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Biomedical subjects

D Yip

Publications and source records attributed to D Yip.

28 records · Page 2Linked to original sources
PubMed1999

Matrix metalloproteinase inhibitors: applications in oncology.

Matrix metalloproteinases (MMP) are a group of zinc dependent enzymes which include the interstitial collagenases, stromelysins, gelatinases and membrane-type metalloproteinases. They are involved in the remodelling and turnover of the extracellular matrix proteins. They play a role in wound healing and the pathogenesis of arthritis. In malignancies they play a role in tumor invasion, metastasis and angiogenesis. A number of synthetic matrix metalloproteinase inhibitors (MMPIs) have been developed for clinical use. In preclinical tumor models they have shown promising activity in achieving inhibition of MMPs and reducing tumor growth and metastatic spread. Some have also shown additive or synergistic effects with cytotoxic agents. Phase I and II studies in human subjects have defined the main side effects of these agents as being musculoskeletal pains or arthralgias. As they are cytostatic agents rather than cytotoxic in activity conventional measurements of radiological response for assessment are not applicable in trials. Biological activity has been demonstrated in certain cancers by the effects on levels of tumor markers as surrogate markers of tumor response and also by a fibrotic stromal reaction seen in tumor tissue. Newer agents have been developed with selective inhibition of certain MMPs in an attempt to reduce the side effects. A number of phase III human clinical trials evaluating MMPs are being carried out at present but only one has been formally reported so far. This study suggested that marimastat had no survival advantage when compared to chemotherapy with gemcitabine in advanced pancreatic carcinoma. Current trials are assessing efficacy of MMPIs in maintenance of remission after other modalities of therapy or in combination with cytotoxic agents. MMPs have also been demonstrated to play an important role in the articular cartilage destruction seen in both rheumatoid arthritis and osteoarthritis. The use of MMPIs in both ex vivo and in vivo models have shown promising results and trials are in process to assess their potential role in the control of articular destruction. The true therapeutic role of MMPIs await the results of these randomized studies.

Animals↗
PubMed1999

The impact of (1:1) cyclosporine A conversion to its microemulsion formulation on the kidney function of patients with cardiac allografts.

Due to the large variations in the absorption and bioavailability of conventional cyclosporine A (CyA), 1:1 (mg:mg) conversion to its microemulsion formulation (Neoral) has been advocated in transplant recipients. However, the renal hazards and biochemical effects of such conversions and not known in cardiac transplant recipients. In this study, 68 cardiac transplant recipients who were receiving conventional CyA, for a period of 61.3 +/- 36.0 (mean +/- standard error (SE)) months, were switched to the microemulsion formulation (Neoral). The biochemical and renal function tests were evaluated at 1, 3, 6, 9 and 12 months pre- and post-conversion of CyA. The results obtained post-conversion were compared with those of the baseline (pre-conversion). Serum creatinine and uric acid levels significantly increased post-conversion to the microemulsion formulation. One patient required discontinuation of the microemulsion in an attempt to reverse severe renal failure. In spite of a significant decrease in the microemulsion dose at 6, 9 and 12 months, there was a significant increase in the whole blood CyA trough levels at 9 and 12 months of conversion. There was no significant change in blood pressure, serum total cholesterol or potassium post-conversion. Our results suggest that after 1:1 (mg:mg) conversion of CyA to its microemulsion formulation, there will be a significant rise in serum creatinine, uric acid and whole blood trough CyA levels necessitating significant dose reduction. This effect is probably due to the markedly improved absorption and bioavailability of the latter.

Absorption↗
PubMed1999

The treatment of metastatic colorectal cancer.

Metastatic colorectal cancer represents an incurable condition, with the exception of a very select group of patients in whom surgical excision of recurrent disease is possible. Chemotherapy offers a significant palliative benefit and may prolong patient survival. The preferred cytotoxic agent is 5-fluorouracil, through the optimal administration schedule is unknown. Recent evidence also supports the use of second-line chemotherapy for patients who develop progressive disease following 5-fluorouracil treatment. Promising results have been obtained with new drugs, in particular oxaliplatin and irinotecan. Novel therapeutic approaches, including immunotherapy and liver directed strategies, are undergoing clinical evaluation. Comprehensive supportive care, with appropriate community and hospital based palliative care, is essential in the management of patients with advanced colorectal cancer.

Antineoplastic Agents↗
PubMed1998

Cardiopulmonary exercise testing identifies low risk patients with heart failure and severely impaired exercise capacity considered for heart transplantation.

OBJECTIVES: The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk. BACKGROUND: Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (VO2) < or = 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size. METHODS: Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise VO2 < or = 14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk. RESULTS: The 55% 3-year survival rate of the 77 patients with a peak exercise VO2 < or = 14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak VO2 < or = 50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1. CONCLUSIONS: Peak exercise SBP and percent predicted peak exercise VO2 are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise VO2 < or = 14 ml/min per kg.

Adult↗
PubMed1997

Omeprazole-induced interstitial nephritis.

Acute renal impairment secondary to interstitial nephritis is a rare complication of omeprazole. We describe a 50-year-old woman who took 20 mg omeprazole twice daily for endoscopically proved ulcerative esophagitis. At the same time, Duke's C colonic cancer was diagnosed and completely resected. Five fluorouracil/folinic acid adjuvant chemotherapy was tolerated without diarrhea or mouth ulceration. Renal function was normal before her first monthly cycle but markedly deteriorated immediately before the second cycle was due. The patient was symptomatic with lethargy, nausea, and mild vomiting, but she was clinically normotensive and only mildly dehydrated. Her serum creatinine concentration increased despite prolonged intravenous hydration, peaking at 4.4 mg/dl 1 week later. Results of a renal ultrasound were normal, and urinary microscopic findings were unremarkable. Renal biopsy showed interstitial nephritis, and renal function improved on cessation of omeprazole, eventually returning to normal. We describe the 12 cases of omeprazole-induced interstitial nephritis reported previously.

Anti-Ulcer Agents↗
PubMed1996

Thymoma and agranulocytosis: two case reports and literature review.

Thymoma with agranulocytosis is a rare association. We describe two cases of agranulocytosis presenting with sepsis which were both found to have coincident benign spindle cell thymomas. One case, associated with promyelocyte arrest and hypogammaglobulinaemia, was treated successfully with granulocyte colony-stimulating factor (G-CSF). Thymectomy had no effect. The other case, associated with complete myeloid aplasia, proceeded to a fatal outcome after failure of treatment with granulocyte-macrophage colony stimulating factor (GM-CSF), plasmapheresis, thymectomy, intravenous immunoglobulin, cyclophosphamide and methylprednisolone. We also review the literature of thymoma in association with agranulocytosis.

Agranulocytosis↗
PubMedDate not supplied

Use of fluorodeoxyglucose positron emission tomography scans in patients with advanced germ cell tumour following chemotherapy: single-centre experience with long-term follow up.

AIMS: Fluorodeoxyglucose positron emission tomography (FDG-PET) may detect residual or recurrent malignancy in patients with germ cell tumours (GCT) following chemotherapy. The objective of the present study was to evaluate the use of FDG-PET in the setting of advanced GCT, and to determine the influence of FDG-PET on subsequent patient management. METHODS: A computerized search of the patient database of the Department of Medical Oncology, Guy's Hospital, London, United Kingdom, and a manual search of medical records, were conducted. All male patients with metastatic or extragonadal GCT treated with chemotherapy between July 1996 and June 1999 inclusive were identified. Data from patients that had a PET scan following chemotherapy were analysed. Reported PET scan findings were compared with subsequent clinical management and patient outcome. RESULTS: A total of 30 patients with metastatic testicular GCT and three patients with extragonadal GCT were treated with chemotherapy. Of these, 15 patients (12 testicular; three extragonadal; 10 non-seminoma; and five seminoma) were investigated following chemo-therapy with at least one FDG-PET scan. Seven patients had two or more PET scans, and a total of 26 FDG-PET scans was performed. The most frequent indication for PET scan was evaluation of a residual mass (11 patients). Three patients had an FDG-PET to evaluate thymic prominence. Minimum follow up from first PET scan was 18 months. Three of 26 PET scans had false positive findings. Four PET scans yielded findings of equivocal significance with repeat PET scan recommended. Relapse of disease occurred in three patients; two of whom had normal previous PET scans and one had a previous equivocal result. PET had an impact on patient management in only one case where it 'prompted' surgical excision of a residual mass. Normal PET scans provided reassurance in patients with residual small masses but did not alter their subsequent -management. CONCLUSIONS: A residual mass was the most common indication for PET. For the majority of patients PET did not have a discernible influence on clinical management. Oncologists should exercise caution in their interpretation of PET scan findings and guidelines for the appropriate use of PET in testicular cancer management need to be developed. Prospective trials are required to define the clinical role of PET in this setting.

Adult↗
PubMedDate not supplied

5-fluorouracil-induced erythema multiforme.

Erythema multiforme is an immunologically mediated skin reaction to a foreign antigen and can occur with many drugs. We report the first two cases of erythema multiforme induced by 5-fluorouracil (5-FU). The first case was in a man with inoperable gastric carcinoma being treated by continual infusion who developed the classic rash involving the neck and upper chest, along with mouth ulceration and plantar-palmar erythrodysaesthesia. Histological confirmation was made by skin biopsy and the lesions resolved spontaneously. They recurred on restarting 5-FU. The second case was in a woman being given adjuvant bolus 5-FU and folinic acid for Duke's C colon cancer who developed the rash during the first cycle. Again, the lesions settled spontaneously but recurred more severely on the second cycle. When treatment was changed to the specific thymidylate synthase inhibitor, raltitrexed, the course was completed uneventfully.

Aged↗
PubMedDate not supplied

Collecting duct carcinoma of the kidney associated with the sickle cell trait.

Collecting duct carcinoma of the kidney is a rare neoplasm that arises from the medullary collecting ducts. It has an aggressive clinical course and patients usually present with metastatic disease. Treatment approaches apart from surgery have been unrewarding. Renal medullary carcinoma is also an aggressive tumour which occurs predominantly in young, black, male patients with sickle cell trait. We describe a case of collecting duct carcinoma in a 61-year-old black female who exhibited the sickle cell trait. Histopathology revealed a high-grade tubular carcinoma with marked desmoplasia, adjacent dysplastic collecting ducts and positive immunohistochemical staining for high and low molecular weight cytokeratins and epithelial membrane antigen. The association of collecting duct carcinoma with sickle cell trait has not been previously reported. This case supports the postulate that collecting duct carcinoma and renal medullary carcinoma may be part of the same spectrum of renal malignancies.

Fatal Outcome↗