Dose: A critical factor in cancer chemotherapy

The effect of dose and dose rate of cancer chemotherapeutic agents in experimental in vivo systems and in various clinical situations has been reviewed. In experimental in vivo systems, the dose-response curve for most chemotherapeutic agents is steep. Although the dose response curve may be linear for cytokinetically homogeneous experimental tumors, it deviates from linearity as a result of tumor heterogeneity. The steepness of the dose-response curve is related to the sensitivity of the tumor to a given drug. Thus, for highly sensitive tumors, the curve is very steep and generally linear; whereas for relatively insensitive tumors, dose may have little effect on response.These observations in general apply to the clinic. When dose has been a randomized variable, a dose-response curve is generally evident in sensitive tumors, such as the leukemias, the lymphomas, testicular cancer and small cell lung cancer. In contrast, when the difference in dose is in the range of twofold, the evidence for superiority of the high dose in such situations as 5-fluorouracil for colorectal cancer and dimethyl-triazeno-imidazole-car?amide (DTIC) for melanoma is less impressive.The use of relatively low dose maintenance treatment following four to six courses of intensive combination chemotherapy for such diseases as testicular cancer and lymphoma may prolong the duration of remission but probably will not increase the cure rate.In adjuvant chemotherapy situations, in which prolonged disease-free survival is improved, the dose-response curve would appear to be quite steep. Conservative dosing in this setting may compromise the cure rate, and the proposed approach is to maintain full dose therapy and consider reducing the total duration of treatment.When high doses or concentrations of antitumor therapy can be achieved, such as in the marrow transplant situation and in isolation perfusion or regional infusion studies, there is in general clear evidence that a substantial increase in response rate occurs.     

The corneal endothelium in vivo: its response to mild trauma

Changes in the specular microscopical appearance of the corneal endothelium are induced by the application of glycerin drops, in clinically used concentrations, to the epithelial surface of living rabbit corneas. Many of the affected cells appear to recover but a large number fall away and are replaced by the spread of neighbouring cells, eventually to leave no trace of their loss. The processes involved are described as seen and photographed in vivo with a modified, “roving”, specular microscope over prolonged periods of observation.The reduction in cell population results in no demonstrable loss of functional efficiency of the endothelium as evaluated by the temperature reversal phenomenon in vitro, after a period of cooling the eyes to 4°C. However, urethane anaesthesia is shown to be suspect in interfering with the pump-leak mechanisms of the endothelium.     

Hemobilia: Calcified hepatic artery aneurysm presenting with massive gastrointestinal bleeding

A case of a calcified and ruptured hepatic artery aneurysm presenting with hemobilia and massive gastrointestinal bleeding is reported and illustrated. The clinical diagnosis should be entertained whenever the trial of findings (abdominal colic, gastrointestinal bleeding, elevated bilirubin levels) is present. Angiography is the method of choice in confirming this diagnosis. A short review of the clinical and radiographic syndrome of hemobilia with emphasis on the occurence, significance, and prognosis of hepatic artery aneurysms is presented.     

Pneumomediastinography in carcinoma of the oesophagus

Forty-one patients with carcinoma of the gullet and oesophagogastric junction have been investigated by means of a new pneumomediastinographic method of pertracheal insufflation. More than 1,600 patients suffering from various pulmonary or mediastinal lesions have undergone this simple time-saving procedure. Pneumomediastinography cannot replace radiography of the gullet or oesophagoscopy in cases of cancer of the oesophagus. Since it reveals valuable details, which remain hidden in conventional radiographs or during oesophagoscopy, it may complement the findings of two traditional methods of investigation. The main advantages of pneumomediastinography in the diagnosis of cancer of the gullet are: it permits accurate assessment of the size and shape of the tumour; in patients submitted to radiotherapy, the local response to this treatment may be determined by changes in the size of the tumour shadow in pneumomediastinal tomograms; it establishes reliably that the tumour does not invade the adjacent organs; it facilitates visualization of some of the enlarged lymph nodes in the mediastinum which are not visible in conventional radiographs or tomograms; and the radiological characteristics of these lymph nodes facilitate an approximate differentiation between inflammatory and metastatic enlargements.     

Casus pro diagnosi; (eosinophiles Granulom,Mycosis fungoides)

Ohne Zusammenfassung     

Suppression and Recovery of Sperm Production in Men Treated with Testosterone Enanthate for One Year. A Study of a Possible Reversible Male Contraceptive

A group of 21 subjects was recruited among men requesting surgical sterilization to conduct a study on the efficacy of testosterone enanthate (TE) as a possible male contraceptive. Sixteen men completed the study. Administration of 200 mg TE (im) every 10 to 12 days maintained azoospermia. Less frequent injections (every 2 or 3 weeks) resulted in break-through of sperm production. The azoospermia was associated with normal plasma testosterone levels, suppressed circulating FSH and undetectable LH. No untoward clinical side effects were noted. In 11 of the 16 subjects observations on recovery of sperm production were made. In all cases resumption of sperm production was noted. In two cases pregnancy occurred (5 to 7 weeks and 11 to 13 weeks after discontinuation of treatment). Since in most subjects long-term recovery data were not available, observations on the quantitative aspects of recovery and relationship to the time interval after cessation of treatment could not be made.