Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome.

There is no established treatment for the neurological features of the recently discovered fragile X-associated tremor/ataxia syndrome (FXTAS). Fifty-six patients with FXTAS completed a questionnaire to determine whether any medications had been effective for neurological symptoms. Of 11 subjects with definite FXTAS, 8 (70%) were on medications for their neurological symptoms, whereas most subjects with possible or probable FXTAS, 31 (70%) of 45 subjects, were not on medications. Although no therapy was uniformly effective for intention tremor, ataxia, Parkinsonism, memory loss, or anxiety, some subjects with intention tremor or Parkinsonism reported improvement with medications frequently used in other movement disorders. Overall, all 22 subjects on medications reported improvement in one or more symptoms. Lack of insight, recall bias, and cognitive impairment may have resulted in an underestimation of the beneficial effect of medical therapy. This study suggests that patients with FXTAS can derive improvement from medication treatment for some of their symptoms.     

Physiological properties of conjugated linoleic acid and implications for human health.

Conjugated linoleic acid (CLA) refers to a mixture of positional and geometric dienoic isomers of linoleic acid found naturally in animal products of ruminant sources. Recent interest in CLA research stems from the well-documented anticarcinogenic, antiatherogenic, antidiabetic, and antiobesity properties of CLA in rodents. However, there has been very little published human research on CLA. This review discusses the physiologic properties of CLA and their potential implications for human health.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G- CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in- vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.      

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.