Search PubMed⌕ Search

Biomedical subjects

B Kerr

Publications and source records attributed to B Kerr.

At least 37 records · Page 2Linked to original sources
PubMed2001

The relationship of femoral intercondylar notch width to height, weight, and sex in patients with intact anterior cruciate ligaments.

Intercondylar notch width, femoral bicondylar width, height, and weight of patients with intact anterior cruciate ligaments were measured to determine whether intercondylar notch width was related to body size. A 45 degrees weight-bearing posteroanterior radiograph was obtained for 315 men and 163 women. Notch width and bicondylar width was measured at one-half notch height. Mean notch width for men was statistically significantly wider than for women (17.1 mm versus 14.7 mm, respectively; P<.01). There was no statistically significant correlation between height and notch width for men (r=-0.0019; P=.97) or women (r=0.1308; P=.10). No significant correlation existed between weight and notch width for men (r=-0.0311; P=.58) or women (r=0.0523; P=.51). Analysis of variance showed height and weight were not significant covariates in notch width for either men (P=.44) or women (P=.91). Women of the same height and weight as men had significantly narrower notches (P<.01). There was a statistically significant correlation between wider femoral bicondylar widths and higher weight for men (r=0.694; P<.01) and women (r=0.821; P<.01). Similarly, there was a statistically significant correlation between wider femoral bicondylar widths and increased height for men (r=0.670; P<.01) and women (r=0.785; P<.01). These data demonstrate height and weight are poor predictors of intercondylar notch width. Therefore, one cannot assume body size is a predictor of notch width. Furthermore, because mean notch width does not increase with increasing height and weight, the notch width index calculation cannot accurately reflect the size of the intercondylar notch.

Adolescent↗
PubMed2000

Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome.

Robinow syndrome is a short-limbed dwarfism characterized by abnormal morphogenesis of the face and external genitalia, and vertebral segmentation. The recessive form of Robinow syndrome (RRS; OMIM 268310), particularly frequent in Turkey, has a high incidence of abnormalities of the vertebral column such as hemivertebrae and rib fusions, which is not seen in the dominant form. Some patients have cardiac malformations or facial clefting. We have mapped a gene for RRS to 9q21-q23 in 11 families. Haplotype sharing was observed between three families from Turkey, which localized the gene to a 4. 9-cM interval. The gene ROR2, which encodes an orphan membrane-bound tyrosine kinase, maps to this region. Heterozygous (presumed gain of function) mutations in ROR2 were previously shown to cause dominant brachydactyly type B (BDB; ref. 7). In contrast, Ror2-/- mice have a short-limbed phenotype that is more reminiscent of the mesomelic shortening observed in RRS. We detected several homozygous ROR2 mutations in our cohort of RRS patients that are located upstream from those previously found in BDB. The ROR2 mutations present in RRS result in premature stop codons and predict nonfunctional proteins.

Abnormalities, Multiple↗
PubMed2000

Clinical pharmacokinetic and in vitro combination studies of nolatrexed dihydrochloride (AG337, Thymitaq) and paclitaxel.

A clinical study of nolatrexed dihydrochloride (AG337, Thymitaq) in combination with paclitaxel was performed. The aims were to optimize the schedule of administration and determine any pharmacokinetic (PK) interactions between the two drugs. In vitro combination studies were performed to assist with schedule optimization. Three patients were entered on each of three different schedules of administration of the two drugs: (1) paclitaxel 0-3 h, nolatrexed 24-144 h; (2) nolatrexed 0-120 h, paclitaxel 48-51 h; (3) nolatrexed 0-120 h, paclitaxel 126-129 h. Paclitaxel was administered at a dose of 80 mg m(-2) over 3 h and nolatrexed at a dose of 500 mg m(-2) day(-1) as a 120-h continuous intravenous infusion. Plasma concentrations of both drugs were determined by high performance liquid chromatography. In vitro growth inhibition studies using corresponding schedules were performed using two head and neck cancer cell lines. In both HNX14C and HNX22B cell lines, synergistic growth inhibition was observed on schedule 2, whereas schedules 1 and 3 demonstrated antagonistic effects. In the clinical study, there was no effect of schedule on the pharmacokinetics of nolatrexed. However, patients on schedules 1 and 3 had a higher clearance of paclitaxel (322-520 ml min(-1) m(-2)) than those on schedule 2 (165-238 ml min(-1) m(-2)). Peak plasma concentrations (1.66-1.93 vs. 0.86-1.32 microM) and areas under the curve (392-565 vs. 180-291 microM min(-1)) of paclitaxel were correspondingly higher on schedule 2. The pharmacokinetic interaction was confirmed by studies with human liver microsomes, nolatrexed being an inhibitor of the major routes of metabolism of paclitaxel. Toxicity was not schedule-dependent. Nolatrexed and paclitaxel may be safely given together when administered sequentially at the doses used in this study. Studies in vitro suggest some synergy, however, due to a pharmacokinetic interaction, paclitaxel doses should be reduced when administered during nolatrexed infusion.

Adult↗
PubMed2000

Gonadotropin-releasing hormone-stimulated sperm binding to the human zona is mediated by a calcium influx.

The mechanism by which GnRH increases sperm-zona pellucida binding in humans was investigated in this study. We tested whether GnRH increases sperm-zona binding in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also examined the GnRH effect on the intracellular free Ca(2+) concentration ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the presence of 400 nM nifedipine, 80 microM diltiazem, or 50 microM verapamil, GnRH did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the extracellular medium because the increase in [Ca(2+)](i) was blocked by the Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and diltiazem. These antagonists, however, were not able to inhibit the progesterone-activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D-Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D-Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.

Calcium↗
PubMed2000

Spondylometaphyseal dysplasia Sedaghatian type associated with lethal arrhythmia and normal intrauterine growth in three siblings.

Spondylometaphyseal dysplasia of the Sedaghatian type is a rare dysplasia, characterized by mild limb shortening, but lethal in the neonatal period. We describe three affected male siblings, the offspring of consanguineous parents. One was stillborn. Neonatal death was due to cardiac arrhythmia in two of the siblings. This report confirms the importance of cardiac pathology in this probably autosomal recessive disorder. This diagnosis should be excluded in any newborn with an arrhythmia as the clinical limb shortening may not be obvious.

Arrhythmias, Cardiac↗
PubMed2000

Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.

PURPOSE: Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis. METHODS: Seventy-six patients with different forms of anterior segment dysgenesis were classified clinically. DNA was obtained and screened by means of polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing. RESULTS: Eight of 76 patients had mutations within the PITX2 gene. Anterior segment phenotypes show wide variability and include a phenocopy of aniridia and Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations and splice-site and homeobox mutations, confirming that haploinsufficiency the likely pathogenic mechanism in the majority of cases. CONCLUSIONS: There is significant phenotypic variability in patients with PITX2 mutations, both within and between families. Developmental glaucoma is common. The umbilical and dental abnormalities are highly penetrant, define those at risk of carrying mutations in this gene, and guide mutation analysis. In addition, there is a range of other extraocular manifestations.

Anterior Eye Segment↗
PubMed1999

Brachydactyly type B: clinical description, genetic mapping to chromosome 9q, and evidence for a shared ancestral mutation.

Autosomal dominant brachydactyly type B (BDB) is characterized by nail aplasia with rudimentary or absent distal and middle phalanges. We describe two unrelated families with BDB. One family is English; the other family is Canadian but of English ancestry. We assigned the BDB locus in the Canadian family to an 18-cM interval on 9q, using linkage analysis (LOD score 3.5 at recombination fraction [theta] 0, for marker D9S938). Markers across this interval also cosegregated with the BDB phenotype in the English family (LOD score 2.1 at straight theta=0, for marker D9S277). Within this defined interval is a smaller (7.5-cM) region that contains 10 contiguous markers whose disease-associated haplotype is shared by the two families. This latter result suggests a common founder among families of English descent that are affected with BDB.

Activin Receptors, Type I↗
PubMed1999

Treatment of human immunodeficiency virus 1-infected infants and children with the protease inhibitor nelfinavir mesylate.

An open-label study was conducted of nelfinavir mesylate, given with reverse transcriptase inhibitors to human immunodeficiency virus 1 (HIV-1)-infected infants and children 3 months to 13 years of age. Doses of nelfinavir mesylate of 20-30 mg/kg yielded drug exposures comparable to those seen in adults. The drug was well tolerated; mild diarrhea was the primary toxic effect observed. Seventy-one percent (39) of the 55 evaluable subjects had an initial decrease in plasma HIV-1 RNA, of at least 0.7 log10 copies/mL; suppression of plasma HIV-1 RNA levels to < 400 copies/mL was observed in 15. Children who began taking at least one new reverse transcriptase inhibitor near the time when nelfinavir mesylate was started, and those with a > or = 24% proportion of CD4 lymphocytes, had a greater chance of achieving and maintaining a decline in plasma HIV-1 RNA to < 400 copies/mL. Suppression of viremia was achieved in children as young as 3 months of age.

Adolescent↗
PubMed1999

Gonadotrophin-releasing hormone antagonists inhibit sperm binding to the human zona pellucida.

Previous work from our laboratory indicated that gonadotrophin-releasing hormone (GnRH) increases human sperm-zona pellucida binding. Here we present evidence that GnRH antagonists inhibit sperm-zona pellucida binding in humans. Motile spermatozoa (10(7) cells/ml) were incubated in modified Tyrode's medium at 37 degrees C, in 5% CO(2) in air. After 4.5 h, aliquots of spermatozoa were treated with saline (control) or with different concentrations of GnRH antagonists (test). Each sperm aliquot was then tested in the hemizona binding assay. In this assay, the control aliquot was incubated with half a human zona pellucida (hemizona) and the test aliquot was incubated with the matching half. After 20 min, the hemizonae were withdrawn and the number of zona-bound spermatozoa counted using phase-contrast microscopy. In addition, the effect of GnRH antagonists upon the pattern of sperm movement, frequency of sperm-zona pellucida collisions, and percentage of living and acrosome-reacted spermatozoa was determined. The results indicated that treatment with GnRH antagonists decreased the number of zona-bound spermatozoa and did not change the pattern of sperm movement, frequency of sperm-zona collisions, and percentage of acrosome-reacted spermatozoa. We suggest that this action of GnRH antagonists may be due to an effect on zona receptors on the sperm plasma membrane.

Female↗
PubMed1999

Unilateral tibial aplasia, pre-axial polysyndactyly, vertebral anomalies and imperforate anus.

Tibial hemimelia is a rare malformation that can be isolated or found with other skeletal abnormalities. We describe a fetus with unilateral tibial aplasia, ipsilateral pre-axial polysyndactyly and femoral hypoplasia, ventriculomegaly, anal atresia and rib and vertebral anomalies. We believe that this combination of malformations has not previously been described.

Abnormalities, Multiple↗
PubMed1998

Memory-scanning task performance in Alzheimer's disease.

Individuals with mild Alzheimer's Disease (AD) and healthy normal control (NC) older adults performed a varied-set version of the Sternberg memory-scanning task with Set Sizes 1, 2, 3, and 4. The AD group (N = 23) had slower and more variable reaction times (RT) than the NC group (N = 38). RT differences between groups were bigger for NO than for YES responses. The linear relationship between RT and set size was not as strong for the AD group as for the NC group. However, in contrast to earlier studies with fewer subjects, participants with AD and healthy older individuals did not differ in the rate at which they scan items in the memory set.

Aged↗
PubMed1998

False family history of breast cancer in the family cancer clinic.

AIMS: Awareness of hereditary breast and ovarian cancer in both the general public and the medical profession is increasing. Individuals who may be at risk on the basis of a family history are requesting risk determination and appropriate management in a variety of settings. Risk determination relies largely on pedigree analysis and epidemiological data. METHODS: We describe five individuals presenting in the family cancer or genetic counselling clinic where a factitious family or personal history led to erroneous risk estimation. Common factors in these families are a history of benign breast disease, poor communication within families, long survival with early onset or bilateral disease, a lack of detailed knowledge of the illness and treatment in close relatives and inconsistencies in the history in repeated consultations.

Adult↗