Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression

In a prospective study of 32 patients with chronic myeloid leukemia the frequency of chromosome abnormalities in addition to the Philadelphia chromosome (Ph) increased when the disease progressed. Before metamorphosis, 10 patients (31%) had developed additional abnormalities. Such abnormalities were present in three of them at the time of diagnosis; in the other seven, they were detected late in the chronic phase. New clonal abnormalities heralded or accompanied a more malignant phase of the disorder, usually a blastic leukemia. During metamorphosis, 78% of the patients had additional abnormalities, which in 68% of these cases comprised at least one of +8, +22q- or i(17q). Clones with additional abnormalities disappeared in eight cases, either spontaneously or in association with cytostatic therapy during the chronic or blastic phase. Involvement of chromosome #8, usually in the form of a trisomy, was found in 7 of 12 patients treated with busulfan, but was not found in any of the 10 hydroxyurea-treated patients, of whom 8 were splenectomized early during the chronic phase. Cells from the spleen, obtained by fine needle aspiration or splenectomy were cytogenetically examined in 18 cases during the chronic phase, but abnormalities in addition to the Ph were noted in only one patient, who was examined in the late chronic phase. The same abnormalities were present in bone marrow cells of this patient.     

Cytogenetic studies of bone marrow and extramedullary tissues and clinical course during metamorphosis of chronic myelocytic leukemia

Of 33 consecutive patients with chronic myelocytic leukemia, examined during metamorphosis, 82% showed chromosome abnormalities in addition to the Ph1. Aberrations most frequently encountered were +8 (39%), +22q - (30%), and i(17q) (18%). Translocations other than the Ph1 were observed in four cases and - Y clones in four cases. Discrepancies in the cytogenetic pattern between bone marrow and extramedullary tissues or blood were noted in a total of 15 patients. In six cases, transformation occurred in extramedullary organs at a time when it was not present in the marrow. In three cases the bone marrow transformation was preceded by a lymph node blastic infiltrate; in one case, by a skin infiltrate; and in one case, by a subdural blastoma. Clonal abnormalities additional to the Ph1 were identified in the tumor tissue from all these cases. Patients with primary extramedullary transformation tended to have a lower median age at onset of metamorphosis, shorter survival, and higher incidence of chromosome abnormalities than the cases without extramedullary involvement. Patients with only Ph1-positive cells and no other anomalies had a slightly longer duration of metamorphosis and longer total survival. Basophilia and thrombocytopenia were more marked in cases with i(17q) than in the rest of the series.     

Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against α2-adrenoceptor mediation

The influence of ₂-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5–4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significantanxiolytic-like effects on standard spatiotemporal measures at 2.0–4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective ₂-adrenoceptor antagonist, idazoxan (0.63–5.0 mg/kg), exerted much weaker behavioural effects in the maze while the ₂-adrenoceptor agonist, clonidine (0.01–0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT_1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.     

Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries

Specimens from the ovarian cortical stroma of 15 postmenopausal women were examined histologically and were incubated for 4 hours in Krebs' bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. Specimens of normal postmenopausal stroma produced measurable amounts of androstenedione, estradiol, and progesterone in vitro. Specimens with stromal hyperplasia produced larger amounts of androstenedione and estradiol than those with normal stroma. Androstenedione was the predominant steroid produced in both groups. The nonnegligible formation of estradiol indicated an aromatizing capacity of the stromal tissue. The addition of hCG elicited a significant increase in cyclic AMP formation in specimens from ovaries with stromal hyperplasia, indicating a preserved responsiveness to gonadotropin in this type of ovaries.     

Adhesion to normal human uroepithelial cells of Escherichia coli from children with various forms of urinary tract infection.

The ability to adhere to normal human uroepithelial cells was compared for Escherichia coli strains isolated from the urine of girls with acute pyelonephritis, acute cystitis, or asymptomatic bacteriuria, and from the stools of school children without bacteriuria. Strains from those with acute pyelonephritis had high adhesive ability, whereas strains from those with acute cystitis had intermediate and strains from girls with asymptomatic bacteriuria or from normal feces had low adhesive ability. Strains of serogroup O4K12 had good adherence regardless of origin. E. coli of the eight O groups commonly found in patients with acute pyelonephritis adhered more than did strains of other O groups. Spontaneously agglutinating strains had less adhesive ability than did the O-typable ones.     

Blood flow of the reproductive system in renal hypertensive rats during pregnancy

An experimental study on pregnant rats was undertaken to explore whether renal hypertension interferes with uteroplacental blood supply and fetal weight. Renal hypertension was induced by standardized clamping of the left renal artery. Two days before expected delivery, blood flow to the reproductive organs was determined by the microsphere technique in normal control rats, rats with short-standing renal hypertension induced early in pregnancy, and rats with established renal hypertension induced 4 weeks before pregnancy. Myometrial and placental blood supply was considerably reduced in renal hypertensive rats compared to that in normotensive pregnant rats, with the reduction in placental blood flow being as much as 68% in rats with established renal hypertension. Nevertheless, there was no reduction in fetal weights, placental weights, or number of fetuses in the litters. These findings suggest that the nutritional blood supply of the placenta normally has a considerable overcapacity, perhaps a necessary safety margin so that the fetus can manage the circulatory demands associated with delivery. If hypertension causes intrauterine growth retardation only by means of reduced placental blood flow, this reduction in flow obviously must be considerable.     

Increased erythrocyte sodium efflux during overfeeding without evidence of mediation by circulating catecholamines or thyroid hormone

Ten slightly obese middle-aged men were instructed to increase their energy intake 25% during a period of 1 week, which was preceded by a control period of seven days. Body weight increased by 0.67 kg (SD 0.60) indicating good compliance with the regimen. Transmembrane sodium fluxes were determined with the use of 22Na. The pre-diet erythrocyte sodium content was 9.7 mmol/L (SD 0.8) decreasing to 8.9 mmol/L (SD 1.1) (P less than 0.05) during overfeeding. The Na-efflux rate constant increased from 0.40 h-1 to 0.54 h-1 (P less than 0.05). Urinary excretion of catecholamines and concentrations of catecholamines and insulin in plasma and of thyroxine, triiodothyronine, and reverse T3 in serum did not change. Thus, overfeeding seems to enhance the total Na efflux in erythrocytes from slightly obese men. There were no measurable changes in thyroid hormone or catecholamine levels leaving the regulatory mechanisms unexplained.     

Coping with pain: A component analysis of Lamaze and cognitive-behavioral procedures

In this study an attempt was made to sort out the active ingredients of the Lamaze childbirth technique, and a possible improvement in the form of in-vivo emotive imagery was explored. Seventy female subjects were randomly assigned to one of seven treatment conditions in a 3 (levels of visual activity) × 2 (levels of respiratory activity)+ 1 (no treatment) design. Measures of pain threshold, pain endurance, and self-reported discomfort obtained in the cold pressor task were obtained before and after treatment. While no significant differences emerged on the respiratory activity factor, the imagery procedure was shown to be more effective than the visual procedure espoused by Lamaze for enhancing subjects' tolerance of ice-water discomfort. Implications of these findings for future research are discussed.