Frequent loss of heterozygosity targeting the inactive X chromosome in melanoma.

After previous preliminary observations of paradoxical deletion events affecting the inactive X chromosome in melanoma, we have surveyed the X chromosome for deletions using 23 polymorphic microsatellite markers in 28 informative (female XX) metastatic melanomas. Ten tumors (36%) showed at least one loss of heterozygosity (LOH) event, and in two cases an entire chromosome showed LOH at all informative loci. Four distinct X chromosome smallest regions of overlap can be resolved. An 18.6-Mb region on the p arm involving 9 of 28 (32%) samples lies between the markers DXS1061 and DXS1068. An equally frequently deleted smallest region of overlap straddled the centromere, bounded by DX1204 on the p arm and DXS983 14.6 Mb away in Xq11-12. One tumor potentially defines this region more tightly to a 10.6-Mb smallest region of overlap bounded by DXS1190 and DXS981 that contains the androgen receptor (AR) gene. A 6.2-Mb deleted region can be defined between the markers DXS8051 and DXS9902 in 8 of 28 (28%) tumors. An additional, less frequently deleted region of 25.7 Mb was found on distal Xq between the markers DXS1212 and DXS1193 in 5 of 28 (18%) tumors. X inactivation analysis of five tumors with LOH, using the AR exon 1 CAG repeat, showed that in each case, the inactive, hypermethylated allele was the one deleted. Analysis of copy number in this region by quantitative PCR showed restoration to disomy and, in one case, trisomy at AR.     

Unique variant of partial anomalous pulmonary venous connection with intact atrial septum

Summary Partial anomalous pulmonary venous connections (PAPVCs) are rare in association with an intact atrial septum. However, the diagnosis should be considered in patients with otherwise unexplained findings of left-to-right shunt and right heart enlargement. An unusual variant is presented, which we considered unsuitable for operative repair, based on findings at catheterization. Developmental, hemodynamic, and surgical considerations are discussed.     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.     

A prospective treatment study of premenstrual symptoms using a triphasic oral contraceptive.

Eighty-two women with complaints of moderate to severe premenstrual symptoms were recruited for a double-blind, controlled trial of a triphasic oral contraceptive (o.c.). Subjects made daily ratings of symptoms for at least one baseline cycle and were then randomly assigned to receive either placebo or o.c. for three months. Twenty-three women dropped out of the study (18 o.c., 5 placebo), 13 failed to show prospective confirmation of moderate to severe premenstrual symptoms, and one placebo subject had an anovulatory cycle. Forty-five women with prospectively-confirmed premenstrual changes (20 o.c., 25 placebo) completed the study. Premenstrual breast pain and bloating were significantly reduced with active treatment compared to placebo (p less than 0.03) but there were no beneficial effects of the o.c. over placebo for any of the mood symptoms. Women who received o.c.s reported decreased sexual interest after starting treatment and this effect was independent of any adverse influence on mood.     

In vitro evaluation of an implantable left ventricular assist device

The development of implantable left ventricular assist devices (LVADs) has almost reached the stage of providing permanent circulatory support in patients who are unsuitable for, or denied, the transplant option. As part of our ongoing haemodynamic evaluation of the Thermo Cardiosystems Inc. (Boston, USA) Mark 14 pneumatic LVAD, pressure-volume loops have been produced from in vitro studies using a modified National Heart Lung and Blood Institute (NHLBI, USA) mock circulatory loop. These studies have demonstrated that during certain phases of the pump cycle non-physiologically high and low pressures are generated within the LVAD. Such abnormal pressures may damage either the bioprosthetic valves in the LVAD or the native heart, and may have adverse effects on cardiovascular control mechanisms.     

Fetal haemoglobin and pregnancy in homozygous sickle cell disease

The pregnancy related changes in fetal haemoglobin (HbF) have been observed in 152 pregnancies in 125 women with homozygous sickle cell (SS) disease and related to steady state levels in the same individual. Statistically significant increases in the first and second trimesters, were followed by significant falls below steady state levels in the third trimester and postpartum period. Although these corresponded to a mean increase of 0.7% and a mean decrease of 1.6%, much greater changes occurred in some individuals. Mean levels had not returned to steady state values 1 year after delivery. The hormonal changes in pregnancy appear to have profound effects on HbF level in SS disease, the mechanisms of which require further study.     

Social and reproductive characteristics of the first 100 couples treated by in vitro fertilisation programme at National Women's Hospital, Auckland

Reproductive and social histories of the first 100 patients attending the in vitro fertilisation (IVF) programme at National Women's Hospital, Auckland, have been studied. The average age at first treatment was 31.6 (SD 3.9) for women, and 34.2 (4.6) for men. The couples had been married 7.6 (3.3) years and had experienced 6.7 (3.2) years infertility. It was a second marriage for 16. The husbands had on average a higher social classing than the population (class: number [population]--1:16 (7%), 2:18 (14%), 3:42 (28%), 4:19 (29%), 5:4 (14%), 6:1 (8%); but this bias diminished in the next 159 couples. Nine couples withdrew before their quota of cycles, 7 from stress. Tubal disease was the cause of infertility in 93, but in 69 its origin was untraceable. In 22 it could be attributed to pelvic inflammatory disease (eight associated with IUCDs and 2 with sexually transmitted disease) and in two to sterilisation. Although 59 women had a history of having conceived, only 34 were parous, and only 11 had a child of the current union.     

Use of steroids to suppress vascular response to radiation

A quantitative measure of the vascular permeability surface area product (PS) for albumin has been made using a double isotope technique. PS was significantly elevated in irradiated rat lung, heart, skin, and muscle, between 19 and 26 days following 18 or 25 Gray thorax irradiation. Administration of dexamethasone from 2 days before irradiation through the day of measurement suppressed the expected increase in PS in lung, heart, and muscle, but not in skin. Shorter periods of steroid administration were not as effective in suppressing this response to radiation exposure. Increased vascular permeability following radiation may be an essential element in the development of radiation fibrosis. We hypothesize that the ability to suppress this response could result in a long term reduction in the incidence of fibrosis.     

Use of a 2.0-mm locking plate/screw system for mandibular fracture surgery.

PURPOSE: In this study, we examined the use of a 2.0-mm locking bone plate/screw system in mandibular surgery. PATIENTS AND METHODS: All patients who were treated with a 2.0-mm locking bone plate/screw system during an 8-month period for fractures of the mandible or other defects of the mandible were prospectively studied. Ease of use of locking plate/screw system, characteristics of the fractures and defects, and complications were tabulated. RESULTS: A total of 80 fractures in 59 patients were treated with the 2.0-mm locking plate/screw system. One hundred two 2.0-mm locking plates were applied to the 80 fractures; 58 fractures received 1 plate and 22 fractures received 2 plates. There were no intraoperative difficulties associated with their application. Fracture reductions were considered to be excellent in all cases. At the latest follow-up, all fractures had healed, but 2 patients had slight malocclusions. Six patients developed postsurgical infections. Only 1 patient required hospitalization for treatment of the infection; all others were managed in the outpatient clinic. Four patients required removal of their plates for varying reasons. CONCLUSIONS: The use of a 2.0-mm locking plate/screw system was found to be simple and to provide sound fixation in all cases.