Abdominal relapse in stage 1 nonseminomatous germ cell tumours of the testis managed by surveillance or with adjuvant chemotherapy

OBJECTIVE: To assess the impact on patterns of recurrence of adjuvant chemotherapy in patients with stage 1 nonseminomatous germ cell tumours (NSGCT) of the testis, who have a high likelihood of relapse on surveillance if certain risk factors are identified in the orchidectomy specimen, and thus the theoretical need for retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: The incidence of abdominal relapse was recorded in 417 men presenting with stage 1 NSGCT over the past 18 years. Up to 1986, 161 men were managed by surveillance alone, and abdominal relapse occurred in 26. From 1986 onwards, men with positive risk factors in the orchidectomy specimen were offered two courses of chemotherapy; 60 accepted and one relapsed in the abdomen, and 196 underwent surveillance and 19 relapsed in the abdomen. RESULTS: Abdominal relapse was significantly reduced from 16% before 1986 to 8% afterward (P = 0.014). Mortality from testicular tumour or treatment toxicity remained low, at 0.6% before 1986 and 2.0% since then. CONCLUSION: The need for RPLND in stage 1 NSGCT remains highly doubtful.     

Therapeutic irradiation of the central nervous system using intrathecal 90Y--DTA.

The erdication of established neuroleukaemia is often difficult, and with subsequent relapses even harder. The use of an intrathecally-injected beta emitting isotope has the advantage of preserving the bone-marrow of the vertebral column and cranium whislt irradiating the meninges. The value of intrathecal 90Y-DTPA(diethylene-triamine penta-acetic acid) has been investigated in nine patients with neuroleukaemia or CNS involvement in malignant lymphoma. Measurements of retention of the isotope in the whole body, spinal, and intracranial subarachnoid spaces have been made, together with blood levels, and are reported. The clinical results are presented. In three out of five evaluable patients 90Y-DTPA failed to maintain a chemotherapy-induced CNS remission and in two out of two evaluable patients malignant cells were not dispersed from the CNS with a single intrathecal injection of 90Y-DTA. It is concluded, therefore, that with this agent and the doses used no useful clinical result is gained.     

Determination of muscle-tendon unit properties during tendon transfer.

Data on passive lengthening and active shortening from electrical stimulation to give a total functional excursion are presented. Length-tension characteristics of certain muscles used for transfer are given. Electrical stimulation of the newly transferred tendon gives useful information that is reproducible. This new knowledge obtained at operation is an important adjunct to the traditional techniques and provides helpful information in performing better procedures.     

Comparison of the antinociceptive effect of acute morphine in female and male Sprague-Dawley rats using the long-lasting mu-antagonist methocinnamox

Male rats are more sensitive than female rats to the antinociceptive action of morphine. The present study used age-matched (9-10 weeks old) male and female Sprague-Dawley rats to investigate whether this difference is due to variation in mu-opioid receptor binding and G protein activation. In the warm-water tail-withdrawal assay at both 50 degrees C and 55 degrees C, morphine was 2-3 times more potent in males than females. In contrast, mu-opioid receptor number and the binding affinity of the mu-opioid agonists morphine and DAMGO in membranes from whole brain, cortex, thalamus, and spinal cord were not different between males and females. Similarly, morphine and DAMGO stimulation of G protein, determined using GTPase and [(35)S]GTPgammaS binding assays, did not show a difference between the sexes. The long-lasting mu-opioid receptor antagonist methocinnamox (0.32 mg/kg), given 24 h prior to morphine, reduced mu-opioid receptor number by approximately 50% in thalamic and spinal cord tissue from female and male rats and reduced the antinociceptive potency of morphine. Pretreatment of male rats with 0.32 mg/kg methocinnamox reduced the antinociceptive potency of morphine to that observed in female rats expressing a full complement of mu-opioid receptors. However, with increasing pretreatment doses of methocinnamox, the maximal antinociceptive effect of morphine was decreased in females but not males. The results suggest that pathways downstream of the mu-opioid receptor and G protein are more efficient in male rats than in female rats such that there is a larger receptor reserve for morphine-mediated antinociception.     

Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells

Reaction to certain motifs in bacterial DNA is an important function of natural immunity. For example, single stranded oligonucleotides (ODN) containing the motif "not C, unmethylated C, G, not G" are powerful mitogens and apoptosis inhibitors for mouse spleen B cells. But replacing GCGTT or ACGTT with GCGGG or ACGGG converted a stimulatory 15-mer ODN into an inhibitory ODN. All inhibitory ODN had three consecutive G, and a fourth G increased inhibitory activity, but a deazaguanosine substitution to prevent planar stacking did not affect activity. Inhibitory ODN blocked apoptosis protection and cell-cycle entry induced by stimulatory ODN, but not that induced by lipopolysaccharide, anti-CD40 or anti-IgM+IL-4. ODN-driven up-regulation of cyclin D(2), c-Myc, c-Fos, c-Jun and Bcl(XL) and down-regulation of cyclin kinase inhibitor p27(kip1) were all blocked by inhibitory ODN. The relative potency of a series of stimulatory and inhibitory ODN was the same for all readouts measured. Interference with uptake of stimulatory ODN could not account for their inhibitory effects. Even if addition of inhibitory ODN was delayed several hours, partial inhibition of stimulatory ODN effects occurred. Inhibitory ODN hold potential as antidotes for excessive ODN stimulation in the clinical setting and provide an important tool for studying ODN recognition.