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.      

Neuropsychological correlates of learning disabilities: Subtype identification by the tryon clustering method

Since Samuel Orton's (1937) assertion that dyslexia reflects abnormal brain organization, the relationship of learning disabilities to brain dysfunction has been the topic of considerable debate. Recently, learning-disabled individuals have been studied in conjunction with those known to have neurological dysfunction, in a search for common subtypes. In the present study, a population of 177 children, ages 9-0 to 14-0, were assessed on an augmented version of the Children's Halstead-Reitan Battery. One hundred twenty-nine Ss were learning-disabled, 37 of whom also had verified brain damage. The remaining 48 children had neither learning disabilities nor evidence of brain damage. Patterns of neuropsychological performance were determined using Tryon's clustering methods. The procedure yielded six subject clusters: (A) and (B)—children with low general intellectual ability; (C) children who are clumsy and lethargic; (D) children with language dysfunction; (E) children with faulty spatial orientation; and (F) children with no detectable neuropsychological deficits. These clusters were similar to those identified by investigators who have used other subject-clustering methods. Brain-damaged individuals were more prevalent in some clusters (e.g., A and B) than in others (e.g., E and F), and substantial numbers of learning disabled subjects were also found in clusters where brain-damaged individuals tended to cluster, indicating similar neuropsychological profiles. The cluster structure was validated by comparison with subtypes identified by other investigators, as well as by tests of association between clusters with exogenous factors (e.g., history of prematurity; seizures).     

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.     

A sensitive method for assay of a novel tricyclic compound using coulometric electrochemical detection

A reversed-phase high-performance liquid chromatographic method using coulometric electrochemical detection in the oxidative mode has been developed for the analysis of 3-(9-chloro-5,6-dihydro-11-H-pyrrolo[2,1-b][3]benzazepine-11-ylidene- N,N-dimethyl-1-propanamine(E)-Z-butenedioate hydrogen maleate (1) in plasma of patients dosed with 2-8 mg/kg/d of the drug. Concentrations as little as 0.1 ng/mL of 1 in plasma can be estimated with a mean coefficient of variation of 7.4 +/- 1.08%. The utility of the procedure was demonstrated by the analysis of 500 patient samples from a rising multiple-dose study.     

Functional properties of recombinant GABAA receptors composed of single or multiple β subunit subtypes

GABA_A receptor (GABAR) isoforms in the central nervous system are composed of combinations of α(1–6), β(1–4), γ(1–4), δ(1) and (1) subunit subtypes arranged in a pentamer. Many regions of the brain express high levels of mRNA encoding several different subunits and even multiple subunit subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and identity of individual subunit subtypes that are coassembled remain uncertain. To examine the role of β subunit subtypes in the functional properties of GABARS and to determine whether multiple β subtypes can be coassembled in functional GABARs, plasmids containing cDNAs encoding rat β1 and/or β3, α5 and γ2L subtypes were cotransfected into L929 fibroblasts. The properties of the expressed receptor populations were determined using whole-cell and single-channel recording techniques. The α5β1γ2L isoform was less sensitive to GABA than the α5β3γ2L isoform. α5β1γ2L isoform currents were also insensitive to the allosteric modulator loreclezole, while α5β3γ2L isoform currents were strongly potentiated by loreclezole. Fibroblasts transfected with plasmids containing cDNAs for both β1 and β3 subtypes along with α5 and γ2L subtypes produced a receptor population with an intermediate sensitivity to GABA which was insensitive to loreclezole. These results suggest that functional GABARs can be formed that contain two different β subunit subtypes with properties different from receptors that contain only a single β subtype and that the β subunit subtypes influence the response of GABARs to GABA and to the allosteric modulator loreclezole.     

Low-Calcium Diets Enhance Phytate-Phosphorus Availability

This study showed that, in chickens, the negative effects of phytate-phosphorus in a low inorganic phosphorus diet could be completely reversed through the additive effects of reduced dietary calcium and increased cholecalciferol. In the future, perhaps greater reliance on more readily available plant phosphorus sources may be instituted in developing countries, where cheap sources of inorganic phosphorus are difficult to obtain.