Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer.

Delay in the Diagnosis of Cerebral Vein and Dural Sinus Thrombosis Influence on Outcome

Background and Purpose-Diagnostic delay of cerebral vein and dural sinus thrombosis may have an impact on outcome. Methods-In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score > 2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field). Results-Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P < 0.001) and of mental status (P = 0.042), seizure (< 0.001), and with parenchymal lesions on admission CT/MR (P < 0.001) were diagnosed earlier, whereas men (P = 0.01) and those with isolated intracranial hypertension syndrome (P = 0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P = 0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P = 0.86) or deaths (P = 0.53). Persistent visual deficits were more frequent in patients diagnosed later (P = 0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score > 2 at the end of follow-up was more frequent in patients diagnosed later (P = 0.02). Conclusions-Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency. (Stroke. 2009; 40: 3133-3138.)

Evaluation of RET polymorphisms in a six-generation family with G533C RET mutation: specific RET variants may modulate age at onset and clinical presentation

P>Context We previously described a six-generation family with G533C RET mutation and medullary thyroid carcinoma, in the largest family reported do date. Of particular interest, phenotype variability regarding the age of onset and clinical presentation of the disease, was observed. Objective We evaluate whether single SNPs within RET oncogene or haplotype comprising the RET variants (defined by Haploview) could predispose to early development of MTC in this family and influence the clinical manifestation. Design Eight SNPs were selected based on their previous association with the clinical course of hereditary or sporadic MTC, in particular promoting an early onset of disease. The variants were initially tested in 77 G533C-carriers and 100 controls using either PCR-direct sequencing or PCR-RFLP. Association between a SNP or haplotype and age at diagnosis or presence of lymph node metastasis was tested in 34 G533C-carries with MTC. Different bioinformatic tools were used to evaluate the potential effects on RNA splicing. Results An association was found between IVS1-126G > T and age at diagnosis. The variant [IVS8 +82A > G; 85-86 insC] was associated with the presence of lymph node metastases at diagnosis. In silico analysis suggested that this variant may induce abnormal splicing. This in silico analysis predicted that the [IVS8 +82A > G; 85-86 insC] could alter the splicing by disrupting and/or creating exonic splicing enhancer motifs. Conclusions We here identified two RET variants that were associated with phenotype variability in G533C-carriers, which highlights the fact that the modifier effect of a variant might depend on the type of mutation.

Heterozygous exon 3 deletion in the Parkin gene in a patient with clinical and radiological MSA-C phenotype

Fondation Philantropique

Diagnosis of Mild Cognitive Impairment Revisited after One Year Preliminary Results of a Prospective Study

Background/Aims: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow- up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow- up in a cohort of older adults. Methods: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow- up with the same clinical and neuropsychological protocol. Results: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow- up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). Conclusion: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits. Copyright (C) 2009 S. Karger AG, Basel

Simplified criteria for the diagnosis of autoimmune hepatitis

Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobutins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff >= 6) and 81% sensitivity and 99% specificity (cutoff 2:7) in the validation set. Conclusion: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.

Neurosyphilis in HIV-infected patients: Clinical manifestations, serum venereal disease research laboratory titers, and associated factors to symptomatic neurosyphilis

Goal: To describe clinical and laboratory features of human immunodeficiency infection (HIV)-infected patients with neurosyphilis. Study Design: Retrospective study of 27 consecutive cases of HIV-infected patients with a positive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Results: Median of age was 36 years and 89% were men. Ten (37%) patients had previous nonneurologic syphilis treatment. At the time of neurosyphilis diagnosis, 10 (37%) patients had early syphilis, and 6 of them were neurologically asymptomatic. Nine (33%) patients had symptomatic neurosyphilis. Twenty-six (96%) patients were classified with early neurosyphilis. The medians of serum VDRL and CD4(+) T cell counts were 1:128 and 182 cell/mu L, respectively. Twenty five (93%) patients presented serum VDRL titers >= 1:16. Five of 6 patients with early syphilis and asymptomatic neurosyphilis, presented serum VDRL >= 1:16. Symptomatic patients showed lower CD4(+) T cell counts (59 cell/mu L vs. 208 cell/mu L, P = 0.03) and higher protein concentration on CSF (118 mg/dL vs. 39 mg/dL, P <0.001) than asymptomatic patients. Conclusions: Most patients had early and asymptomatic neurosyphilis, and more than one third had early syphilis. Patients with symptomatic neurosyphilis showed lower CD4(+) T cell counts and higher protein concentration on CSF than those asymptomatic. Most patients had serum VDRL titers >= 1:16, regardless of syphilis stage.

Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients

Objective: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyper-prolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. Design, setting, and patients: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. Main outcome measure: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. Results: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR-treated patients. Conclusion: Prolactinomas, drug-induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

Fabry Disease in Hemodialysis Patients in Southern Brazil: Prevalence Study and Clinical Report

Background. Fabry disease (FD) is a lysosomal storage disorder caused by a deficiency of -Galactosidase A (-Gal A). Fabry nephropathy typically progresses throughout the fifth decade to end-stage renal disease (ESRD), requiring hemodialysis and/or kidney transplantation. Objective. To estimate the prevalence of FD among ESRD males on hemodialysis treatment in Rio Grande do Sul, the southernmost state of Brazil. Methods. Screening for -Gal A activity was performed by a dried blood spot (normal reference value: 1.5 nmoles/hour/mL). Positive screening results were confirmed by plasma -Gal A activity assay (reference value: 3.3 nmoles/hour/mL). Results. Five hundred fifty-eight male patients on hemodialysis were evaluated. Of these, only two had low -Gal A activity and were diagnosed with Fabry disease (0.36%). One of these, age 42, had left ventricular hypertrophy and renal manifestations of Fabry disease without the classic symptoms. The other, age 46, had the classical manifestations of angiokeratomas, acroparesthesias, hypohidrosis, and ocular opacities. Conclusions. Although the prevalence of Fabry disease was very low in our study (0.36%), routine screening of male hemodialysis patients would enable earlier identification of many other affected relatives in their families who might benefit from specific clinical treatment.

Evaluation of Adult Chronic Chagas` Heart Disease Diagnosis by Molecular and Serological Methods

Chagas` disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi presents heterogeneous populations and comprises two main genetic lineages, named T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on conventional serological tests, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based on parasitological methods, including hemoculture. The objective of this study was to evaluate the diagnostic procedures of Chagas` disease in adult patients in the chronic phase by using a PCR assay and conventional serological tests, including TESA-blot as the gold standard. Samples were obtained from 240 clinical chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were 70% for PCR using the kinetoplast region, 75% for PCR using the nuclear repetitive region, 99% for IIF, and 95% for ELISA. According to the serological tests results, we recommend that researchers assess the reliability and sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0 (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of sensitivity. Based on our analysis, we concluded that PCR cannot be validated as a conventional diagnostic technique for Chagas` disease. These data have been corroborated by low levels of concordance with serology test results. It is recommended that PCR be used only for alternative diagnostic support. Using the nuclear repetitive region of T. cruzi, PCR could also be applicable for monitoring patients receiving etiologic treatment.

Access to tuberculosis diagnosis in Itaborai City, Rio de Janeiro, Brazil: the patient`s point of view

SETTING: Itaborai Municipality in Rio de Janeiro, Brazil. OBJECTIVE: To evaluate access to tuberculosis (TB) diagnosis for users of the Family Health Program (FHP) and Reference Ambulatory Units (RAUs). DESIGN : A cross-sectional study was conducted in Itaborai City, Rio de Janeiro, Brazil. Between July and October 2007, a sample of 100 TB patients registered consecutively with the TB Control Program was interviewed using the primary care assessment tool. The two highest scores, describing `almost always` and `always`, or `good` and `very good`, were used as a cut-off point to define high quality access to diagnosis. RESULTS: FHP patients were older and had less education than RAU interviewees. Sex and overcrowding did not differ in the two groups. Patient groups did not differ with regard to the number of times care was sought at a unit, transport problems, cost of attending units and availability of consultation within 24 h. Adequate access to diagnosis was identified by 62% of the FHP patients and 53% of the RAU patients (P = 0.01). CONCLUSION: In Itaborai, Rio de Janeiro, TB patients believe that the FHP units provide greater access to TB diagnosis than RAUs. These findings will be used by the Department of Health to improve access to diagnosis in Itaborai.

Comparability between telephone and face-to-face Structured Clinical Interview for DSM-IV in assessing social anxiety disorder

PURPOSE. This article evaluates the comparability of the telephone and in-person Structured Clinical Interview for DSM-IV (SCID) interviews in assessing patients with social anxiety disorder (SAD) as an independent anxiety diagnosis. DESIGN AND METHODS. One hundred subjects were randomly selected and interviewed with the SCID, once by telephone and once in person (1-3 months later). FINDINGS. The prevalence of SAD assessed with the telephone interviews was 56%, whereas the in-person prevalence was 52%, with no statistically significant difference. The test-retest kappa for the 200 interviews was .84, indication of excellent agreement. PRACTICE IMPLICATIONS. These findings, along with the existing evidence of their validity, should encourage the use of SCID by telephone for SAD diagnostic interviews.

Dorsal root ganglionectomy for the diagnosis of sensory neuropathies. Surgical technique and results

Background: Inflammatory diseases stand out among sensory neuronopathies because, in their active phase, they can be treated with immunosuppressive agents. Immunosuppressive therapy may present severe adverse effects and requires previous inflammatory activity confirmation. Sensory neuronopathies are diagnosed based on clinical and EMG findings. Diagnostic confirmation and identification of inflammatory activity are based on sensory ganglion histopathological examination. We describe the surgical technique used for dorsal root ganglionectomy in patients with clinical/EMG diagnosis of sensory neuronopathies. Methods: The sensory ganglion was obtained from 15 patients through a small T7-T8 hemilaminectomy and foraminotomy to expose the C7 root from its origin to the spinal nerve bifurcation. In 6 patients, the dural cuff supposed to contain the ganglion was resected en bloc; and in 9 patients, the ganglion was obtained through a longitudinal incision of the dural cuff and microsurgical dissection from the ventral and dorsal roots and radicular arteries. All ganglia were histopathologically examined. Results: No ganglion was found in the dural cuff in 2 patients submitted to en bloc removal, and the ganglion was removed in all patients who underwent microsurgical dissection. All but 2 patients that had ganglion examination presented a neuronopathy of nerve cell loss, 3 with mononuclear inflammatory infiltrate. These patients underwent immunosuppressive therapy, and 2 of them presented clinical improvement. No surgical complications were observed. Conclusions: Microsurgical dorsal root ganglionectomy for diagnosing inflammatory sensory ganglionopathies was effective and safe. Although safe, en bloc resection of the proximal dural cuff was not effective for this purpose. (c) 2008 Published by Elsevier Inc.