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Biomedical subjects

L Haddad

Publications and source records attributed to L Haddad.

32 records · Page 2Linked to original sources
PubMed1997

Development of a microsatellite-based approach to co-segregation analysis of familial hypercholesterolaemic kindreds.

Co-segregation studies based on a selection of intragenic restriction fragment length polymorphisms of the low density lipoprotein receptor (LDLR) gene have been used extensively both for research and diagnostic studies of familial hypercholesterolaemia (FH) families, because direct mutation screening remains complex. Here we describe the development and application of a more efficient approach to co-segregation studies based on highly informative dinucleotide and tetranucleotide repeats flanking the LDLR gene. A series of microsatellites (D19S391, D19S394, D19S221 and D19S179) were selected for study on the basis of linkage analysis in the CEPH families using intragenic polymorphisms for a TA repeat (exon 18) in the LDLR gene, and earlier data for a Pvu II polymorphism (intron 15). A physical map of the region of chromosome 19 also contributed to this selection. One marker in particular, D19S394, sited 150 kilobases telomeric to the gene, was extremely useful, displaying 90% heterozygosity, robust PCR of tetranucleotide repeats without stutter bands, and no recombination with the LDLR gene (theta = 0, LOD 68). Use of this marker in the families of twenty-three FH probands from Hampshire demonstrated co-segregation of the hyperlipidaemia phenotype with the LDLR gene region, except in one family with defective apolipoprotein B-100, and a family turning out to display familial combined hyperlipidaemia. This approach should facilitate the search for any families where FH does not co-segregate with the LDLR gene, and will enhance the repertoire of molecular diagnostic tools available for FH.

Adolescent↗
PubMed1997

Identification of a common low density lipoprotein receptor mutation (R329X) in the south of England: complete linkage disequilibrium with an allele of microsatellite D19S394.

Familial hypercholesterolaemia is commonly caused by mutations in the low density lipoprotein receptor (LDLR) gene and more than 300 different mutations have been described worldwide. Some mutations occur at relatively higher frequency in certain populations, reflecting both chance and demography, most evident in founder populations. As part of a study of kindreds of 78 probands from Southampton and south west Hampshire, we identified the same mutation (R329X) in 9/78 (11.5%) probands. In all (100%) of these probands, length allele 259nt of the 17 allele microsatellite D19S394, sited approximately 250 kilobases telomeric and 5' to the LDLR gene, was observed, although in the general population this allele has a prevalence of only 16.1%. A simple diagnostic assay for R329X was constructed in conjunction with more detailed family studies. Both the R329X and linked D19S394 allele also cosegregated with the FH phenotype within each kindred. Although R329X involves a CpG site, it is highly likely that the families are identical by descent for R329X, we surmise with a common ancestor within 500 to 1000 years, although the mutation is not restricted to this geographical area. This relationship illustrates that the linkage disequilibrium of gene LDLR with marker D19S394 will enable rapid recognition using D19S394 genotype of possible common FH mutation(s) within a cohort of FH patients from a particular locality or ethnic group.

Alleles↗
PubMed1996

A 10 year review of the endoscopic treatment of 125 spinal cord injured patients with vesical outlet obstruction: does bladder neck dyssynergia exist?

The management of 125 patients with post-traumatic neuropathic bladder and vesical outlet obstruction is described and a policy of endoscopic treatment is suggested. A total of 1652 spinal cord injured patients were treated during the period of 1983-1992. About 8% had an outlet of obstruction which required endoscopic treatment. The outcome of transurethral resection of the external sphincter and/or bladder neck was retrospectively analyzed in 82 patients, and a prospective study was conducted on the other 43 patients. We have demonstrated that patients with a complete spinal cord lesion at any level, and those with a high incomplete lesion (above T-9) have benefited from external sphincterotomy combined with bladder neck resection. We emphasize that patients with a low incomplete lesion (T-9 and below) have benefited from bladder neck resection alone. Bladder neck (internal sphincter) obstruction or dyssynergia may require to be considered in the management of the neuropathic bladder.

Adolescent↗
PubMed1995

High-throughput method for determination of apolipoprotein E genotypes with use of restriction digestion analysis by microplate array diagonal gel electrophoresis.

Molecular epidemiological research has identified the association of a common apolipoprotein E (apo E) isoform (E4 as opposed to E3), with risk both of coronary artery disease and of Alzheimer dementia. In addition, the role of apo E genotype (usually E2/E2) in Type III hyperlipidemia is well known. However, both for diagnostic and research purposes, apo E genotyping is cumbersome. The preferred approach is electrophoretic sizing of restriction digestion fragments, enabling simultaneous analysis of the two codons (112 and 158) that represent the six common genotypes (E2/E2; E2/E3; E2/E4; E3/E3; E3/E4; E4/E4). However, the consequent demands of high-yield PCR, high-resolution, high-throughput electrophoresis, and sufficient detection sensitivity have left shortfalls in published protocols. In conjunction with a high-throughput electrophoresis system we described recently, microplate array diagonal gel electrophoresis (MADGE), we have constructed extensively optimized, simplified protocols for DNA isolation from mouthwash samples for PCR setup and high-yield PCR, for restriction digestion, and for subsequent MADGE gel image analysis. The integral system enables one worker to readily undertake apo E genotyping of as many as hundreds of DNA samples per day, without special equipment.

Apolipoproteins E↗
PubMed1994

Troubleshooting implantable cardioverter defibrillator system malfunctions: the role of impedance measurements.

High impedance measurements may be used to troubleshoot ICD system malfunction. In four different cases a defective system was identified or confirmed by an abnormal impedance: two secondary to lead fractures, one to an adapter faulty connection, and one to a loose set-screw connection. This led to further diagnostic procedures that ultimately localized the difficulty. Though the problems with ICD may be of diverse origins, routine use of impedance measurement for the troubleshooting of these systems may serve as an early sign of malfunction and would point the need for further investigation.

Aged↗
PubMed1987

Doubling time and annual doubling rate of human prostatic cancer.

The doubling time (DT) of human prostatic cancer is calculated for the first time; its various parameters and the relative importance of each are reviewed. A crude volume-doubling time (DTcv), a theoretical doubling of the number of cells (DTt), and an annual doubling rate (ADR), are defined and calculated for each of 12 patients who had undergone needling of the prostate for diagnostic purposes and in whom tumor cells were implanted in the track of the biopsy needle and had grown into a subcutaneous perineal nodule. The harmonic average DTcv was six days and DTt eight days, and the average ADR was 45 doublings per year. From the study of the calculated DTs and ADRs, it became obvious that the 12 patients fell into three distinct groups: Group I = slow tumor growth rate, an average ADR of 9 doublings per year, and a harmonic average DTt of forty days; Group II = medium tumor growth rate, an average ADR of 35 doublings/year, and a harmonic average DTt of ten days; and Group III = rapid tumor growth rate, an average ADR of 100 doublings/year, and a harmonic average DTt of four days.

Biopsy↗
PubMedDate not supplied

Effect of the menstrual cycle in ethanol pharmacokinetics.

Differences in ethanol pharmacokinetics within the menstrual cycle have previously been reported and attributed to variations in body composition, hormonal influences and gastric emptying. To establish the role of the menstrual cycle in ethanol pharmacokinetics associated with changes in body composition, ethanol blood concentrations were measured in nine healthy women during the midfollicular (P1, days 8-10) and midluteal (P2, days 22-24) phases of the menstrual cycle after a postprandial oral ethanol dose (0.3 g kg(-1)). Total body water was assessed by dual-energy x-ray densitometry (DEXA) on both occasions. Median total body water did not vary during either phase of the menstrual cycle (P1 = 54.54%, P2 = 54.66%; P = 0.9296). Median area under the ethanol concentration-time curve (AUC) was lower during P1 (215.33 mg.h dl(-1)) than during P2 (231.33 mg.h dl(-1))(P = 0.8253). No significant differences were found on ethanol pharmacokinetics in either phase of the menstrual cycle.

Administration, Oral↗
PubMedDate not supplied

Health promotion behaviors of Jordanian women.

Many developing countries are undergoing industrialization and modernization, which has produced both positive and negative implications for health. This study was designed to adapt a well-known health measure to an Arab-Muslim population and to derive health promotion data for primary health care program planning for women in Jordan. A convenience sample of 512 literate females in Jordan was recruited from community settings such as secondary schools (teachers), primary health care centers (nursing staff and patients), universities (faculty and staff), colleges, and office worksites using an Arabic translated version of the Health Promoting Lifestyle Profile (HPLP) instrument. Subjects scored highest on self-actualization, interpersonal support, and nutrition but scored lower on the exercise and health responsibility domains. Unmarried women, however, scored higher on exercise and stress management. These findings support the development of educational efforts to increase women's awareness of relationships between lifestyle and health for both themselves and for their families.

Adult↗