Does mitochondrial genome mutation in subjects with maternally inherited diabetes and deafness decrease severity of diabetic retinopathy?

Two types of retinopathy, diabetic and pigmentary, may be seen in subjects with maternal inheritance diabetes and deafness. The potential for interactions between the two retinopathies has not been explored. The mitochondrial mutation may affect development of diabetic retinopathy in subjects with MIDD by altering normal pathways of glucose metabolism. We identified five unrelated MIDD kindreds with 61 living maternal line family members. Twenty-three of the family members, 12 with diabetes mellitus and 11 without volunteered to be studied. Subjects were graded for severity of diabetic retinopathy and presence or absence of pigmentary retinopathy after slit lamp biomicroscopy, retinal photography of seven standard fields and fluorescein angiography. Blood was taken, in the fasted state, from MIDD subjects (duration of diabetes 17.0 ± 6.9 yr) and non-diabetic subjects with the mutation, for assay of sorbitol and glucose and values compared with diabetic and non-diabetic control subjects without the mutation. Diabetic retinopathy was absent in 9/12 subjects (75 %), with 3 having mild non-proliferative retinopathy. No one had cataract. Red blood cell sorbitol levels, adjusted for ambient blood glucose, were significantly lower in MIDD subjects compared with diabetic subjects (1.16 ± 0.5 cf. 2.03 ± 1.1, × 10⁻³ g mmol⁻¹, p = 0.04). Pigmentary retinopathy was present in 15 of 23 subjects, of whom 13 had some abnormality of glucose tolerance. Abnormal glucose tolerance was strongly associated with the development of pigmentary retinopathy (odds ratio 19.5, p = 0.008). In conclusion, there appears to be a decreased prevalence of diabetic retinopathy and cataract in MIDD, which we propose is due to reduced glucose metabolism by the polyol pathway. Abnormal glucose tolerance increases the clinical expression of pigmentary retinopathy in subjects with a mitochondrial genome mutation. A greater understanding of the metabolic effects of mitochondrial DNA mutations has the potential to give insight into the mechanisms of diabetic retinopathy and other complications of diabetes mellitus. © 1998 John Wiley & Sons, Ltd.     

The prevalence of colorectal neoplasia in patients with end-stage renal disease: a case–control study

BACKGROUND AND PURPOSE: The scarcity of organs for transplantation has led to aggressive pretransplant evaluations. Many younger kidney transplant patients with end-stage renal disease, who would be ordinarily at average risk for colorectal cancer, undergo screening colonoscopy as part of this evaluation. The purpose of this study was to determine the prevalence of colorectal neoplasia in patients with end-stage renal disease who are potential transplant candidates. MATERIALS AND METHODS: We performed a retrospective chart review analysis on 57 kidney transplant candidates who underwent pretransplant screening colonoscopy between August 1999 and December 2004. The control group was comprised of 60 age- and gender-matched subjects without end-stage renal disease who underwent routine screening colonoscopy. RESULTS: The prevalence of polyps in end-stage renal disease patients was 37 vs 22% in the control group (p = 0.07, not significant). None of the risk factors studied were found to predict the presence of polyps in the study group. CONCLUSION: These results suggest that screening guidelines for colorectal cancer for the general population should be adequate for potential kidney transplant recipients.     

Small fibre dysfunction,microvascular complications and glycaemic control in type 1 diabetes: a case–control study

Aims/hypothesis  

The aim of this study was to determine the influence of microvascular disease on C-fibre function in patients with type 1 diabetes of moderate duration.     

Thyroid cancer in patients with acromegaly: a case–control study

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.     

Functioning and health-related quality of life in Chinese patients with systemic sclerosis: a case–control study

The objective of the study was to study the functioning and health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) and its associated factors. Consecutive SSc patients and an equal number of age- and gender-matched healthy controls were recruited for the assessment of functioning and HRQoL by the Health assessment questionnaire disability index (HAQ-DI) and Medical Outcomes Study Short Form 36 (SF-36), respectively. The extent of skin involvement of SSc was assessed by the modified Rodnan skin score (mRSS), and disease severity was assessed by the Medsger severity index. Factors associated with functioning and HRQoL in SSc patients were studied by linear regression. Seventy-eight Chinese SSc patients were studied (87 % women; age 50.2?±?12.1 years; disease duration 7.8?±?6.5 years; 81 % limited cutaneous subtype). The median mRSS of the patients was 8 (IQR 0–10). Patients with SSc had significantly higher HAQ-DI (0.69?±?0.69 vs 0.04?±?0.18; p?<?0.001) but lower SF36 scores (p?<?0.05 in all domains) than matched controls. Linear regression revealed that the mRSS was inversely associated with the physical component (beta?=??0.39; p?=?0.001) and mental component scores (beta?=??0.27; p?=?0.031) of the SF36 but positively correlated with the HAQ-DI score (beta?=?0.51; p?<?0.001) adjusted for age, sex, and disease duration. The SF36 and HAQ-DI scores also correlated significantly with the Medsger SSc severity index in the general, peripheral vascular, skin, tendon/joint, and heart domains. SSc patients had impaired physical and social functioning and poorer HRQoL than healthy individuals. The extent of skin involvement, tendon/joint contracture, damage in the heart, and peripheral vascular system were associated with poorer functioning and HRQoL.     

Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case–control study

Objective: To determine whether anorectal biofeedback therapy can improve the symptoms of fecal incontinence (FI) in patients with scleroderma when compared to patients with functional FI, and also whether there is any effect on anorectal physiology or quality of life (QOL). FI in patients with scleroderma is highly prevalent and is associated with significant loss of QOL. Biofeedback has been proven to be an effective treatment for functional FI, but there are no data to support its use in scleroderma.

Materials and methods: 13 consecutive female patients (median age 59, IQR 47–65 years) with scleroderma, and 26 age- and parity-matched female patients with functional FI (disease controls, 2:1), underwent biofeedback therapy for management of FI. Fecal incontinence severity index (FISI), anorectal physiology, feeling of control and QOL were collected before and after 6 weeks of biofeedback therapy, with additional scoring repeated at 6-month follow-up.

Results: After biofeedback treatment FISI, feeling of control and QOL significantly improved in both groups (p?p?Conclusions: Patients with scleroderma benefit from biofeedback therapy to the same extent as that achieved in patients with functional FI. There are significant improvements in symptoms, physiology and QOL. Biofeedback is an effective, low-risk treatment option in this patient group.     

Serum level of zinc in asthmatic patients: A case–control study

BackgroundHypozincemia could lead to a variety of defects in growth and the immune system, while it seems to be associated with increased rate of asthmatic attacks in children.MethodsThis study was performed to assess the serum zinc level in 100 paediatric asthmatic patients in comparison with a control group.ResultsMean serum level of zinc in the asthmatic patients was 70.5 ± 22.6 μg/dL, which was significantly lower than 80.9 ± 16.9 μg/dL in the control group (p < 0.001). Forty-two asthmatic patients (42%) had hypozincemia, while this rate was 12% in healthy children (p < 0.001). There was a significant association between the zinc level and severity of asthma (p < 0.001). However, no significant association was detected between the serum level of zinc and other factors, including control and treatment of the disease.ConclusionsAs for high rate of hypozincemia in the asthmatic children, evaluation of serum zinc level in asthmatic children could be suggested, while zinc substitution in the diet of those with hypozincemia could be recommended.     

Evaluation of some trace elements and antioxidants in sera of patients with rheumatoid arthritis: a case–control study

Clinical Rheumatology - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that destroys joints. The concentrations of elements (Zn, Cu, Mg, Mn, Fe, Ni, Cr, K, Na, Ca, Pb, and...     

Quality of life in subjects with type 2 diabetes mellitus with diabetic retinopathy: A case–control study

AimsDiabetic retinopathy (DR) as a common complication of Type 2 Diabetes Mellitus (T2DM) affecting negatively quality of life (QoL). Assessing of QoL in patients with DR is a prerequisite for the evaluation of their needs and for understanding the perception of the patients themselves about their health status and how the disease affects their lives. Additionally, QoL indicators detect individual psychosocial problems that may impact therapeutic response.Materials and methodsA total of 70 subjects with T2DM and DR as well as 70 T2DM individuals without DR were included. For the evaluation of QoL we used (a) WHO QoL – BREF for the estimation of QoL, (b) Life Satisfaction Scale for the estimation of satisfaction from life, and (c) the special recording document for demographic, socioeconomic, and clinical data. At the same time, blood was collected for the measurement of glucose control and renal function. DR was diagnosed by dilated fundoscopy.ResultsPatients with DR had significantly worse scores in all scales of QoL and Life Satisfaction in comparison with those without DR. We found significant impact of the severity of DR in many domains of the QoL and Life Satisfaction. Multivariate logistic regression analysis demonstrated that DR was associated with worse QoL and Life Satisfaction scores as well as lower income, while no significant associations were found with education level, family, insurance and employment status as well as type of residence.ConclusionDR affects QoL and Life Satisfaction and is associated with lower income.     

Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study

Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case–control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95 % confidence intervals (95 % CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31–365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person–years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95 % CI 1.04–2.24; OR = 1.62; 95 % CI 1.02–2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95 % CI 1.05–4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.     

Carotid and femoral atherosclerosis in antiphospholipid syndrome: Equivalent risk with diabetes mellitus in a case–control study

BackgroundAntiphospholipid syndrome (APS) may carry a worse prognosis for vascular complications when co-existing with subclinical atherosclerosis; however, the association between the two conditions remains ambiguous.MethodsWe evaluated ultrasonographic markers of subclinical atherosclerosis in carotid and femoral arteries of 86 patients with thrombotic APS [43 primary APS (PAPS), 43 systemic lupus erythematosus-associated APS (SLE/APS)], 86 patients with diabetes mellitus (DM) and 86 healthy controls, individually matched for age and gender, and investigated their associations with traditional and disease-related factors in APS.ResultsCarotid plaques were found in 28% of PAPS, 23% of SLE/APS, and 30% of DM patients versus 9% of controls (p = 0.006). Femoral plaques were found in 33% of PAPS, 19% of SLE/APS, 20% of DM, and 9% of controls (p = 0.032). Multivariate regression-derived relative risk estimates for atherosclerotic plaques in any location were 2.72 for PAPS, 2.63 for SLE/APS, and 1.98 for DM (p = 0.004, 0.009, and 0.032 respectively), after adjusting for age, gender, hypertension, dyslipidemia, smoking, BMI, and family history of coronary disease. Among patients with APS, atherosclerotic plaques were associated with the number of traditional CVD risk factors in both PAPS (RR = 2.75, p < 0.001) and SLE/APS (RR = 1.84, p < 0.001), and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.ConclusionsPatients with PAPS and SLE/APS have a nearly 2.5-fold risk of atherosclerotic plaques in carotid and femoral arteries compared to healthy controls, similar to DM patients. Atherosclerotic plaques are associated with the number of traditional risk factors in both APS and SLE/APS, and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.     

Symptomatic knee osteonecrosis in patients with systemic lupus erythematosus: a case–control study

To explore the associated risk factors of symptomatic knee osteonecrosis (KON) in patients with systemic lupus erythematosus (SLE), we conducted a retrospective case–control study to compare the clinical and laboratory features between SLE patients with and without symptomatic KON matched by age and gender. Univariate and multivariate regression analyses were used to evaluate possible associated risk factors. Twenty (one male, nineteen females) out of 3941 lupus patients were identified as symptomatic KON, which was confirmed by magnetic resonance imaging. The mean age at KON onset was 34.4 (range 12–67) years, and the median course of lupus at KON onset was 72.5 (range 8–123) months. Univariate and multivariate analyses identified that the prevalence of cutaneous vasculitis (OR 5.23; 95 % CI 1.11–24.70), hyperfibrinogenemia (OR 4.75; 95 % CI 1.08–20.85), and elevated IgG levels (OR 6.05; 95 % CI 1.58–23.16) were statistically higher in KON group, and hydroxychloroquine (HCQ) usage was statistically lower in KON group (OR 0.27; 95 % CI 0.07–0.97). Glucocorticoid usage, in terms of maximal dose, duration of treatment, and the percentage of receiving methylprednisolone pulse therapy, did not show statistical difference between the two groups (p > 0.05). Symptomatic KON is a relatively rare complication of SLE. Cutaneous vasculitis, hyperfibrinogenemia, and elevated IgG levels are possible risk factors, whereas HCQ may provide a protective effect. Our results suggest that lupus activity as well as hypercoagulation status may play a role in the pathogenesis of KON in lupus.     

Bone disease in adult patients with β-thalassaemia major: a case–control study

Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case–control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with β-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients.     

Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study

BackgroundFibroblast growth factor-23 (FGF-23) is actively involved in phosphate homeostasis and skeletogenesis.Aim of the workTo assess the serum level of FGF-23 in systemic sclerosis (SSc) patients (both diffuse dSSc and limited lSSc subtypes) in order to find if it has a role in the pathogenesis of the disease and study its relation to the clinical manifestations.Patients and methodsThe study included 30 dSSc patients, 30 lSSc and 28 age and sex matched controls. In patients, clinical examination and laboratory investigations were performed and Medsger severity scale assessed. Serum FGF-23 was measured using ELISA.ResultsThe age of dSSc patients was 36.94 ± 9.89 years and the lSSc 38.36 ± 10.04 years. The serum FGF-23 level was 23.44 ± 14.86 pg/ml in dSSc patients, 20.01 ± 13.92 pg/ml in lSSc patients and 23.09 ± 11.45 pg/ml in the control (p = 0.58). No significant difference in the FGF-23 level was found according to the presence of lung fibrosis (p = 0.6). There was no significant difference in FGF levels among patients according to the severity (p = 0.39). In SSc patients there was a significant correlation between FGF and serum phosphorus especially in dSSc patients (r = 0.6, p = 0.003). Serum urea significantly correlated with FGF-23 in those with dSSc (r = 0.46, p = 0.037). There was no significant difference in the FGF-23 levels (p = 0.18) between those with a normal and impaired glomerular filtration rate.ConclusionThe mean serum level of FGF-23 in this study showed no significant difference between systemic sclerosis patients and their subtypes with the normal subjects. It seems to have no role in the clinical manifestations of the disease.     

Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: A matched case–control study

AimsThis study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas.MethodsIn type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls.ResultsThe 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3–4.3, P = 0.004) with glibenclamide; 2-fold (0.9–4.6, P = 0.099) with glipizide; 2.9-fold (1.6–5.1, P = 0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7–1.7, P = 0.385) with glimepiride, 0.4-fold (0.7–1.3, P = 0.192) with gliclazide, and 0.4-fold (0.7–1.1, P = 0.09) with either.ConclusionsInitiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.     

Profile of patients with a positive HCV viral load in a large French psychiatric hospital (2019–2021): A case–control study

Hepatitis C virus (HCV) is highly prevalent in people with mental disorders (PWMDs). However, in the international context of HCV elimination, no previous study has explored the features of seropositive PWMDs with vs. without a positive viral load (VL). We retrospectively retrieved all HCV serology results of patients hospitalized in 2019, 2020 and 2021 in the second-largest psychiatric hospital of France. Using the medical records of all patients found seropositive for HCV, the following data were collected: sex (male, female), age (in years), previous history of illicit drug use except cannabis (yes or no) and previous history of incarceration (yes or no). We conducted a case–control comparison of these variables between the PWMDs who had and did not have a positive VL, thus providing odds ratios and 95% confidence intervals (ORs [95% CI]). In a total of 13,276 inpatients, 2540 (19.1%) underwent at least one HCV serology; 55 of them (2.16%) were found positive. A VL count was performed for 48 of them, finding 15 (31.3%) individuals with active HCV. Compared with those with a negative VL, these 15 individuals were less likely to have previous documented illicit drug use (OR = 0.18; 95% CI [0.05–0.68]) and to have been previously incarcerated (OR = 0.23; 95% CI [0.06–0.99]); age and sex did not statistically differ. In the context of HCV elimination, PWMDs yet to be treated for HCV are more likely to be those with no identified risk factor for HCV, which supports a strategy of systematic screening for HCV among PWMDs.     

HLA-B, DR and DQ antigens polymorphism in Tunisian patients with ankylosing spondylitis (a case–control study)

The objective of the study is to assess the distribution of HLA-B genes, HLA-B27 subtypes, HLA-DRB1 and HLA-DQB1 alleles in patients with ankylosing spondylitis (AS) and in control subjects in the Tunisian population and to compare their distribution with that found in other countries. This is a case–control study that included 100 consecutive patients (85 males/15 females) with AS according to the modified New York criteria and 100 control individuals. HLA-B, B27 subtypes and class II (DR and DQ) typing of all subjects was performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). HLA-B27 was found in 62% of patients against 3% in controls (P = 0.0000, OR = 52.6, 15.6 < CI < 166.7). On the other hand, B*07 and B*51 were significantly decreased in comparison with controls (P = 0.01, OR = 0.3, 0.1 < CI < 0.8 and P = 0.0000, OR = 0.2, 0.1 < CI < 0.4, respectively). Eight B*27 subtypes were identified in the AS group, but the most frequent ones were B*2702 (32%) and B*2705 (24%). Among HLA-DRB1 alleles, a significant increase in DRB1*11 was found in comparison with controls (P = 0.01, OR = 2.2, 1.2 < CI < 4.5). However, DRB1*13 had a negative association with AS (P = 0.01, OR = 0.4, 0.2 < CI < 0.8). For HLA-DQB1 alleles, a significant positive association with DQB1*03 was observed in AS group (P = 0.03, OR = 1.8, 1.0 < CI < 3.4). Multivariate analysis by logistic regression revealed that DRB1*11 and DQB1*03 had no direct links with the disease, but were dependent on the presence of HLA-B27. Moreover, B*07 and B*51 seemed to have independently a negative correlation with AS, but DRB1*13 seemed to depend on B*51. Haplotypes carrying B27 were significantly associated with AS and those carrying B*07 or B*51 were negatively correlated with the disease. In conclusion, our study confirms that B27 predisposes to AS while B*07 and B*51 are negatively correlated with the disease.