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ObjectiveIt is established that external pituitary irradiation (EPI) effectively reduces serum GH levels in acromegaly. However, its effect in normalising serum IGF1 has been disputed. We looked at the number of our patients who achieved persistently normal IGF1 levels whilst free of adjunctive treatment for at least 1 year after EPI.Patients and designWe identified 63 acromegalic patients between 1964 and 2004 who received EPI. Six were excluded: three had surgery after EPI, two had no medical records available, and one had a pituitary Yttrium implant.MeasurementsPatients received 4500–5000 cGy in fractionated doses. IGF1 levels were correlated with their respective age-related reference ranges.ResultsAfter EPI, the number of patients with normal IGF1 and free of adjunctive medical treatment for at least 1 year were four patients by 3 years, nine patients by 5 years and seventeen by 10 years, with the current number of 25/57 (44%). Concordance between IGF1 levels and random GH dropped from 90% at the time of EPI to 65% at 3 years, 66% at 5 years and 71% at 10 years.ConclusionsWe have demonstrated that, with time, EPI achieves a normal IGF1 in significant numbers of patients with acromegaly, thus obviating the need for life-long expensive medical therapy. For each patient this benefit has to be weighed against the possibility of new hypopituitarism as a result of the treatment. Any decision to use EPI is easier in the context of pre-existent hypopituitarism.

Thymidine kinase (TK) exists in two forms, TK1 and TK2. TK levels and oestrogen receptor status (OR) were measured in tumours from 86 patients with operable breast cancer and the patients were monitored for recurrence over 24 months. During the monitored period, 13 patients showed recurrence. These patients also exhibited higher total TK levels per mg tumour (P0.01) and higher TK1 levels (P0.001) than those who did not show recurrence. TK1 levels relative to TK2 were significantly higher (P0.05) in OR-negative tumours (n = 29) than in OR-positive tumours (n = 57). OR-negative (n = 9) and OR-positive (n = 4) patients who recurred had significantly higher TK1 levels relative to TK2 than did those who not recur (n = 20 and n = 53, respectively). These preliminary results indicate that breast tumour TK levels may have value in determining prognosis.

CA NT is a transplantable murine mammary carcinoma that causes progressive anemia accompanied by granulocytosis and splenomegaly. Serum erythropoietin (Epo) levels, as measured by RIA, did not become elevated in anemic tumor-bearing mice; there was no correlation between hematocrit and serum Epo levels. Treatment with recombinant human (rHu) Epo prevented anemia in tumor-bearing mice when given in large doses, commencing on days 3-5 of tumor growth. Recombinant human Epo-treated mice had smaller spleens than controls. When treatment commenced on day 7, the development of anemia was retarded but not completely prevented. Treatment commenced on day 14 was less effective. This study demonstrates that treatment with rHu Epo can markedly influence the course of tumor-induced anemia.

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1. Attempts were made to induce emotional sweating in normal subjects by subjecting them to painful stimuli such as compression of pins on the forearm skin, immersion of the fingers in iced water, compression of the thoracic cage by rib calipers and ischaemic exercise of the forearm muscles.2. Changes in sweating were estimated by continuously monitoring the rate of total body weight loss.3. Of the painful stimuli used, only ischaemic forearm exercise significantly increased the rate of sweat secretion.4. Tasks in mental arithmetic caused much greater increases in sweat secretion than any of the pain stimuli except ischaemic pain.5. It is concluded that many varieties of pain, even when severe, do not induce sweating under laboratory conditions.

In a multi-facet study we evaluated the efficacy of P6 electroacupuncture (10 Hz applied for 5 min) as an antiemetic in patients receiving a variety of cancer chemotherapy drugs. The study involved 130 (15 in an open pilot study, 10 in a randomized placebo controlled crossover study and 105 in a definitive study) patients who had a history of distressing sickness after previous treatment, and who, on the basis of a previous survey, would be expected to have a 96% chance of this with subsequent therapy. Sickness was either completely absent or reduced considerably in 97% of patients and no side effects were encountered. The limited crossover study, using a ‘dummy’ acupuncture (ACP) point showed that the beneficial effects were limited to the P6 point. Logistic and ethical considerations excluded the possibility of carrying out a larger placebo-controlled study. While in our hands P6 ACP was an effective antiemetic in patients having cancer chemotherapy, because of the time involved and the brevity of the action (8 h) an alternative approach to electro-ACP is required before this technique is adopted clinically.

Levels of the nucleotide pathway enzyme thymidine kinase (TK) were assayed in the mononuclear leukocytes and serum of 70 female patients with breast cancer and 98 male and 77 female non-cancer hospital patients. The total TK levels in both mononuclear leukocytes and serum from patients with breast cancer were significantly higher than in controls. The serum TK levels showed a significant correlation with cancer stage. No such correlation was observed with mononuclear leukocyte TK levels. Serum TK from 20 patients with breast cancer and 19 control patients was further assayed to ascertain the relative contributions of the thymidine kinase isozymes TK1 and TK2 to total TK levels. The increase in serum TK from breast cancer patients appears to be due to an increase in both TK1 and TK2 levels.

The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients. Images Figure 4 Figure 5

T lymphocyte subsets in the peripheral blood of patients with benign and malignant breast disease

Serum levels of the nucleotide salvage pathway enzyme, thymidine kinase, were assayed in 92 patients with cancer (comprised of 17 cancer types) and 42 subjects without cancer. Patients with cancer as a whole did not have significantly higher levels of thymidine kinase than the control patients. Although the numbers of patients from each specific cancer type were small, four cancers; namely breast, bone, prostate and rectal, had significantly increased thymidine kinase levels relative to controls. Breast cancer also exhibited a significant cor-relation between cancer stage and the level of serum thymidine kinase.