Effect of hormone replacement therapy on lacrimal fluid peroxidase activity in woman

OBJECTIVE: Lacrimal fluid peroxidase (POD) is an antioxidant and antimicrobial enzyme involved in the protection of the ocular surface. Our recent findings showed the existence of significant cyclic variations in POD activity that were positively correlated with those of 17beta-estradiol plasma levels throughout the menstrual cycle of fertile women. During the menopause, women lacrimal fluid POD activity significantly (P<0.05) decreased according to the natural oestrogen reduction. Since a possible influence of oestrogen on human POD activity was suggested, aim of the present investigation is to evaluate whether hormone replacement therapy (HRT) might influence this enzyme activity. METHODS: Lacrimal fluid POD activities of 10 healthy postmenopausal women (mean age: 52.0) and eight healthy postmenopausal women (mean age: 53.0) treated by oral or transdermal routes containing oestrogen or oestrogen plus progestin were determined. Enzyme activity of each tear sample (5 microl) was spectrophotometrically determined by the 5,5'-dithiobis, 2-nitrobenzoic acid thiocyanate (NBS-SCN) assay; total protein content of tears was determined too. 17beta-Estradiol plasma levels were assayed by ELISA test. RESULTS: HRT significantly (P<0.05) increased tear POD low postmenopausal levels. The significant (P<0.05) rise of 17beta-estradiol plasma levels of treated women was not strictly correlated to the enzyme activity increase in tears. CONCLUSIONS: The suggested estrogen regulation of lacrimal fluid POD activity could be one possible cause for the female gender predilection in some ocular diseases. HRT is able to increase tear POD activity levels of postmenopausal women, probably contributing to the effective relieve of ocular surface complications occurring during menopause.     

A new single-nucleotide deletion of PMP22 in an HNPP family without recurrent palsies

In this study we describe four patients from the same kindred who were affected by an autosomal-dominantly inherited peripheral neuropathy. They presented an unusual combination of clinical, electrophysiological, and pathological findings in association with a new mutation of the PMP22 gene. Clinically, three patients had carpal tunnel syndrome symptoms and one patient had late-onset peroneal atrophy. Motor and sensory nerve conduction velocities were reduced without focal slowing at entrapment sites. Nerve biopsy disclosed diffuse hypomyelination with focal thickening of the myelin sheath in some fibers. Sequence analysis of the PMP22 gene showed a single-nucleotide deletion (227delG) in the affected patients. This mutation, which has not been reported previously, leads to an open reading frame shift and probably to a truncated and unstable PMP22 protein. We conclude that this novel 227delG mutation of PMP22 gives a mild form of hereditary neuropathy with liability to pressure palsy with atypical clinical and electrophysiological findings.     

Robust Determination of Fatigue Crack Propagation Thresholds from Crack Growth Data

The robust determination of the threshold against fatigue crack propagation ΔKth is of paramount importance in fracture mechanics based fatigue assessment procedures. The standards ASTM E647 and ISO 12108 introduce operational definitions of ΔKth based on the crack propagation rate da/dN and suggest linear fits of logarithmic ΔK– da/dN test data to calculate ΔKth. Since these fits typically suffer from a poor representation of the actual curvature of the crack propagation curve, a method for evaluating ΔKth using a nonlinear function is proposed. It is shown that the proposed method reduces the artificial conservativeness induced by the evaluation method as well as the susceptibility to scatter in test data and the influence of test data density.     

Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia

RATIONALE: Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date. OBJECTIVE: To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder. METHODS: Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline. RESULTS: Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28). CONCLUSIONS: In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.     

Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe's disease

We describe three brothers suffering from Krabbe's disease with onset in the fifth decade. The proband showed a complete deficiency of leukocyte enzyme galactocerebrosidase and was found to be heterozygous for two previously described mutations: G > A809 and 502T/del consisting of a 30 kb deletion. In all three brothers the neurological examination showed features of asymmetrical peripheral neuropathy associated with pyramidal signs and the electrophysiological examination showed a generalized slowing of nerve conduction velocities. Two patients died at 59 and 61 years of age due to respiratory failure. Both the proband and his brother underwent a sural nerve biopsy. In the former the most striking finding was the presence of uniformly thin myelin sheaths without evidence of demyelination; a complete absence of fibers was found in the latter. Our findings confirm that peripheral neuropathy may be the presenting feature of late-onset Krabbe's disease. Hypomyelination rather than demyelination may represent the distinguishing pathological finding of this condition.     

Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations

PURPOSE: The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25-70% of the patients having a family history of febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder. METHODS: We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families. Familial clustering and syndromic concordance within the affected relatives in both groups were investigated. RESULTS: The frequency of FS or epilepsy in relatives of SMEI patients did not significantly differ from that in controls (FS: 13 of 867 vs. 12 of 674, p = 0.66; epilepsy: 15 of 867 vs. six of 674, p = 0.16). Different forms of epilepsy were identified in both relatives of SMEI probands and controls. Twenty-eight relatives with FS and epilepsy were distributed in 20 (27%) of 74 SMEI families; among the controls, 18 affected relatives were clustered in 13 (18.5%) of 70 families. No pedigree showed several affected members, including the four with inherited mutations. CONCLUSIONS: A substantial epileptic family background is not present in our SMEI patients with SCN1A mutations. These data do not confirm previous observations and would not support polygenic inheritance in SMEI. The investigation of the family background in additional series of SMEI patients will further shed light on the genetics of this syndrome.