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Biomedical subjects

P Price

Publications and source records attributed to P Price.

At least 199 records · Page 11Linked to original sources
PubMed1990

The growth rate of metastatic non-seminomatous germ cell testicular tumours measured by marker production doubling time--I. Theoretical basis and practical application.

Changes in serum tumour marker levels in non-seminomatous germ cell testicular tumours (NSGCTT) are used to monitor tumour growth and response to treatment. A novel method of calculating the actual tumour marker production (TMP) per day is reported; estimation of the rate of change of TMP is a measure of the tumour growth or regression rate. TMP is calculated mathematically from the rate of increase in serum marker level and its natural half life. TMP is assumed to be proportional to the number of marker producing cells in the tumour. TMP was calculated over the time between orchidectomy and the start of chemotherapy. The rate of increase in TMP with time is expressed as the marker production doubling time (MPDT) and is a measure of the growth rate. In a group of 51 patients with metastatic NSGCTT, TMP varied from 0.012 to 5985 iu/l/day (AFP) and 0.08-5404 iu/l/day (HCG). MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients; greater than 80% of cases had a MPDT less than or equal to 32 days. In 45/51 (88%) patients, there was no discrepancy in MPDT between markers. The use of changes in serum marker level to follow tumour progression and regression is simple, but the calculation of actual TMP provides clearer information about the change in number of marker producing cells and can be used as non-invasive method for measuring the tumour growth rate of metastatic disease and response to treatment.

Biomarkers, Tumor↗
PubMed1990

The growth rate of metastatic nonseminomatous germ cell testicular tumours measured by marker production doubling time--II. Prognostic significance in patients treated by chemotherapy.

Tumour growth rates have been measured in metastatic non-seminomatous germ cell testicular tumours (NSGCTT) by estimating the rate of rise of tumour marker production (TMP). TMP was calculated for the time between orchidectomy and the start of chemotherapy in a group of 58 patients with metastatic NSGCTT treated with BEP combination chemotherapy (bleomycin, etoposide and cisplatin). Calculation of TMP (iu/l/day) took account of the continuing clearance of marker from the serum. TMP increased with time in 51 patients and this rise generally appeared to be exponential. The rate of this increase was expressed as the marker production doubling time (MPDT) and is a measure of the tumour growth rate. MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients. Patients who failed BEP first line therapy had shorter MPDTs than those who responded (AFP P = 0.08, HCG P = 0.003). It was found that patients with a MPDT less than or equal to 4 days were more likely to fail treatment than those who had a MPDT greater than 4 days (AFP P = 0.009, HCG P = 0.005). MPDTs were independent of initial serum marker concentration. Patients with small volume disease had longer MPDTs than patients with large volume disease (AFP P = 0.02, HCG P = 0.04). Rapid tumour growth rate reflected by short MPDT carries a poor prognosis in patients with NSGCTT treated by BEP chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Duct carcinoma in situ: predictors of local recurrence and progression in patients treated by surgery alone.

Between 1972 and 1982, 60 patients with histologically proven duct carcinoma in situ (DCIS) without evidence of invasive disease were treated by surgery alone. Treatment was not randomised and was total mastectomy (19), subcutaneous mastectomy (6) or local excision (35). Follow-up was by clinical examination and mammography with a median follow-up of 9 years (range 4-16 years). Twenty-six patients (43%) have recurred locally. The estimated proportion recurrence free at 7 years is 59% (95% CI 46-72%). Local recurrence on the chest wall occurred in one patient having total mastectomy and in the chest wall or nipple in three patients having subcutaneous mastectomy. Twenty-two patients recurred locally in the breast after conservative surgery. The 7-year recurrence-free rates were 94%, 44% and 45% respectively in the three groups. Of those patients who recurred locally 14/26 (54%) did so with invasive disease. Of the 34 who did not develop local recurrence, two developed metastases. The only factor which correlated with local recurrence and invasive local recurrence on multivariate analysis was conservative surgery (hazard ratio 4.71 (1.59-14.0), P = 0.001, and 4.05 (1.00-18.7), P = 0.03, respectively). DCIS can be an aggressive local disease and local excision may be inadequate treatment.

Breast Neoplasms↗
PubMed1990

Depression of humoral responses by murine cytomegalovirus infection.

The ability of mice infected with murine cytomegalovirus (MCMV) to respond to unrelated antigens in vivo was studied in genetically sensitive BALB/c and genetically resistant CBA mice. Suppressed humoral responses were observed following intraperitoneal or intravenous antigen challenge a few days after infection. IgG production was depressed more frequently than IgM. The suppression was correlated with splenic atrophy and hyporesponsiveness of the residual spleen cells in vitro. The peritoneal macrophage response to intraperitoneal adjuvant challenge was also modified by the infection. Subcutaneous antigenic challenge elicited normal or elevated humoral and delayed-type hypersensitivity responses, during which peripheral lymph nodes were consistently expanded. Antigen administered intraperitoneally without adjuvant on the day of infection also evoked elevated humoral responses. This correlates with the host's ability to respond to MCMV itself, possibly via primed cells seeded to the lymph nodes before the spleen was damaged by the infection.

Animals↗
PubMed1990

Cytomegalovirus infection of adipose tissues induces steatitis in adult mice.

Young adult mice infected with MCMV were shown to develop inflammatory lesions in the peripancreatic and salivary gland adipose tissues. MCMV replication was detected by immunoperoxidase staining and electron microscopy in adipocytes, fibroblasts, endothelial cells and pericytes in brown and white adipose tissues. More infected cells were detected in C3H mice than in BALB/c, BALB.B, BALB.K or C57BL/6 mice. Peripancreatic steatitis consisted of a monocytic infiltrate surrounding focal necrosis of adipocytes, the severity of which was influenced by the route of inoculation, virus dose, and genetic susceptibility to disseminated MCMV-disease. C57BL/6 mice showed the greatest susceptibility with severe coalescing focal inflammation around areas of coagulative necrosis. Salivary gland adipose tissues exhibited lymphocytic steatitis, which was reduced in Nu/Nu mice.

Adipose Tissue↗
PubMed1989

Morphological and functional changes during cytomegalovirus replication in murine macrophages.

Structural and functional changes were studied in murine peritoneal macrophages infected with murine cytomegalovirus by using centrifugal enhancement to achieve a high-level (greater than 90%) pulsed infection. During 3 d of culture the infected cells became enlarged and rounded with smooth surface contours. Transmission electron microscopy demonstrated various stages of viral maturation in the nucleus and cytoplasm. Intracellular organization was generally retained, apart from the development of large, irregular, intracytoplasmic vacuoles, in which enveloped virions and cell debris accumulated. The infected macrophages lost most surface markers tested (F4/80, Mac-1, FcR, and the receptor for gluteraldehyde-fixed sheep red blood cells), but H-2 expression was increased. Moreover, ingestion of colloidal gold or horseradish peroxidase was depressed, and the levels of acid phosphatase activity, lymphocytostatic activity, and interleukin 1 production were also decreased. The latter may explain the observed loss of accessory cell function.

Acid Phosphatase↗
PubMed1989

The inflammatory macrophage response to murine cytomegalovirus in genetically susceptible mice.

Adherent suppressor cells have often been implicated in the depression of immunocompetence following CMV infections. We have reported that high levels of cytostatic macrophages in the peritoneal cavities of infected mice correlate with genetically-based sensitivity to CMV disease, suggesting they may modulate protective immune responses. This study investigates the properties and kinetics of such cells. Genetically-susceptible BALB/c mice infected with MCMV accumulated activated peritoneal macrophages, 7 days post-infection. These cells suppressed 3H-thymidine-incorporation and lymphokine production in syngeneic lymphocyte cultures and hence appeared to have depressed accessory cell function, although interleukin-1 production and the capacity to take up colloidal gold were enhanced. The cytostatic activity was located in a low density fraction (1.05 g/ml), which was expanded by MCMV infection. The lowest density cells had higher frequencies of infection but the proportion of cells releasing virus (less than 0.2%) was below the proportion activated, as shown by the shift in the density profile or enhanced colloidal gold uptake. A comparable accumulation of cytostatic activated peritoneal macrophages occurred in mice treated with cyclosporine A, but nude mice showed macrophage activation without cytostasis, so the role of T cells is not resolved. The spleens of infected mice maintaining high levels of virus in this organ atrophied, and the remaining cells were unable to proliferate in culture. In contrast, mice clearing the virus developed splenomegaly and restricted responsiveness, which may be governed by cytostatic cells equivalent to those in the peritoneal cavity. The spread of virus to the lymph nodes was limited and MCMV-primed cells were readily demonstrable.

Animals↗
PubMed1989

Inflammatory and immunological responses to murine cytomegalovirus in resistant CBA mice.

The resistance of CBA mice to MCMV is associated with the resistance of H-2k cells to infection in vitro, high NK and virus-specific DTH responses, and minimal accumulation of cytostatic peritoneal macrophages. This study investigates the functional capacity of lymphoid cells from infected CBA mice, using this strain as a model for successful control of CMV. Splenic viral replication was high 1-3 days p.i. and cell numbers were depressed, but T and B cells frequencies were maintained. The remaining spleen cells were hyporesponsive in culture and accessory cell function was marginally deficient. By 7 days p.i., virus titres declined, responsiveness increased and the residual defect was associated with cytostatic macrophages. The lymph nodes did not atrophy, exhibited low levels of viral replication and proliferative capacity was retained. The beige mutation did not affect the local response to intraperitoneal infection, but spleen cell numbers and responsiveness declined progressively. The results suggest the spleen may contribute to CMV disease by the replication of virus in susceptible cells until the NK response reduces virus titres and hence limits acute virus-induced immunosuppression. Macrophage-mediated suppression persisted in the spleen during recovery so clonal expansion of protective virus-primed T cells may occur predominantly in the lymph nodes.

Animals↗
PubMed1988

Immunohistochemical distribution of c-erbB-2 in infiltrating and in situ breast cancer.

An immunohistochemical study of c-erbB-2 expression was performed on invasive and in situ breast cancer. Strong membrane staining was seen in 16% of the infiltrating ductal carcinomas and 44% of the in situ lesions. c-erbB-2 was overexpressed in ductal rather than lobular tumours. Our results indicate that a small sub-group of breast carcinomas are associated with over-expression of this oncogene which may define an important subgroup of in situ and infiltrating ductal carcinomas.

Breast Neoplasms↗
PubMed1988

Renal impairment following the combined use of high-dose methotrexate and procarbazine.

A major side-effect of high-dose methotrexate is renal toxicity, which may develop unexpectedly despite adequate standard precautions such as hydration and alkalinisation of the urine. The pathogenesis is unclear. Recent reports suggest that the combination of high-dose methotrexate with non-chemotherapeutic agents may cause such renal impairment. Three cases of unexpected renal impairment following the combined use of high-dose methotrexate and another cytotoxic agent, procarbazine, are reported. Possible mechanisms of this interaction are discussed, as are recommendations for future combined administration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Maternal use of prescribed drugs associated with recognized fetal adverse drug reactions.

To quantitate the frequency of exposure in pregnancy to selected drugs listed by the American Medical Association's Department of Drugs as having known or suspected association with fetal adverse drug reactions, we examined the prescription records of 18,886 Michigan Medicaid recipients who delivered a liveborn infant between April 1, 1981, and March 31, 1983. Focusing only on specific trimesters considered risk periods for each drug-fetal occurrence of adverse drug reaction, the use of tetracyclines during the first trimester of pregnancy was the most prevalent (21.3 exposed women/1000) prescribed drug associated with known or suspected fetal adverse drug reactions. The second most prevalent was phenobarbital in the first trimester, with 10.8 women exposed/1000. Following a close third was the use of the sulfonamides in the second trimester, with 10.0 women exposed/1000. The prescribing of nitrofurantoin and the sulfonamides in the last trimester and tetracyclines throughout pregnancy appears excessive. There are few indications for the outpatient use of the tetracyclines during pregnancy. Practitioners caring for pregnant women need to carefully evaluate the need for these drugs and consider when risks may outweigh benefits.

Adolescent↗
PubMed1988

Murine cytomegalovirus binds reversibly to mouse embryo fibroblasts: implications for quantitation and explanation of centrifugal enhancement.

In a study of the infection of mouse embryo fibroblasts with murine cytomegalovirus (MCMV), we found that plaque number is directly related to virus concentration and not to the total amount of virus contained in the inoculum. These results suggested that virus binding was reversible and that during infection a binding equilibrium is established which limits the amount of bound virus. Further analysis revealed three categories of plaque based on reversibility after virus adsorption. One group was removed simply by washing cell monolayers after virus removal. A second group of plaques was lost gradually with time, giving complete reversal after 5 min at 37 degrees C. The rate of reversal was temperature dependent, and probably represented true virus dissociation. The final group was irreversible plaques, the number of which increased with increasing infection time. The number of reversible plaques remained constant with time of infection, and represented about 70% of the total plaques after 1 h of virus adsorption. Centrifugation of the virus inoculum onto the fibroblast monolayer at 1000 X g increased plaque numbers up to 100-fold, but had little effect on plaque number when carried out after the virus inoculum was removed. In contrast centrifugation increased the number of reversible plaques, suggesting an increase in the number of virus particles attached to the cell monolayers. We suggest that centrifugation enhances MCMV infection by three mechanisms related to reversibility of binding: (1), it increases the rate of virus association; (2), it decreases the rate of dissociation; (3), by increasing the length of time each virus particle is bound it increases the probability of virus being taken into the cell.

Adsorption↗
PubMed1988

Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.

Single fraction radiotherapy can be used effectively to palliate painful bone metastases. The optimal single dose of radiotherapy required for pain relief is unknown. Twenty-six patients have been treated with a single fraction of 4 Gy to the site of the bone pain. Partial pain relief was seen in 9/21 (5%). Response occurred within 3 weeks of radiotherapy. These results question the mechanism of pain relief following radiotherapy and suggest a method of pain control using single repeatable low dose treatments.

Aged↗