Neuroradiology and clinical aspects of Usher syndrome

We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US 1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.     

Improved, low-cost selective culture medium for Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans is considered to be one of the major oral putative pathogens, especially in cases of juvenile periodontitis. This microorganism requires nutritionally complex media for growth, and therefore the media for its primary isolation usually include blood agar or serum in their base. In this study we present a new medium, Dentaid-1, which improves the detection of A. actinomycetemcomitans in periodontal samples. In its composition, blood and serum have been omitted, hence reducing its cost and making it a more restrictive medium against the growth of other microorganisms with high nutritional requirements. The growth yields of pure cultures of the bacteria on Dentaid-1 were comparable to those on nonselective blood agar. Moreover, clinical efficacy was evaluated in subgingival samples from 77 subjects with adult periodontitis. Dentaid-1 detected A. actinomycetemcomitans in 24 subjects, while a previously described tryptic soy-serum-bacitracin-vancomycin agar detected the microorganism in only 19 subjects (79.1%). Dentaid-1 is a low-cost, noninhibitory formula for the improved diagnosis and monitoring of patients subgingivally infected by this important oral putative pathogen.     

COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.     

Medullary carcinoma of the thyroid in the multiple mucosal neuromas syndrome

The clinical features of the multiple mucosal neuromas (MMN) syndrome permit the recognition of these patients and their potential development of the associated medullary thyroid carcinoma (MTC). The distinctive physical appearance caused by the mucosal neuromas, the Marfanoid habitus and, occasionally, the positive family history aid in establishing the diagnosis. Neurogangliomas are frequently present in the gastrointestinal tract of these patients who may have megacolon, constipation and diarrhea. The third instance of the MMN syndrome is reported in the newborn as intestinal obstruction. It is suggested that the syndrome be considered in the differential diagnosis of Hirschsprung's disease and bowel obstruction in the neonate. Serum calcitonin measurements following stimulation by calcium or pentagastrin infusion reliably detect incipient MTC and may be used to select those MMN patients requiring thyroid surgery. Recognition of patients with the MMN syndrome and subsequent calcitonin screening and early surgical intervention will significantly reduce the chance of their developing terminal MTC. All MMN patients with mucosal neuromas or intestinal neurogangliomas should have such evaluations at least yearly. Relatives who are at risk for inheriting this dominant disease should be similarly evaluated, regardless of their normal appearance.     

Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men

Spermatozoa from 32 infertile patients and 13 controls with normal semen parameters were analysed using dual and triple colour fluorescence in-situ hybridization (FISH) techniques, in order to investigate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y. The patients were divided into three groups according to their karyotypes or the karyotypes of their offspring: 15 were infertile men with abnormal semen parameters and normal karyotypes (group 1), 13 were infertile men with abnormal karyotypes and normal or abnormal semen (group 2) and four were infertile men with abnormal semen and normal karyotypes but whose wives conceived a child (or a fetus) with a numerical chromosomal abnormality through an intracytoplasmic sperm injection cycle (group 3). Patients with abnormal semen parameters showed a significantly higher aneuploidy rate for the investigated chromosomes in their spermatozoa compared to controls (P < 0.005). Our data suggest the presence of a correlation between poor semen parameters and an increase in aneuploidy rate of chromosomes 13, 18, 21, X and Y in spermatozoa (r = -0.81071, P < 0.002); therefore the risk of a chromosomal aneuploidy in spermatozoa seems to be inversely correlated to sperm concentration and total progressive motility. Patients with abnormal karyotypes showed a higher incidence of diploidy and chromosomal aneuploidies compared to controls (P < 0.002). This strongly suggests the presence of an interchromosomal effect of the cytogenetic rearrangement. Men who fathered a child with an abnormal karyotype through intracytoplasmic sperm injection did not present a higher aneuploidy rate for the investigated chromosomes in spermatozoa compared to patients with infertility due to a similar male factor but showed higher incidence of chromosomal aneuploidy compared to normal controls.     

Efficacy and safety of the second generation basal insulin analogs in type 2 diabetes mellitus: A critical appraisal

Type 2 diabetes mellitus is a progressive disease, which requires insulin treatment when other management is no longer effective. Although, insulin plays a vital role in the treatment of diabetes, conventional basal insulins have certain limitations, which have led to the development of more stable and peak less analogues.ObjectivesTo analyze the efficacy and safety of second generation vs. first generation basal insulins, and the efficacy and safety of second generation vs. second generation basal insulins, in patients with type 2 diabetes mellitus, from the evidence provided by head-to-head randomized controlled trials.MethodsThe following electronic databases were searched: PubMed and MEDLINE, Scopus, BIOSIS, Embase, ClinicalTrials.gov, Google Scholar, and Springer Online Archives Collection, from January 1966 to October 2018. Articles resulting from these searches and relevant references cited in those articles were examined.ResultsThe efficacy among insulins evaluated was similar, however, second generation insulins cause a lower risk of hypoglycemia compared to first generation insulins. A single study showed similar metabolic control with subtle differences in the risk of hypoglycemia among second generation insulins.ConclusionsThe second-generation basal insulins result in metabolic control similar to first generation insulins, with lower risk of hypoglycemia. Second-generation insulins have comparable efficacy, with some differences in the risk of hypoglycemia.     

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.