RESUMO
BACKGROUND: Although occupational injuries among building construction workers are a major public health concern, limited studies have focused on the prevalence and factors associated with injuries among building construction workers in sub-Saharan Africa. Accordingly, this study investigates the prevalence and factors associated with occupational injuries among building construction workers in the Gambia. METHOD: Using a cross-sectional design, 504 building construction workers with more than 12 months of work experience in the construction industry and aged ≥18 years were recruited from 22 registered companies in the Kanifing Municipality of the Gambia. Data were collected using a structured questionnaire and an observational checklist. RESULTS: More than 56% of the building construction workers reported sustaining work-related injuries in the past 12 months. Majority of injuries reported were abrasions/lacerations (28.2%), followed by cuts (26.6%), backaches (23.8%) and piercing/punctured wounds (22.8%). Results of the multivariate logistic regression analysis showed that being male worker (adjusted OR (aOR), 3.06; 95% CI 1.31 to 7.19), had <8 hours of work daily (aOR 3.46, 95% CI 1.44 to 7.78), smoke tobacco (aOR 1.97; 95% CI 1.36 to 2.85) and consume alcohol (aOR 0.27; 95% CI 0.08 to 0.95) were significantly associated with injuries from building construction work. CONCLUSION: Our findings show that injuries among building construction workers are prevalent in the Gambia. Male gender, work hours, tobacco use and alcohol consumption were associated with occupational injuries in building construction. Introducing and enforcing workplace safety policies in the building construction industry may help reduce occupational injury among construction workers in the Gambia.
Assuntos
Indústria da Construção , Traumatismos Ocupacionais , Humanos , Masculino , Adolescente , Adulto , Feminino , Traumatismos Ocupacionais/epidemiologia , Traumatismos Ocupacionais/prevenção & controle , Prevalência , Estudos Transversais , Gâmbia/epidemiologiaRESUMO
ABSTRACT: Adhitya, IPGS, Yu, W-Y, Bass, P, Kinandana, GP, and Lin, M-R. Effects of Kinesio taping and transcutaneous electrical nerve stimulation combined with active stretching on hamstring flexibility. J Strength Cond Res 36(11): 3087-3092, 2022-Active stretching (AS), Kinesio taping (KT), and transcutaneous electrical nerve stimulation (TENS) are frequently used to ameliorate pain and improve the ranges of motion (ROM) of athletes; however, the effectiveness of KT and TENS combined with AS in ameliorating short hamstring syndrome is yet to be determined. In this single-blinded randomized trial, 135 male soccer players with bilateral short hamstring syndrome were assigned to 3 intervention groups-AS, KT + AS, and TENS + AS-through block randomization. Each subject received the intervention twice per week for 4 weeks. The ROM of both legs was assessed through passive knee extension and straight leg raising tests at baseline and the end of the intervention. After the 4-week intervention, significant ROM changes in both legs were detected in the AS (9.5°-18.4°), KT + AS (14.9°-22.4°), and TENS + AS (14.9°-22.3°) groups. Compared with the AS group, both the KT + AS (3.8°-5.7°) and TENS + AS (3.9°-5.7°) groups showed significantly increased ROM in both legs over the intervention period, and no significant differences were observed in ROM changes between the KT + AS and TENS + AS groups. In conclusion, both KT and TENS in combination with AS may increase ROM more than AS alone, and the improvements obtained using KT with AS and TENS with AS may be similar.
Assuntos
Fita Atlética , Músculos Isquiossurais , Exercícios de Alongamento Muscular , Estimulação Elétrica Nervosa Transcutânea , Humanos , Masculino , Amplitude de Movimento Articular/fisiologiaRESUMO
Renal risk stratification in systemic immunoglobulin light-chain (AL) amyloidosis is according to estimated glomerular filtration rate (eGFR) and urinary protein creatinine ratio (uPCR), the latter attributed to glomerular dysfunction, with proximal tubular dysfunction (PTD) little studied. Urinary retinol binding protein 4 (uRBP), a low molecular weight tubular protein and highly sensitive marker of PTD, was prospectively measured in 285 newly diagnosed, untreated patients with systemic AL amyloidosis between August 2017 to August 2018. At diagnosis, the uRBP/creatinine ratio (uRBPCR) correlated with serum creatinine (r = 0·618, P < 0·0001), uPCR (r = 0·422, P < 0·0001) as well as both fractional excretion of phosphate and urate (r = 0·563, P < 0·0001). Log uRBPCR at diagnosis was a strong independent predictor of end-stage renal disease {hazard ratio [HR] 2·65, [95% confidence interval (CI) 1·06-6·64]; P = 0·038}, particularly in patients with an eGFR >30 ml/min/1.73 m2 [HR 4·11, (95% CI 1·45-11·65); P = 0·008] and those who failed to achieve a deep haematological response to chemotherapy within 3 months of diagnosis [HR 6·72, (95% CI 1·83-24·74); P = 0·004], and also predicted renal progression [HR 1·91, (95% CI 1·18-3·07); P = 0·008]. Elevated uRBPCR indicates PTD and predicts renal outcomes independently of eGFR, uPCR and clonal response in systemic AL amyloidosis. The role of uRBPCR as a novel prognostic biomarker merits further study, particularly in monoclonal gammopathies of renal significance.
Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/urina , Nefropatias/urina , Rim/fisiopatologia , Proteínas Plasmáticas de Ligação ao Retinol/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT. CASE PRESENTATION: We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation. CONCLUSION: This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.
Assuntos
Amiloidose/complicações , Amiloidose/metabolismo , Endodesoxirribonucleases/genética , Exodesoxirribonucleases/genética , Peptídeos e Proteínas de Sinalização Intercelular/análise , Enzimas Multifuncionais/genética , Nefrite Intersticial/complicações , Nefrite Intersticial/genética , Adulto , Amiloidose/diagnóstico , Biópsia , Diagnóstico Precoce , Humanos , Cariótipo , Masculino , Mutação , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologiaRESUMO
BACKGROUND: Physical violence against women is a major public health problem in African countries; however, no studies have focused on factors associated with violent injuries to women in Africa. OBJECTIVES: A matched case-control study was conducted to investigate risk factors for injuries from physical violence against African women in The Gambia. METHODS: Over a 12-month study period, study participants were recruited from emergency departments of eight government-managed health care facilities. Cases were female patients aged ≥ 15 years who had been violently injured. Matched by the health facility, date of injury, sex, and age, a control patient for each case was selected from those injured due to nonviolent mechanisms. RESULTS: In total, 194 case-control pairs were recruited. Results of a conditional logistic regression showed that being a Fula (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.06-5.66), living in an extended family compound (OR 3.07; 95% CI 1.22-7.72), having six or more female siblings (OR 3.10; 95% CI 1.38-6.97), having been raised by grandparents (OR 3.34; 95% CI 1.06-10.51), and having been verbally (OR 3.04; 95% CI 1.56-5.96) or physically abused (OR 3.36; 95% CI 1.34-8.39) in the past 12 months were significantly associated with injury from physical violence. CONCLUSION: Most risk factors identified for violent injury among African women are unique to the studied geography. Violence prevention programs, if designed based on these identified risk factors, may be more effective for this population.
Assuntos
Abuso Físico/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Feminino , Gâmbia/epidemiologia , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Although intimate partner violence (IPV) against women is prevalent in sub-Saharan Africa, studies that investigated factors associated with IPV among Gambian women are limited. In this study, we examined the prevalence and factors associated with the different forms of IPV against Gambian women. We used a sample of 3,116 currently married women age (15 ~ 49 years) from The Gambia Demographic and Health Survey 2013. Logistic regression models were used to examine factors associated with Physical Violence (PV), Sexual Violence (SV), and Emotional Violence (EV). Over 40% (n = 1,248) of women reported at least one form of IPV. The prevalence of PV, SV and EV was 20.6%, 4.3%, and 15.1% respectively. Women married at age 18 ~ 24 (adjusted Odds Ratio [aOR]SV = 1.55), lived with 3 ~ 4 (aORPV = 1.69; aOREV = 2.10) and ≥5 (aORPV = 1.77; aOREV = 2.64) children, witnessed parental violence (aORPV = 1.66; aORSV = 2.75; aOREV = 2.25), partner's primary education (aORPV = 1.76), accused of unfaithfulness (aORPV = 2.42; aORSV = 3.62; aOREV4.10), and partner's alcohol consumption (aORPV = 2.56; ORSV = 3.91; aOREV = 2.82) are more likely to report IPV. Conversely, women who lived in Kerewan area (aORPV = 0.43; aORSV = 0.38; aOREV = 0.50), had high income (aORPV = 0.65), Wolof (aORPV = 0.68) and Jola (aORPV = 0.65) ethnicity and unemployed (aORPV = 0.59; aORSV = 0.56) were less likely to report IPV. Interventions to prevent IPV should focus on education on its effects, and programs that reject sociocultural practices as determinants of IPV.
Assuntos
Violência por Parceiro Íntimo/estatística & dados numéricos , Casamento/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Parceiros Sexuais/psicologia , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Feminino , Gâmbia/epidemiologia , Humanos , Violência por Parceiro Íntimo/etnologia , Violência por Parceiro Íntimo/psicologia , Casamento/etnologia , Casamento/psicologia , Pessoa de Meia-Idade , Prevalência , Angústia Psicológica , Fatores de Risco , Delitos Sexuais/psicologia , Adulto JovemRESUMO
While men are known to be at high risk of recurrent injuries from physical violence, the risk factors in African men have not been investigated. We conducted a matched case-control study to identify factors associated with recurrent injuries from physical violence in The Gambia. Eligible participants were injured male patients aged ≥ 15 years. Over the 12-month study period, 257 cases with recurrent injuries from physical violence, and 257 control patients each from two control groups (violence controls and nonviolence controls) were recruited from eight emergency rooms located in six districts of the Greater Banjul Metropolitan Area, The Gambia. The two control groups matched cases at the same health facility, date of injury, and age, in which violence controls (VCs) experienced only one violence-related injury in the past 12 months and nonviolence controls (NCs) experienced no violence-related injuries. Results of the multivariable conditional logistic regression showed that for both the VC and NC groups, a polygamous family (ORVC, 3.62; ORNC, 2.79), > 8 family members (ORVC, 5.60; ORNC, 4.81), being brought up by a family relative (ORVC, 5.17; ORNC, 2.11), having smoked cigarettes in the past week (ORVC, 3.53; ORNC, 4.03), and perceiving no family support (ORVC, 1.12; ORNC, 1.19) were significantly associated with the occurrence of recurrent violent injuries. Furthermore, compared to the NCs, three additional factors of > 2 male siblings (ORNC, 1.84), low household income (ORNC, 3.11), and alcohol consumption in the past week (ORNC, 4.66) were significantly associated with the occurrence of recurrent violent injuries. These findings may fill in a knowledge gap that will be beneficial for developing effective intervention programs to reduce recurrent injuries from physical violence among African men.
Assuntos
População Negra/estatística & dados numéricos , Violência/etnologia , Ferimentos e Lesões/etnologia , Adolescente , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/etnologia , Estudos de Casos e Controles , Fumar Cigarros/etnologia , Serviço Hospitalar de Emergência , Gâmbia/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Overweight and obese women are at risk of pregnancy and delivery complications. This study investigates the trend and association between maternal overweight and obesity on caesarean births in Malawi. METHODS: We utilised cross-sectional population-based Demographic Health Surveys (DHSs) data collected from mothers aged 18-49 years in 2004/05, 2010, and 2015/16 in Malawi. The outcome measure was caesarian birth within 5 years preceding the surveys. The main independent variable was maternal Body Mass Index (BMI) measured as weight in kilograms by height in meters squared (kg/m2) and categorized according to the World Health Organization (WHO) guidelines. Generalized estimating equations (GEE) regression models were constructed to analyze total samples of 6795, 4474 and 4363 in 2004/05, 2010 and 2015/16 respectively. RESULTS: There was an observed increase in the trend of caesarean births as well as maternal overweight and obesity from 2004 to 2015. The results of the multivariate analyses showed that maternal overweight (adjusted odds ratio [aOR] = 1.35; 95% Confidence Interval [CI] 1.01-1.83) in 2015/16 and (aOR = 1.36; 95% CI: 1.10-1.65) from 2004 to 2015 were risk factors for caesarean births in Malawi. In addition, being obese (aOR = 2.15; 95% CI: 1.12-4.11) in 2004/05, (aOR = 1.66; 95% CI: 1.08-2.55) in 2010, (aOR = 2.18; 95% CI: 1.48-3.21) in 2015/16, and (aOR = 2.16; 95% CI: 1.65-2.84) from 2004 to 2015) increased the risk of caesarean births. In addition, women who had one parity, and lived in the northern region were significantly more likely to have undergone caesarean birth. CONCLUSIONS: In order to reduce non-elective cesarean birth in Malawi, specific public health programs should be focus on reducing overweight and obesity among women of reproductive age. More focus attention may be given to women with one parity, particularly in the urban and the northern region of Malawi.
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Cesárea/estatística & dados numéricos , Obesidade/complicações , Sobrepeso/complicações , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Malaui , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Razão de Chances , Sobrepeso/epidemiologia , Paridade , Gravidez , Resultado da Gravidez , Prevalência , Fatores de RiscoRESUMO
Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5-15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5-9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined.
Assuntos
Amiloidose/diagnóstico , Amiloidose/mortalidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Falência Renal Crônica/patologia , Nefrectomia/mortalidade , Proteinúria/patologia , Adulto , Idoso , Amiloidose/metabolismo , Amiloidose/cirurgia , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/etiologia , Proteinúria/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Anti-glomerular basement membrane (GBM) antibodies are highly specific for Goodpasture's or anti-GBM disease, in which they are generally directed against the non-collagenous (NC1) domain of the alpha 3 chain of type IV collagen(α3(IV)), and less commonly, toward the α 4(IV) or α 5(IV) chains, which form a triple helical structure in GBM and alveolar basement membrane (ABM). Alterations in the hexameric structure of the NC1 (α3 (IV)), allows novel epitopes to be exposed and an immune response to develop, with subsequent linear antibody deposition along the GBM, leading to a crescentic glomerulonephritis. Positive anti-GBM antibodies are assumed to be pathogenic and capable of binding GBM in vivo, especially in the context of rapidly progressive glomerulonephritis. We have investigated patients with circulating anti-GBM antibodies, reactive to α3 (IV) and human GBM by immunoassays and Western blotting respectively, with focal necrotising crescentic glomerulonephritis but no linear GBM antibody deposition on immunohistochemistry. Three out of four were also ANCA positive. Despite not binding native GBM, patients' sera showed linear binding to primate glomeruli by indirect immunofluorescence, in the 2 cases tested. Following treatment, significant improvements in kidney function were found in 3/4 patients. CASE PRESENTATION: We present four patients with crescentic glomerulonephritis and circulating anti-GBM antibodies, but no glomerular binding. CONCLUSIONS: These novel findings, demonstrate that in some patients anti-GBM antibodies may not bind their own GBM. This has important implications for clinical diagnosis, suggesting that histological confirmation of kidney injury by anti-GBM antibodies should be obtained, as non-binding GBM antibodies may be associated with significant renal recovery.
Assuntos
Autoanticorpos/sangue , Glomerulonefrite/sangue , Glomerulonefrite/diagnóstico , Glomérulos Renais/patologia , Idoso , Feminino , Humanos , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The effect of maternal anemia on childhood hemoglobin status has received little attention. Thus, we examined the potential association between maternal anemia and childhood anemia (aged 6-59 months) from selected Southern Africa countries. METHODS: A cross-sectional study using nationally representative samples of children aged 6-59 months from the 2010 Malawi, 2011 Mozambique, 2013 Namibia, and 2010-11 Zimbabwe demographic and health surveys (DHS) was conducted. Generalized linear mixed models (GLMMs) were constructed to test the associations between maternal anemia and childhood anemia, controlling for individual and community sociodemographic covariates. RESULTS: The GLMMs showed that anemic mothers had increased odds of having an anemic child in all four countries; adjusted odds ratio (aOR = 1.69 and 95% confidence interval [CI]:1.37-2.13) in Malawi, (aOR = 1.71; 95% CI: 1.37-2.13) in Mozambique, (aOR = 1.55; 95% CI: 1.08-2.22) in Namibia, and (aOR = 1.52; 95% CI: 1.25-1.84) in Zimbabwe. Furthermore, the odds of having an anemic child was higher in communities with a low percentage of anemic mothers (aOR = 1.52; 95% CI: 1.19-1.94) in Mozambique. CONCLUSIONS: Despite the long-standing efforts to combat childhood anemia, the burden of this condition is still rampant and remains a significant problem in Southern Africa. Thus, public health strategies aimed at reducing childhood anemia should focus more on addressing infections, and micronutrient deficiencies both at individual and community levels in Southern Africa.
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Anemia/epidemiologia , Mães/estatística & dados numéricos , Adolescente , África Austral/epidemiologia , Pré-Escolar , Estudos Transversais , Demografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multinível , Fatores de Risco , Adulto JovemRESUMO
Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m2. We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m2, in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy.
Assuntos
Amiloide/metabolismo , Cadeias Leves de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Imunossupressores/uso terapêutico , Insuficiência Renal Crônica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Estimativa de Kaplan-Meier , Rim/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapiaRESUMO
OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. DESIGN: Prospective observational animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function. At predefined time points (3, 6, 12, 24, 48, 72 hr), animals (≥ 6 per group) underwent echocardiography, blood and urine sampling, and had kidneys taken for histological analysis. Comparison was made against sham-operated controls and naïve animals. MEASUREMENTS AND MAIN RESULTS: The systemic proinflammatory response was maximal at 6 hours, corresponding with the nadir of stroke volume. Serum creatinine peaked late (24 hr), when clinical recovery was imminent. Histological evidence of tubular injury and cell death was minimal. After a recovery period, all biomarkers returned to levels approaching those observed in sham animals. Apart from urine clusterin and interleukin-18, all other urinary biomarkers were elevated at earlier time points compared with serum creatinine. Urine neutrophil gelatinase-associated lipocalin was the most sensitive marker among those studied, rising from 3 hours. While serum creatinine fell at 12 hours, serum cystatin C increased, suggestive of decreased creatinine production. CONCLUSIONS: Novel information is reported on the temporal profile of a panel of renal biomarkers in sepsis in the context of systemic and renal inflammation and recovery. Insight into the pathophysiology of acute kidney injury is gleaned from the temporal change markers of renal injury (urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, calbindin), followed by a marker of cell cycle arrest (urine insulin-like growth factor-binding protein 7) and, finally, by functional markers of filtration (serum creatinine and cystatin C). These clinically relevant findings should have significant influence on future clinical testing.
Assuntos
Sepse/fisiopatologia , Animais , Biomarcadores , Moléculas de Adesão Celular/urina , Cistatina C/sangue , Modelos Animais de Doenças , Hemodinâmica , Mediadores da Inflamação/metabolismo , Testes de Função Renal , Lipocalina-2/urina , Lipocalinas/urina , Masculino , Estudos Prospectivos , Ratos , Ratos Wistar , Sepse/sangue , Sepse/urina , Fatores de TempoRESUMO
Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in the kidney, resulting in renal dysfunction. Fifty-three patients with biopsy-proven LCDD were prospectively followed at the UK National Amyloidosis Center. Median age at diagnosis was 56 years, and patients were followed for a median of 6.2 years (range, 1.1-14.0 years). Median renal survival from diagnosis by Kaplan-Meier analysis was 5.4 years, and median estimated patient survival was 14.0 years; 64% of patients were alive at censor. Sixty-two percent of patients required dialysis, and median survival from commencement of dialysis was 5.2 years. There was a strong association between hematologic response to chemotherapy and renal outcome, with a mean improvement in glomerular filtration rate (GFR) of 6.1 mL/min/year among those achieving a complete or very good partial hematologic response (VGPR) with chemotherapy, most of whom remained dialysis independent, compared with a mean GFR loss of 6.5 mL/min/year among those achieving only a partial or no hematologic response (P < .009), most of whom developed end-stage renal disease (ESRD; P = .005). Seven patients received a renal transplant, and among those whose underlying clonal disorder was in sustained remission, there was no recurrence of LCDD up to 9.7 years later. This study highlights the need to diagnose and treat LCDD early and to target at least a hematologic VGPR with chemotherapy, even among patients with advanced renal dysfunction, to delay progression to ESRD and prevent recurrence of LCDD in the renal allografts of those who subsequently receive a kidney transplant.
Assuntos
Cadeias Leves de Imunoglobulina , Falência Renal Crônica/etiologia , Paraproteinemias/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/mortalidade , Paraproteinemias/terapiaRESUMO
BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the treating physicians with the specific disorder. Yet, advances in genetics have tremendously enhanced our ability to establish specific and sometimes surprising diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome associated with intermittent hypoglycemic episodes, the specific cause for which remained elusive for over 30 years, despite numerous investigations, including three kidney and one liver biopsy. The most recent kidney biopsy showed dysmorphic mitochondria, suggesting a mitochondrial disorder. When her son presented with hypoglycemia in the neonatal period, he underwent routine genetic testing for hyperinsulinemic hypoglycemia, which revealed a specific mutation in HNF4A. Subsequent testing of the mother confirmed the diagnosis also in her. CONCLUSION: Modern sequencing technologies that test multiple genes simultaneously enable specific diagnoses, even if the underlying disorder was not clinically suspected. The finding of mitochondrial dysmorphology provides a potential clue for the mechanism, by which the identified mutation causes renal Fanconi syndrome.
Assuntos
Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/genética , Fator 4 Nuclear de Hepatócito/genética , Procurador , Síncope/diagnóstico , Síncope/genética , Adulto , Síndrome de Fanconi/complicações , Feminino , Seguimentos , Testes Genéticos/tendências , Humanos , Recém-Nascido , Masculino , Síncope/complicaçõesRESUMO
BACKGROUND: Minimal change disease (MCD) accounts for 10-15% of all adult nephrotic syndrome cases and requires normal renal histology by light microscopy and negative immunohistology. Foot process effacement on electron microscopy (EM) is typical. Renal amyloid deposits demonstrate pathognomonic green birefringence when viewed under cross-polarized light after staining tissue with Congo red (CR) and may reveal fibrils on EM. Late diagnosis and delayed treatment of renal amyloidosis negatively impact on renal and patient survival. METHODS: A retrospective analysis was performed on 2116 patients referred to the National Amyloidosis Centre between 2001 and 2013, in whom renal amyloidosis was confirmed histologically. Twenty-seven of these patients had renal histology initially interpreted to be MCD. RESULTS: Among 26 patients in whom biopsy specimens and/or reports were retrieved, the median age at MCD diagnosis was 62 years and presenting proteinuria averaged 7.8 g/24 h. The median time period between the two diagnoses was 241 days (range: 20-2632 days). MCD was diagnosed without CR in 17/26 (65%) biopsies, but all specimens contained amyloid on retrospective CR staining. MCD was diagnosed without EM in 17/26 (65%) cases and all of 10 such biopsies subsequently demonstrated fibrils. Sixteen patients were subjected to two or more renal biopsies when their proteinuria proved steroid refractory. CONCLUSION: This study highlights the need to stain renal biopsies from proteinuric adults with CR, examine them under cross-polarized light and perform EM wherever possible. If the suspicion of renal amyloidosis remains high, despite apparent negative histology, specimens should be reviewed at specialist centres before undertaking a second kidney biopsy.
Assuntos
Amiloidose/diagnóstico , Erros de Diagnóstico , Rim/ultraestrutura , Nefrose Lipoide/diagnóstico , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
Background: We examined the factors associated with knowledge of hypertension risk factors and symptoms among Gambian women. Methods: This cross-section study was based on 11, 865 female participants (aged 15-49 years) of The Gambia Demographic and Health Survey 2019-2020. We performed descriptive statistics, and multivariate-adjusted logistic regression models. Results: Only 34.89 % and 36.82 % of the participants knew at least one risk factor and symptom of hypertension, respectively. Women who had never measured their blood pressure had a reduced odds of knowing a hypertension risk factor (OR = 0.68; 95 %CI: 0.60---0.77; P < 0.01) and symptom (OR = 0.56; 95 %CI: 0.49---0.64; P < 0.01). Compared to women with higher education, those with no education had a lower odds of knowing a hypertension risk factor (OR = 0.18; 95 %CI: 0.12---0.27; P < 0.01) and symptom (OR = 0.32; 95 %CI: 0.23---0.45; P < 0.01). Similarly, women who never used the internet had reduced odds of mentioning a hypertension risk factor (OR = 0.55; 95 %CI: 0.48---0.61; P < 0.01) and symptom (OR = 0.61; 95 %CI: 0.54---0.69; P < 0.01). Those who never watched television had decreased odds of knowing a hypertension risk factor (OR = 0.74; 95 %CI: 0.63--0.86; P < 0.01) and symptoms (OR = 0.68; 95 %CI: 0.58---0.80; P < 0.01). Conclusion: Fewer women could mention at least one hypertension risk factor and symptom. We also found that knowledge of hypertension risk factors and symptoms was associated with education level and socio-economic status.
Assuntos
Adenina Fosforribosiltransferase/deficiência , Adenina/análogos & derivados , Rim/química , Erros Inatos do Metabolismo/complicações , Microscopia de Polarização , Insuficiência Renal Crônica/etiologia , Urolitíase/etiologia , Adenina/análise , Adenina Fosforribosiltransferase/genética , Adenina Fosforribosiltransferase/metabolismo , Idoso , Biópsia , Cristalização , Humanos , Rim/patologia , Masculino , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Urolitíase/complicações , Urolitíase/diagnóstico , Urolitíase/genética , Urolitíase/metabolismo , Urolitíase/patologiaRESUMO
We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA(27-35). We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2(+) patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2(-) control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4(+) and PSMA(27)-specific CD8(+) T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4(+) T-cell response and PSMA(27)-specific CD8(+) T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4(+) and CD8(+) vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA(27) vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing.