Women's acceptability of screening for HIV in pregnancy.

AIMS: To elicit acceptability of HIV screening during pregnancy in women of reproductive age in Christchurch. METHODS: In-depth face-to-face interviews were conducted with women of reproductive age recruited from seven different service sites in Christchurch. RESULTS: Women wanted to know about treatment that significantly reduces the risk of mother-to-child transmission. They wanted to know about other antenatal screening and were prepared to provide general consent, rather than specific consent for HIV testing. All study participants favoured routine offer of HIV testing during pregnancy for all women and most would agree to be tested, if the test was offered and recommended. CONCLUSIONS: The results of this study indicate the need to develop and test a user-friendly approach for offering routine HIV testing during standard antenatal care in New Zealand.

Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter.

To investigate the usefulness of heat shock protein (HSP) promoter for breast cancer gene therapy, hyperthermia and HSV thymidine kinase (tk) suicide gene combination therapy was examined with mouse mammary cancer cell line FM3A. HSP promoter activity was markedly increased after heat shock (41-45 degrees C), with maximum activation (about 400-fold) at 3 hr. An in vitro cytotoxic assay showed that HSP-tk-transduced FM3A cells became more sensitive (more than 50,000 times) to ganciclovir (GCV) with heat shock, but untreated cells showed no increased cytotoxic sensitivity to GCV compared with control FM3A cells. In addition to promoter-oriented selective cell killing, a "chemosensitization effect" as a bystander effect was demonstrated by hyperthermia and suicide gene combination therapy, using a non-heat-inducible promoter. Immunohistochemical analysis revealed that this synergistic killing effect was dependent on apoptotic cell death with upregulation of both Fas and FasL (Fas ligand) expression. We also examined the efficacy of HSP-tk gene therapy in vivo by implanting breast cancer in subcutaneous and intraperitoneal models of BALB/c nude mice targeted by the HVJ-anionic liposome method. Significant tumor regression was observed in HSP-tk-transduced tumors followed by hyperthermia therapy, but no such inhibition was noted in either the mock vector transfection or hyperthermia group compared with control tumor-bearing mice. Our results demonstrate that this combination system is synergistically effective in mediating Fas-dependent apoptosis for a specific gene therapy targeting HSP-expressing mammary carcinomas, even in advanced and heat-resistant breast cancer.

Retrovirus-mediated suicide gene/prodrug therapy targeting thyroid carcinoma using a thyroid-specific promoter.

To develop gene therapy targeting thyroid carcinoma, the recombinant retrovirus (LNTGTK) carrying herpes simplex virus thymidine kinase (HSV-TK) gene under the control of thyroglobulin (TG) promoter was constructed and its efficacy was investigated in 3 thyroid cell lines; a differentiated normal rat thyroid cell line (FRTL5), malignant rat thyroid carcinoma cells derived from FRTL5 (FRTC) and a human anaplastic thyroid carcinoma cell line (FRO). TG mRNA was detected by Northern blot analysis in FRTL5 cells and by RT-PCR in FRTC cells when cultured with 2 U/L TSH and its expression levels were decreased by TSH withdrawal. However, either methods revealed no TG expression in FRO cells. In vitro cytotoxic assays demonstrated TG expression status-dependent cell killing by transduction of LNTGTK followed by ganciclovir (GCV) treatment. Thus, LNTGTK transduction increased the GCV sensitivity approximately 13,000- and approximately 160-folds in the presence of TSH and approximately 4- and approximately 27-folds in the absence of TSH in FRTL5 and FRTC cells, respectively. In contrast, there was no difference in the GCV cytotoxicity between parental and transduced FRO cells. Significant growth inhibition, but not complete eradication, of transduced FRTC cells was observed in in vivo subcutaneous tumor models of nude mice. These results demonstrate that retrovirus-mediated transduction of HSV-TK gene under the control of the TG promoter confers the GCV sensitivity selectively to TG-expressing thyroid cells. This system may therefore be feasible for gene therapy targeting TG-expressing thyroid carcinomas.

Distribution of the parathyroid hormone-related peptide and its receptor in the saccus vasculosus and choroid plexus in the red stingray (Dasyatis akajei: Elasmobranch).

1. The exact role of the parathyroid hormone-related peptide (PTHrP) is not fully understood. We used immunohistochemistry to localize the PTHrP and its receptor in the brain of the red stingray, particularly in the saccus vasculosus (SV) and choroid plexus. 2. Immunoreactive PTHrP and its receptor were detected in the epithelial cells of the SV and the choroid plexus. In addition, the neuronal perikarya in the nucleus of the SV located in the hypothalamus is positive for the PTHrP. 3. No PTHrP-containing neurons were detected in the choroid plexus. Extracts of SV and choroid plexus showed positive reactions against the PTHrP and its receptor antibody in Western blot analysis. 4. High levels of immunoreactive PTHrP were detected in the plasma equivalent to those present in human humoral malignant hypercalcemia. In contrast, the immunoreactive PTHrP concentration in the cerebrospinal fluid was below detectable levels. 5. Our results suggest that the regulation of the PTHrP in the SV differs from that in the choroid plexus in the red stingray.

Premenstrual tension among hysterectomized women.

What is the prevalence of premenstrual tension (PMT) among women who have no uterus? Three hundred and seventeen hysterectomized women aged 28-45 years, were asked to describe their health before and after surgery. Most of the women (88%) felt that their general health improved postoperatively. There was a significant reduction in the percentage of women reporting moderate to severe PMT in all or almost all cycles: pre- versus post-hysterectomy, 56.1 versus 18.9; p < 0.001. Of the 178 women who considered PMT to have been a regular feature of their prehysterectomy menstrual cycles, 73% either lost their symptoms after surgery or felt that they were now minimal. It is concluded that the prevalence of PMT among hysterectomized women is low compared with that among women who have a uterus.

Assessment of the effect of ovarian suppressants on women with the premenstrual syndrome: iterative spectral analysis.

The daily mood symptoms of four women with the premenstrual syndrome (PMS) were recorded before, and after spontaneous or induced ovarian failure. Response was assessed by iterative spectral analysis and the results compared with techniques based on changes in the mean or median mood score, or the measurement of premenstrual tension in arbitrary 'menstrual' cycles. Only iterative spectral analysis had the capacity to establish the significance of a change in symptom cyclicity, an important attribute for a condition such as the PMS.

Retention of normal ovarian function after hysterectomy.

What are the long-term effects of hysterectomy on the ovaries of normal women? Ninety-three women aged 29-44 years (median, 38 years) who had undergone hysterectomy for benign reasons 0.3-9.1 years prior to investigation, contributed urine samples twice weekly for a period of 53-149 days (median 102 days) for pregnanediol analysis. The interval between successive pregnanediol peaks and their increment over baseline were measured. The median peak interval was 27.3 days, and 93.3% of all intervals were of 21- to 35-days duration. Of the 337 peaks observed, 96.7% met the criteria previously used to define an ovulatory cycle. These are similar to the figures reported for menstruant women of comparable age. ANOVA showed no significant effect of age or time since hysterectomy on either the interval between peaks or peak increment (P > 0.10 in all cases). The evidence suggests that the ovaries of women who have no uterus behave like those of intact women.

The premenstrual syndrome: amelioration of symptoms after hysterectomy.

What is the role of the uterus in the aetiology of the premenstrual syndrome (PMS)? Twelve women kept a daily symptom record before and after hysterectomy. Psychological and physical symptom patterns were analysed by Fourier analysis and the response to hysterectomy by maximum likelihood ANOVA. Hysterectomy was associated with a 66% reduction in mean premenstrual tension (PMT) severity for both psychological and physical symptoms (p less than 0.005). The milder symptoms appeared unrelated to post-operative changes in health or ovarian function. Seven women experienced mood-related PMT in every pre-hysterectomy cycle; the persistence of unfailing mood-related PMT in one of these women after hysterectomy suggests that her symptoms were hormonally controlled and the loss of regular PMT in the other six women suggests that a uterine factor, or psychological factors associated with the menstrual cycle were implicated. We conclude that a uterus is not essential for the expression of PMT, but that its removal often results in the amelioration of symptoms.

Symptom cyclicity in women with the premenstrual syndrome: an 8-year follow-up study.

Does premenstrual tension (PMT) change with time? In 1982 and again in 1990, nine women with the premenstrual syndrome kept a daily record of eight psychological and five physical symptoms for three menstrual cycles. Urine samples were collected once or twice weekly for the analysis of pregnanediol. Premenstrual tension was estimated by Fourier analysis. By 1990, all the women continued to menstruate at regular intervals and there was little change in either PMT prevalence or in mean PMT severity (ANOVA, p = 0.43 for psychological symptoms and 0.52 for physical symptoms). It is concluded that age-related changes in PMT may be trivial.

Premenstrual syndrome in hysterectomized women: mood and physical symptom cyclicity.

In 36 hysterectomized women presenting with PMS, a daily record of eight mood states and five physical symptoms was kept during 109 ovarian cycles. Premenstrual tension (PMT) was estimated at a point 92% through the ovarian cycle after fitting a five-term Fourier series to the data. Although significant mood and physical-symptom swings were common (present in 71% and 69% of cycles respectively), the incidence of symptoms late in the luteal phase (PMT) was low (36%). In nine women no PMT was detected, in twenty-two women PMT was sporadic, and in five there was evidence of the consistent appearance of both mood and physical symptom-related PMT. Symptoms clustered significantly around a point 85% through the ovarian cycle for moods, and 83% for physical symptoms; this differs significantly from the 92% observed in menstruant women with PMS and is consistent with the removal of a factor associated with menstrual onset, which may contribute to the symptoms perceived by women as PMT.

Physical symptom cyclicity in women with and without the premenstrual syndrome.

A daily record of five physical symptoms was kept by 44 women self-selected as having the premenstrual syndrome (PMS+ group, 133 menstrual cycles) and 48 women self-selected as not having PMS (PMS- group, 100 cycles). Symptoms were analysed after fitting the first five terms of a Fourier series. PMS+ women differed significantly from PMS- women in (i) the incidence of significant physical symptom swings (present in 81.2% vs 33.0% of cycles), (ii) the incidence of significant physical symptoms in the premenstruum (PMT: present in 80.5% vs 24.0% of cycles), and (iii) PMT severity (mean +/- SE, 1.37 +/- 0.08 vs 0.27 +/- 0.04). Pregnanediol excretion and the distribution of stomach cramps were similar in the two groups. The small but significant symptom increase observed in the premenstruum of PMS-women is consistent with the view that premenstrual physical symptoms, unlike premenstrual psychological symptoms, may be associated with the normal menstrual cycle. For confirmation more evidence is required.

Mood cyclicity in women with an without the premenstrual syndrome.

A daily record of seven mood states was kept (a) by 44 women self-selected as having the premenstrual syndrome (PMS+ group, 133 menstrual cycles) and (b) by 48 women self-selected as not having PMS (PMS- group, 100 cycles). Mood patterns were analysed after fitting the data to a 5-term Fourier series. PMS+ women differed significantly from PMS- women in (i) the self-rating of PMS at interview (62.1 +/- 2.8 (SE) vs 8.8 +/- 1.2), (ii) the incidence of significant mood swings (present in 76.7 vs 54.0% of cycles, (iii) the incidence of premenstrual tension (PMT present in 69.9% vs 8.0% of cycles), (iv) the score for PMT severity (96.0 +/- 12.6 vs 4.1 +/- 5.2), (v) the background mood score (31.6 +/- 10.0 vs 23.6 +/- 12.0). It is concluded that significant mood changes occur both in women with PMS and in women without PMS, but that the changes are larger and the dysphoria concentrated in the premenstrual period in the PMS+ group. In PMS- women dysphoria occurred sporadically and was not confined to the premenstruum.