GA Hicks

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

Pre- and postsynaptic adenosine 5'-triphosphate-sensitive potassium (ATP-K+) currents were studied using whole-cell recordings from substantia nigra zona compacta "principal" neurons in midbrain slices. The GABAA and GABAB receptor-mediated synaptic potentials were unaffected by the ATP-K+ channel inhibitor glibenclamide (30 microM) or by the opener diazoxide (500 microM), indicating that ATP-K+ channels on GABA-ergic terminals are not active, nor can they be activated pharmacologically, under control conditions. However, application of a glucose-free solution to reduce intracellular ATP levels caused a reduction of the GABAB IPSP in all neurons. This was substantially reversed by the sulfonylurea inhibitor tolbutamide (300 microM) in 50% of the neurons tested. The reduction of the GABAB IPSP was a presynaptic effect since postsynaptic hyperpolarizations induced by the GABAB receptor agonist baclofen (10 microM) were unaffected by glucose-free solutions. Diazoxide (500 microM) induced a slowly developing hyperpolarization or outward current in 64% of principal neurons, which was tolbutamide- (100-300 microM) or glibenclamide- (30 microM) sensitive. In contrast, the GABAB receptor agonist baclofen (30 microM) induced a rapid hyperpolarization or outward current in all neurons tested that was unaffected by tolbutamide (300 microM). Although both the diazoxide-induced current and the baclofen-induced current were inhibited by Ba2+ (300 microM), the currents elicited by diazoxide and baclofen summated. The reversal potential for the diazoxide-induced current was also less negative than that for baclofen, which was close to EK. In the presence of intracellular cesium, diazoxide induced a tolbutamide-sensitive inward current in a proportion of neurons, indicating that it has other actions in addition to activating a potassium current. Our results suggest that functional ATP-K+ channels exist both pre- and postsynaptically in the SN, where they modulate the activity of principal neurons. They are different to the potassium channels activated by the GABAB receptor agonist baclofen.

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.