PubMed Health⌕ Search

Biomedical subjects

G Higgins

Publications and source records attributed to G Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1999

Coronary C-reactive protein distribution: its relation to development of atherosclerosis.

Two hundred and ninety-nine paraffin-embedded human coronary artery sections from 68 autopsies, both male and female and with various causes of death, were examined for distribution of C-reactive protein (CRP) using the indirect immunofluorescence technique and high-resolution confocal microscopy. The results demonstrate, for the first time, the existence of CRP in human coronary arteries, with evidence of CRP deposits being associated with lipids within in the artery walls. Grades of CRP immunoreactivity positively correlate with relative intimal thickness and negatively correlate with relative lumen size. It is suggested, therefore, that CRP may be related to the development of atherosclerosis and that the development of coronary atherosclerosis is associated with a relapsing inflammatory/necrotic process occurring within the coronary intima.

Adult↗
PubMed1999

Rett syndrome: randomized controlled trial of L-carnitine.

Rett syndrome is a severe neurodevelopmental disorder of unknown etiology, occurring almost exclusively in female patients. The etiology and functional significance of plasma carnitine deficiency seen in some patients with Rett syndrome is unknown. To investigate whether L-carnitine might be of benefit in Rett syndrome, a randomized, placebo-controlled, double-blind crossover trial of L-carnitine has been completed in 35 subjects. Eight-week treatment phases were completed for both a placebo and L-carnitine. Outcome was measured by parents/caregivers and at medical follow-up using three established tools: the Rett Syndrome Motor Behavioral Assessment, the Hand Apraxia Scale, and the Patient Well-Being Index. Analysis comparing change between baseline and week 8 of treatment for L-carnitine and the placebo showed that both parents/caregivers and medical follow-up detected improvements in the subjects' well-being. In addition, medical review showed an improvement on the Hand Apraxia Scale for a higher proportion of girls on L-carnitine. Identification of predictors of clinical improvement has been limited by the power of the study. These findings suggest that L-carnitine is of benefit in some patients with Rett syndrome. While L-carnitine did not lead to major functional changes in ability, the type of changes reported could still have a substantial impact on the girls and their families. Information is still needed, however, to determine if only subgroups of girls with the disorder are responsive to L-carnitine and the appropriate duration of therapy.

Adolescent↗
PubMed1999

Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.

PURPOSE: The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor-based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation. PATIENTS AND METHODS: A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival. Patients were assigned to three risk categories depending on the number of unfavorable characteristics. Patient selection in phase II studies was addressed by developing a table of expected median survival for patient cohorts that had varying proportions of patients from the three risk categories. RESULTS: Two factors had independent prognosis: Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (P =.0001). The median survival time of patient cohorts could vary from 9 to 26 months simply by altering the proportion of patients from different risk categories. CONCLUSION: The presence of baseline KPS less than 80% or visceral metastasis has an impact on survival. Reporting the proportion of patients with zero, one, and two risk factors will facilitate understanding of the relevance of the median survival in phase II trials. Phase III trials should stratify patients according to the number of risk factors to avoid imbalance in treatment arms.

Adult↗
PubMed1999

Outcome of postchemotherapy surgery after treatment with methotrexate, vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

PURPOSE: The role of postchemotherapy surgery for patients with metastatic transitional cell carcinoma (TCC) is controversial. We retrospectively analyzed our experience with patients who underwent postchemotherapy surgery after methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy to assess an impact on long-term survival. PATIENTS AND METHODS: This report is based on the retrospective analysis of 203 patients with unresectable primary tumors or metastatic TCC, previously reported in five trials of M-VAC chemotherapy. Fifty patients underwent postchemotherapy surgery for suspected or known residual disease. Characteristics of patients selected for surgery, results of surgery, and the impact of surgery on survival were assessed. RESULTS: In 17 patients, no viable tumor was found at postchemotherapy surgery, pathologically confirming a complete response to chemotherapy. Three patients had unresectable residual TCC. In 30 patients, residual, viable TCC was completely resected, which resulted in a complete response to chemotherapy plus surgery. Ten (33%) of these 30 patients remained alive at 5 years, similar to results observed for patients who attained a complete response to chemotherapy alone (41%). Analysis by baseline extent of disease suggested that patients with unresectable primary tumors or with metastases restricted to lymph node sites were most likely to survive for 5 years. CONCLUSION: Postchemotherapy surgical resection of residual cancer may result in 5-year disease-free survival in some patients who would otherwise succumb to disease. Optimal candidates include patients whose prechemotherapy sites of disease are restricted to the primary or lymph node sites and who have a major response to chemotherapy.

Adult↗
PubMed1998

The Medical Journal of Australia Internet peer-review study.

BACKGROUND: Peer review of medical papers is a confidential consultancy between the reviewer and the journal editor, and has been criticised for its potential bias and inadequacy. We explored the potential of the internet for open peer review to see whether this approach improved the quality and outcome of peer review. METHODS: Research and review articles that had been accepted for publication in The Medical Journal of Australia (MJA) were published together with the reviewers' reports on the worldwide web, with the consent of authors and referees. Selected readers' e-mailed comments were electronically published as additional commentary; authors could reply or revise their paper in response to readers' comments. Articles were edited and published in print after this open review. FINDINGS: 60 (81%) of 74 authors agreed to take part in the study, together with 150 (92%) of 162 reviewers. There was no significant difference in the performance of commissioned reviewers before and during the study. Four articles were not included because of insufficient time before print publication. Of the remaining 56 papers, 28 received 52 comments from 42 readers (2% of readers submitted comments). Most readers' comments were short and specific, and seven articles were changed by the authors in response. INTERPRETATION: Open peer review is acceptable to most authors and reviewers. Postpublication review by readers on the internet is no substitute for commissioned prepublication review, but can provide editors with valuable input from individuals who would not otherwise be consulted. Readers also gain insight into the processes of peer review and publication.

Attitude↗
PubMed1998

The incorporation of lamotrigine into the routine automated sequential trace enrichment of dialysates assay of anticonvulsants.

We have extended automated sequential trace enrichment of dialysates and high performance liquid chromatography to include the simultaneous assay of lamotrigine with other anticonvulsant drugs: phenobarbitone, carbamazepine and phenytoin. The procedure is reliable and precise (between-batch coefficients of variation < 2.8%) with no interference from other commonly prescribed drugs. Patients on lamotrigine presented with serum concentrations up to 67 mumol/L with no adverse effects, suggesting that the therapeutic range may need re-appraisal.

Anticonvulsants↗
PubMed1998

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Adult↗
PubMed1997

European community. Euro-cash dispensers.

Applications for funding should be well-targeted and must demonstrate a track record in the area of the proposed initiative. Applications not related to a trust's core business are unlikely to succeed.

Europe↗
PubMed1997

Prevalence of respiratory viruses and Mycoplasma pneumoniae in sputum samples from unselected adult patients.

Sputum samples from adult patients are routinely used for bacteriological tests, but not for the diagnosis of viral/mycoplasmal infections. We examined 511 sputum samples submitted for bacterial tests from patients at the Royal Adelaide Hospital. Each specimen was tested directly (and after six days of cell culture amplification) for antigens to influenza A and B, parainfluenza 1, 2 and 3, adenovirus, respiratory syncytial virus (RSV) and Mycoplasma pneumoniae. Respiratory viruses or M. pneumoniae were found in 11% of all specimens but were most common (14%) in sputa reported as containing only "oral flora". Respiratory virus or M. pneumoniae infection was significantly more common in medical patients (12%) than in surgical patients (5%), and was most common in oncology (hematology/radiotherapy) patients (25%). Influenza A and RSV were equally common in medical patients, while RSV was the most frequent isolate in oncology patients. Respiratory viral infection is an underdiagnosed condition in adults, particularly the immunocompromised, which can be successfully diagnosed by virological examination of sputum.

Adenoviridae↗
PubMed1997

Detection of Chlamydia trachomatis in urine samples by nucleic acid tests: comparison with culture and enzyme immunoassay of genital swab specimens.

Two commercially available nucleic acid-based tests, ligase chain reaction (LCR; Abbott Laboratories) and PCR (Roche Diagnostics), for the detection of Chlamydia trachomatis in male and female urine samples were compared with culture and enzyme immunoassay (EIA) (Microtrak; Syva) for C. trachomatis detection in genital samples. The samples were collected from 1,005 patients who attended a sexually transmitted disease clinic. In this study population, the prevalence of the infection was 4%. Specimens which were reactive in any of the tests were retested with a different PCR test using primers directed against the major outer membrane protein gene. With a "gold standard" of a positive culture, or any other positive test result if it was confirmed by an independent test, the Roche PCR (95% sensitive, 99.9% specific) was more sensitive than the LCR (75% sensitive, 100% specific) (chi2, P < 0.0001) while both tests were more sensitive than culture (58% sensitive, 100% specific) or EIA (45% sensitive, 100% specific) (chi2, P < 0.001). The Roche PCR and Abbott LCR tests of urine identified 65% and 30% more positive patients, respectively, than did testing by culture of urethral or cervical specimens. Nucleic acid testing of urine specimens for C. trachomatis is a more sensitive and convenient method for the detection of genital infection.

Bacteriological Techniques↗
PubMed1995

Internal quality assurance in a clinical virology laboratory. I. Internal quality assessment.

AIMS: In April 1991 an internal quality assessment scheme (IQAS) was introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. The IQAS was established to identify recurring technical and procedural problems, to check the adequacy of current techniques, and to calculate the frequency of errors. METHODS: Between April 1991 and December 1993, 715 anonymous clinical serum samples were submitted to the laboratory to test 3245 individual procedures of diagnostic viral serology. RESULTS: A total of 485 (14.9%) procedural and 61 (1.9%) technical discrepancies were observed, the technical discrepancies mainly being recorded in complement fixation tests. Twenty two (0.7% of total procedures) of the technical discrepancies were diagnostically significant. CONCLUSIONS: Evaluation criteria developed with the introduction of IQAS to viral serology, and technical and procedural discrepancies are assessed. As yet, IQAS has not been introduced to other sections of the diagnostic virology laboratory (virus isolation, electron microscopy, immunofluorescence, and enzyme linked immunosorbent assays for viral and chlamydial antigens).

Humans↗
PubMed1995

Internal quality assurance in a clinical virology laboratory. II. Internal quality control.

AIMS: In April 1991 additional quality control procedures were introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. Internal quality control (IQC) samples were gradually included in the serological assays performed in the laboratory and supplemented kit controls and standard sera. METHODS: From April 1991 to December 1993, 2421 IQC procedures were carried out with reference sera. RESULTS: The IQC samples were evaluated according to the Westgard rules. Violations were recorded in 60 of 1808 (3.3%) controls and were highest in the IQC samples of complement fixation tests (25/312 (8%) of controls submitted for complement fixation tests). CONCLUSIONS: The inclusion of IQC samples in the serological assays performed in the laboratory has highlighted batch to batch variation in commercial assays. The setting of acceptable limits for the IQC samples has increased confidence in the validity of assay results.

Complement Fixation Tests↗
PubMed1993

Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5.

We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen.

Adult↗
PubMed1993

Immunohistochemical study of intimal microvessels in coronary atherosclerosis.

Two hundred ninety-nine human coronary artery paraffin-embedded tissue blocks were examined for intimal microvessel invasion by probing for factor VIII-associated antigen with indirect immunofluorescence and high resolution confocal microscopy. The results obtained confirm that intimal microvessels originate in the adventitia and show that the richness of intimal microvessels is strongly positively correlated with intimal thickness and negatively correlated with relative lumen size. A number of plasma constituents were examined in serial sections. Comparison of immunofluorescence distribution patterns of these components with intimal microvessel distribution patterns reveals that intimal microvessels leak plasma albumin into artery walls, exude fibrinogen, and are associated with the build-up of plasma cells within atherosclerotic lesions. Therefore, intimal microvessels are demonstrated to play important roles in the development of atherosclerosis.

Antibodies↗
PubMed1993

Plasma protein insudation as an index of early coronary atherogenesis.

Two hundred ninety-nine paraffin-embedded coronary artery blocks from 68 autopsy cases were serially sectioned. The blocks were selected to provide a range from normal through various stages of atherosclerosis, and sections were examined with the indirect immunofluorescence technique for intramural distribution of plasma albumin, fibrinogen, and immunoglobulin gamma (IgG). Cryostat-sections of 44 blocks from 22 of the same cases were examined with the same technique for distribution of apolipoprotein B. Alteration of protein insudation in the artery wall was a sensitive index of coronary atherogenesis. The sequence in which these proteins were involved in the initiation and development of early atherosclerotic lesions was analyzed by determining the average relative intimal thickness and relative lumen size that was associated with the first occurrence of altered insudation of each of these proteins. Results indicate that changed plasma albumin insudation is the earliest sign of a focal intimal lesion, and increasing albumin insudation shows the strongest association with intimal plaque growth. The other proteins tested showed altered insudation, in the order IgG, fibrinogen, apolipoprotein B. The results indicate that a progressive increase in permeability of the coronary artery endothelium occurs in the early stages of atherogenesis. Patterns of IgG localization provide evidence of both early systemic and subsequent local immune reactions being involved in atherogenesis. Altered albumin and apolipoprotein B insudation levels have stronger correlation coefficients with relative intimal thickness and relative lumen size than do those IgG and fibrinogen. The extremely high correlation coefficients shown by albumin emphasizes the importance of edema in determining plaque size and lumen stenosis.

Adult↗