Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

High dose remote afterloading radiotherapy for cervix carcinoma in Tanzania: early results.

From February 1977 through January 1979, 206 patients with histologically confirmed cervix carcinoma were treated with high dose rate afterloading irradiation at the Muhimbili Medical Center of the University of Dar es Salaam, Tanzania. Tribal and regional patterns of disease conform to geographical distributions of referring hospitals. The age at presentation, namely, at over 40 years, is similar to that reported elsewhere from East Africa. Parity among patients ranged from 0 to 14 pregnancies. Vaginal bleeding was the most common symptom in 69 percent of patients. Squamous cell carcinoma was noted in 96 percent of cases. Seventy-six percent of patients had early stage disease. Good initial responses to treatment were recorded in 57 percent of patients. Follow-up of cervical cancer patients is poor. Fifty-six (27 percent) patients were followed 1 to 17 months after treatment. Due to poor follow-up, no definite conclusions are reached regarding late radiation reactions and patient survival. The role or radiotherapy in reducing morbidity, however, is of importance.

Advanced skin cancer in Tanzanian albinos: preliminary observations.

Ten cases of advanced squamous cell carcinoma of the skin in albinos, treated by radiotherapy from 1973 to 1979 at the Muhimbili Medical Center of Dar-es-Salaam, have been reviewed. Age, sex, duration of symptoms, anatomic distribution, stage of disease, and treatment are reviewed. The relationship between albinism, sunlight, and skin cancer is discussed and a practical program of prevention is suggested. Advanced carcinoma of skin in albinos may be managed successfully with judicious radiation therapy. Excellent objective responses have been noted. No assessment of long-term control is made due to poor follow-up of patients.

Is there a genetic basis for the differences in cancer incidence between Afro-Americans and Euro-Americans?

The data of the Third National Cancer Survey show for many cancer types, large differences in cancer incidence between Euro-Americans and Afro-Americans.(1) As in other racial studies, it is difficult to separate environmental and genetic factors. For the cancers which are more frequent among Afro-Americans, environmental factors seem to be primarily responsible. However, among the cancers less frequent in Afro-Americans, there are some for which the racial differences have a genetic basis. This is clearly the case for skin and lip cancers caused by the ultraviolet B of the sun. Genetic factors are probably also responsible for the racial differences in the incidence of malignant melanomas, testis cancers, astrocytomas, and Ewing's sarcomas. Perhaps there is also a genetic basis for some of the racial differences in the incidence of malignant lymphomas and leukemias. For all these cancers, Afro-Americans are less susceptible. The only cancer to which Afro-Americans appear more susceptible on the basis of genetic makeup, is fibrosarcoma. This is in accord with the high frequency of keloids, a benign counterpart of fibrosarcoma in Afro-Americans.

Remote afterloading for intracavitary irradiation of cervix carcinoma.

The technique of remote afterloading for intracavitary radiotherapy was developed by Henschke et al 15 years ago, and since then the technique has received wide acceptance, both abroad and in the United States. Here at Howard University, it plays an integral part in the intracavitary portion of the treatment of cervix carcinoma. Most applications are done on an outpatient basis without anesthesia or sedation. This has become possible by dilating the cervical canal painlessly with thin laminaria rods. Spread of the lateral colpostats is accomplished by inflating a Foley balloon secured to the applicator with contrast medias, instead of using the customary gauze packing for increased rectal distance.A single cobalt-60 source of 1 mm diameter and 3 to 7 Curies is used, which can be moved during the treatment to simulate linear sources of different lengths and loading. Our present treatment policy calls for 4,000 rad given to the whole pelvis in 20 fractions of 200 rad three times per week plus eight fractions of 400 rad by the remote afterloading technique given one fraction per week concomtant with the external irradiation. Only 18 patients have been treated to date with minimal adverse tissue reactions. There is only an 18-month maximum follow-up, so survival figures are still pending but all patients so treated are currently living without recurrence.

Technique of locoregional irradiation in breast cancer.

In medicine, one modality of treatment cannot be replaced by another unless the new method is equal, if not superior, to the existing one. Currently, much is heard about using irradiation alone for the treatment of early breast cancer. Uniform irradiation of the breast, underlying chest wall, and the regional lymph nodes is a complex procedure and unless done properly, a geographical miss of the tumor and/or unnecessary irradiation of adjacent normal structures can occur, leading to inferiority of the treatment method.

Radiation from the uranium collimators of the Varian 4-MeV accelerator.

The uranium collimator of the Varian 4-MeV accelerator produces a dose rate of 100 mR/h near the collimator opening. It can be decreased to 4% by a 6-mm Lucite shield at the level of the collimator opening. A better solution is a lead glass-mylar (EM) shield which decreases the uranium radiation to less than 3% and also provides better skin sparing during treatment than the open collimator.

Problems and solutions in achieving uniform dose distribution in superficial total body electron therapy.

In treating mycosis fungoides (MF) and Sezary syndrome patients with electron beam, the entire thickness and the area of the skin from crown to sole should be irradiated uniformly. To achieve irradiation of the entire thickness of the skin, electron beams of 3 - 4 MeV energy with 80 percent depth dose at 6 mm is sufficient. This unique property of limited penetration of electron beam does not cause any systemic toxicity during or after total body electron therapy. However, this property of limited penetration of electrons poses the problem of self-shielding in the curvaceous human body. The optic lens, which is within the range of penetrability of electron beam energy used for total body electron therapy, is to be shielded artificially.The purpose of this paper is to discuss the problems of self and artificial shielding in the superficial total body electron therapy for MF and Sezary syndrome.

Aspirin for reducing cancer metastases?

Distant metastases are the principal cause of death from cancer. Many animal experiments in the last 25 years have shown consistently that distant metastases can be significantly reduced by anticoagulants and fibrinolytic agents. Since aspirin inhibits platelet function and increases fibrinolytic activity in humans, it may be effective in preventing metastases in cancer patients. It is suggested that aspirin be offered as an option to cancer patients who are at risk for distant metastases.

Five years' experience with the gold button technique for intraoral interstitial implants with iridium-192 seeds.

To simulate crossing of the ends in standard removable interstitial implants, we used the loop technique for intraoral tumors when treating them with afterloading interstitial removable implants. Because of technical problems, we changed to a straight tube method with heavy end-loading to compensate for the uncrossed ends. High doses to the normal mucosa close to heavy end-loading is reduced 2.5 times by the use of gold buttons in place of standard stainless steel buttons, thus decreasing unnecessary mucosal reactions and morbidity.

The gold button technique for intraoral interstitial implants with iridium-192 seeds.

The higher the radiation dose, the better is tumor control. High tumor doses are feasible only by interstitial irradiation. To achieve uniform dose distribution throughout the area or volume of implant, one has to use established distribution rules. In straight tube technique we have to use heavy endloading to compensate for uncrossed ends. In implants for intraoral lesions, heavy endloading gives a high dose to the opposing normal mucosa. The new gold button technique considerably reduces the dose to the normal mucosa, thus minimizing the morbidity.