Autosomal recessive idiopathic torsion dystonia in a kindred of mixed ancestry

A family with idiopathic torsion dystonia (dystonia musculorum deformans) was seen in a peripheral clinic in the Richtersveld in the north-western Cape. This rare inherited form of neurological disease has maximal prevalence in individuals of Ashkenazi Jewish ancestry, and there is controversy regarding the exact mode of inheritance. The kindred documented in this study was of mixed ancestry (Cape Coloured), and autosomal recessive inheritance was suggested by the finding of affected male and female siblings born to normal parents in an isolated inbred community.     

Giving up driving in Alzheimer's disease—an integrative therapeutic approach

For patients with Alzheimer's disease (AD), a recommendation to stop operating a motor vehicle can be a serious event complicated by a loss of self-esteem and personal dignity. Patients are often reluctant to give up an activity so essential, both practically and symbolically, to independent living. We describe here a patient with moderately progressed AD who lacked insight of his need to cease driving. Through an integrative treatment approach, combining behavioral and psychodynamic modalities, we helped him to formulate effective ways of coping with his loss of access to independent transportation. We favor a psychotherapeutic strategy that combines behavioral and managerial measures with dynamic patient interaction, thereby developing the patient's insight of the need to give up driving while fostering his sense of autonomy.     

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.      

Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction

Y chromosome deletions encompassing the AZFc region have been reported in 13% of azoospermic men and 7% of severely oligozoospermic men. We examined the impact of these Y deletions on the severity of testicular defects in 51 azoospermic men undergoing intracytoplasmic sperm injection (ICSI) after testicular sperm extraction (TESE) and 30 men with severe oligozoospermia undergoing ICSI after ejaculation of spermatozoa. In addition, five azoospermic patients shown previously to have Y chromosome deletions underwent histological evaluation of their previously obtained testis biopsy specimens. A further 27 azoospermic men underwent TESE-ICSI, but not Y chromosome DNA testing. Ten of 51 azoospermic men (20%) who underwent TESE-ICSI and Y-DNA testing were found to be deleted for portions of the Y chromosome AZFc region. Of these 10, five had spermatozoa retrievable from the testis, and in two cases the wives became pregnant. Of the 41 azoospermic men with no Y chromosome deletion, 22 (54%) had spermatozoa retrievable from the testis, and in 12 cases (29%) the wives became pregnant. Four of 30 (13%) severely oligozoospermic patients were found to be deleted for AZFc and in three (75%) of these pregnancy was achieved. The other 26 severely oligozoospermic couples who had no AZFc deletions underwent ICSI, and 12 (46%) have an ongoing or delivered pregnancy. The embryo implantation rate was not significantly different for azoospermic (22%), oligozoospermic (16%), Y-deleted (14%) or Y-intact (18%) men. Of the total of 19 infertile men who had Y chromosome deletions, 14 had deletions within Y chromosome intervals 6D-6F, in the AZFc region. Twelve of those 14 had some spermatozoa (however few in number) in the ejaculate or testis. Five of the Y-deleted men had deletions that extended more proximally on the Y chromosome, and in none of these could any spermatozoa be observed in either ejaculate or testis. These results support the concept that, in azoospermic or oligozoospermic men with Y chromosome deletions limited to intervals 6D-6F (AZFc), there are generally very small numbers of testicular or ejaculated spermatozoa. Larger Y deletions, including and extending beyond the AZFc region and encompassing more Y genes, tend to be associated with a total absence of testicular spermatozoa. In those cases where spermatozoa were retrieved, the presence of Y deletions had no obvious impact on fertilization or pregnancy rate.      

Aetiology of congenital absence of vas deferens: genetic study of three generations

Bilateral congenital absence of the vas deferens (CAVD) is aform of male sterility (found in otherwise normal men) of unknownaetiology. Because males with cystic fibrosis (CF) almost invariablyhave CAVD as well, we investigated the hypothesis that men withisolated CAVD might share a common genetic background with maleswith CF. Genetic testing for CF was carried out in three generationsof subjects: 44 patients with CAVD and their wives, 24 of theirparents, and 13 of their offspring generated by microsurgicalepididymal sperm aspiration (MESA) and in-vitro fertilization(IVF). DNA extracted from peripheral lymphocytes was amplifiedby the polymerase chain reaction (PCR) and then analysed for12 mutations in the cystic fibrosis transmembrane conductanceregulatory (CFTR) gene. Among 44 patients tested with CAVD,26 (59%) were positive for at least one CF mutation, while thecarrier frequency for CF mutations in the general populationis only 4%. Four patients were found to be compound heterozygotes,three with genotypes Delta F-508/R117H, one with R553X/R117H.Among 24 parents tested, 15 (seven fathers, eight mothers) hadsons with CAVD who were positive for CF mutations. Of these,nine (four fathers and five mothers) were found to be carriersfor CF mutations. These four fathers, although carriers of CFmutations, were obviously fertile. Of the 13 offspring tested,six (three boys and three girls) had CF positive fathers. Ofthese, three (two girls and one boy) were found to be carriersfor CF mutations. These MESA/IVF children are the first offpsringto whom men with CAVD have been able to transmit CF mutations.All of the MESA/IVF male offspring (like their grandfathers)had a normal vas deferens bilaterally, including one carrierfor Delta F-508. This study revealed, by genetic testing ofotherwise normal men with sterility caused by CAVD, a new populationof patients with a variant form of CF and highlighted the possibilitythat carrier frequency for CF is higher than previously thought.Compound heterozygosity for CF mutations and not carrier conditionis associated with isolated CAVD. It is concluded that geneticcounselling and screening for CF should be offered to couplesundergoing sperm aspiration and IVF procedures when CAVD isa factor in their infertility.