Concomitance of Gitelman Syndrome and Familial Mediterranean Fever: A Rare Case Presentation

We report a case that has Gitelman syndrome (GS) and familial Mediterranean fever (FMF) presenting with recurrent arthritis of right knee and heel pain. Investigations showed hypokalemia and hypomagnesemia with urinary magnesium wasting. Genetic analysis revealed the presence of heterozygous E148Q mutation in the MEFV gene. Management with potassium, magnesium supplements, spironolactone for GS, and colchicine for FMF resulted in a signi?cant improvement in symptoms. To the best of our knowledge, this is the first report of association between GS and FMF. Further studies are needed to identify if there is an association between these two diseases and the genes responsible for these diseases.     

Normative data on hand grip strength in a Greek adult population

The objectives of this study were to establish data concerning normal hand grip strength (GS) and to explore possible associations with anthropometric parameters. GS was measured in 232 individuals in a standard arm position using the Jamar dynamometer. We examined differences between right/left and dominant/nondominant hands. Possible correlations of GS with anthropometric values were evaluated. Right hand and dominant hand GS were found to be higher and statistically significant compared to left hand and nondominant hand GS, respectively. Men had higher values of GS compared to women. A negative association was observed between age and dominant hand GS. A positive association was documented between height and dominant hand GS, while the respective comparison for weight and dominant hand GS documented a statistically significant positive association only in the male group. A positive association between BMI and dominant hand GS was seen in female individuals. Additional factors associated with GS should be the goal of future investigations.     

Pharyngeal Presentation of Goltz Syndrome: A Case Report with Review of the Literature

Focal dermal hypoplasia (Goltz syndrome; GS) is an X-linked dominant disorder caused by a mutation in the porcupine homolog (PORCN) gene and is typically embryonically lethal for males. The presence of disease in males is usually the result of post-zygotic mutation, but may also be due to mosaicism. The presentation of this disorder is highly variable, but generally is characterized by cutaneous, skeletal, ocular, oral, dental, and aural defects. Cutaneous manifestations include foci of hypoplastic skin, abnormal pigmentation, and papillomatous growths. We present both the first case of a patient with GS related laryngeal obstruction due to papillary lymphoid hyperplasia in an adult, and the first case in a male patient. Clinical, histologic, and genetic features of the disease are discussed. Operative technique for management of the patient with pharyngeal lesions is detailed, and intraoperative photos are showcased. The challenge in airway evaluation and management is also highlighted as manifestations of GS are rarely encountered in the airway and can cause laryngeal obstruction.     

The association of HLA-DR antigens with acute steroid-resistant rejection and poor kidney graft survival

The association of an early steroid-resistant rejection (SRR) with HLA-DR antigens was analyzed in 410 kidney transplantations. A severe SRR leading to a poor (45%) 1-year graft survival (GS) occurred in 22 transplantations (5%). An acute reversible rejection (ARR) with a GS of 94% was found in 80 transplantations (20%). For the 308 (75%) transplantations with no early rejection episodes the GS was 91%. HLA-DR5 and -DR8 present in the donor as incompatible antigens were strongly associated with SRR. Further, a mismatched DR1 from the kidney donor predicted a rejection, either reversible or irreversible. These findings may have practical implications for an early diagnosis of SRR and for considering of rescue therapy whenever transplantation with disparities in these loci has been performed.     

脑胶质肉瘤的MRI表现与病理对照分析

目的探讨脑胶质肉瘤(GS)的MRI表现及相关病理学基础。方法回顾性分析22例经手术病理证实为GS的患者临床、MR及病理检查资料。结果 20例发生于大脑凸面,2例发生于深部脑白质;16例肿块呈圆形或类圆形,6例呈不规则形。22例肿瘤MRI均表现为不均匀团块状异常信号;20例为囊实性,2例为实性。4例为GS合并出血。肿瘤T2WI 21例呈以稍高信号或高信号为主的混杂信号,1例呈等信号;T1WI 18例呈不均匀稍低信号,4例呈不均匀低信号。21例可见瘤周水肿,1例瘤周无水肿。增强扫描表现为不均匀厚壁环状或花环状明显强化17例,壁结节强化7例,瘤内栅栏状强化14例。GS病理表现主要为胶质母细胞瘤成分与肉瘤成分呈间隔交替存在或肉瘤将胶质母细胞瘤分隔呈岛屿状。结论脑胶质肉瘤多位于大脑凸面,呈厚壁环形或花环状强化、壁结节及栅栏状强化是其特征性MRI表现,确诊仍需依靠病理学检查。     

Grip strength: a measure of the proportion of protein loss in surgical patients

Measurements of voluntary hand grip strength (GS) are a sensitive predictor of postoperative complications. The loss of body protein is thought to be important in the development of these postoperative complications, but the relationship between GS and body protein status has not been studied. We have measured GS (by hand dynamometry), total body protein (indirectly by mid-arm muscle circumference, and directly by in vivo neutron activation analysis) and the proportion of protein loss (protein index) in 80 patients with gastrointestinal disease and 87 normal volunteers. Using regression analysis, a matched study and clinical decision analysis, it has been demonstrated that GS is a sensitive measurement of the degree of protein loss. The results support more widespread use of GS measurements in the identification of patients at high risk of postoperative complications and in the monitoring of patient response to nutritional intervention.     

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.     

Pulmonary tuberculosis with neuromyelitis optica: an uncommon association of a common disease

Systemic tuberculosis has been reported with varying neurological manifestations like meningitis, tuberculomas, myositis and neuropathy. Neuromyelitis optica (NMO) is a well known neurological entity which has been described in association with several systemic disorders like systemic lupus erythematosis, diabetes mellitus, hypothyroidism, exposure to insecticides etc. However, only a few cases of NMO have been reported in association with Mycobacterium tuberculosis. Here, we report a case of pulmonary tuberculosis in association with NMO to highlight the under-reported association of NMO with pulmonary tuberculosis presenting in a peculiar anatomical fashion i.e. longitudinal myelitis with predominant posterior column involvement.     

The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading

The 5'AMP-activated protein kinase (AMPK) is a potential antidiabetic drug target. Here we show that the pharmacological activation of AMPK by 5-aminoimidazole-1-beta-4-carboxamide ribofuranoside (AICAR) leads to inactivation of glycogen synthase (GS) and phosphorylation of GS at Ser 7 (site 2). In muscle of mice with targeted deletion of the alpha2-AMPK gene, phosphorylation of GS site 2 was decreased under basal conditions and unchanged by AICAR treatment. In contrast, in alpha1-AMPK knockout mice, the response to AICAR was normal. Fuel surplus (glucose loading) decreased AMPK activation by AICAR, but the phosphorylation of the downstream targets acetyl-CoA carboxylase-beta and GS was normal. Fractionation studies suggest that this suppression of AMPK activation was not a direct consequence of AMPK association with membranes or glycogen, because AMPK was phosphorylated to a greater extent in response to AICAR in the membrane/glycogen fraction than in the cytosolic fraction. Thus, the downstream action of AMPK in response to AICAR was unaffected by glucose loading, whereas the action of the kinase upstream of AMPK, as judged by AMPK phosphorylation, was decreased. The fact that alpha2-AMPK is a GS kinase that inactivates GS while simultaneously activating glucose transport suggests that a balanced view on the suitability for AMPK as an antidiabetic drug target should be taken.     

Gitelman’s syndrome: towards genotype-phenotype correlations?

Gitelman’s syndrome (GS) is a salt-losing tubulopathy characterized by hypokalemic alkalosis with hypomagnesemia and hypocalciuria. The disease is associated with inactivating mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na⁺–Cl⁻ cotransporter (NCCT) that is expressed in the apical membrane of the cells lining the distal convoluted tubule (DCT). GS is relatively frequent, and more than 100 mutations scattered through SLC12A3 have been identified thus far. Although the disease is recessively inherited, up to 40% of patients are found to carry only a single mutation, instead of being compound heterozygous or homozygous. The phenotype of GS is highly heterogeneous in terms of age at presentation, and nature/severity of the biochemical abnormalities and clinical manifestations. This phenotypical heterogeneity is observed not only between all patients harbouring SLC12A3 mutations but also among family members or patients with identical mutations. In this review, we discuss the potential explanations for the failure to identify mutant alleles in SLC12A3, as well as the different mechanisms that can account for the inter- and intra-familial phenotype variability in GS, including genetic heterogeneity, position and nature of the mutations, functional consequences, compensatory mechanisms, and modifying genes.     

Risk factors associated with perineural invasion in prostate cancer

ObjectivesThe prognostic importance of perineural invasion (PNI) in prostate cancer (PC) has been postulated by some authors. Few studies have investigated the risk factors associated with PNI. The aim of this study was to identify factors associated with PNI in PC.Patients and methodsThe study group of 113 patients diagnosed with PC during the period 2005–2010 consisted of 66 who underwent radical prostatectomy (RP) and 66 who did not. Each group was further divided into those with and without PNI. The association between clinicopathological parameters and PNI in prostate biopsy (Pbx) and RP specimens was investigated using t-test and logistic regression analysis. Discordance in PNI prevalence and PNI up-migration between Pbx and RP specimens were also studied.ResultsIn patients who did not undergo RP, Pbx Gleason score (GS) ≥ 7 was a significant predictor for the presence of PNI. In patients who underwent RP, Pbx GS > 7 increased the risk of PNI in Pbx and RP samples, while a high RP GS predicted PNI in the RP specimen. The discordance rate for PNI in Pbx and RP specimens was 27.3%. Up-migration to a PNI positive cancer between Pbx and RP specimens was seen in 45.5% of cases and RP GS was the only factor associated with PNI up-migration.ConclusionThe association of PNI with a high GS and the high rate of discordance between Pbx and RP specimens indicate that in patients with a high GS on Pbx, the pathologist should look more carefully for PNI, and the surgeon should be aware of sampling errors and the unreliability of Pbx specimens in detecting PNI.     

Autosomal dominant polycystic kidney disease associated with familial sensorineural deafness

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by both renal and non-renal disorders. Extrarenal involvement includes noncystic manifestations such as cardiovascular abnormalities, colonic diverticula and intracranial aneurysms. Familial sensorineural hearing loss (SNHL) has been included in the definition of Alport's syndrome. However, other types of nephropathy have been occasionally associated with hereditary deafness. The association of ADPKD with hereditary SNHL has not been previously documented. We report a family with ADPKD associated with bilateral sensorineural deafness in a pedigree of four affected members in four generations.     

Pyonephrosis and renal abscess associated with kidney tumours.

Whilst the diagnosis of pyonephrosis and renal abscess is fairly easy, the source of obstruction and infection is an important indicator of treatment. The association of kidney tumours with these inflammatory manifestations has not previously been emphasised. Reviewing our cases of pyonephrosis and renal abscesses, we report 4 patients with concomitant tumours of the kidney and discuss their management.     

Effects of antihypertensive drugs in experimental type 2 diabetes-related nephropathy

BACKGROUND: It has been extensively reported that antihypertensive drugs reduce proteinuria and glomerulosclerosis (GS) in many experimental nephropathies and in humans. However, the role of calcium channel blockers (CCBs) in the prevention of proteinuria and GS remains controversial and in most cases only dihidropyridine-CCBs are studied. Few studies have reported whether the time at which drug administration is initiated plays a role in the reduction of proteinuria and GS. METHODS: Fifty-six male Obese Zucker rats (OZR) were used as a model of spontaneous type 2 diabetes-related nephropathy. Biochemical and histological analysis were performed to compare the efficacy of a non-dihydropyridine-CCB diltiazem [DZM; 100 mg/kg body weight (BW)/day], an ACEI quinapril (10 mg/kg BW/day), or both in diminishing proteinuria and GS, and to determine their role in effective prevention and treatment. RESULTS: Only quinapril was able to diminish proteinuria. As far as histological lesions, both treatments were effective, although only quinapril prevented GS. The combination of quinapril plus DZM did not demonstrate any beneficial effects. Surprisingly, quinapril ameliorated the damage of podocytes whereas DZM did not, thus leading to doubt concerning the efficiency of DZM in long-term studies. Nonetheless, the combination of quinapril plus DZM demonstrated a greater reduction in podocyte damage than treatment with DZM alone, which shows an interesting association in the prevention of longer-term glomerular damage. Few differences were found between prevention and treatment. CONCLUSIONS: Quinapril, but not DZM, was able to diminish proteinuria in OZR. Both treatments were effective in diminishing GS, although only quinapril totally prevented it. The combination of both drugs prevented long-term glomerular damage, which is intriguing.     

Combined assessment of cardiac systolic dysfunction and coronary atherosclerosis used to predict future cardiac deaths after starting hemodialysis

BACKGROUND/AIMS: Identification of end-stage renal disease (ESRD) patients at high risk for cardiac events is important for clinical dialysis management. The present study determined whether the combination of cardiac function and coronary atherosclerosis could predict future cardiac events after starting renal replacement therapy (RRT). METHODS: We prospectively assessed left ventricle ejection fraction (EF) and Gensini score (GS) using angiographic severity of coronary atherosclerosis in 88 consecutive ESRD patients [mean age 62 years; 69 males (78%); 55 patients (64%) with diabetic nephropathy] at the initiation of RRT. EF was analyzed by echocardiogram, and GS was scored by coronary angiography within 3 months after starting RRT. The study end point was cardiac death. For analysis of the association between cardiac death and EF and GS measures, the univariate and multivariate Cox proportional hazards model was used. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and accuracy of event-free prediction were evaluated. RESULTS: Twenty-four patients (27%) had low cardiac function (EF <50%; low EF) and 44 patients (50%) had severe coronary atherosclerosis (GS >15; high GS). During a follow-up period of 3 years, cardiac death occurred in 21 patients (24%). The PPV of low EF and high GS was 42 and 39%, respectively; the highest PPV (53%) was obtained when low EF and high GS were combined. The cumulative survival rate at 5 years in patients with both low EF and high GS was significantly lower than those with high EF and low GS (91 vs. 22%, p < 0.0005). CONCLUSION: The combined assessment of cardiac function and coronary atherosclerosis at the initiation of RRT strongly predicts future cardiac events.     

Amyloidosis and Reiter's syndrome: report of a case and review of the literature

Reiter's syndrome is classically described as the triad of urethritis, conjunctivitis, and arthritis, It has many manifestations and has rarely been reported to occur in association with amyloidosis. Four cases of systemic amyloidosis have previously been reported. This case describes a patient who developed progressive renal amyloidosis after a 17-year history of severe Reiter's syndrome. Immunofluorescent staining of the renal biopsy was strongly positive for AA protein, the type of protein found in secondary amyloidosis. This is the first case in which amyloidosis has been proven to be secondary to Reiter's syndrome and not merely the coincidental occurrence of two rare diseases.     

Gastric siderosis: patterns and significance

Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%) patients with pattern A, in all patients with pattern B (n = 4, 100%), and in none of patients with pattern C (n=3, 0%). Varying degrees of mucosal inflammation were noted in patients with pattern A cases, and 2 had evidence of active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis, only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal siderosis is relatively uncommon (3%) but is important to look for as it may lead to a diagnosis of hemochromatosis in some cases. Three patterns are recognized: A) a "nonspecific" stromal cell predominant pattern, which may be associated with gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B) extracellular coarse clumps of crystalline iron deposition associated with oral iron medications, mild gastritis, and reactive gastropathy type changes ("Iron-pill gastritis"); and C) gastric glandular siderosis, which may be associated with systemic iron overload/hemochromatosis.