This article discusses 103 patients with a nonseminomatous testicular germ cell tumor. Treatment of 87 patients in clinical Stages I, II-A, and II-B consisted of bilateral retroperitoneal lymph node dissection. In Stage I (54 patients), no further treatment was given. The three-year survival was 96%, while recurrence-free survival was 98%. Of 33 patients in Stages II-A and II-B, 26 received adjuvant chemotherapy with dactinomycin, and ten of these were given radiotherapy (peritoneum/mediastinum) as well. The three-year survival was 88% and recurrence-free survival was 85%. Seven patients in Stages II-A and II-B received no adjuvant chemotherapy; four of them died. Treatment of 14 patients in Stage II-C primarily consisted of dactinomycin therapy, subsequently combined with surgery and radiotherapy. The three-year survival was 28.5%. These findings raise the question whether adjuvant single-agent chemotherapy with dactinomycin for patients with a nonseminomatous testicular germ cell tumor should not be re-evaluated.
The viability of cells present in waste products originating during CO2-laser evaporation of Cloudman S91 mouse melanomas was investigated. Cytologic smears showed mainly carbonized particles and thermally damaged cells but some morphologically intact cells as well. Viability was tested with the trypan blue test, by in vitro culture and intramuscular and intraperitoneal inoculations in syngeneic mice. No dye-excluding cells were found in the trypan blue test. Growth was noted neither in vitro nor in vivo in the 127 mice, intramuscularly or intraperitoneally injected with 10(5) x 10(5)/10 microliter smoke or debris particles, and killed four weeks after inoculation. Viable tumor cells, derived from a Cloudman melanoma cell line and added to the smoke and debris suspensions, remained viable. Thus, a toxic influence of smoke and debris particles in viable tumor cells, which would make the viability tests meaningless, was excluded. It is highly unlikely that viable tumor cells do occur in the waste products of CO2-laser tumor vaporization.
Spleens with proven though small Hodgkin lesions were examined expecially in relation to the lymphoid tissue normally engaged in the immune response. These Hodgkin foci were always very close to small arteries and surrounded by a lymphocyte corona. Most of the red and white pulp seemed normal, but in some instances abnormal looking large and also multinucleated cells were found scattered through the p.a.l.s. and especially through some follicles. It is considered possible that these isolated cellular abnormalities in the white pulp, when associated with pre-existent Hodgkin foci, represent early Hodgkin lesions. The implications for the dissemination of the disease are discussed. Spread of malignant cells to the spleen is only acceptable within the concept of a homing principle. It is also possible that the lesions arise "de novo". The nature of the observed abnormal cells is not clear. An explanation for the origin of these Sternberg-Reed-like cells from B-lymphocytes would be in accordance with recent data, but another possibility still is that they originate from antigen trapping cells.
Seventeen patients with a local recurrence or intransit metastases of a malignant melanoma of the arm or leg were treated by normothermic regional perfusion with phenylalanine mustard. Seven of these patients had regional lymph node metastases as well. The follow-up period was either five to eight years or until the time of death. Two years after treatment, eleven of the seventeen patients were still alive. After a five year follow-up, six patients were still alive without demonstrable recurrence or metastases. Only three patients had a recurrence in an extremity; two of these three patients simultaneously showed general metastization.
Rhesus monkeys with a history of drinking methadone, but presently drug-free, were injected with low doses of methamphetamine (MA). They immediately developed oral dyskinesias resembling the symptoms of tardive dyskinesia in humans, a condition resulting from chronic blockade of striatal dopamine receptors by neuroleptics. Nine of 11 control monkeys failed to develop dyskinesias during prolonged MA administration. A stressful stimulus intensified the MA-elicited oral dyskinesias, an effect analogous to exacerbation of tardive dyskinesias by emotional stress. Control monkeys were then injected with methadone, chlorpromazine, haloperidol, or saline for 45 days. Ten days following this chronic treatment, MA immediately elicited oral dyskinesias in the methadone and chlorpromazine monkeys. Acute administration of the dopaminergic blocking agents chlorpromazine, spiroperidol, and clozapine eliminated MA-elicited dyskinesias, whereas the α-adrenergic blocker phentolamine was ineffective. Physostigmine blocked the dyskinesias in 1 of 2 cases. Sedative doses of phenobarbital and diazepam had no effect on oral dyskinesias. These data indicate that chronic treatment with methadone or other dopamine receptor blocking agents leads to receptor supersensitivity to the actions of MA.
Eight rhesus monkeys that had drunk subdependence-producing doses of methadone daily for 10-22 months, and had subsequently been drug-free for 2-17 months, were injected with low doses of methamphetamine (MA). They immediately exhibited oral dyskinesias resembling the symptoms of tardive dyskinesia in humans, a condition resulting from chronic blockade of striatal dopamine receptors by neuroleptics. Eleven control monkeys failed to develop dyskinesias during prolonged MA administration. Control monkeys then received parenteral methadone, chlorpromazine, haloperidol, or saline for 45 days. Upon subsequent retest with MA, the methadone and chlorpromazine monkeys immediately displayed oral dyskinesias. Dopaminergic antagonists blocked MA-elicited dyskinesis, whereas neither a noradrenergic blocker nor sedative doses of phenobarbital and diazepam had any effect on dyskinesias. We suggest that receptor supersensitivity is produced by chronic treatment with methadone or other dopamine receptor blockers. Following treatment, stimulation of hypersensitive striatal receptors by the dopamine released by MA results in oral dyskinesias. The clinical implications for methadone maintenance treatment program patients are discussed.
The case history of a 22-months old boy with a malignant embryonal tumor of the prostate is given. Five years after initiation and three years after termination of a combined therapy with cytostatic drugs (actinomycin D, vincristine sulfate and cyclophosphamide) and surgery he is in good health without any signs of recurrence or metastatic disease. On this moment it is still impossible to be certain whether this therapy is the key for treatment of these tumors, but the successes published and the result till now in this case can be an indication that we are going in the right direction. Perhaps we may even hope that in the future we will have cytostatic drugs and combinations of therapy which will enable us to avoid mutilating operations.
Repetitive electric shocks applied to the dorsal midbrain (DM) paced the copulatory behavior of sexually experienced male rats. DM stimulation also accelerated the rate of copulation, the achievement of ejaculation and the resumption of copulation after ejaculation and increased the number of ejaculations in an hour test.
Rhesus monkeys with a history of drinking methadone but currently drug-free and control monkeys with no drug history were injected with methamphetamine hydrochloride (2 to 5 milligrams per kilogram of body weight). In six of seven monkeys which had consumed methadone the lowest dose immediately elicited pronounced oral dyskinesias virtually identical to those of human tardive dyskinesia. The control monkeys did not exhibit oral dyskinesias even after prolonged treatment with the highest dose. The clinical implications may be related to the functioning of brain dopaminergic systems.
The authors present a survey of changed views on the treatment of patients with malignant melanoma of the extremities. In addition to conventional therapy, regional perfusion is discussed. Over the period 1964-1970, 115 perfusions were performed in 75 patients. The perfusions were confined to patients with a tumor infiltrating beyond the stratum papillare. The 4-year survival of 30 patients with a primary tumor, without demonstrable metastases at the moment of perfusion, was found to be 77%. The percentage of local recurrences was significantly lower after perfusion than after conventional surgery.
The effect of systemic injection of physostigmine (0.1 mg/kg) on spontaneous and evoked neuronal activity and on behavior has been examined in the freely moving rat. There was a decrease in the frequency of firing of hippocampal neurons in a large majority of cases. There was a smaller but significant decrease in the frequency of firing of midbrain neurons, although in a few cases increases were observed. There were either no changes or small increases in the frequency of discharge of hypothalamic neurons. Parkinsonian-type tremors recorded as increases in movements were observed in all animals after methscopolamine, physostigmine, and neostigmine. Decreases in the rate of neuronal discharges in the hippocampus and the midbrain occurred after methscopolamine; increases were observed in the hypothalamus. Neostigmine caused large increases in behavior, but no increases in the frequency of discharge of neurons. The results show that the hippocampus contains a large number of neurons whose rate of firing was modified by cholinergic agents which cross the blood-brain barrier; the midbrain contains a smaller number of such neurons, whereas the hypothalamus contains neurons responsive to cholinergic agents acting at the periphery.
Stimulation bound copulation was obtained from a ventral midbrain extension of the hypothalamic medial forebrain bundle. Electrical stimulation at this site accelerated the achievement of ejaculation and the resumption of copulation after ejaculation. Sexual activity was temporarily depressed immediately after stimulation. The results are discussed in terms of a preoptic medial forebrain bundle ventral midbrain system influencing copulation in the male rat.
Correlations between liver cell necrosis in biopsy specimens and the serum levels of SGOT, SGPT and urocanase were studied in 186 patients. Because urocanase is a specific liver enzyme, its appearance in serum may be expected to be representative of liver cell necrosis. The results demonstrate that urocanase measurements have no advantage over transaminase determinations. This applies to the whole patient group as well as to smaller groups of patients with different types of liver disease.