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Biomedical subjects

T Read

Publications and source records attributed to T Read.

At least 19 recordsLinked to original sources

Cohort analysis of two multidisciplined adherence intervention programmes for patients on antiretroviral therapy.

The aim was to analyse data from two randomized controlled trials (RCTs) to determine if an adherence intervention programme for antiretroviral therapy (ART) resulted in a reduction in viral load. A cohort analysis of pre- and post-intervention viral loads and CD4 counts using paired analysis was undertaken on participants who received the intervention programme. Analysis was also undertaken on a control group. The intervention participants had an increase in mean CD4 count (450-478, P = 0.26), and a decline in log viral load (2.48-2.36, P = 0.056). The control group had a decline in mean CD4 counts (596-570, P = 0.53), and an increase in log viral load (2.09-2.11, P = 0.78). The use of an adherence intervention programme is associated with a decrease in mean viral load, which is in contrast to the control group that demonstrated an increase in viral load over time.

Antiretroviral Therapy, Highly Active↗

Testing men who have sex with men for Neisseria gonorrhoeae and Chlamydia trachomatis prior to the introduction of guidelines at an STD clinic in Melbourne.

BACKGROUND: Guidelines for testing men who have sex with men (MSM) were published in 2002. They did not recommend asymptomatic screening for urethral gonorrhoea or pharyngeal screening for chlamydia. To determine if these guidelines were appropriate, we audited gonorrhoea and chlamydia testing of MSM at our Centre. METHODS: We carried out two audits at our Centre between August 2001 and July 2002. The first was an audit of testing MSM for gonorrhoea and/or chlamydia over 12 days. The second was an audit of all positive tests over this 12-month period for gonorrhoea or chlamydia among MSM. RESULTS: During the 12 selected days 89 of 286 men tested (31%) were MSM. Among the MSM testing positive for gonorrhoea and/or chlamydia infection (15, 17%), symptomatic urethral infection was the most common (n = 8). No rectal and pharyngeal infections had site-specific symptoms. Based on the guidelines, 100 of the 334 tests ordered (30%) were not recommended according to the guidelines, and none of these 100 tests yielded a positive result. Over the 12-month audit period, 135 MSM were diagnosed with gonorrhoea and/or chlamydia. For gonorrhoea, site specific symptoms were present in 42 of 43 cases of urethral infection (98%), six of 23 cases of rectal infection (26%), and no cases of pharyngeal infection had symptoms. For chlamydia, site-specific symptoms were present in 29 of 48 cases of urethral infection (60%), six of 33 cases of rectal infection (18%), and in one of the two cases of pharyngeal chlamydia identified. A substantial proportion of cases occurred in clients with HIV infection (21, 16%). CONCLUSIONS: These findings strongly support screening among MSM and in particular not testing asymptomatic MSM for urethral gonorrhoea or any MSM for pharyngeal chlamydia.

Adult↗

Age and type of procedure influence the choice of patients for laparoscopic colectomy.

BACKGROUND: The aim of this retrospective, case-matched controlled study was to determine the benefit of laparoscopic-assisted colectomy (LC) for the elderly (>75 years of age) and the young (<75 years of age) compared to an open colectomy (OC) control group. METHODS: A retrospective review of 39 patients older than 75 years of age and 38 patients younger than 75 years of age who underwent LC for colorectal cancer between 1991 and 1999 was performed. LC patients were matched with an open control group for procedure, age, gender, year of procedure, and surgeon. Procedures included right and left colectomy, anterior resection of the rectosigmoid, and abdominoperineal resection. Measured intraoperative variables included anesthesia time, operative time, and estimated blood loss. Postoperative parameters consisted of duration of intravenous or epidural narcotic usage, return of bowel function (RBF), length of stay, and independence at discharge. These variables were compared in the entire group of 154 patients. RESULTS: Mean ages were 81.4 and 81.8 years for LC and OC age >75 and 62.9 and 62.7 for LC and OC age <75. Mean anesthesia time and operative time were significantly longer (p < 0.05) for LC compared to OC (46.8 vs 39.3 and 159.3 vs 111.7 min, respectively) for age >75 and for age <75 (47.1 vs 40.3 and 182.8 vs 135.5 min, respectively). LC achieved faster recovery in both age groups: RBF (3.9 vs 4.9 days for age >75; 6.7 vs 7.7 days for age <75) (p < 0.05). Narcotic usage was shorter for the LC group age <75 (3.3 vs 4.4 days; p < 0.05). There was no significant difference in independence at discharge between LC and OC in either age group. Faster recovery was seen with left LC in age >75 and right LC in age <75 compared to OC. CONCLUSION: The advantages of LC over OC are the same for the elderly and the young. There may be a selective benefit of laparoscopic left colectomy in the elderly and laparoscopic right colectomy in the young.

Age Factors↗

Detection of varicella zoster virus in genital specimens using a multiplex polymerase chain reaction.

OBJECTIVE: To compare the relative proportions of varicella zoster virus (VZV) and herpes simplex viruses in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection. METHODS: Swabs of genital lesions from 6210 patients attending general practices, infectious diseases clinics within hospitals, or sexual health centres for treatment of their genital lesions were tested using polymerase chain reaction (PCR) technology. The multiplexed PCR was capable of detecting herpes simplex virus types 1 and 2 (HSV-1, HSV-2), VZV, and cytomegalovirus in a single sample. RESULTS: A total of 2225 patients had viruses detected by PCR. HSV-1 was detected in 36%, HSV-2 in 61%, and VZV in 2.9% of PCR positive samples. Of the 65 patients with VZV genital infection, many were thought to have HSV infection before laboratory testing. CONCLUSIONS: The finding of VZV in nearly 3% of virus positive genital specimens demonstrates that this virus needs to be considered as a differential diagnosis for genital herpetic lesions. Advice provided to patients with VZV genital infection regarding the source of infection, likelihood of recurrence, and potential for transmission of the virus will be different from that given to patients with HSV infection.

Adolescent↗

Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23.

We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.

Chromosome Aberrations↗

Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment.

BACKGROUND: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen. METHODS AND MATERIALS: During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%). RESULTS: With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery). CONCLUSION: Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.

Adult↗

New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families.

Genetic linkage of schizophrenia to markers at 5q11.2-13.3 had been reported previously in five Icelandic and two British families, but attempts at replication in independent samples have been unsuccessful. We report here an update on the diagnoses and results of linkage analyses using newer highly polymorphic microsatellite markers at or near the loci D5S76 and D5S39 in the original sample of pedigrees and in two new family samples from Iceland and from Britain. The new results show a reduction in evidence for linkage in the original sample and evidence against linkage in the two new family samples. Although it is possible that a rare locus is present, perhaps in the region 5p14.1-13.1 rather than 5q11.2-13.3, it appears most likely that the original positive lod scores represent an exaggeration of the 'true' lod scores due to random effects and that the small lod scores we now obtain could have arisen by chance.

Chromosomes, Human, Pair 5↗

No evidence for linkage of schizophrenia to DXS7 at chromosome Xp11.

There have been claims that a gene on the X chromosome may contribute to susceptibility to schizophrenia. Crow (1988) initially proposed that such a gene might lie in the pseudoautosomal region, but when evidence that weakened this hypothesis accumulated, he proposed that a susceptibility locus might be present elsewhere on the sex chromosomes instead. DeLisi et al. (1994) found a small nonsignificant positive lod score between the marker DXS7 and schizophrenia, but other failed to replicate this finding. Another study reported by Crow and DeLisi's group was also weakly positive for this marker (Dann et al., 1997). This locus was then investigated in a collaborative study by Laval et al. (1997), which produced a nonparametric lod score of 2.44. Using a sample of 17 pedigrees from Britain and Iceland, we have also tested the hypothesis of linkage between DXS7 and schizophrenia. The 17 families were selected from a larger sample on the basis of an absence of male-to-male transmission for schizophrenia. These families were originally selected for having multiple cases of schizophrenia within them and for having no cases of bipolar affective disorder. We genotyped subjects for a marker at DXS7 and performed classical lod score and model-free linkage analysis using broad and narrow definitions of affection with schizophrenia. We found strongly negative lod scores and no evidence for linkage using model-free analysis. Therefore, this study does not support the hypothesis of linkage of schizophrenia to DXS7, and the evidence for a susceptibility locus on this part of the X chromosome is weakened.

Chromosome Mapping↗

Exclusion of linkage between schizophrenia and the gene encoding a neutral amino acid glutamate/aspartate transporter, SLC1A5.

An abnormality in glutamatergic function has been hypothesized as being of etiological importance in schizophrenia. Twenty-three multiplex English and Icelandic schizophrenia families were genotyped with a polymorphic dinucleotide repeat sequence in the 3'-untranslated region of the glutamate/aspartate transporter gene called SLC1A5. Using the lod and a model-free method of linkage analysis (MFLINK), no evidence of linkage between SLC1A5 and schizophrenia was found. Our results do not support the hypothesis that SLC1A5 gene mutations or allelic variants provide a major gene contribution to the etiology of schizophrenia. However, because of the likelihood of heterogeneity of linkage in schizophrenia, there is a case for testing other pedigrees for linkage to the SLC1A5 locus. The SLC1A5 locus is one of a complex family of genes encoding neutral amino acid transporter proteins and the genetic relation between these other loci and schizophrenia has not yet been established.

Alleles↗

Linkage study of the D5 dopamine receptor gene (DRD5) in multiplex Icelandic and English schizophrenia pedigrees.

OBJECTIVE: The authors investigated the possibility that genetic variation or mutation of the dopamine D5 receptor gene might modify susceptibility to schizophrenia. METHOD: Twenty-three Icelandic and English pedigrees containing multiple cases of schizophrenia were genotyped by using a highly informative microsatellite for the D5 dopamine receptor gene DRD5. RESULTS: By means of three different affection models, negative lod scores were obtained under assumptions of autosomal dominant and recessive inheritance. There was no evidence for locus heterogeneity. Nonparametric extended relative pair analysis also produced negative results. CONCLUSIONS: These data indicate that mutations of the D5 dopamine receptor gene are not a major cause of schizophrenia in these pedigrees. Because of the probable existence of locus heterogeneity, the D5 receptor gene may be of etiologic importance in other families with schizophrenia.

Base Sequence↗

Lack of evidence for close linkage of the glutamate GluR6 receptor gene with schizophrenia.

OBJECTIVE: Previous research has consistently implicated genetic factors in the pathogenesis of schizophrenia. It has been hypothesized that an abnormality in glutamatergic function is of etiologic importance in schizophrenia, and therefore the glutamate receptor family of genes are potential susceptibility loci for schizophrenia. To test this hypothesis the authors sought to detect linkage between the GluR6 glutamate receptor gene and schizophrenia. METHOD: Twenty-three English and Icelandic families containing multiple cases of schizophrenia were genotyped with a microsatellite trinucleotide repeat polymorphism localized at the GluR6 glutamate receptor locus. Lod scores, model-free linkage analysis, and extended relative pair analysis were used to test for linkage. RESULTS: No statistically significant evidence of linkage between GluR6 and schizophrenia was found. CONCLUSIONS: The results do not support the hypothesis that GluR6 allelic variants provide a major gene contribution to the etiology of schizophrenia in a large proportion of these pedigrees.

Alleles↗

The lac-z reporter gene: a tool for in vitro studies of malignant glioma cell invasion.

A reporter gene (lac-z) was introduced into rat (BT4C) and human (D-54 MG) proliferating glioma cell lines by means of liposomal transfection. Lac-z-transfected glioma cells were first cultured as multicellular spheroids and then confronted with fetal brain aggregates. After various intervals the lac-z reporter gene product, bacterial beta-galactosidase, was histochemically detected in the cocultures. beta-Galactosidase was only detected in the glioma cells which showed an intense blue staining, which made them easily distinguishable from fetal tissue. Both glioma cell lines showed a clear pattern of migration and increasing invasion with time as the tumor cells infiltrated and destroyed the brain aggregates. Spheroid growth curves showed no significant differences between transfected and nontransfected cell lines. Likewise, flow cytometry measurements revealed no significant changes in ploidy between transfected and nontransfected rat glioma cells. In comparison, a shift in ploidy was observed in the human glioma cells after lac-z transfection. Stable integration of the lac-z gene into tumor cells was verified by Southern blot analysis. The results indicate that transfection of the lac-z reporter gene into glioma cells lines does not affect their growth or invasion potential in vitro. The lac-z reporter gene can thus be exploited to facilitate visualization of single migrating tumor cells and quantification of tumor invasion in in vitro coculture systems.

Animals↗

Linkage analysis of chromosome 22q12-13 in a United Kingdom/Icelandic sample of 23 multiplex schizophrenia families.

A possible linkage to a genetic subtype of schizophrenia and related disorders has been reported on the long arm of chromosome 22 at q12-13. (Pulver et al., 1994: Am J Med Genet 54:36-43; Coon et al., 1994: Am J Med Genet 54:72-79; Pulver et al., 1994: Am J Med Genet 54:44-50). However formal statistical tests in a combined sample could not reject homogeneity and prove that there was a linked subgroup of families. We have studied 23 schizophrenia pedigrees to test whether some multiplex schizophrenia families may be linked to the microsatellite markers D22S274 and D22S283 which span the 22q12-13 region. Two point followed by multipoint lod and non-parametric linkage analyses under the assumption of heterogeneity provided no evidence for linkage over the relevant region.

Chromosomes, Human, Pair 22↗