In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.

The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changing antibiotic prescribing by educational marketing

A controlled cross-over study in 12 Victorian public hospitals was performed to examine the power of marketing techniques in influencing prescribing. The targeted prescribing behaviour was the use of antibiotic prophylaxis in surgery, and the criteria for judging the appropriateness of therapy were its duration and timing, as are detailed in the fourth edition of the booklet Antibiotic guidelines. The first intervention was mounted in 1985 in six hospitals (two metropolitan teaching hospitals, one suburban general hospital and three rural hospitals), and six matched hospitals acted as control hospitals. One year later, the intervention was mounted in the six hospitals that previously had been the control hospitals. The interventional campaign consisted of material that was similar to that which is used by the pharmaceutical industry, including an "academic" representative. Its effect was assessed by audits that were performed before and after the first interventional campaign and again, one year later, after the second interventional campaign. The proportion of antibiotic courses that were assessed as satisfactory in terms of duration increased significantly after the first campaign in the hospitals where the intervention was mounted. No significant changes in prescribing occurred in the control hospitals. In the hospitals which were control hospitals in 1985, and in which the intervention occurred in 1986, the proportion of antibiotic courses that were assessed as satisfactory also increased significantly after the interventional campaign. A fall-off in performance occurred during the 12 months after the campaign in the 1985-interventional hospitals. Calculated cost savings more than outweighed the costs of the campaign. We conclude that inappropriate prescribing behaviour in hospitals can be modified successfully by educational marketing techniques.     

Trisomy 8 as the sole chromosomal aberration in myelocytic malignancies: a multicolor and locus-specific fluorescence in situ hybridization study

Trisomy 8 is the most common chromosomal aberration in myelocytic malignancies, occurring both as a sole change as well as in addition to other abnormalities. In spite of this, next to nothing is known about its pathogenetic importance or its molecular genetic consequences. Possible mechanisms involved in the transformation process include dosage effects of genes mapping to chromosome 8 and presence of specific mutations or cryptic fusion genes on the duplicated chromosome. In the latter case, +8 would be secondary to a cryptic primary rearrangement and not involved in leukemogenesis as such, but rather in tumor evolution. Although hidden genetic changes have been found in some trisomies, for example, mutations in KIT in acute myelocytic leukemia (AML) with +4 and in MET in hereditary papillary kidney carcinoma with trisomy 7, none associated with +8 have so far been discovered. To address this issue, we have investigated a total of 13 cases of AML, myelodysplastic syndromes, and chronic myeloproliferative disorders with trisomy 8 as the sole chromosomal anomaly. All cases were studied by combined binary ratio multicolor fluorescence in situ hybridization (FISH) and with FISH using locus-specific probes for both arms of chromosome 8, the subtelomeric regions of 8p and 8q, and the leukemia-associated genes FGFR1, MOZ, ETO, and MYC. No cryptic changes were detected, thus excluding the possibility of gross genetic rearrangements or aberrations involving these loci on chromosome 8.     

Localization of evoked potentials in the digastric,masseteric, supra- and intertrigeminal subnuclei of the cat

Summary Extracellular focal potentials were evoked and mapped in the trigeminal motor nucleus and its surrounding borderzone in the cat. Graded electrical stimulation was used for orthodromic and antidromic excitation of the masseteric and digastric motoneurones and for orthodromic stimulation of the lingual and inferior alveolar nerves. The method of referring Horsley Clarke coordinates of microelectrode recording positions to their location of the actual histological section was studied and the total error affecting the method was calculated for the H, AP and L axes. The characteristics and the distribution of the evoked focal potentials were described and related to the histological section from the actual experiment. A phase reversal of the negative focal potential evoked by the lingual and inferior alveolar nerves in the main sensory nucleus and in the intertrigeminal nucleus was observed to indicate the dorso-lateral border of the motor nucleus. Other borders were given by the antidromic potentials evoked in the nucleus. Digastric motoneurones were found medially in the caudal third and ventro-medially in the middle third of the motor nucleus. The masseteric motoneurones were located laterally in the middle and rostral thirds of the nucleus. Potentials evoked in the supratrigeminal and intertrigeminal subnuclei, adjacent to the motor nucleus, were considered and discussed in relation to the available evidence of interneurones subserving trigeminal reflex arcs.     

Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies

Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are found in approximately 1% of karyotypically abnormal acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). The MYC gene at 8q24 has been reported to be amplified in the majority of the cases, and generally it has been assumed that MYC is the target gene. However, only a few studies have focused on the extent of the amplicon or on the expression patterns of the amplified genes. We have studied six cases (five AML and one MDS) with MYC-containing dmin. Detailed fluorescence in situ hybridization analyses identified a common 4.3 Mb amplicon, with clustered proximal and distal breakpoints, harboring eight known genes (C8FW, NSE2, POU5FLC20, MYC, PVT1, AK093424, MGC27434 and MLZE). The corresponding region was deleted in one of the chromosome 8 homologues in five of the six cases, suggesting that the dmin originated through extra replication (or loop-formation)--excision--amplification. Northern blot analysis revealed that MYC was not overexpressed. Instead, the C8FW gene, encoding a phosphoprotein regulated by mitogenic pathways, displayed increased expression. These results exclude MYC as the target gene and indicate that overexpression of C8FW may be the functionally important consequence of 8q24 amplicons in AML and MDS.     

Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.     

High-level language ability in healthy individuals and its relationship with verbal working memory

The aims of the study were to investigate healthy subjects’ performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20–79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegård, Hartelius, & Ahlsén, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.