METHODS: We will recruit 205 women who meet inclusion criteria and enrol them on a composite intervention which consists of four parts: (1) use of non-hormonal pharmacotherapy for the management of troublesome vasomotor symptoms of menopause tailored to the timing of predominant symptoms, (2) digital cognitive behavioural therapy for insomnia through the web based Sleepio service, (3) access to information regarding self-management strategies for the common symptoms of menopause and their consequences and (4) identification of a partner or other support person who commits to providing support during the study period. OUTCOMES: The primary outcome will be cancer specific quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). Secondary outcomes will include sleep quality, bother/interference of vasomotor symptoms and communication between couples about their cancer diagnosis and their menopause experience. Sleep will be measured using the Sleep Condition Indicator (SCI) tool, bother/interference of vasomotor symptoms will be measured by the Hot Flush Rating Scale (HFRS) and communication will be measured using the Couples' Illness Communication Scale (CICS). These validated scales will be administered at baseline, four weeks, three months and six months. REGISTRATION: This study is registered on ClinicalTrials.gov with number NCT04766229.

8.
Front Med (Lausanne) ; 8: 642318, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34513853

RESUMEN

Objective: We aimed to use SARS-CoV-2 antibody tests to assess the asymptomatic seroprevalence of individuals in high-risk hospital cohorts who's previous COVID-19 exposure is unknown; staff, and patients requiring haemodialysis or chemotherapy after the first wave. Methods: In a single Center, study participants had five SARS-CoV-2 antibody tests done simultaneously; one rapid diagnostic test (RDT) (Superbio Colloidal Gold IgM/IgG), and four laboratory tests (Roche Elecsys® Anti-SARS-CoV-2 IgG [RE], Abbott Architect i2000SR IgG [AAr], Abbott Alinity IgG [AAl], and Abbott Architect IgM CMIA). To determine seroprevalence, only positive test results on laboratory assay were considered true positives. Results: There were 157 participants, of whom 103 (65.6%) were female with a median age of 50 years (range 19-90). The IgG component of the RDT showed a high number of false positives (n = 18), was inferior to the laboratory assays (p < 0.001 RDT vs. AAl/AAr, p < 0.001 RDT vs. RE), and had reduced specificity (85.5% vs. AAl/AAr, 87.2% vs. RE). Sero-concordance was 97.5% between IgG laboratory assays (RE vs. AAl/AAr). Specificity of the IgM component of the RDT compared to Abbott IgM CMIA was 95.4%. Ten participants had positivity in at least one laboratory assay, seven (9.9%) of which were seen in HCWs. Two (4.1%) hematology/oncology (H/O) patients and a single (2.7%) haemodialysis (HD) were asymptomatically seropositive. Asymptomatic seroprevalence of HCWs compared to patients was not significant (p = 0.105). Conclusion: HCWs (9.9%) had higher, although non-significant asymptomatic seroprevalence of SARS-CoV-2 antibodies compared to high-risk patients (H/O 4.1%, HD 2.7%). An IgM/IgG rapid diagnostic test was inferior to laboratory assays. Sero-concordance of 97.5% was found between IgG laboratory assays, RE vs. AAl/AAr.

9.
Kidney Int Rep ; 5(11): 1945-1955, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33163715

RESUMEN

INTRODUCTION: The standard low-phosphorus diet restricts pulses, nuts, and whole grains and other high phosphorus foods to control hyperphosphatemia. We conducted a randomized controlled trial to evaluate the effectiveness, safety, and tolerability of the modified diet, which introduced some pulses and nuts, increased the use of whole grains, increased focus on the avoidance of phosphate additives, and introduced the prescription of low-biological-value protein such as bread. METHODS: We conducted a multicenter, pragmatic, parallel-arm, open-label, randomized controlled trial of modified versus standard diet in 74 adults on hemodialysis with hyperphosphatemia over 1 month. Biochemistry was assessed using monthly laboratory tests. Dietary intake was assessed using a 2-day record of weighed intake of food, and tolerability was assessed using a patient questionnaire. RESULTS: There was no significant difference in the change in serum phosphate between the standard and modified diets. Although total dietary phosphorus intake was similar, phytate-bound phosphorus, found in pulses, nuts, and whole grains, was significantly higher in the modified diet (P < 0.001). Dietary fiber intake was also significantly higher (P < 0.003), as was the percentage of patients reporting an increase in bowel movements while following the modified diet (P = 0.008). There was no significant difference in the change in serum potassium or in reported protein intake between the 2 diets. Both diets were similarly well tolerated. CONCLUSION: The modified low phosphorus diet was well tolerated and was associated with similar phosphate and potassium control but with a wider food choice and greater fiber intake than the standard diet.

10.
Nephron ; 141(2): 87-97, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30415243

RESUMEN

BACKGROUND/AIMS: Three-day-a-week chronic haemodialysis (cHD) involves 1 long (72 h) and 2 short (48 h) inter-dialytic periods (IDPs). We aimed to determine whether BP control following the long IDP is inferior to the short IDPs. METHODS: All pre- and post-dialysis BP and weight measurements over a 4-week period were retrospectively analyzed among 135 clinically stable cHD patients at 2 academic centres with comparisons between measurements recorded following short and long IDPs. Subsequently, 23 clinically stable cHD patients underwent 24-h ambulatory blood pressure monitoring (ABPM) during the final day/night cycle of the long IDP and 1 short IDP within the same week. RESULTS: In combined and separate analyses of the 2 retrospective cohorts, pre-dialysis BP parameters were not different following long and short IDPs despite greater inter-dialytic weight gain (IDWG) during the long IDP. Subgroup analyses of the total cohort showed no evidence for inferior BP control during the long IDP among those with high %IDWG. In the ABPM study, nocturnal hypertension and loss of nocturnal dipping were frequent. Furthermore, daytime systolic blood pressure (SBP) and pulse pressure were modestly higher during the last day/night cycle of the long compared with short IDP. CONCLUSION: In stable cHD patients, the greater IDWG that occurred during the long IDP was not associated with overtly inferior BP control as reflected in pre-dialysis BP measurements. However, modestly higher daytime SBP was evident towards the end of the long IDP by 24 h ABPM. Thus, while fluid gain has well-documented associations with hypertension and adverse cardiovascular outcomes, the excess IDWG that occurs during the long IDP exerts relatively minor effects on BP control in patients on well-established dialysis regimens that are better identified by ambulatory monitoring.


Asunto(s)
Atención Ambulatoria , Presión Sanguínea , Hipertensión/prevención & control , Diálisis Renal , Aumento de Peso , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
Int J Stroke ; 12(7): 761-769, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28643553

RESUMEN

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.


Asunto(s)
Ataque Isquémico Transitorio/epidemiología , Riñón/metabolismo , Grupos de Población , Insuficiencia Renal Crónica/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Tasa de Filtración Glomerular , Humanos , Irlanda/epidemiología , Ataque Isquémico Transitorio/mortalidad , Riñón/patología , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/mortalidad , Accidente Cerebrovascular/mortalidad , Análisis de Supervivencia
12.
Biochem Biophys Res Commun ; 474(3): 579-586, 2016 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-27130823

RESUMEN

Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.


Asunto(s)
Apoptosis/fisiología , Hepatocitos/citología , Hepatocitos/fisiología , Prolina Dioxigenasas del Factor Inducible por Hipoxia/metabolismo , FN-kappa B/metabolismo , Procolágeno-Prolina Dioxigenasa/metabolismo , Animales , Hipoxia de la Célula/fisiología , Línea Celular , Regulación Enzimológica de la Expresión Génica/fisiología , Células HEK293 , Humanos , Ratones
13.
Nephrol Dial Transplant ; 28 Suppl 4: iv22-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24081855

RESUMEN

The interplay between chronic kidney disease (CKD) and obesity represents the convergence of two of the most common contemporary clinical issues, and is of particular interest and significance in the context of the burden presented by each at present, and the dismal projections associated with both of these conditions for the future. That obesity leads to CKD through its association with other risks, such as hypertension, type 2 diabetes mellitus and atherosclerosis, is well established; however, it is likely that obesity itself is an independent risk factor for the development of CKD. The aetiology of this obesity-related glomerulopathy (ORG) is not clear, but it appears to be strongly influenced by chronic inflammation, manifest as a disturbance of the balance between pro-inflammatory and pro-resolving lipid mediators, adipokines and mononuclear cells. This review examines the association between obesity and CKD, the role of inflammation therein, and the potential for pro-resolving lipid mediators to restore homoeostasis and offer therapeutic potential in ORG.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/etiología , Mediadores de Inflamación/metabolismo , Metabolismo de los Lípidos/fisiología , Obesidad/complicaciones , Animales , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Humanos , Obesidad/metabolismo
14.
Diabetes ; 58(7): 1641-50, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19401426

RESUMEN

OBJECTIVE: Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy. RESEARCH DESIGN AND METHODS: Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes. RESULTS: A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1(+/-) mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1(+/-) and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1(+/-) mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1. CONCLUSIONS: These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.


Asunto(s)
Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/prevención & control , Eliminación de Gen , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Albuminuria , Animales , Creatinina/sangre , Creatinina/orina , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Hemoglobina Glucada/metabolismo , Homeostasis , Péptidos y Proteínas de Señalización Intercelular/genética , Lípidos/sangre , Masculino , Ratones , Ratones Noqueados
15.
Am J Kidney Dis ; 45(6): 1034-9, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15957132

RESUMEN

BACKGROUND: We report the induction of gremlin, a bone morphogenetic protein antagonist, in cultured human mesangial cells exposed to high glucose and transforming growth factor beta (TGF-beta) levels in vitro and kidneys from diabetic rats in vivo. METHODS: Gremlin expression was assessed in human diabetic nephropathy by means of in situ hybridization, immunohistochemistry, and real-time polymerase chain reaction and correlated with clinical and pathological indices of disease. RESULTS: Gremlin was not expressed in normal human adult kidneys. Conversely, abundant gremlin expression was observed in human diabetic nephropathy. Although some gremlin expression was observed in occasional glomeruli, gremlin expression was most prominent in areas of tubulointerstitial fibrosis, where it colocalized with TGF-beta expression. Gremlin messenger RNA levels correlated directly with renal dysfunction, determined by means of serum creatinine level, but not with proteinuria level. There was a strong correlation between gremlin expression and tubulointerstitial fibrosis score. CONCLUSION: In aggregate, these results indicate that the developmental gene gremlin reemerges in the context of tubulointerstitial fibrosis in diabetic nephropathy and suggests a role for TFG-beta as an inducer of gremlin expression in this context.


Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Nefropatías Diabéticas/metabolismo , Regulación de la Expresión Génica , Mesangio Glomerular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Factor de Crecimiento Transformador beta/fisiología , Proteínas Morfogenéticas Óseas/genética , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Citocinas , Nefropatías Diabéticas/patología , Fibrosis , Regulación de la Expresión Génica/efectos de los fármacos , Mesangio Glomerular/patología , Glucosa/farmacología , Humanos , Hibridación in Situ , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Renales/metabolismo , Nefritis Intersticial/metabolismo , Proteínas , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta1
16.
Nephrol Dial Transplant ; 19(12): 3124-9, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15494354

RESUMEN

BACKGROUND: The utility of subjective measures of physical function as discriminative, evaluative and predictive tools in patients with ESRD is accepted, but objective performance tests also provide valuable information on patient status. The aims of this study were to determine what objective physical limitations exist in a select group of dialysis patients, designated as 'high-functioning' on the basis that they had low comorbidity and subjectively perceived themselves to function well, and to examine relationships between the objective and subjective measures. METHODS: Twelve patients (male, 7; female, 5) aged 18-55 years, with scores of > or = 75 points in the Short Form-36 Physical Function scale (PF) and low comorbidity (Charlson score < or = 2) were recruited for comparison with age and sex-matched sedentary controls. Objective performance measures included vibration perception threshold (VPT), peak quadriceps isokinetic and isometric muscle torque, time to reach peak isometric torque, balance (body sway with eyes open and closed), temporal gait parameters and the sit to stand test (STST). RESULTS: Dialysis patients demonstrated significant deficits by comparison with controls in subjective PF score (P < 0.001), VPT (P < 0.01), quadriceps isometric and isokinetic torque (P < 0.05, P < 0.005), body sway with eyes open (P < 0.01) and closed (P < 0.05), self selected (P < 0.005) and maximum (P < 0.01) walk speed, duration of gait cycle (P < 0.05) and STST (P < 0.001). There was significant agreement between the subjective PF score and VTP (P < 0.01), isokinetic torque (P < 0.05), body sway with eyes open (P < 0.05) and closed (P < 0.05), self-selected walk speed (P < 0.01) and STST (P < 0.01). CONCLUSIONS: Subtle but significant deficits in subjective and objective physical function existed even in this select group of dialysis patients. These findings define in more detail the underlying neuromuscular impairments and support the early implementation of active targeted rehabilitation programmes. The subjective and objective measures used here offer a useful panel of tests for clinical use in high-functioning dialysis patients.


Asunto(s)
Fallo Renal Crónico/terapia , Actividad Motora/fisiología , Terapia de Reemplazo Renal/efectos adversos , Adolescente , Adulto , Femenino , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Terapia de Reemplazo Renal/psicología
17.
Nephrol Dial Transplant ; 19(11): 2778-83, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15340098

RESUMEN

BACKGROUND: Acute interstitial nephritis (AIN) is a recognized cause of reversible acute renal failure characterized by the presence of an interstitial inflammatory cell infiltrate. METHODS: In order to evaluate the clinical characteristics and management of this disorder, we performed a retrospective study of all cases of AIN found by reviewing 2598 native renal biopsies received at our institution over a 12 year period. Presenting clinical, laboratory and histological features were identified, as was clinical outcome with specific regard to corticosteroid therapy response. RESULTS: AIN was found in 2.6% of native biopsies, and 10.3% of all biopsies performed in the setting of acute renal failure during the period analysed (n = 60). The incidence of AIN increased progressively over the period observed from 1 to 4% per annum. AIN was drug related in 92% of cases and appeared to be idiopathic in the remainder. The presenting symptoms included oliguria (51%), arthralgia (45%), fever (30%), rash (21%) and loin pain (21%). Median serum creatinine at presentation was 670 micromol/l [interquartile range (IQR) 431-1031] and 58% of cases required acute renal replacement therapy. Corticosteroid therapy was administered in 60% of cases. Serum creatinine at baseline was similar in the corticosteroid-treated and conservatively managed groups; 700 micromol/l (IQR 449-1031) vs 545 micromol/l (IQR 339-1110) P = 0.4. In this, the largest retrospective series to date, we did not detect a statistically significant difference in outcome, as determined by serum creatinine, between those patients who received corticosteroid therapy and those who did not, at 1, 6 and 12 months following presentation. CONCLUSION: The results of this study do not support the routine administration of corticosteroid therapy in the management of AIN.


Asunto(s)
Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Nefritis Intersticial/tratamiento farmacológico , Enfermedad Aguda , Anciano , Biopsia , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/patología , Estudios Retrospectivos , Resultado del Tratamiento
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