Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions.

PURPOSE To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. METHODS Multimodal imaging case series. RESULTS Six women and 2 men were included (mean age, 31.5 ± 5.8 years). Vision ranged from 20/20-1 to hand motion (mean, 20/364). Spectral domain optical coherence tomography demonstrated extensive attenuation of the external limiting membrane, ellipsoid and interdigitation zones, adjacent to the visible multifocal choroiditis/punctate inner choroidopathy lesions. The corresponding areas were hyperautofluorescent on fundus autofluorescence and were associated with corresponding visual field defects. Full-field electroretinogram (available in three cases) showed markedly decreased cone/rod response, and multifocal electroretinogram revealed reduced amplitudes and increased implicit times in two cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n = 4), oral acyclovir/valacyclovir (n = 2), intravitreal/posterior subtenon triamcinolone acetate (n = 3), and anti-vascular endothelial growth factor (n = 2). Visual recovery occurred in only three cases of whom two were treated. Varying morphological recovery was found in six cases, associated with decrease in hyperautofluorescence on fundus autofluorescence. CONCLUSION Multifocal choroiditis/punctate inner choroidopathy can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of multifocal choroiditis/punctate inner choroidopathy with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging.

In the human urothelium and suburothelium, intradetrusor botulinum neurotoxin type A does not induce apoptosis: preliminary results

Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.

[Lymphadenopathy and diabetes insipidus - association]

We report the case of a 62 year old women with chronic idiopathic myelofibrosis who developed acute lymphadenopathy. At the same time diabetes insipidus, osteolytic bone lesions and exanthema of the skin were diagnosed. Suspected Langerhans cell histiocytosis could be proven by repeated biopsies of affected organs. Therapy was started in accordance with the recommendations of the Histiocyte Society.

[When eating becomes dangerous...]

We report the case of a 59-year-old women with idiopathic insulin auto-immune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia. It is characterized by extremely high levels of insulin in the presence of high titers of insulin antibodies despite the absence of previous insulin injections. Early postprandial increase in glucose concentrations due to impaired insulin action resulting from the buffering effect of the antibodies and late postprandial hypoglycemia as a consequence of the dissociation of insulin from the antibodies was observed. A correct diagnosis is important to avoid unnecessary investigations and surgery in these patients who are best treated conservatively - with a good prognosis - by fractionating carbohydrate intake during the day.

Different disparities of gender and race among the thrombotic thrombocytopenic purpura and hemolytic-uremic syndromes

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) represent multiple disorders with diverse etiologies. We compared the gender and race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years for their first episode of TTP or HUS to appropriate control groups. The relative frequency of women and white race among patients with TTP-HUS-associated with a bloody diarrhea prodrome and the relative frequency of women with quinine-associated TTP-HUS were significantly greater than their control populations. The relative frequency of women and black race among patients with idiopathic TTP and TTP-associated with severe ADAMTS13 deficiency was significantly greater than their control populations. The relative frequency of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP was significantly greater than among a population of patients with SLE, and the relative frequency of black race among patients with other autoimmune disorders preceding TTP was significantly greater than their control population. No significant gender or race disparities were present among patients with hematopoietic stem cell transplantation-associated thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated with drugs other than quinine. The validity of these observations is supported by the enrollment of all consecutive patients across 21 years from a defined geographic region, without selection or referral bias. These observations of different gender and race disparities among the TTP-HUS syndromes suggest the presence of different risk factors and may serve as starting points for novel investigations of pathogenesis.

Survival and relapse in patients with thrombotic thrombocytopenic purpura

Survival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%, P = .83) and for patients with idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261 (93%) of 282 patients since 1995. Survival was not different between patients with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136 of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor titer of 2 or more Bethesda units/mL was associated with lower survival (P = .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16 of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.

[Urinary incontinence]

Incontinence is a common age-dependent and increasing problem in women that may mainly present as stress incontinence, overactive bladder, mixed incontinence or other forms. A thorough history, gynaecological and neurological examination and urinalysis as initial step will lead to the diagnosis and treatment. If midstream urine is difficult to receive, a catheter urine will be easy to obtain. Further investigations as urodynamics, cystoscopy and ultrasound may be required. As initial step, stress incontinence should be treated with physiotherapy and pelvic floor exercises, if not successful with operations as suburethral slings. Slings have good long-term success rates of approximately 85 % with a low morbidity and can even be inserted under local anaesthetic. The treatment of idiopathic overactive bladder consists of bladder training, a behavioural therapy, and mainly anticholinergics. Anticholinergics may cause side effects particularly in the elderly who are under several medications that may add anticholinergic effects as antidepressants, antibiotics or antihistaminics.

Evidence for a role of anti-ADAMTS13 autoantibodies despite normal ADAMTS13 activity in recurrent thrombotic thrombocytopenic purpura

Severe ADAMTS13 deficiency is a critical component of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura but is found only in about 60% of patients clinically diagnosed with this disease.

[Spontaneous hematomas and isolated prolongation of aPTT]

We report a case of a 64 year old woman with spontaneous hematomas. A prior history of bleeding disorder was not known up to now. The result of investigation of coagulation was an isolated prolonged aPTT that was caused by an inhibitor of factor VIII without underlying disease (idiopathic acquired hemophilia A). Therapy with steroids and cyclophosphamid resulted in partial remission.

Indications to teriparatide treatment in patients with osteoporosis

To prevent osteoporotic fracture occurrence, a variety of treatment regimens with different mechanisms of action is available. The antiresorptive bisphosphonate drugs are currently the most commonly prescribed agents in the management of patients with osteoporosis. The recombinant amino-terminal fragment of human parathyroid hormone (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing bone mass and improving bone microarchitecture. Teriparatide treatment reduces vertebral and non-vertebral fracture risk markedly in women and men with idiopathic osteoporosis, or with glucocorticoid-induced osteoporosis. Teriparatide should thus be considered as first line treatment for postmenopausal women and for men with severe osteoporosis.

Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO(4)/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm(2)): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm(2)): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.

Hairy pinnae after orchiectomy and chemotherapy for testicular cancer: acquired localized hypertrichosis of the ears

Acquired localized hypertrichosis has rarely been reported. Here, we describe a patient with localized hypertrichosis of the pinnae that occurred 4 months after orchiectomy and chemotherapy for a testicular carcinoma. To our knowledge, this is the first case of an acquired hypertrichosis of the pinnae after cancer therapy. We propose that in our patient either hypogonadism or the hormonal imbalance caused by the cancer therapy led to the development of the hairy pinnae, perhaps alongside a genetic predisposition for hairy ears.

[Surgical therapy of gynecomastia]

Nowadays surgical intervention is an essential part of the treatment of idiopathic gynecomastia. Choosing the right method is crucial and is based on the current status in the clinical and histological evaluation. Before finalizing the process of choosing a specific method a prior interdisciplinary evaluation of the patient is necessary to ascertain clear indications for a surgical intervention. Liposuction is one of the methods which have become popular in recent years. The advantages are the possible combination with traditional techniques, such as subcutaneous mastectomy or periareolar mastopexy. The main indication is for gynecomastia stage IIa/b and is justifiable due to the reduction in surgical complications and scarring. Furthermore this technique provides an excellent aesthetical outcome for the patient. A total of 162 patients suffering from gynecomastia stages I-III (according to Simon) were surgically treated between 2000 and 2010 and these cases were retrospectively evaluated. The results showed a decline in the use of a T-shaped incision in combination with subcutaneous mastectomy with periareolar tightening compared to an increase in the use of subcutaneous mastectomy in combination with liposuction. The excised tissue should always be sent for histological examination to make sure no malignant cells were present.

Characterization of novel StAR (steroidogenic acute regulatory protein) mutations causing non-classic lipoid adrenal hyperplasia

Context Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH). Objective StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. Design To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. Setting Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. Patients Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. Results StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (~30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. Conclusions StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.