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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1999

The fatty acid distribution in low density lipoprotein in diabetes.

Atherosclerosis is commonly found in diabetes. There is an association between small dense low density lipoprotein (LDL) phenotype, which is more prevalent in the diabetic state, and atherosclerosis. Small dense LDL is more easily oxidised and it is possible that fatty acid compositional changes, particularly an increase in polyunsaturated fatty acids, could underlie this association. However, there is little information about fatty acids in the different LDL phenotypes in the literature. This study examined LDL subfraction composition in 18 non-insulin-dependent diabetic (NIDDM) patients and 11 control subjects. LDL was isolated and fractionated into LDL 1, 2 and 3 by density gradient ultracentrifugation. NIDDM patients had significantly more fatty acids in all LDL subfractions than control subjects (P<0.01). Palmitic and linoleic acid were significantly greater in all subfractions in the diabetic patients compared to control subjects (P<0.01) and palmitoleic and oleic acids were also greater in LDL1 and LDL2 in diabetic patients (P<0.01). We conclude that in NIDDM fatty acids are increased in all LDL subfractions and this may be the reason for the increased atherosclerosis in diabetes irrespective of phenotype.

Aged↗
PubMed1999

A 1.5-Mb contig within the cat eye syndrome critical region at human chromosome 22q11.2.

We have constructed a 1.5-Mb contig spanning the distal half of the critical region for cat eye syndrome on human chromosome 22 from D22S543 to D22S181. The contig consists of 20 P1 artificial chromosome (PAC) clones and 11 bacterial artificial chromosome (BAC) clones screened from 2 BAC and 2 PAC libraries. Continuous overlap between the clones was confirmed using vectorette PCR and riboprobes. Despite the instability of this region in a previous YAC contig, only 1 BAC showed a minor instability and then in only one isolation. This contig is now providing the basis for genomic sequencing and gene identification in the cat eye syndrome critical region.

Abnormalities, Multiple↗
PubMed1999

Intensification regimen 2 for advanced head and neck squamous cell carcinomas.

OBJECTIVE: To determine the feasibility, toxicity, and compliance of an intense treatment regimen for patients with advanced, previously untreated, resectable head and neck squamous cell carcinomas. DESIGN: Prospective, nonrandomized, controlled (phase 1 or 2) clinical trial; median time at risk, 25 months (range, 7 days to 36 months). SETTING: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus. PATIENTS: Forty-three patients (median age, 59 years; range, 32-76 years) with resectable, previously untreated stage III or IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx or stage II squamous cell carcinomas of the hypopharynx (referred sample of patients). INTERVENTIONS: Days 1 to 4, perioperative, slightly accelerated, hyperfractionated radiotherapy (9.1 Gy) to off cord fields; days 1 to 3, cisplatin, 30 mg/m2 per day; day 4, surgical resection and intraoperative radiotherapy boost (7.5 Gy); days 45 to 52, postoperative radiotherapy (40 Gy to the primary site and upper neck and 45 Gy to the supraclavicular areas); days 24, 45, and 66, paclitaxel, 135 mg/m2 per 24 hours, with routine granulocyte colony-stimulating factor support; and days 25 and 46, cisplatin, 100 mg/m2. MAIN OUTCOME MEASURES: Toxicity, compliance, local control, and distant metastatic rates. RESULTS: Patient compliance was 91% (39 of 43 patients), but protocol compliance was only 58% (25 of 43 patients), reflecting increased toxicity of the systemic regimen (2 [5%] of the 43 patients experienced grade 5 hematologic toxicity due to the regimen; 16 [37%], grade 4; and 10 [23%], grade 3). Local-regional control was 92% (23 of 25 patients), and the distant metastatic rate was 8% (2 of 25) in patients completing treatment per protocol. One patient had surgical salvage of a second primary tumor. CONCLUSIONS: Local control and patient compliance were encouraging, but systemic toxicity was unacceptable. Thus, the paclitaxel was changed to a weekly regimen.

Adult↗
PubMed1999

The role of microsomal triglyceride transfer protein and dietary cholesterol in chylomicron production in diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine factors involved in chylomicron production in the streptozotocin diabetic rat, our hypothesis being that the synthesis of the chylomicron is abnormal in diabetes. METHODS: Diabetic rats (n = 20) were paired with control rats (n = 20). Cholesterol emulsion was given by gavage and the lymph duct was cannulated. Lymph was collected for 4 h. Chylomicrons were prepared from the lymph by ultracentrifugation. Lymph apolipoprotein B48 was isolated by gradient gel electrophoresis and quantified by densitometric scanning. Intestinal microsomal triglycerol transfer protein mRNA was measured by solution hybridisation nuclease protection, using a rat specific [32P]-labelled cRNA probe. RESULTS: Serum triglyceride and cholesterol were greatly increased in diabetic compared with control animals (258 +/- 77 and 8.9 +/- 6.4 mg/ml vs 1.04 +/- 0.37 and 0.54 +/- 0.03 mg/ml, p < 0.0001). Lymph chylomicron triglyceride and cholesterol were also higher in diabetic rats (29.4 +/- 27.3 and 0.28 +/- 0.3 mg/h vs 16.8 +/- 10.6 and 0.18 +/- 0.09 mg/h, p < 0.05). Lymph chylomicron apo B48 was similar in the two groups. Intestinal microsomal triglycerol transfer protein mRNA was higher in the diabetic rats (12.6 +/- 3.2 vs 3.8 +/- 3.0 amol/microgram RNA, p < 0.0001) and there was a positive correlation between lymph triglyceride and microsomal triglycerol transfer protein mRNA in the whole group (r = 0.65, p < 0.01). CONCLUSION/INTERPRETATION: The study shows that microsomal triglycerol transfer protein mRNA is raised in diabetes without an increase in apolipoprotein B48 in the lymph suggesting that microsomal triglycerol transfer protein regulates chylomicron triglyceride content but not particle number.

Animals↗
PubMed1999

Selective termination for structural, chromosomal, and mendelian anomalies: international experience.

OBJECTIVE: Our purpose was to evaluate the outcomes of selective termination for fetal anomalies at 8 centers with the largest known experiences worldwide. STUDY DESIGN: Outcomes in 402 cases of selective termination in pregnancies with dizygotic twins from 8 centers in 4 countries were analyzed by year, gestational age at procedure, and indication. Reductions of fetuses were as follows: 2 to 1, n = 345; 3 to 2, 39; >/=4 to 2 or 3, n = 18. Potassium chloride was used in all procedures. RESULTS: Selective termination resulted in delivery of a viable infant or infants in >90% of cases. Loss up to 24 weeks occurred in 7.1% of cases in which the final result was a singleton fetus and in 13.0% of cases in which the final result was twins. Loss was 6.6% as a result of structural abnormalities, 7.0% for chromosomal abnormalities, and 10% for mendelian abnormalities (difference not statistically significant). Loss rates for procedures were as follows: 9-12 weeks, 5.4%; 13-18 weeks, 8.7%; 19-24 weeks, 6.8%; and >/=25 weeks, 9.1% (difference not statistically significant). Mean gestational age at delivery was 35.7 weeks. No differences were seen in outcomes by maternal age. The rate of very early premature deliveries has fallen in recent years. There were no known cases of disseminated intravascular coagulation or serious maternal complications. CONCLUSION: (1) Selective termination, in the most experienced hands, can be technically performed in all 3 trimesters with good outcomes in >90% of cases. (2) The previously observed increase in second- versus first-trimester losses has diminished. (3) Third-trimester procedures, where legal, can be performed with a good outcome for the surviving fetus.

Chromosome Aberrations↗
PubMed1999

Development and integration of an extended embryo culture program.

OBJECTIVE: To study and evaluate a sequential, extended embryo culture system. DESIGN: Prospective study. SETTING: University-affiliated IVF clinic. PATIENT(S): All couples who were treated between October 1997 and July 1998. INTERVENTION(S): A standard human tubal fluid plus 10% serum substitute supplement (SSS) culture medium was used. The embryos were transferred to extended culture medium (S2 or G2) on day 3. MAIN OUTCOME MEASURE(S): Blastocyst formation and implantation and pregnancy rates. RESULT(S): Forty percent of the 20 donated cryopreserved embryos progressed to the blastocyst stage by day 6. Clinically, 7 (5.6%) of the 125 cycles did not result in a transfer. Blastocyst formation rates ranged from 33%-63% in the five study groups. Implantation rates ranged from 15%-52% and pregnancy rates ranged from 37%-75%. CONCLUSION(S): Extended culture to day 5 or 6 results in acceptable blastocyst formation rates, implantation rates, and pregnancy rates.

Adult↗
PubMed1999

Association between low-density lipoprotein composition and its metabolism in non-insulin-dependent diabetes mellitus.

Atheroma is related to low-density lipoprotein (LDL) composition. LDL in diabetic patients-a group with increased risk of severe atheroma-has been shown by our group and others to have various compositional alterations that are potentially atherogenic. Little is known about the relationship between LDL turnover and composition. This study examined the relationship between LDL composition and turnover in non-insulin-dependent diabetes mellitus (NIDDM) patients. Twenty-two NIDDM patients with a mean plasma cholesterol of 6.6+/-1.5 mmol/L were studied. Twelve subjects were hypercholesterolemic (mean cholesterol, 7.7+/-0.8 mmol/L), and eight of these agreed to be studied a second time after 4 weeks of treatment with simvastatin. LDL was isolated by density gradient ultracentrifugation, iodinated, and reinjected into the patient. LDL turnover was determined by measuring the clearance of [125I]-LDL from plasma over a 10-day period. The LDL residence time, determined using a biexponential model, correlated negatively with the body mass index (BMI) (r = -.73, P<.001) and serum triglycerides (r = - .57, P<.01). There was a significant inverse correlation between LDL residence time and the LDL esterified to free cholesterol ratio in hypercholesterolemic subjects (r = -.94, P<.001). There was a significant inverse relationship between LDL residence time and both hemoglobin A1c (HbA1c) and fasting blood glucose in these subjects before treatment (P<.005). After simvastatin therapy, the relationships were no longer significant. Simvastatin treatment was associated with a shorter LDL residence time (P<.01) and a decrease in LDL glycation (P<.001) with virtually no change in diabetic control (HbA1c, 6.0%+/-3.1% v. 6.3%+/-3.3%, NS). This study suggests that a decrease in residence time by upregulation of the LDL receptor with simvastatin alters LDL composition in a way that is likely to render the particle less atherogenic.

Aged↗
PubMed1999

Microsatellite instability is rare in rectal carcinomas and signifies hereditary cancer.

We analysed microsatellite instability (MSI) in a consecutive series of 165 rectal carcinomas. Data on a personal and/or family history of cancer were collected from all patients and revealed metachronous cancer in 9 patients, 2 of whom had developed colorectal cancer, and a suspected familial aggregation of colorectal cancer in three families. Only three of the 165 (2%) rectal cancers showed MSI. The patients whose tumours displayed MSI had clinical histories suggesting hereditary cancer--a family history of colorectal cancer and/or synchronous colorectal cancers. Denaturing gradient gel (DGGE) analysis was used to screen the MSI+ patients for mutations in the hMLH1 and hMSH2 genes and revealed two new germline mutations; a 1 bp deletion in exon 10 of hMSH2 creating a premature stop-codon and a splice donor site mutation in intron 16 of hMLH1. Considering colorectal carcinomas as a group, MSI has been reported to occur in approximately 10-20% of the tumours and thus can not, per se be used for clinical detection of hereditary tumours. This study shows, however, that MSI is rare in rectal carcinomas and when present strongly suggests a hereditary predisposition for colorectal cancer development.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Variability of polymerase chain reaction detection of the bcl-2-IgH translocation in an international multicentre study.

BACKGROUND: The capacity of the polymerase chain reaction (PCR) to detect very low numbers of cells bearing a t(14;18) translocation has led to its application in assessment of the results of treatment for follicular lymphoma, and suggestions that therapy might be guided by molecular studies. To test the reliability of PCR a collaborative study was undertaken to compare results from different laboratories in Europe and North America. METHODS: Twenty laboratories with records of publication in molecular diagnostics were sent blood from normal donors with varying numbers of t(14;18)-bearing cells added from a cell line with a translocation in the major breakpoint region (MBR) of the bcl-2 gene. Samples contained 1000, 100, 10, 1 or 0 cells per ml of whole blood and were sent blinded in duplicate. PCR methodology varied widely, with the total number of amplification cycles between 30 and 70, and 13 different primers used for the MBR region. Twelve laboratories used nested PCR and eight single round amplification. RESULTS: The sensitivity of nested and single round PCR was similar at 100 cells/ml but below this the nested method proved significantly more sensitive. The false positive rate was 28%, with 11 samples from 9 laboratories reported as positive when no t(14;18) cells were added. PCR product size and sequence analysis showed that false positives were due to contamination from cell-line DNA rather than background translocations in the donors. There was no significant difference in false positive rates between nested and single round techniques. CONCLUSION: The polymerase chain reaction to detect bcl-2-IgH rearrangements is presently carried out with widely disparate results. Further effort is required to bring forward a standard PCR protocol which can be re-tested in different laboratories to improve accuracy and reproducibility. The application of quantitative techniques such as real-time PCR may resolve many of the problems presently encountered.

Adult↗
PubMed1999

CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial.

BACKGROUND: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. PATIENTS AND METHODS: Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. RESULTS: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. CONCLUSION: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.

Adolescent↗
PubMed1999

Novel retinoids with receptor selectivity and functional selectivity.

Retinoids mediate a number of physiological pathways through their effects on cellular growth and differentiation. Upon binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs), retinoids regulate cellular processes by directly modulating the expression of responsive genes. The wide-ranging effects of retinoid action are attributable to two main factors-the ubiquitous distribution of several subtypes and isoforms of RARs and RXRs, and the ability of these receptors to regulate numerous genes upon ligand activation. The broad range of effects mediated by retinoids means not only that they have many potential therapeutic applications but also that non-selective retinoids are associated with a high incidence of adverse effects. The design of retinoids that are receptor-selective and function-selective is a strategy that is proving successful in developing novel retinoids that offer not only good efficacy but also good tolerability. Tazarotene, a receptor-selective retinoid indicated for the topical treatment of psoriasis, is at the forefront of this new generation of retinoids. In the near future, other receptor-selective retinoids may prove useful for the treatment of other dermatological diseases, cancer, and diabetes.

Antineoplastic Agents↗
PubMed1999

Monitoring the clearance of fetal RhD-positive red cells in FMH following RhD immunoglobulin administration.

Anti-RhD immunoglobulin was administered to RhD-negative women based on estimates of fetal bleed size obtained using a direct immunofluorescence flow cytometric technique employing a FITC-conjugated monoclonal human anti-D (BRAD 3). The effectiveness of the dose administered was assessed by (i) measuring the fraction of RhD-positive fetal cells in the maternal circulation at d0, and between d2 and d10 post RhD Ig administration, (ii) quantifying the amount of anti-D detectable in maternal plasma following RhD Ig injection in the perinatal period and (iii) assessing maternal serum for the presence of immune anti-D in follow-up samples taken 3 months to 3 years after delivery. Fifty-four women were assessed, 29 having fetal bleeds in excess of 4 mL. Follow-up samples were received from 20/29 mothers after RhD Ig administration; 43-99% and 69-99% of fetal cells had been cleared by d2/3 and d5/6, respectively, in 14/20 mothers, whereas less than 50% had been cleared in the remaining mothers. Long-term follow-up samples were obtained from eight of the 29 mothers (four with bleeds >/=20 mL, two with bleeds >95 mL): none had detectable anti-D in the serum 4 months to 3 years after delivery despite the persistence of up to 36% fetal RhD-positive cells in the maternal circulation six days after delivery.

Erythrocytes↗
PubMed1999

The A1166C mutation in the angiotensin II type I receptor and hypertension in the elderly.

1. Using a nested case-control study of 661 non-institutionalized elderly (> or = 60 years) residents of Dubbo, New South Wales, Australia, the aim of this study is to determine whether the A1166C polymorphism of the angiotensin II type I (AT1) receptor gene is associated with hypertension in the elderly. 2. Individuals were classified as isolated systolic hypertension (ISH, n = 146), systolic diastolic hypertension (SDH, n = 188), or normotensive, age- and sex-matched controls (n = 327). AA, CC and AC genotypes were determined using restriction fragment length polymorphism analysis of DNA generated by nested polymerase chain reaction. 3. A univariate analysis (chi 2) was complemented by a logistic regression analysis, facilitating adjustment for potential confounders. The unadjusted genotype and allele frequencies in ISH or SDH subjects did not differ significantly from the control subjects (chi 2 = 3.0, P = 0.55, 4 d.f.; chi 2 = 3.0, P = 0.23, 2 d.f., respectively). After adjustment for potential confounders neither genotype nor allele predicted ISH or SDH in this cohort. 4. From this study we conclude that the A1166C polymorphism of the AT1 receptor gene is not a marker for ISH nor for SDH in this large, elderly community sample.

Angiotensin II↗
PubMed1999

Are doctors still failing to assess and treat asthma attacks? An audit of the management of acute attacks in a health district.

This audit aimed to observe the management of acute asthma by primary and secondary care within a Health District. Asthma attacks occurring during the first 6 weeks of 1996 to patients between the ages of 3 and 74 years in Canterbury and Thanet District were notified by general practitioners, out-of-hours co-operatives and hospitals. Data were obtained retrospectively from the patient records. A total of 378 episodes was registered: 342 (90%) to primary care. Of these 234 (76% of patients aged 6 years or over) had a peak flow recorded; 114 (30%) were given emergency bronchodilation: oxygen was not used in primary care; 204 (54%) were given systemic steroids; and 43 (11%) were referred for hospital care of whom 36 were admitted. Of the attacks, 212 (69% of the patients aged 6 years or over) could be classified by percentage predicted peak flow and management compared to the Guidelines published by the British Thoracic Society. Twenty-eight patients presented with 'life-threatening' asthma: 20 (71%) were given emergency bronchodilation; oxygen was used in only two; 24 (86%) were given systemic steroids; and six (21%) were referred for admission. In their confidential enquiry into the asthma deaths the British Thoracic Society identified a failure to appreciate the severity of the attack, resulting in inadequate emergency treatment and delay in referring to hospital. These data suggest that, 15 years later, these problems may still exist.

Acute Disease↗
PubMed1999

Distribution of mesothelioma cases in different occupational groups and industries in Australia, 1979-1995.

Australia was a producer and user of asbestos and has one of the highest national incidences of mesothelioma in the world. The incidence is still rising and expected to do so for another 10-20 years. A study was conducted in 1996 to examine the past and current incidence rates of mesothelioma in a number of industries and occupations as the basis for predicting future outcomes. Occupational histories of a total of 3758 mesothelioma cases collected by two sequential national schemes--the Australian Mesothelioma Surveillance Program (1979-1985) and Australian Mesothelioma Register (1986-1995)--were reviewed and coded by the authors. The building industry contributed the largest number of cases nationwide followed by shipbuilding and repair, asbestos cement production, crocidolite mining and milling, railway locomotive construction and repair, coal-fired power stations, and other engineering operations. The mean latency between initial occupational asbestos exposure and diagnosis of the disease was 37.4 years (range = 4-66 years) for cases notified between 1979 and 1985, and 41.4 years (range = 6-84 years) for those between 1986 and 1995. Trends for each industry group have been changing considerably in the past 16 years, with the traditional primary asbestos industry cases from crocidolite mining and milling now on the decline and cases from asbestos cement production having plateaued. In contrast, more recently, more cases were observed from the asbestos user industries such as the building industry, and from occupations such as plumbers, carpenters, machinists, and car mechanics. These increases might be a reflection of the longer latency effects of the intermittent and less severe exposures in these larger occupational groups.

Aged↗