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Biomedical subjects

J A Dickson

Publications and source records attributed to J A Dickson.

17 recordsLinked to original sources
PubMed1979

Hyperthermia in the treatment of cancer.

There is now considerable evidence that heat can be used to destroy tumours. The metabolism of many types of cancer cell is selectively damaged at temperatures of 42-43 degrees C, and deficient tumour blood-flow at raised temperature represents a further exploitable Achilles heel. A striking feature of tumour heating is that metastases may regress with cure of the host; this has occurred with recurrent melanoma and sarcomas of the limbs. Heat acts synergistically with X-rays and some cytotoxic drugs to increase the therapeutic ratio for local tumour control. Guidelines for tumour heating are now being formulated against a strong experimental background in animal systems. The association of a wide variety of disciplines from oncology to electronics has already resulted in techniques for selectively treating human tumours at 50 degrees C and in internal heat applicators for insertion via natural passages. It is predicted that heat will achieve a place, most likely as an adjuvant, in cancer therapy. Work on animals and in vitro is of limited value in helping to define this place. The complexity of the tumour/host response to heat and the deficiencies in our knowledge of the biophysics of heating militate against early routine application of hyperthermia in the clinic.

Bacillus↗
PubMed1979

Temperature gradients in pigs during whole-body hyperthermia at 42 degrees C.

Temperature was simultaneously measured by thermistors in multiple deep-body and peripheral sites in adult pigs heated continuously at 42 degrees C (rectal) and above for 4-24 h. During hyperthermia, the relations between different body temperatures were maintained and up to 1.0 degrees C separated temperature measurements at sites such as liver and bone marrow. These persistent temperature gradients must be borne in mind when evaluating tumor response in patients subjected to whole-body heating for disseminated cancer. Temperatures recorded by rectal, deep esophageal, or tympanic membrane sensors provided a reliable index of core temperature (including brain temperature) under equilibrium conditions at 42 degrees C, but only esophageal and tympanic sensors could safely be used to monitor the induction phase of hyperthermia and the adjustive changes in body-heat content required to stabilize core temperature during sustained hyperthermia. Pigs withstood repeated heating at 42 degrees C for 6 h, and recovered rapidly, but died after 24 h of hyperthermia. Pigs subjected to unrestrained heating died at 45 degrees C (esophagus).

Animals↗
PubMed1979

Effects of hyperglycemia and hyperthermia on the pH, glycolysis, and respiration of the Yoshida sarcoma in vivo.

Tissue (extracellular) pH (pHe) and intracellular pH (pHi) were measured together in vivo in the solid Yoshida sarcoma and normal organs (liver, gastrocnemius muscle) of noninbred Wistar rats. pHe was monitored by insertion of a miniature capillary glass electrode, and pHi was measured indirectly by equilibrium partitioning of the weak organic acid 5,5-dimethyloxazolidine-2,4-dione across the cell membrane. Under normal conditions, tumor, liver, and gastrocnemius had a similar pHe of 7.05--7.30; tumor pHi was consistently higher (7.2) than that of the normal tissues (6.8--7.1). Curative hyperthermia (42 degrees C for 1 hr) did not significantly change tumor pHe or pHi. After ip glucose injection [6 g/kg body wt; blood glucose level greater than 400 mg/100 ml (22 mmoles/liter) for 4 hr], tumor pHe decreased markedly to 6.6 within 4 hours and did not return to normal for a further 12--14 hours, whereas tumor pHi was hardly affected. No marked change was noted in pHe or pHi of the normal organs following glucose loading of the host. In tumor slices removed from hyperglycemic hosts, marked reduction of both respiration and glycolysis was observed. Hyperglycemia (4 hr) plus hyperthermia at 40 degrees C (1 hr) had a synergistic inhibitory effect on metabolism that was equivalent to heat alone at 42 degrees C, and respiration and glycolysis almost ceased after 3--4 hours. However, tumor heating at 40 degrees C in hyperglycemic hosts was not equivalent to hyperthermia at 42 degrees C: With the former treatment, tumor regression did not occur, and animal survival did not differ from that of control untreated rats. The data do not support the postulate that the effects of heat on tumor cells are mediated via low pHi or that hyperglycemia leads to a lowered pHi which sensitizes the tumor to destruction at 40 degrees C instead of 42 degrees C.

Animals↗
PubMed1978

Rapid method for measuring intracellular pH in vivo.

Intracellular pH (pHi) was simultaneously measured in 6 normal tissues and a malignant tumour of rats by a rapid triple isotope technique, based on the in vivo distribution of 5,5-dimethyl-2,4-oxazolidinedione-2-14C (DMO), tritiated water and sodium chloride-36. Results compared favourably with pH measured directly in the same rat by capillary glass electrode, and with values of other workers for pHi in rat tissues. Mean pHi of normal tissues was close to pH 7, and in each organ there was a linear relationship between pHi and extracellular pH (pHe) over the normal range of pHe encountered (pH 6.9-7.6). Organ pHi altered in response to administration of NH4Cl or NaHCO3 to the host.

Animals↗
PubMed1978

Effect of hyperthermia on the immune response of normal rabbits.

Sequential skin responses to dinitrochlorobenzene challenge and repeat assays of serum antibody titer after two injections of bovine serum albumin were used as functional indices of cellular and humoral immunocompetence following hyperthermia in normal adult New Zealand White rabbits. The animals were subjected to different degrees of local hyperthermia by watercuff or radio-frequency heating of the normal thigh muscles maintained at 42 degrees for 1 hr on 3 consecutive days or 47--50 degrees for 30 min, respectively, or to total body hyperthermia (42 degrees for 1 hr on three occasions) in a humidified incubator. No alteration occurred in the response of heated rabbits to dinitrochlorobenzene challenge over a 3-month period. The humoral immune response to bovine serum albumin was significantly depressed (p less than 0.02) in the treated animals, and the reduction was independent of method and degree of heating. The results suggest that the B-lymphocytes are more susceptible to hyperthermic damage than is the T-cell population.

Animals↗
PubMed1977

Milk bolus obstruction in the neonate.

Seventeen cases of neonatal intestinal obstruction due to inspissated milk curds were seen at this hospital in the 9 years 1964-1972. The obstruction started on the 2nd to 10th day of life. Half the babies passed blood from the rectum and in most the x-rays were diagnostic. All survived, 14 after operation and 3 after medical treatment with a Gastrografin enema. Incomplete absorption of solids, particularly the fat from cows' milk feeds, is suggested as the cause.

Animals↗
PubMed1976

Rectal biopsy in the diagnosis of neurological disease in childhood.

A surgical technique for taking a full thickness rectal biopsy for neurological diagnosis is described. The indications for, and results of 93 biopsies are reviewed. A definite neurological diagnosis was made in 38 (41 per cent). The usefulness of rectal biopsy is now largely confined to Batten's disease, which was found in 32 (34 per cent of the total). Alternatives and objections to rectal biopsy for neurological diagnosis are discussed. It is concluded that rectal biopsy is a safe and reliable procedure.

Biopsy↗
PubMed1976

The sensitivity of a malignant cell line to hyperthermia (42 degrees C) at low intracellular pH.

The postulate that low intracellular pH acts as a preconditioner for the destructuve effects of hyperthermia (42 degrees C) was examined, using a heat-sensitive line of malignant cells derived from rat mammary gland (SDB). Intracellular pH (pHi) was measured indirectly, from the distribution of the weak, non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolidinedione (DMO) between intra- and extra-cellular water. Respiration, aerobic and anaerobic and anaerobic glycolysis of the cells were studied at normal pHi (pH 7-0-7-4) or at low pHi (pH 6-2-6-6) and at 38 degrees C or 42 degrees C over 6 h in Warburg manometers; the ability of the cells to replicate in culture was examined after 3 h or 6 h incubation in the flasks. The relationship between pHi and extracellular pH (pHe) depended upon the buffer system used and the exact pH in question; no assumption regarding pHi based only on pHe measurement could be made. At 38 degrees C and low pHi, the Pasteur effect became negative due to a relatively greater inhibition of anaerobic than aerobic glycolysis. Respiration was unaffected and cell replicative ability unimpaired. At 42 degrees C and normal pHi, respiration was totally inhibited after 4 h and the Pasteur effect was decreased, in this case due to a compensatory increase in aerobic glycolysis without alteration in anaerobic CO2 production. Low pHi in the presence of hyperthermia enabled cell respiration to continue at a reduced level with no further change in glycolysis. There was delayed cell replication after 3 h at 42 degrees C and inability to multiply following 6 h hyperthermia: low pHi did not influence these results. It is concluded that with these cancer cells, pHi values maintained in the region of 1-0 pH unit below normal for 6 h had no deleterious effect on the cells. No sensitizing effect of the low pHi for the destructive effect of hyperthermia on the cells was observed.

Adenocarcinoma↗