The outcome and survival of metal-on-metal hip resurfacing in patients aged less than 50 years: a prospective observational cohort study with minimum ten-year follow-up.

AIMS: The aim of this study was to report the implant survival and patient-reported outcome measures (PROMs) in a consecutive series of patients aged less than 50 years at the time of arthroplasty using the Birmingham Hip Resurfacing system (BHR), with a minimum follow-up of ten years. PATIENTS AND METHODS: A total of 226 patients with osteoarthritis of the hip, who underwent BHR and presented to a single surgeon, were included in the study. Survival of the implant was confirmed by cross-checking with the Australian Orthopaedic Association National Joint Replacement Registry. Kaplan-Meier survival curves with 95% confidence intervals (CIs) were constructed. Pre- and postoperative PROMs were compared with t-tests, and postoperative scores were compared using anchor analysis with age and gender matched normative data. RESULTS: At median follow-up of 12 years (interquartile range (IQR) 10 to 13), six BHRs were revised, with a cumulative rate of survival of 96.8% (95% confidence interval (CI) 94.2 to 99.4) at 15 years, and with a significantly lower (p = 0.019) cumulative rate of revision than the national average for the same device at ten years. Most revisions (n = 4) were undertaken early, less than three years postoperatively, and occurred in women. Patient-reported general health (Veteran's Rand-36), disease state (Western Ontario and McMaster Universities Osteoarthritis Index), function (modified Harris Hip Score) and level of activity (Tegner activity score) maintained significant (p < 0.01 for each) improvements beyond ten years postoperatively and were equal to, or exceeded, age- and gender-matched normative data in more than 80% of the patients. CONCLUSION: Longer term PROMs after BHR, from a single surgeon, for patients aged less than 50 years remain under-reported. We found that the outcome after a BHR, at a minimum of ten years postoperatively, remained satisfactory, particularly for self-reported hip function.

Molecular analysis of CYP21 and C4 genes in Brazilian families with the classical form of steroid 21-hydroxylase deficiency.

The most common enzymatic defect of steroid synthesis is deficiency of the adrenal steroid 21-hydroxylase. Inhibition of the formation of cortisol results in an increased pituitary release of ACTH which in turn drives the adrenal cortex to overproduce androgens. This hormonal setting affects the development of genetic females by misdirecting the differentiation of external genitalia towards the male type. Since the isolation of the gene encoding 21-hydroxylase enzyme in 1984, gene deletions, large gene conversions, and microconversions have been reported to be responsible for the disease. In this paper, we report a study of this genetic defect in 22 families with one or more affected offspring diagnosed as having the classical form of congenital adrenal hyperplasia. The DNA from 30 patients was analyzed with three restriction enzymes. Hybridization with a 21-hydroxylase cDNA probe and the 5' end of a C4 genomic probe disclosed gene deletion in 7.3% (3/41) of the disease-related chromosomes. The rate of large gene conversion was 17.1% (7/41), and no abnormality in the hybridization pattern was observed in 75.6% (31/41) of the disease alleles. Densitometry of the autoradiographs was used to determine the ratio of the copy-number of the 21-hydroxylase gene (CYP21B) to the copy-number of its pseudogene (CYP21A). Differences in phenotype, the low frequency of gene deletion, and the high frequency of gene conversion compared with other studies in different populations indicated that 21-hydroxylase deficiency in the Brazilian population may involve different molecular mutations.

Molecular analysis of CYP21 and C4 genes in Brazilian families with the classical form of steroid 21-hydroxylase deficiency

The most common enzymatic defect of steroid synthesis is deficiency of the adrenal steroid 21-hydroxylase. Inhibition of the formation of cortisol results in an increased pituitary release of ACTH which in turn drives the adrenal cortex to overproduce androgens. This hormonal setting affects the development of genetic females by misdirecting the differentiation of external genitalia towards the male type. Since the isolation of the gene encoding 21-hydroxylase enzyme in 1984, gene deletions, large gene conversions, and microconversions have been reported to be responsible for the disease. In this paper, we report a study of this genetic defect in 22 families with one or more affected offspring diagnosed as having the classical form of congenital adrenal hyperplasia. The DNA from 30 patients was analyzed with three restriction enzymes. Hybridization with a 21-hydroxylase cDNA probe and the 5' end of a C4 genomic probe disclosed gene deletion in 7.3 percent (3/41) of the disease-related chromosomes. The rate of large gene conversion was 17.1 percent (7/41), and no abnormality in the hybridization pattern was observed in 75.6 percent (31/41) of the disease alleles. Densitometry of the autoradiographs was used to determine the ratio of the copy-number of the 2 1-hydroxylase gene (CYP21B) to the copy-number of its pseudogene (CYP21A). Differences in phenotype, the low frequency of gene deletion, and the high frequency of gene conversion compared with other studies in different populations indicated that 21-hydroxylase deficiency in the Brazilian population may involve different molecular mutations.

Two cases of Y; autosome translocations: A 45,X male and a clinically trisomy 18 patient.

We report on 2 cases of Y; autosome translocations. One is a male with normal external genitalia and 45,X karyotype without evidence of mosaicism or apparent translocation on cytogenetic analysis. In situ hybridization showed that the euchromatic portion of the Y-chromosome is translocated to the chromosome 15. The other case is a clinically trisomy 18 male patient, with modal number of 46, a small metacentric marker with appearance of an i(18p) and cytogenetic and molecular evidence of Y;18 translocation. The occurrence of Y;18 translocation associated with clinical signs of trisomy 18 is reported here for the first time.

Isolation and characterization of Y chromosome DNA probes.

A sorted, cloned Y chromosome phage library was screened for unique Y chromosome sequences. Of the thousands of plaques screened, 13 did not hybridize to radiolabeled 46,XX total chromosomal DNA. Three plaques were characterized further. Clone Y1 hybridized to multiple restriction enzyme fragments in both male and female DNA with more intense bands in male DNA. Clone Y2, also found in female and male DNA, is probably located in the pseudosutosomal region because extra copies of either the X or Y chromosomes increased Y2 restriction enzyme fragment intensity in total cellular DNA. Clone Y5 was male specific in three of four restriction enzyme digests although in the fourth a light hybridizing band was observed in both male and female DNA. Clone Y5 was sublocalized to band Yq 11.22 by hybridization to a panel of cellular DNA from patients with Y chromosome rearrangements. Clone Y5 can be used to test for retention of the proximally long arm Y suggested to cause gonadal cancer in carrier females. The long series of GA repeats in Y5, anticipated to be polymorphic, may provide a sensitive means to follow Y chromosome variation in human populations.

True agonadism: report of a case analyzed with Y-specific DNA probes.

We report on a 5-year-old girl with a male karyotype (46,XY), severe psychomotor and physical retardation, minor anomalies, and female external genitalia with a blindly ending vagina. She has normal adrenal function, prepubertal serum gonadotropin and testosterone levels, which did not rise after hCG stimulation. On abdominal exploration no gonads were found, and only mesonephric and Müllerian remnants. She was HY positive, and no deletion was detected in the Y chromosome using 5 different probes. Although a genetic defect is not excluded, pregnancy complications suggest an environmental insult to the developing testes.

Use of Y-chromosome-specific DNA probes to evaluate an XX male.

1. The function of a Y human chromosomal DNA sequence was evaluated. The Y-5 probe was isolated from a flow-sorted chromosome library and detects Y-specific sequences. 2. The Y-5 probe and other Y-specific probes were used to analyze an XX male patient without ambiguous genitalia. 3. DNA sequences from the short arm of the chromosome Y that were detected with pDP1007 and pDP105 in the patient's genome explain the testis differentiation observed in this case. 4. Failure of the patient's DNA to hybridize to the Y-5 probe shows that the primitive gonads can differentiate into testes even in the absence of this chromosome region. In contrast, a gene controlling spermatogenesis may exist in this region because the patient is azoospermic.

Use of y-chromosome-specific DNA probes to evaluate an XX male

The function of a Y human chromosomal DNA sequence was evaluated. The Y-5 probe was isolated from a flow-sorted chromosome library and detects Y-specific sequences. The Y-5 probe and other T-specific probes were used to analyze an XX male patient without ambiguous genitalia. DNA sequences from the short arm of the chromosome Y that were detected with pDP1007 and DP105 in the patient's genome explain the testis differentation observed in this case. Failure of the patient's DNA to hybridize to the Y-5 probe shows that the primitive gonads can differentiate into testes even in the absence of this chromosome region. In contrast, a gene controlling spermatogenesis may exist in this region because the patient azoospermic

The in vivo effect of cobalt chloride on chromosomes.

Este trabalho apresenta o estudo cromossomico de celulas somaticas e germinativas de hamsters machos (Mesocricetus auratus, 2n = 44) com 6 a 16 semanas de idade. As analises das celulas somaticas foram realizadas em preparacoes citologicas da medula ossea de 13 animais controles e de 10 animais inoculados com solucao salina de cloreto de cobalto (CoCl2). Para obtencao de metafases meioticas, foram feitas preparacoes citologicas de 6 animais de cada grupo. Somente os animais tratados com CoCl2 mostraram celulas somaticas e espermatocitos resultantes da meiose I, com aumento significativo de hiperdiploidia e pseudodiploidia