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Biomedical subjects

R McLachlan

Publications and source records attributed to R McLachlan.

18 recordsLinked to original sources
PubMed2002

Genetic follow-up of male offspring born by ICSI, using a multiplex fluorescent PCR-based test for Yq deletions.

De-novo deletions involving AZFa, b, c and d are one of the most common chromosomal aberrations in man resulting in defective spermatogenesis and male infertility. Currently, Yq deletion screening involves either single or multiplex PCR using Y-specific sequence tagged site markers and the subsequent analysis of the amplification products on ethidium bromide-stained agarose gels. To improve the practicality of routine and high throughput Yq testing, we have developed a more sensitive multiplex fluorescent (FL)-PCR screening system using genomic DNA extracted from cheek buccal cells as a readily available PCR template. For genetic follow-up studies of ICSI-conceived children, we also developed a DNA fingerprinting system based on the co-amplification of four highly polymorphic markers to validate family samples and detect any potential extraneous DNA contamination that could cause a misdiagnosis. Multiplex FL-PCR analysis of buccal cell DNA from two infertile men who conceived three sons by ICSI demonstrated that their Yq deletions were vertically transmitted. Fine mapping with additional Yq markers revealed identical deletion endpoints involving the loss of AZFdc sequences. This firstly indicates that the extent of the Yq deletion was unchanged on ICSI transmission and secondly supports the view that AZFdc deletions may arise by a common de-novo event. Analysis of paternal, maternal and sibling DNA fingerprints showed the co-inheritance of parental alleles by each male child and confirmed the expected relationship between each family member. The application of these new FL-PCR based screening tests in genetic follow-up studies will assist in confirming transmission of specific genetic defects to male offspring conceived by ICSI and provide a basis for genetic counselling and potential treatment options as these boys approach sexual maturity.

Adult↗
PubMed2000

Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions.

OBJECTIVE: To determine the prevalence and type of Yq microdeletions in 86 consecutive men that fathered 99 sons by intracytoplasmic sperm injection (ICSI) and to determine the incidence of vertical transmission and de novo deletions in these boys. DESIGN: Prospective clinical observational study. SETTING: Genetics laboratory associated with a university IVF unit. PATIENT(S): Eighty-six consecutive infertile men presenting to an IVF clinic and their 99 ICSI-conceived sons. Fifty of the 86 men (58%) had idiopathic seminiferous tubule failure (STF); the remainder had a variety of other clinical indications for ICSI. INTERVENTION(S): Collection of peripheral and cord blood samples. MAIN OUTCOME MEASURE(S): The Yq genetic status of fathers who underwent ICSI and of their sons by the presence or absence of 22 Y-specific markers covering the four azoospermia factor (AZF) subregions. RESULT(S): Yq deletions of the AZFd/c region were detected in two (6.9%) of 29 azoo- or severely oligospermic men with STF. Identical deletions were found in their respective sons. No de novo deletions were detected in the remaining 97 sons conceived by men without deletions. CONCLUSION(S): The detection of Yq deletions only in men with severe STF is consistent with previous studies, with the AZFd/c region being most commonly affected. This study demonstrates the vertical transmission of these Yq deletions through the use of ICSI and supports the notion that, in most cases, Yq deletions will be inherited by male offspring. The absence of de novo Yq deletions in the male offspring indicates that these events are rare following ICSI in men with both STF and other common male factor indications.

Fathers↗
PubMed2000

Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg).

There are few published data on the recovery of fertility after 'little' Bu-Cy (busulfan 16 mg/kg, cyclophosphamide 120 mg/kg) conditioning for BMT. To address this, we identified 19 females aged less than 40 years at transplant and 47 males from a single centre who were alive a minimum of 2 years after BMT with little Bu-Cy as conditioning and who were evaluable for testing. FSH, LH, testosterone and inhibin B levels were measured in males. Twenty-six also had semen analysis, a median of 5 years post transplant; 21 had detectable sperm, with 11 having counts >20 x 10(6)/ml. There was an association between prolonged chronic graft-versus-host disease and low sperm counts. FSH and inhibin B levels correlated with sperm counts but not to the extent that they could reliably predict counts in individual patients. An additional six of seven males attempting to father children did so, a median of 3.2 years post transplant. Low testosterone levels were noted in 12% of males, most of whom had symptoms consistent with androgen deficiency. FSH, LH and oestradiol levels in the absence of hormone replacement therapy were measured in females; all remained amenorrheic with endocrine evidence of ovarian failure. These results have implications for fertility counselling and hormone replacement therapy both pre- and post BMT.

Adult↗
PubMed1999

Psychosis after resection of ganglioglioma or DNET: evidence for an association.

PURPOSE: David Taylor and Murray Falconer suggested that some patients may develop a psychotic illness after resection of a ganglioglioma that led to intractable seizures. They implied that the mechanism of this association remained unclear. This concept is currently not universally accepted (M. Trimble, personal communication). METHODS: We studied six children or young adults from four centers who developed psychosis after resection of a ganglioglioma or dysembryoplastic neuroepithelioma (DNET). RESULTS: All patients were operated on because of intractable epilepsy. The lesions involved mainly the temporal lobe. Patients had good outcomes for seizure control. In none of the six was potentially psychogenic medication used nor were the psychotic symptoms postictal in nature. The psychosis was schizophreniform with paranoid features and prominent depressive symptoms. Although some behavioral abnormalities were described preoperatively, none had been psychotic before operation. This type of psychotic reaction was not encountered in the four centers in a comparable period after resection of other types of lesions. This complication is rare; it occurred in only one of 39 patients who had such a lesion resected. CONCLUSIONS: Psychotic illness may rarely occur after resection of a ganglioglioma or DNET for treatment of intractable epilepsy. This does not seem to occur after removal of other types of lesions. Because the patients had good outcomes for seizures, the mechanism may be related to "forced normalization." The original observations of Taylor and Falconer are confirmed by this study; the reasons for the selective occurrence, however, remain speculative.

Adolescent↗
PubMed1998

Azoospermia associated with a mutation in the ligand-binding domain of an androgen receptor displaying normal ligand binding, but defective trans-activation.

Although male infertility affects a significant proportion of couples trying to conceive, the cause of defective spermatogenesis is not known in a large number of cases. Ligand binding studies indicate that a number of these subjects may have defects of the androgen receptor (AR). Genetic screening in subjects with defective spermatogenesis and in 110 fertile controls identified an azoospermic (no sperm in any ejaculates) patient with an amino acid substitution (Gln-->Glu) in residue 798 of the AR gene. This germline mutation was pathogenic because it was not observed in fertile controls, was associated with features of minimal androgen insensitivity in our patient, has been related to more severe grades of androgen insensitivity, and caused a subtle, but significant, decrease in receptor trans-activation function in vitro that is consistent with the phenotype. Despite being located in the middle of the ligand-binding domain of the receptor, the Q798E mutation did not cause any ligand binding defect, indicating that this highly conserved residue has a trans-activation function but does not directly form part of the ligand binding pocket of the receptor. The trans-activation defect of the mutant receptor can be rectified in vitro with the androgenic drug, fluoxymesterone, but not with mesterolone or nortestosterone. Further studies are required to determine the therapeutic relevance of this finding.

Adult↗
PubMed1997

Outcome assessment in epilepsy: comparative responsiveness of quality of life and psychosocial instruments.

PURPOSE: Few data exist on the ability of instruments to detect within-patient change over time in epilepsy, a property referred to as responsiveness. Our aim was to compare the responsiveness of three instruments [i.e., Epilepsy Surgery Inventory-55 (ESI-55) and Washington Psychosocial Inventory (WPSI), both epilepsy specific, and Symptom Checklist-90-Revised (SCL-90-R), non-epilepsy specific]. METHODS: Instruments were administered at baseline and at 1 year in a prospective cohort of surgically (43) and medically (14) treated patients with temporal lobe epilepsy. Coefficient of Responsiveness and relative efficiency were computed for each scale and for the dimensions of mental health, physical health, and role function. RESULTS: The ESI-55 contained the most responsive scales, whereas SCL-90-R contained the largest number of scales with moderate responsiveness. The largest number of scales with low responsiveness belonged to the WPSI. Sensitivity to between-treatment differences in change was highest for ESI-55 and SCL-90-R. The most efficient scales in detecting differences between treatment groups in the mental, physical, and role-function dimensions were ESI-55 emotional well-being, ESI-55 health perceptions, and SCL-90-R hostility, respectively. CONCLUSIONS: Our results support the responsiveness of ESI-55 scales and suggest that SCL-90-R is a responsive tool for the assessment of psychologic function and distress in epilepsy. Comparatively, WPSI is relatively unresponsive to small or medium-size changes.

Adult↗
PubMed1995

The management of male subfertility by in vitro fertilisation techniques.

Although IVF was developed for the treatment of tubal infertility, it is clear that it has a significant application in treatment of couples where the problem is one of male subfertility. This is particularly relevant because, despite the developments in reproductive medicine, in most males there is no identifiable cause for the poor semen quality. Therefore, for these men there is no efficacious method of treatment. Varicocele ligation and the use of agents such as clomiphene citrate, mesterolone empirical antibiotic therapy, and anabolic steroids have not been show to be beneficial when subject to controlled trials. The concept of improving the chance of fertilisation by taking the oocytes to the sperm in vitro is therefore the first feasible therapeutic option available to these subfertile couples. However, these possibilities should not obviate the need for a thorough assessment of the subfertile male and continuing research into the basis of male infertility. During the past decade new methods of sperm preparation, modified methods of insemination, and the use of microinjection have been developed. IVF is now a realistic option for couples if the male is subfertile. It has been suggested by some critics of these techniques that the brunt of the discomfort and risk has to be borne by the women where the problem appears to be solely with the male partner. Nevertheless, as having children is a 'couple' decision, prospective couples need to consider whether such procedures are acceptable to them.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Primary Sjögren's syndrome and gamma heavy chain disease.

We describe a patient who has primary Sjögren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis. Sjögren's syndrome is known to be complicated by lymphoproliferative disorders and tubulointerstitial nephritis but gamma heavy chain disease is rare (approximately 100 cases described). There is one previously reported case of gamma heavy chain disease associated with primary Sjögren's syndrome and 2 cases associated with secondary Sjögren's syndrome. Our patient and the 3 other patients described in the literature did not have evidence of an underlying lymphoproliferative disorder.

Aged↗
PubMed1993

Plasma intestinal alkaline phosphatase isoenzymes in neonates with bowel necrosis.

AIM: To determine if the intestinal isoenzymes of alkaline phosphatase (ALP) are biochemical markers of bowel necrosis in neonates. METHODS: Plasma ALP isoenzymes were measured in 22 babies with bowel necrosis, histologically confirmed, and in 22 matched controls. The isoenzymes were also measured in 16 infants with signs of necrotising enterocolitis, who recovered without histological confirmation of bowel necrosis. The isoenzymes were separated by polyacrylamide gel electrophoresis. Auxiliary tests for identification included neuraminidase digestion and treatment with monoclonal and polyclonal antiplacental antibodies. RESULTS: Intestinal ALP was detected in 16 infants with bowel necrosis--13 had fetal intestinal ALP (FI-ALP) and three had adult intestinal ALP (AI-ALP). FI-ALP was detected in nine of the controls. In the babies with bowel necrosis intestinal ALP was found over all gestations, but in the controls only in those less than 34 weeks. The percentages of total ALP activity due to intestinal ALP were significantly higher in those with bowel necrosis compared with matched controls (p = 0.028). In babies of all gestations diagnostic sensitivity for the presence of intestinal ALP as a marker of bowel necrosis was 73% and diagnostic specificity 59%. In babies greater than 34 weeks' gestation, diagnostic sensitivity fell to 60% but the test became completely specific. In two babies FI-ALP increased from zero/trace to high activity coincident with the episode of bowel necrosis. In 16 babies with signs of necrotising enterocolitis but unconfirmed bowel necrosis FI-ALP was detected in four. CONCLUSION: Intestinal ALP seems to be released into the circulation in some babies with bowel necrosis, but its detection does not have the diagnostic sensitivity and specificity to be a reliable biochemical marker of the condition.

Alkaline Phosphatase↗
PubMed1989

Monoclonal immunoglobulins: affinity blotting for low concentrations in serum.

I describe a simple, economical technique for identifying low concentrations of monoclonal immunoglobulins in the presence of excessive amounts of immunoglobulins of other classes. The technique involves binding of specific antibody to nitrocellulose, separating proteins by isoelectric focusing or zone electrophoresis in agarose gels, using capillary transfer to bind proteins to the nitrocellulose via their antibody affinity, and then detecting transferred proteins with enzyme-labeled antibody. A monoclonal immunoglobulin can be completely characterized in 2 h. No expensive equipment is required. Affinity blotting is about 10-fold as sensitive as native blotting, 100-fold as sensitive as silver staining.

Antibodies, Monoclonal↗
PubMed1988

Demonstration of monoclonal IgE by isoelectric focusing: first reported case of IgE myeloma in Australia.

A 56-year-old man who presented with back pain was diagnosed with multiple myeloma. Serum protein analysis by isoelectric focusing identified a monoclonal IgE lambda of unique spectrotype compared with other monoclonal immunoglobulins. The similarity of the spectrotype of this monoclonal IgE to that of two purified monoclonal IgEs suggests that these proteins have a characteristic spectrotype, sufficiently different from those of other immunoglobulin classes to allow its recognition.

Antibodies, Monoclonal↗
PubMed1985

The medical and psychological investigation of psychogenic polydipsia: a case study.

The case of a 17 year-old female with psychogenic polydipsia is reported; 13 out of 18 members of her maternal family were known to have had polydipsia and polyuria, but only two had undergone endocrine investigations--one had diabetes insipidus and one also had psychogenic polydipsia. There are probable contributions of non-genetic family factors including imitation and identification to the development of this patient's condition. Detailed family and developmental histories may be of particular assistance in the understanding of the psychogenesis of the disorder in some patients.

Adolescent↗
PubMed1982

Chronic lymphatic leukemia developing in a patient with multiple myeloma: immunologic demonstration of a clonally distinct second malignancy.

A patient with multiple myeloma who subsequently developed chronic lymphocytic leukemia is reported. Initial studies demonstrated clinical and hematological features of multiple myeloma with an IgM lambda paraprotein. Skeletal disease was a significant presenting feature, although relapse occurred in extraosseous sites, particularly the pleura. He developed chronic lymphatic leukemia 31 months later and immunological studies showed the malignant lymphocytes to have kappa (Kappa) light chain surface immunoglobulin, demonstrating separate clonal origin of this patient's two B-cell malignancies.

Aged↗
PubMed1980

Monoclonal antibodies to murine cell surface antigens. I. Lyt-1.1.

The production and properties of a monoclonal anti-Lyt-1.1 antibody are described. The monoclonal antibody is of the IgG2a subclass, is cytotoxic, and reacts with Staphylococcal protein A. The tissue culture supernatant has the same activity (titer on thymus > 1/1000) as an anti-Lyt-1.1 produced by a standard immunization procedure, and after in vivo passage of the hybridoma cell line, the serum titer was > 1:10(6). The monoclonal antibody has the same strain and tissue distribution as the conventional antibody, including reactions on Lyt-1 congenic strains, and it precipitates a cell surface molecule of m.w. approximately 67,000. In nonprimed mice, there were similar numbers of Thy-1+ and Lyt-1+ cells in spleen, lymph node, and thymus. By using the monoclonal reagent, T-helper and T-killer cells in an allogenic system were shown to be Lyt-1.1.

Animals↗