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Biomedical subjects

C Garrett

Publications and source records attributed to C Garrett.

At least 37 records · Page 2Linked to original sources
PubMed2000

Feasibility of surveillance of changes in human fertility and semen quality.

To show that male fertility is declining is not simple. Few men volunteer and recruitment bias may lead to over-representation of the subfertile. Semen analysis has errors arising from counting and poorly standardized criteria, which may be overcome by automation. Time to pregnancy (TTP)-the number of menstrual cycles taken to conceive-measures fertility and allows male recruitment bias to be estimated. We review automated measurement of sperm concentration, motility and morphology and present a preliminary report on a study to assess a retrospective TTP questionnaire, recruitment bias and feasibility for large-scale surveillance of fertility.

Feasibility Studies↗
PubMed2000

The human acrosome reaction.

We developed tests of sperm-oocyte interaction: sperm-zona binding, zona-induced acrosome reaction, spermzona penetration and sperm-oolemma binding, using oocytes which failed to fertilise in clinical in vitro fertilization (IVF). Although oocyte defects contribute to failure of sperm oocyte interaction, rarely are all oocytes from one woman affected. Low or zero fertilization in standard IVF was usually caused by sperm abnormalities. Poor sperm-zona pellucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morphology. The size and shape of the acrosome is particularly important for sperm binding to the oocyte. The proportion of acrosome intact sperm in the insemination medium was related to the IVF rate. Inducing the acrosome reaction with a calcium ionophore reduced sperm-zona binding. Blocking acrosome dispersal with an acrosin inhibitor prevented spermzona penetration. Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding. Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normal sperm-zona binding. Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrated the zona. In contrast, fertilization and pregnancy rates were high with intracytoplasmic sperm injection. We call this condition defective zona pellucida induced acrosome reaction. Discovery of the nature of the abnormalities in the signal transduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler tests and treatments for the patients and also provide new leads for contraceptive development.

Acrosome Reaction↗
PubMed1999

A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3.

In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR) inheritance have been reported, but no genes have been identified or localized for nonsyndromic SD in humans. We performed genomewide scanning by homozygosity mapping in a large consanguineous ARSD Arab Israeli family with six definitely affected members. Significant linkage was found to chromosome 19q13, with a LOD score of 6.9. This was confirmed in a second Pakistani family with three affected members, with a LOD score of 2.4. The combined-haplotype data identify a critical region between D19S570 and D19S908, an interval of 8.5 cM on 19q13.1-19q13.3. This is the first study to localize a gene for nonsyndromic SD. ARSD is clinically heterogeneous and is likely to result from mutations in developmental genes or from regulating transcription factors. Identification of these genes will improve the understanding of the molecular processes contributing to both normal and abnormal human vertebral development.

Adolescent↗
PubMed1999

Comparison of human cervical mucus and artificial sperm penetration media.

The cervical mucus penetration tests aid research and determine the clinical importance of positive sperm antibody tests. Limited availability and variability of human cervical mucus have instigated the search for mucus substitutes for these tests. This study compares sperm migration in cervical mucus with that in artificial media including hyaluronate solution, egg white and albumin Tyrode solution. Results were quantified by measuring the migration distance (the maximum distance of capillary migration from a semen reservoir by spermatozoa after 1 h) and the sperm concentration at half the migration distance. The mean of both measures for cervical mucus and hyaluronate solution were equivalent [4.4 +/- 1.1 (SD) versus 4.3 +/- 1.0 cm and 118 +/- 51 versus 111 +/- 44x10(3)/ml], and higher than in egg white and albumin Tyrode solution. Antisperm antibodies impaired sperm penetration in cervical mucus and hyaluronate solution in a similar manner (r = 0.92). These results suggest that hyaluronate solution sufficiently resembles human cervical mucus in terms of penetrability that it may be used as a substitute for mucus in capillary tube tests of sperm function. The higher penetrability of cervical mucus and hyaluronate solution is probably related to a channelling effect due to their polymeric structure.

Albumins↗
PubMed1999

Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome.

Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.

Cerebellum↗
PubMed1999

The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria.

The Silver-Russell syndrome (SRS) is characterised by severe intrauterine growth retardation, with a preserved head circumference, leading to a lean body habitus and short stature. Facial dysmorphism and asymmetry are considered typical features of the syndrome, although the range of phenotypic variance is unknown. Fifty seven subjects varying in age from 0.84 to 35.01 years, in whom the diagnosis of SRS had been considered definite or likely, were re-evaluated in a combined clinical and molecular study by a single observer (SMP). In 50 patients the clinical findings complied with a very broad definition of SRS. Notable additional findings included generalised camptodactyly seen in 11 (22%), many with distal arthrogryposis. Thirteen of the 25 males required genital surgery for conditions including hypospadias and inguinal hernia. Fourteen (36.8%) subjects above school age have received a statement of special educational needs. Molecular genetic analysis was performed in 42 subjects and has identified maternal uniparental disomy of chromosome 7 in four. The phenotype was generally milder with birth weights for one patient above and three below -2 SD from the mean. Two children had classical facial dysmorphic features, and two had a milder facial phenotype. Of relevance to the possible molecular mechanism underlying this condition, none of the four disomic patients had significant asymmetry.

Abnormalities, Multiple↗
PubMed1998

Quantitative sperm mucus penetration: modified formulae for calculating penetration efficiency.

In 1980 Katz et al. derived a formula for the percentage of successful collisions (PSC) as a quantitative measure of sperm-cervical mucus penetration efficiency. The use of PSC waned after its validity was questioned by reports of values >100% and the observation that PSC varied with the cross-sectional area of the mucus column. The aim of the present study was to develop a more accurate measure of mucus penetration efficiency by correcting the original formula for the effects of sperm depletion in the semen reservoir. Two formulae were derived using different models for the sperm-mucus interaction: (i) each motile spermatozoon was assumed to have an equal chance of mucus penetration on collision; (ii) a select subpopulation of spermatozoa was assumed to penetrate with 100% efficiency on collision. Both modified formulae gave PSC values higher than the original estimates. Under the experimental conditions employed in this work, where large capillaries were used, the depletion corrections ranged from 4 to 46% (n=8, mean 20%) for model (i) and from 190 to 320% (n=8, mean 250%) for model (ii). The invariance of PSC (ii) results with respect to capillary cross-sectional area (1.52 mm2, 31.1%; 5.4 mm2, 28.2%) suggests that the assumptions of model (ii) provide the more accurate description of the sperm-mucus interaction.

Female↗
PubMed1997

Nine novel L1 CAM mutations in families with X-linked hydrocephalus.

Mutations in the gene for neural cell adhesion molecule L1 are responsible for the highly variable phenotype found in families with X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type I. To date, 32 different mutations have been observed, the majority being unique to individual families. Here, we report nine novel mutations in L1 in 10 X-linked hydrocephalus families. Four mutations truncate the L1 protein and eliminate cell surface expression, and two would produce abnormal L1 through alteration of RNA processing. A further two of these mutations are small in-frame deletions that have occurred through a mechanism involving tandem repeated sequences. Together with a single missense mutation, these latter examples contribute to the growing number of existing mutations that affect short regions of the L1 protein that may have particular functional significance.

Amino Acid Sequence↗
PubMed1997

Selectivity of the human sperm-zona pellucida binding process to sperm head morphometry.

OBJECTIVE: To obtain quantitative measures of morphometric selectivity of the human spermzona pellucida binding process as determined by light microscopy. DESIGN: Fully automated sperm head morphometric based on a 32-dimensional parameterization of images of Shorr-stained sperm. Zona pellucida selected sperm removed from reinseminated oocytes that previously failed IVF. SETTING: Academic research group associated with a tertiary infertility service. PATIENT(S): Semen samples from 51 infertile patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Differences in morphometric parameter means observed before and after swim-up and binding to zonae pellucidae. RESULT(S): Significant differences between insemination and bound sperm were observed in 17 parameter means and 21 standard deviations. The sperm-zona pellucida binding process preferentially selects sperm heads with a large anterior region with relatively low optical density, as well as high axial symmetry and minimal neck anomalies. Bias against sperm with pyriform morphology was not observed. CONCLUSION(S): A causal link has been established between sperm head morphometry, particularly within the acrosomal region, and the ability of sperm to bind to the human zona pellucida. As sperm-zona binding is necessary for fertility, it is possible to derive a physiologically based assessment for clinical diagnosis of male infertility using the "zona-preferred" morphometry results.

Acrosome↗
PubMed1997

Travel times and radiotherapy uptake in two English counties.

OBJECTIVES: To examine whether longer travel times for radiotherapy are associated with reduced overall uptake of radiotherapy treatment, or with reduced uptake of palliative as opposed to radical radiotherapy. DESIGN: Correlations of weighted average travel times for radiotherapy with overall radiotherapy uptake, and of travel times to one cancer centre with the ratio of palliative to radical radiotherapy at that centre. SETTING: The fourteen local authority (county) Districts of Bedfordshire and Hertfordshire. SUBJECTS: Residents of Bedfordshire and Hertfordshire registered by the Cancer Registries as attending hospital with a diagnosis of cancer, and registered as receiving radiotherapy treatment. Residents recorded by single cancer centre as receiving radical or palliative radiotherapy at that centre. RESULTS: There was no significant correlation between travel times for treatment and overall radiotherapy uptake (r = 0.40, P = 0.18), or with the ratio of palliative to radical radiotherapy at a single centre (r = -0.29, P = 0.34). Both measures of uptake showed considerable variability. Longest travel times were about one hour. CONCLUSIONS: Travel times up to one hour do not appear to reduce radiotherapy uptake, and the variability observed is likely to be due to other factors. The recommendation of the Chief Medical Officer's expert advisory group on cancers, that radiotherapy should be provided in larger cancer centres, is unlikely to result in lower radiotherapy uptake with travel times of this order.

England↗
PubMed1997

Prenatal sonographic diagnosis of cleidocranial dysostosis.

Cleidocranial dysostosis is an autosomal dominant disorder characterized by absence or hypoplasia of the clavicles, skull abnormalities, and abnormal dentition. The prenatal diagnosis of this condition has been reported once previously in a known high-risk pregnancy. In this report we describe the prenatal findings of cleidocranial dysostosis at 19 weeks' gestation in a woman affected with this disorder but undiagnosed before the fetal scan. This report is unique in the sense that an autosomal dominant condition diagnosed in the fetus led to a similar diagnosis in the mother.

Adult↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Molecular polymorphisms associated with host range in the highly conserved genomes of burrowing nematodes, Radopholus spp.

Six polymorphic bands of DNA were amplified from purified Radopholus citrophilus genomic DNA from one strain of each of the sibling species R. citrophilus and R. similis in random amplified polymorphic DNA analyses involving 380 single 10-base primers. Four of these polymorphic DNA fragments were successfully cloned and amplified through subsequent use of primers designed to complement the terminal sequences of the polymorphic DNA. Results of ensuing studies using mini-prepped DNA from 14 burrowing nematode strains collected from Florida, Hawaii, and Central America, characterized for their ability to parasitize citrus, indicated that a 2.4-kb fragment appeared to be associated with citrus parasitism in burrowing nematode populations from Florida. However, a fragment of comparable size was also detected in R. citrophilus from Hawaii and from burrowing nematode populations collected from Belize and Puerto Rico. Overall, findings suggest that the genome organization of the burrowing nematode sibling species R. citrophilus and R. similis is highly conserved. This remarkable genetic similarity should facilitate identification of genetic sequence related to important phenotypes such as citrus parasitism. Detection of R. citrophilus-specific DNA fragments in burrowing nematodes collected from Belize and Puerto Rico suggests that R. citrophilus is resident in some Central American countries.

Animals↗
PubMed1996

Three sibs with microcephaly, congenital heart disease, lung segmentation defects and unilateral absent kidney: a new recessive multiple congenital anomaly (MCA) syndrome?

We present three sibs with similar dysmorphic features, including brain, heart and lung malformations that have not been reported previously. Cytogenetic studies have failed to demonstrate a chromosomal abnormality. Although parental consanguinity was not present, we suggest that this may constitute a new recessive syndrome.

Abnormalities, Multiple↗
PubMed1996

Cultural barriers to health care for refugees and immigrants. Providers' perceptions.

What are the barriers to good health care for immigrants who have come to the Minneapolis-St. Paul metropolitan area since the early 1980s? Why do immigrants often delay or avoid seeking mainstream health care services? The research described here examines these questions from the perspective of nonimmigrant health care providers in the Twin Cities. The 24 metropolitan health care providers interviewed in our study confirmed the existence of significant barriers to health care-barriers that probably differ from those experienced by nonimmigrant patients. Refugees and immigrants from other cultures had varying culturally based reactions to Western-style, allopathic medicine-some positive and many negative. Providers and administrators must consider these barriers when serving a growing population of immigrant patients.

Adult↗
PubMed1996

A translocation at 12q2 refines the interval containing the Holt-Oram syndrome 1 gene.

A gene for Holt-Oram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using a combination of chromosome painting and FISH with YACs and cosmids, it has been possible to map these breakpoints within the critical HOS1 interval and thus provide a focus for HOS gene-identification efforts.

Arm↗
PubMed1995

Exencephaly in autosomal dominant brachydactyly syndrome.

Exencephaly was diagnosed at 17 weeks in a 27-year-old primigravida with abnormalities of the hands and a family history suggestive of autosomal dominant brachydactyly and clinodactyly. In this family there was also a history of 'anencephaly'. To our knowledge, this is the first report on the association of exencephaly and autosomal dominant brachydactyly. As the relationship between hand and cranial anomalies is well established, we suggest that this association in our case could be due to a defect in the same gene.

Adult↗