Search PubMed⌕ Search

Biomedical subjects

C J Williams

Publications and source records attributed to C J Williams.

At least 163 records · Page 9Linked to original sources

Mammary transfer of vitamin D3 in the rabbit doe.

Mammary transfer of vitamin D3 from a single intravenous injection containing 100 000 IU vitamin D3 in ethanol, was studied in lactating rabbit does. Significant amounts of the injected vitamin D3 appeared in the milk of does. The highest concentration was observed in the first milk sampling (24 h after administration) which was followed by a decreasing pattern in the five postinjection days. Vitamin D3 concentration in the neonate tissues were smaller than in their dams. In the maternal tissue the highest concentration occurred in the liver, whereas muscle had the lowest value. Among the various neonatal tissues liver contained the highest amounts although in the other tissues appreciable amounts of vitamin D3 were recovered.

Animals↗

Plasma vitamin D3 response in cattle and sheep exposed to ultraviolet radiation.

Plasma levels of vitamin D3 were determined in a group of 10 cows housed indoors and exposed during the winter to ultraviolet irradiation (UVR). Exposure to UVR was associated with marked rises in plasma vitamin D3 concentrations. The pattern and magnitude of the plasma vitamin D3 response to UVR exposure in sheep raised in total confinement was also investigated. Exposure to sun lamps produced a significant increase in sheep plasma vitamin D3 concentrations. There was no significant difference in the plasma levels of vitamin D3 due to length of time of exposure to UVR.

Animals↗

Failure of scalp hypothermia to prevent hair loss when cyclophosphamide is added to doxorubicin and vincristine.

Scalp hypothermia can prevent alopecia caused by low doses of doxorubicin alone or in simple combinations. The technique was used in 60 patients with breast cancer (24 receiving adjuvant therapy; 36 with advanced recurrent disease) receiving chemotherapy with iv doxorubicin (40 mg/m2) and vincristine (1.4 mg/m2) on Day 1 together with oral cyclophosphamide (200 mg/m2) on Days 2-5. The patients' desire to continue scalp hypothermia, reflecting their perception of benefit, and an objective assessment of hair retention were the study end points. The mean number of cycles of chemotherapy given (6.1 in patients receiving adjuvant therapy; 3.8 in those with advanced disease) exceeded the number of cycles with hypothermia (2.1 in patients receiving adjuvant therapy; 1.6 in those with advanced disease); no patients retained enough hair to encourage them to continue scalp hypothermia throughout chemotherapy. All patients were rated as having poor hair retention. Scalp hypothermia is ineffective when used with combinations of drugs, each causing alopecia, or with high doses of doxorubicin.

Alopecia↗

Usefulness of letters from hospitals to general practitioners.

In an investigation of the communication between specialist hospital departments and general practitioners 97 general practitioners were asked to say how important selected items of information that the hospital could pass on would be for management of a patient receiving chemotherapy. In addition, the records of 68 patients were examined for coverage of these topics. General practitioners considered technical topics to be more important than social ones. Hospital letters covered technical topics well, apart from details of possible side effects, but did not do the same even for the two social topics that most doctors considered to be essential--namely, what patients have been told about their diagnosis and prognosis. Letters from hospitals to general practitioners cover technical topics well but should include more information relating to the social aspects of the patient's disease.

Antineoplastic Agents↗

Correlations between clonogenicity and prognostic factors in human breast cancer.

The pursuit of more effective systemic treatments in breast cancer has been limited by a failure to maintain or grow tumour cells in vitro. This study reports our experience in obtaining clonogenic growth in 54 primary breast cancers obtained at mastectomy. Of 47 assays free of infection, clonogenic growth was achieved in 22 (41 per cent). Only 5 of 23 oestrogen receptor positive tumours grew compared to 14 of 21 oestrogen receptor negative tumours chi 2 = 9.03; P less than 0.01). None of the 5 cytosolic receptor positive tumours contained a nuclear receptor for oestrogen. Growth was not related to tumour stage, menopausal status, age or histological grade. Receptor negative tumours had higher thymidine labelling indices, but these were no different to the tumours grown in the assay.

Breast Neoplasms↗

Late recurrence in Hodgkin's disease: a report of two cases.

Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.

Adult↗

Combination chemotherapy using high or low dose methotrexate for small cell carcinoma of the lung--a randomised trial.

Eighty-three patients with histologically proven small cell carcinoma of the lung were entered into a prospective randomised clinical trial to evaluate two induction regimes. A 'low' dose methotrexate regime which employed three cycles of etoposide, adriamycin and methotrexate given at conventional dosage was compared with a regime which employed three cycles of etoposide and adriamycin together with five courses of high dose methotrexate and folinic acid rescue. All patients achieving a complete response (CR) received prophylactic cranial irradiation. Patients with limited disease who achieved a CR received additional radiotherapy to the primary site. An alternative four drug regime (procarbazine, vincristine, cyclophosphamide and CCNU) was evaluated in patients failing to achieve or subsequently relapsing from a complete response. Response rates for the low dose and high dose methotrexate arms were 54 and 55% respectively with median survivals of 8.6 and 9.7 months. Median survival for complete and partial responders was 20.2 and 11 months respectively. The alternative four drug regime showed limited activity in patients failing to achieve a complete response after primary therapy. We conclude that high dose methotrexate as used in this study has no role in small cell lung cancer. The 'low' dose regime was well tolerated by outpatients, is effective and is suitable for generalised use in the palliation of small cell lung cancer.

Aged↗

Second look laparotomy in the management of epithelial cell carcinoma of the ovary.

Case histories from 20 patients undergoing postchemotherapy "second look" laparotomy for metastatic epithelial cell carcinoma of the ovary were reviewed in an attempt to evaluate the usefulness of this procedure and its likely impact on patient survival. The patient population comprised 18 patients treated with a combination of cisplatin, adriamycin and cyclophosphamide (PACe) and 2 patients treated with chlorambucil. The findings at second look were often predictable, and related to the adequacy of initial surgery. Complete tumour regression identified a group of patients with a relatively good prognosis. However in most patients residual tumour was found which rarely proved resectable. Second line chemotherapy was poorly tolerated, and appeared to have little impact on the disease particularly after combination chemotherapy had been used initially. There was little evidence that second look surgery itself positively contributed to survival. This procedure and its timing should be regarded as experimental and a suitable subject for randomised clinical trials.

Adult↗

A comparison of two doses of tamoxifen (Nolvadex) in postmenopausal women with advanced breast cancer: 10 mg bd versus 20 mg bd.

In a comparative double-blind trial involving 263 postmenopausal women with advanced breast cancer treated with tamoxifen, the mean objective tumour response rate and duration was 32% and 15 months respectively. No significant difference was found in clinical response and adverse effects between those randomised to 10 mg and those to 20 mg twice daily. Although the mean serum concentration of tamoxifen in the 20 mg bd group was significantly higher no correlation between serum level and clinical benefit was demonstrated.

Adult↗

Response of differentiated but not anaplastic teratoma to interferon.

A Phase 2 trial was conducted using intramuscular lymphoblastoid interferon (IFN, Wellcome Research Laboratories), 4 MU per day, in 10 patients with chemotherapy-resistant teratomas. There was stabilisation of disease in 2 patients both of whom were in retrospect considered to have had differentiated teratoma at the time of IFN administration. There was progression of presumed active anaplastic germ cell tumour in 8 patients. One of these patients, a 15-year-old boy with biopsy proven differentiated teratoma has received 2 courses of lymphoblastoid IFN and 1 course of recombinant leukocyte A IFN (Roche Products Ltd.) lasting 5 1/2, 8 and 8+ months respectively. He has had a mixed response in his differentiated tumour which on each occasion has been maintained for the duration that he received IFN. Rising HCG levels during his second course of interferon required additional cytotoxic chemotherapy. Lymphoblastoid IFN does not appear to be active against anaplastic germ cell tumours but both lymphoblastoid and recombinant leukocyte A IFN may be useful in the treatment of unresectable differentiated teratoma.

Adolescent↗

Vitamin D3 levels in certain sheep tissues at various times after the intramuscular administration of vitamin D3.

Twenty crossbred wethers were injected intramuscularly with 1 X 10(6) IU of Vitamin D3 and four killed at the end of each of five time periods (1, 2, 3, 4 and 7 months). The results indicated that in these sheep dosed with this large dose of vitamin D3, their depletion in this liposoluble vitamin was a long process. The rate of uptake varied for the different tissues examined. Among the various tissues, vitamin D3 was stored primarily in the adipose tissue. One month after administration of vitamin D3, levels amounted to approximately 220 ng/g fresh tissue and 7 months later there were still appreciable amounts of D3 (2.5 ng/g fresh tissue). Kidney, pancreas, liver had also accumulated a significant amount of the administered dose (1st month: 58, 32 and 20 ng/g fresh tissue, respectively) which was retained in these sheep's organs for over 4 months (13, 32 and 15 ng/g fresh weight). In three muscles (heart and two skeletal muscles) appreciable amounts of vitamin D3 were recorded, which remained high until 4 months after administration (over 8 ng/g fresh tissue). The lowest uptake was recorded in the skin (9 ng/g the first month and 4 ng/g fresh weight at the end of experiment). All these results show that vitamin D3 was taken up rapidly by various tissues and was retained for a long period of time.

Adipose Tissue↗

Poor prognosis non-Hodgkin's lymphoma in the elderly: clinical presentation and management.

Thirty-eight patients age 65 years and older with a diagnosis of non-Hodgkin's lymphoma of poor prognostic type were seen over a five and a half year period. These patients represented 19 per cent of our total new patient non-Hodgkin's lymphoma population during this time. Advanced age, coexisting medical illness, widespread lymphoma and poor treatment compliance were common problems. Despite this we were able to render 26 per cent of patients disease-free for periods from 12 to over 48 months. Age should not be considered a bar to staging and effective therapy. Palliative management was unsuccessful, and we believe that treatment should be given with the intention of cure. Features suggesting that a patient was more likely to achieve a lasting complete remission included early stage (I-IIA), a lack of systemic ('B') symptoms, an absence of bone marrow or bulky gastrointestinal tract disease and no pre-existing serious medical condition.

Aged↗

Genetic expression of aflatoxin metabolism. Effects of 3-methylcholanthrene and beta-naphthoflavone on hepatic microsomal metabolism and mutagenic activation of aflatoxins.

The effects of pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (beta NF) on the hepatic microsome-mediated mutagenesis of aflatoxin B1 (AFB1) and benzo[a]pyrene, and on the metabolism of aflatoxins B1 and B2, were investigated in inbred mouse strains. The inbred strains of mice studied included Ah nonresponsive strains (DBA/2Ha, AKR/Sn and RF/J), which were also nonresponsive to the induction of the metabolism of AFB1 to AFM1 (AFB1-4-hydroxylase activity), and Ah responsive strains (C57BL/6Ha, ICR/Ha, C3H/St, A/St, Balb/cCr, C57e/Ha and CBA/Pi), which were also responsive to the induction of AFB1-4-hydroxylase activity. The hepatic microsome-mediated enzyme activities studied included: mutagenic activation of AFB1 and benzo[a]pyrene in the Ames Salmonella typhimurium TA-98 system; metabolism of AFB1 and AFB2 to AFM1 and AFM2, respectively; and benzo[a]pyrene metabolism measured as the formation of fluorescent phenolic metabolites, i.e. aryl hydrocarbon hydroxylase (AHH) activity. Time-course and dose-response studies in C57BL/6Ha mice revealed that the metabolism of aflatoxin B1/B2 to aflatoxin M1/M2 (AFB1/B2-4-hydroxylase activity) was induced by both MC and beta NF. In the nonresponsive strains studied, pretreatment with MC or beta NF produced essentially little alteration of AFB1-4-hydroxylase activity or AHH activity or the mutagenic activation of AFB1 and benzo[a]pyrene. On the other hand, AFB1-4-hydroxylase activity in the responsive strains was induced 4- to 10-fold by MC (60 mg/kg) and 2.5- to 7-fold by beta NF (150 mg/kg). Also in the responsive strains, induction of AFB1-4-hydroxylase activity was strongly associated with (a) the depression of the mutagenic activation of AFB1, and (b) with the induction of both AHH and the mutagenic activation of benzo[a]pyrene. In summary, the results described in this report suggest that: (a) induction of AFB1-4-hydroxylase activity by MC (or beta NF) is associated with the depression of AFB1 mutagenesis and with the induction of benzo[a]pyrene mutagenesis; and (b) induction by MC (or beta NF) of AHH activity, AFB1-4-hydroxylase activity and AFB2-4-hydroxylase activity is controlled by either the same or closely linked genetic factors.

Aflatoxins↗

Synthesis and processing of a type I procollagen containing shortened pro-alpha 1(I) chains by fibroblasts from a patient with osteogenesis imperfecta.

Skin fibroblasts from a patient with a lethal form of osteogenesis imprefecta were found to synthesize equal amounts of normal pro-alpha 1(I) chains and pro-alpha 1(I) chains which are about 10% shorter because of a deletion of about 100 amino acids in the middle of the alpha chain domain. The pro-alpha 1(I) chains were incorporated into three different kinds of trimers: a normal type I trimer with normal length pro-alpha 1(I) chains; a type Is trimer with one shortened pro-alpha 1(I) chain and two normal length chains; and a type Iss trimer containing two shortened pro-alpha 1(I) chains and one normal length pro-alpha 2(I) chain. As judged by resistance to digestion by chymotrypsin and trypsin, the type Is and Iss trimers denatured at a temperature at least 3 degrees C lower than normal type I procollagen. Procollagen containing the shortened pro-alpha 1(I) chains was slowly secreted by the cells but was degraded by extracellular proteinases within 6 h of chase into the medium. The results indicated that the presence of the shortened pro-alpha 1(I) chains in procollagen trimers produces a delay in rate of helix formation, overmodification of the polypeptides by post-translational enzymes, a decrease in the thermal stability of the trimers, and increased susceptibility of the protein to endogenous proteinases. Additionally, the fibroblasts of this patient synthesized and secreted a type III-like species of procollagen with unusual chromatographic properties.

Endopeptidases↗

Population distribution of placental benzo(a)pyrene metabolism in smokers.

Human placental microsomes isolated from term placentas derived from nonsmoking women and women smoking 1 to 40 cigarettes a day were analyzed for the metabolism of benzo(a)pyrene measured as various metabolites by HPLC and/or as aryl hydrocarbon hydroxylase (AHH)6 activity. In accordance with other reports, AHH activity was several times higher in smokers than in nonsmokers. Regression analysis on 13 different placental tissues from women smoking from 1 to 40 cigarettes demonstrated a high correlation (r = 0.8 to 0.9) between AHH activity (or the formation of benzo(a)pyrene phenols resolved by HPLC) versus the formation of the procarcinogenic benzo(a)pyrene-7,8-diol. Subsequent studies on placentas derived from 67 women who smoked 10 to 40 cigarettes per day demonstrated a definite dose-response relationship between AHH activity and the number of cigarettes smoked/day. The dose-response curve was sigmoidal in shape; however, when the data were plotted on a semi-log scale the curve assumed a linear shape, reaching saturation of AHH induction beyond 20 to 25 cigarettes/day. While mean AHH activity was dependent upon the number of cigarettes smoked/day, considerable interindividual variability in AHH (ranging more than 1,000-fold in some cases) was observed among individuals with comparable smoking histories, i.e. smoking the same number of cigarettes. Population distribution suggested clustering of the population in the low-AHH-activity region while cord-blood thiocyanate analysis and twin studies suggested that genetic factors contributed to a major portion of the inter-individual variability in AHH activity observed among smokers.

Aryl Hydrocarbon Hydroxylases↗

The effects of undernutrition of suckled pigs on subsequent growth and body composition after nutritional rehabilitation.

The effect of nutritional restriction and rehabilitation imposed between 5 and 35 d and 35 and 166 d of age, respectively, on body and tissue growth were investigated in 96 Yorkshire pigs from 12 litters. One-half of the pigs were allowed to suckle continuously until weaning (fully fed, FF); the remainder were removed from the sow for 16 h of each 24 h period (1600 to 0800 h), during which time they received only water (restricted feeding, RF). All pigs were fed ad libitum from 35 d of age. Although significantly lower body and tissue (liver, kidney and gastrocnemius muscle) weights were observed in the RF pigs at 35 and 70 d of age, by 166 d, because of compensatory growth between 35 and 166 d, the difference in body and muscle weights between the two groups of pigs (RF and FF) was reduced to 5%, but the difference in kidney and liver weight remained as high as 15 and 9%, respectively. Total DNA, RNA and protein in the tissues examined were also lower in the RF pigs at 35 and 70 d of age, but increased after ad libitum feeding to more than 90% of the corresponding value in the FF pigs by the time they reached 166 d of age. The results of these measurements and the comparison of the protein: DNA ratios of the tissues indicated that growth retardation in the RF pigs was associated with reduced cell proliferation in liver and kidney and nuclear proliferation in muscle rather than any decrease in cell (or fiber) volume. Percentage of fat was lower while percentage of protein was higher (on a dry matter basis) in the RF pigs than in the FF pigs at 35 d of age. No significant difference in fat and protein content in the carcasses between the RF and FF pigs at 70 or 166 d of age or 90 kg body weight was noted. The carcass of intact males had more protein and less fat than that of females.

Animals↗