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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 559 records · Page 31Linked to original sources
PubMed1986

Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug.

Animals↗
PubMed1986

Preparation and characterization of a polyvalent human melanoma antigen vaccine.

A polyvalent melanoma tumor antigen vaccine was prepared from antigens shed by a pool of human melanoma cells cultured in serum-free medium. The vaccine contained multiple melanoma associated antigens (MAAs) and was free of detectable fetal calf serum (FCS) proteins and Dr antigens. Three batches of vaccine prepared several months apart contained the same spectrum of tumor antigens. Thirteen patients with metastatic malignant melanomas were immunized intradermally with escalating doses of the vaccine in a Phase I study. There was no toxicity other than transient urticaria at the injection site. Humoral immunity, assayed by indirect immunoprecipitation, was augmented in five (38%) patients. Cellular immunity, assayed by delayed-type cutaneous hypersensitivity, was induced in four (31%) patients. Skin tests to a control vaccine prepared from pooled allogeneic lymphocytes were negative. Cutaneous metastases regressed completely in one patient who is now disease free after 2 years, and multiple cutaneous metastases have remained stable for 14 months in another patient. These results indicate that active immunization to a partially characterized polyvalent melanoma antigen vaccine is safe and can increase immunity to melanoma in some patients.

Adult↗
PubMed1985

Computerized tomography scan findings in children with acute lymphocytic leukemia treated with three different methods of central nervous system prophylaxis.

Computerized tomography (CT) scans of the head were done on 93 children with acute lymphocytic leukemia in continuous complete remission who had been randomly assigned to three different methods. of central nervous system (CNS) prophylaxis. Twenty-nine children had received six doses of intrathecal methotrexate, 30 had received six doses of intrathecal methotrexate plus 2400 rad of cranial irradiation, and 34 had received six doses of intrathecal methotrexate plus three courses of intermediate-dose intravenous methotrexate. The overall incidence of abnormal scans was 35%, of which 91% were felt to represent minimal abnormalities. CT scan abnormalities were noted in 30% of the children receiving intrathecal methotrexate only, in 40% of those receiving intrathecal methotrexate plus cranial irradiation, and in 35% of those receiving intrathecal methotrexate plus intermediate dose methotrexate. These differences were not statistically significant. None of the three methods of CNS prophylaxis resulted in significant CT scan abnormalities. However, the few moderately or markedly abnormal scans evaluated were restricted to patients who received intrathecal methotrexate plus cranial irradiation. The clinical significance of CT scan abnormalities in leukemic children receiving these treatments remains unclear.

Brain Neoplasms↗
PubMed1985

Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast.

Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC.

Bone Neoplasms↗
PubMed1985

Systemic infection with Trichosporon capitatum in two patients with acute leukaemia.

Trichosporon capitatum was isolated from the blood of two patients with acute leukaemia who were undergoing induction chemotherapy. Both patients died of their infections, and the fungus was cultured from their tissues after death. Systemic infection was proved by demonstrating the same pattern of fluorescein-labelled lectin staining of fungal elements in the tissues as was shown by the fungal isolates.

Adult↗
PubMed1985

The anti-inflammatory effects of dexamethasone and therapeutic ultrasound in oral surgery.

A single blind, controlled trial was carried out to assess the anti-inflammatory effects of 10 mg dexamethasone given pre- and post-operatively and also ultrasound therapy in patients following the removal of impacted lower third molars. Facial swelling and trismus were significantly reduced in both the dexamethasone- and the ultrasound-treated groups compared with an untreated control group. This first report of the anti-inflammatory properties of ultrasound in a controlled clinical trial indicates its potential clinical use in reducing post-operative morbidity in oral surgery.

Adolescent↗
PubMed1985

A prospective study of the treatment of high-grade histology non-Hodgkin's lymphoma involving the gastrointestinal tract.

Thirty-six patients presenting with stage II-IV primary gastrointestinal non-Hodgkin's lymphoma of high-grade pathology were treated in a prospective study from 1975 to 1983 with combined modality therapy. A complete response rate of 56% was obtained and the overall 5-yr survival rate was 36%. The 5-yr relapse-free survival rate of the complete remitters was 79%. Multivariate analysis revealed that the remission achieved (P less than 0.001) and the completeness of primary surgery (P = 0.018) would reliably predict the duration of overall survival. The finding of diffuse histiocytic histology (Rappaport) predicted longer relapse-free survival. The majority of deaths were related to intra-abdominal complications and not to disseminated lymphoma. Gastrointestinal tract non-Hodgkin's lymphoma of high-grade pathology of all stages is curable with a combination of chemotherapy and radiotherapy following surgery to remove as much macroscopic disease as is possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast.

Recurrence and survival rates were studied in 175 women with breast cancer who, until the development of recurrent disease, received no treatment other than a modified radical (Patey) mastectomy, and in whom the oestrogen (REc) and progesterone (RPc) receptor content of the primary tumour was measured. At the time of first relapse most patients received endocrine therapy. At a minimum follow-up of 58 months post menopausal patients who possessed REc had an increased relapse-free survival (RFS) (P = 0.02). When examined by node status patients with 1-3 axillary nodes containing tumour also had an improvement in RFS (P = 0.02). There was no benefit for node-negative or premenopausal patients. In 163 patients in whom RPc was measured, RFS was unaffected by the possession of this receptor regardless of the degree of node involvement or menopausal status. Patients with REc had a significantly longer survival following mastectomy than patients without it (P = 0.006). This was most marked in post-menopausal (P = 0.003) and node-positive (P = 0.03) patients. Survival following mastectomy was also increased in patients possessing RPc (P = 0.04) and again was most marked for post-menopausal patients (P = 0.01), although no difference could be identified within node subgroups. There were significant differences in the post-relapse survival of REc and RPc positive and negative patients (REc P = 0.03, RPc P = 0.001). Patients with both receptors survived approximately 37 months longer than their receptor-negative counterparts. This study failed to confirm that the measurement of REc and RPc can reliably predict early relapse in breast cancer. The greater overall survival of receptor-positive patients is mainly due to an increase in survival following relapse. This may reflect the response of receptor-positive tumours to endocrine therapy given for recurrent disease.

Breast Neoplasms↗
PubMed1985

Combined modality management of local and disseminated adult soft tissue sarcomas: a review of 257 cases seen over 10 years at the Christie Hospital & Holt Radium Institute, Manchester.

Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). The commonest sites were lower limb (33%), visceral (21%), trunk (13%), retroperitoneum (12%) and upper limb (10%). Leiomyosarcoma (27%), liposarcoma (14%) malignant fibrous histiocytoma (10%) and neuro plus fibrosarcomas (15%) were the most frequent histological subtypes. A high proportion of uterine sarcomas (17%) is a point of distinction from many other series. Histological grade was specified in 72% of cases and the distribution (Grade I--27%; II--6%; III--67%) reflected a referral bias towards advanced disease. Local resection of the primary tumour was performed in 76% of cases. In many instances this only amounted to 'shelling out' and true compartmental excisions were rare. Amputation was performed in 31% of patients with limb sarcomas. Ninety-eight patients (38%) had experienced one or more local recurrences prior to referral and the overall local recurrence rate was 56%. Suitable patients (78%) received chemotherapy, 50% entering multicentre trials in collaboration with the EORTC. The commonest regime used in patients with advanced disease was CYVADIC which produced an overall response rate of 37%. Ifosfamide, used as a single agent in 16 patients, induced 3CR and 5PR for an overall response rate of 50%. When used in combination with MTX and VADIC, there was no difference in response rate, but numbers in these pilot studies were small. Seventeen high risk patients received adjuvant chemotherapy with VAC, but the results (11 relapses) were disappointing. An EORTC trial, comparing adjuvant CYVADIC chemotherapy with control has accrued 307 patients, 49 of these from the Christie Hospital. Preliminary results within this centre - 13/25 relapses in the control arm, 5/23 in the chemotherapy arm-suggest an advantage for chemotherapy but the data are statistically not significant. Post-operative radical radiotherapy after resection of the primary tumour or local recurrence was performed in 51 patients, with local control in 65% of cases, although metastases developed in 41%. At the time of analysis (1st April 1984) 98 (38%) were alive, of whom 72 showed no evidence of disease and 52 had never relapsed. Malignant disease was the cause of death in 92%. Overall survival was not influenced by sex, but patients less than 40 years of age fared significantly better (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Effect of alkyltins on rabbit articular and growth-plate chondrocytes in monolayer culture.

The effect of four different alkyltins (trimethyltin, triethyltin, dibutyltin, and dioctyltin) on the metabolism of rabbit articular and growth-plate chondrocytes was investigated using a monolayer cell-culture system. In most instances the compounds tested exhibited a general cytotoxic effect on these cells, inhibiting the synthesis of both DNA and sulfated proteoglycans. The effect of these compounds on proteoglycan synthesis was both quantitative and qualitative, as demonstrated by CsCl isopycnic density gradient centrifugation and gel exclusion chromatographic techniques. However, certain tin compounds tested, at specific concentrations, exerted a stimulatory effect on chondrocyte proliferation. Regarding DNA synthesis, growth-plate chondrocytes were more sensitive to the effect of the triethyltin, dibutyltin, and dioctyltin than were articular chondrocytes. The data are discussed in relation to the possible effects of the alkyltins on skeletal growth and development as well as the mechanism of action of the alkyltins at the molecular level.

Animals↗
PubMed1985

Erythromycin stearate, 1.5 g, for the oral prophylaxis of streptococcal bacteraemia in patients undergoing dental extraction: efficacy and tolerance.

Erythromycin stearate, 1.5 g, was effective in reducing the prevalence of streptococcal bacteraemia following dental extraction when administered orally under supervision 1 h before extraction. Blood samples were collected from adult patients for culture and erythromycin assay 1 to 2 min after the dental procedure. High dilution techniques involving the use of 1 litre bottles of broth were used to inactivate erythromycin present in blood cultures. Viridans streptococci were isolated from 6 of 40 patients receiving erythromycin (15%) compared with 18 of 42 control patients (43%). The mean serum erythromycin concentration at the time of extraction was 3.7 mg/l for 34 patients receiving erythromycin who had negative blood cultures compared with 1.8 mg/l for the six patients given erythromycin who had viridans streptococci isolated from the blood. Both the 1.5 g erythromycin stearate and placebo oral doses were well tolerated in a double blind comparative study which included 109 adult dental patients.

Administration, Oral↗
PubMed1985

Histogenesis of post-mastectomy angiosarcoma--an ultrastructural study.

An example of post-mastectomy angiosarcoma was studied by electron microscopy to determine its histogenesis. Unequivocal evidence of endothelial differentiation was found in well and poorly differentiated areas. Positive staining for factor VIII related antigen and negative staining for epithelial membrane antigen further confirmed that the tumour was a true angiosarcoma rather than a peculiar form of carcinomatous metastasis.

Blood Vessels↗
PubMed1985

Granular cell angiosarcoma of the skin: histology, electron microscopy and immunohistochemistry of a newly recognized tumor.

We report a unique angiosarcoma of the skin of the face in which a large part of the tumour was of granular cell appearance. Histologically the granular cells resembled those of conventional granular cell tumours. By electron microscopy the granules were identical to those of granular cell tumours but other features were lacking. Stains for vimentin and factor VIII related antigen were positive, but for S-100 protein and CEA were negative. The occurrence of granular cell change in an angiosarcoma supports the view that granular cell tumours are histogenetically diverse.

Actin Cytoskeleton↗