Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated With Dose-escalated Image-guided Intensity-modulated Radiotherapy.

AIMS: To quantify and qualify late genitourinary toxicity in a cohort of patients with localised prostate cancer treated with image-guided intensity-modulated radiotherapy (IMRT) to doses ≥78 Gy. MATERIALS AND METHODS: The cohort consisted of 300 patients treated with definitive dose-escalated IMRT between 2007 and 2013. Ninety-seven patients received 78-80 Gy in 38 fractions, and 203 received 82-84 Gy in 40 fractions. International Prostate Symptoms Score (IPSS) and supplemental quality of life data were recorded at baseline, weekly during treatment and at follow-up. Genitourinary toxicities were recorded using modified Radiation Therapy Oncology Group criteria during weekly treatment review and at each follow-up. Kaplan-Meier curves were used to assess the cumulative incidence of grade ≥ 2 genitourinary toxicity at 3 years. Baseline patient characteristics and symptoms were then used in univariate and multivariate analyses to identify predictors of late urinary toxicity. RESULTS: The median follow-up was 58 months (range 9-109 months). The actuarial cumulative 3 year rates of grade ≥ 2 and grade 3 genitourinary toxicity were 14.9% and 2.8%, respectively. There was no grade 4 toxicity. History of transurethral resection of the prostate (TURP), alpha blocker use before radiation, any hormone use, baseline IPSS ≥ 14 and pre-existing incontinence or nocturia were significantly associated with late ≥ 2 genitourinary toxicity on univariate analysis. On multivariate analysis, only previous TURP retained significance, with a hazard ratio of 2.54 (P=0.002). CONCLUSION: Our study showed acceptable levels of late grade 2 genitourinary toxicity and low rates of late grade 3 genitourinary toxicity in a cohort of patients with prostate cancer treated with image-guided IMRT to doses between 78 and 84 Gy. Variables associated with increased late ≥ 2 genitourinary toxicity include previous TURP, alpha blocker use, hormone use and pre-existing urinary dysfunction.

Promising results with image guided intensity modulated radiotherapy for muscle invasive bladder cancer.

AIM: To describe the feasibility of image guided intensity modulated radiotherapy (IG-IMRT) using daily soft tissue matching in the treatment of bladder cancer. METHODS: Twenty-eight patients with muscle-invasive carcinoma of the bladder were recruited to a protocol of definitive radiation using IMRT with accelerated hypofractionation with simultaneous integrated boost (SIB). Isotropic margins of .5 and 1 cm were used to generate the high risk and intermediate risk planning target volumes respectively. Cone beam CT (CBCT) was acquired daily and a soft tissue match was performed. Cystoscopy was scheduled 6 weeks post treatment. RESULTS: The median age was 83 years (range 58-92). Twenty patients had stage II or III disease, and eight were stage IV. Gross disease received 66 Gy in 30 fractions in 11 patients (ten with concurrent chemotherapy) or 55 Gy in 20 fractions for those of poorer performance status or with palliative intent. All patients completed radiation treatment as planned. Three patients ceased chemotherapy early due to toxicity. Six patients (21 %) had acute Grade ≥ 2 genitourinary (GU) toxicity and six (21 %) had acute Grade ≥ 2 gastrointestinal (GI) toxicity. Five patients (18 %) developed Grade ≥2 late GU toxicity and no ≥2 late GI toxicity was observed. Nineteen patients underwent cystoscopy following radiation, with complete response (CR) in 16 cases (86 %), including all patients treated with chemoradiotherapy. Eight patients relapsed, four of which were local relapses. Of the patients with local recurrence, one underwent salvage cystectomy. For patients treated with definitive intent, freedom from locoregional recurrence (FFLR) and overall survival (OS) was 90 %/100 % for chemoradiotherapy versus 86 %/69 % for radiotherapy alone. CONCLUSION: IG- IMRT using daily soft tissue matching is a feasible in the treatment of bladder cancer, enabling the delivery of accelerated synchronous integrated boost with good early local control outcomes and low toxicity.

Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer.

BACKGROUND: The REAL-2 and ML17032 trials demonstrated that the oral fluoropyrimidine, capecitabine, is noninferior to 5-fluorouracil (5-FU) for overall survival (OS) and progression-free survival (PFS), respectively, in advanced oesophago-gastric cancer. METHODS: Individual patient data were collected on all patients randomised within the trials (n = 1318). Kaplan-Meier survival curves were generated and the log-rank test was used to compare OS and PFS between patients receiving 5-FU combinations and capecitabine combinations. Stepwise multivariate Cox regression analysis was used to calculate corrected hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and PFS. Logistic regression was used for objective response rate. Forest plots with tests of heterogeneity were generated. RESULTS: OS was superior in the 654 patients treated with capecitabine combinations compared with the 664 patients treated with 5-FU combinations; HR 0.87 (95% CI 0.77-0.98, P = 0.02). Poor performance status, age <60 and metastatic disease were independent predictors of poor survival. There was no significant difference in PFS between treatment groups on multivariate analysis. Assessable patients treated with capecitabine combinations were significantly more likely to have an objective response to treatment than those treated with 5-FU combinations; odds ratio 1.38 (95% CI 1.10-1.73, P = 0.006). CONCLUSION: OS is superior in patients treated with capecitabine combinations compared with 5-FU combinations in advanced oesophago-gastric cancer.

Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial.

BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). RESULTS: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.

Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.

OBJECTIVE: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.

Inhibins/activins as diagnostic markers for ovarian cancer.

It is widely recognised that the early detection and subsequent assessment of recurrence of ovarian cancers are key steps for successful treatment. Available serum markers (e.g. CA125) are sensitive for some epithelial carcinomas (e.g. serous, endometrioid, clear cell), however, these markers are less sensitive for granulosa cell tumours and mucinous carcinomas. Serum inhibin is an ovarian product which decreases to non detectable levels after menopause, however, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as granulosa cell tumours) continue to produce inhibin which provides a basis for a serum diagnostic test. Studies from this and other laboratories have investigated the suitability of inhibin as a diagnostic marker by identifying which inhibin (inhibin A (alphabetaA), inhibin B (alphabetaB), free alpha subunit) or activin (betaAbetaA) form is associated with these cancers. Available data show that inhibin assays which detect all inhibin forms, i.e. assays which detect the alpha subunit both as the free form and as an alphabeta subunit dimer provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test. This review will discuss the data supporting these observations and show recent studies in which a new alpha subunit monoclonal antibody-based ELISA is used as a potential diagnostic test. Furthermore, based on the high sensitivity/specificity characteristics of the respective assays for the various types of ovarian cancer, the combination of the inhibin assay with CA125 detects the majority of all ovarian cancers.

Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer.

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free alpha-subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the alphaC region of the inhibin alpha-subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and alpha-subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin alpha-subunit and their precursor forms present in serum and follicular fluid from healthy women. The alphaC ELISAs recognized all known forms of inhibin and the free inhibin alpha-subunit, although differences between alphaC ELISAs were observed in their ability to detect high mol wt forms. To assess which of the alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the alphaC ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

Systematic assessment and evaluation of diversity content presented in classroom lectures: the FRDC tool.

The Fair Representation of Diversity Content (FRDC) Tool was developed to systematically assess and evaluate both qualitative and quantitative dimensions of diversity content incorporated into lectures in an undergraduate nursing course addressing basic nursing concepts and has relevance for other disciplines as well as Nursing.

Combined inhibin and CA125 assays in the detection of ovarian cancer.

BACKGROUND: The reproductive hormone inhibin has been used as a diagnostic marker of ovarian mucinous and granulosa cell cancers. The aims of this study were to develop a new inhibin immunofluorometric assay (alphaC IFMA) to replace an inhibin RIA as a diagnostic marker of these ovarian cancers and to assess whether the alphaC IFMA in combination with CA125, which detects serous cancers, leads to an improved biochemical diagnosis of all ovarian cancers. METHODS: Serum inhibin concentrations were determined in healthy postmenopausal women (n = 165) and women with ovarian cancers (n = 154), using an inhibin RIA and an alphaC IFMA, which detects inhibin forms containing the alphaC subunit as well as the free alphaC subunit. RESULTS: The alphaC IFMA gave a similar or better discrimination of mucinous (90% vs 71%) and granulosa cell (100% vs 100%) cancers compared with the inhibin RIA. Combination of CA125 and alphaC IFMA values by canonical variate analysis or by multiROC analysis showed that the percentage of all ovarian cancers detected was significantly increased compared with either CA125 or alphaC IFMA alone. CONCLUSIONS: The alphaC IFMA shows a similar or better specificity compared with the RIA, but with increased sensitivity. In combination with CA125, the alphaC IFMA provides an effective dual test for the detection of the majority (90%) of ovarian cancers.

Timing of mating, sperm dynamics, and ovulation in a wild population of agile Antechinus (Marsupialia: dasyuridae).

Timing of mating, sperm transport and storage, and ovulation were examined in a wild population of agile Antechinus (Marsupialia: Dasyuridae) in order to ascertain the validity of direct comparisons between captive and field-based mating studies in this species. Mating commenced in early August, and all females had ovulated by the 27th of the month. Fifty-five percent of the mated females caught that had not yet ovulated were captured on 19-20 August. This corresponded with a peak (67%) in the ovulation date determined for pregnant females. Approximately 25.9 x 10(3) spermatozoa per side were recovered from the reproductive tract of each mated female captured (range: 1.7 x 10(3)-75.5 x 10(3) spermatozoa per side). Spermatozoa were consistently found in greater numbers in the lower isthmus (19.7 x 10(3) +/- 19.9 x 10(3) spermatozoa per side) of the oviduct ( approximately 67% of all sperm found in the female tract; range 17-94%) than elsewhere in the reproductive tract. Few spermatozoa were found in the upper isthmus, and none were detected in the ampulla. Sperm number in the female reproductive tract supports the hypothesis that females will mate several times within the one estrus. At the conclusion of the rut, approximately 80.0 x 10(3) spermatozoa remained in each testis and approximately 630 x 10(3) spermatozoa in each epididymis. Most epididymal spermatozoa were restricted to the distal corpus/proximal cauda regions of the duct. This study shows that both field and laboratory reproductive data correlate well in the agile Antechinus and that successful breeding is indeed an exercise in reproductive brinkmanship.

Concurrent use of simvastatin and estrogen--progestin therapy compared with each therapy alone for hypercholesterolemia in postmenopausal women.

OBJECTIVE: Substantial improvements in lipoprotein-lipid profiles have previously been shown with both simvastatin and combined estrogen-progestin therapy in postmenopausal hypercholesterolemic women. Since little is known about the impact of the concomitant use of these therapies, the effects of concurrent hormone therapy and simvastatin in hypercholesterolemic postmenopausal women have been evaluated. METHODS: Twenty-three postmenopausal women with fasting serum total cholesterol levels greater than 250 mg/dl received, in a randomized cross-over design, simvastatin (10 mg daily) for 8 weeks or postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens plus 5 mg of medroxyprogesterone acetate daily) for 8 weeks, with an 8-week wash-out interval between the two treatment periods. In a third, non-randomized treatment period after a second wash-out interval, each woman received a combination of simvastatin and postmenopausal hormone therapy in the same dosage regimens as above. Fasting blood was sampled monthly from baseline to measure total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides and lipoprotein(a). RESULTS: For total cholesterol, the mean decreases with hormone therapy, simvastatin and combination therapy were 12% (95% confidence interval 6-17%), 26% (20-31%) and 28% (24-31%), respectively, and for LDL cholesterol 21% (14-27%), 37% (30-44%) and 46% (41-51%), respectively. Simvastatin was more effective than hormone therapy (p < 0.001), while the effect of the combined therapy was even greater (total cholesterol, p = 0.012; LDL cholesterol, p < 0.001). The level of HDL cholesterol increased similarly with each treatment: 4% (-3-11%), 6% (2-10%) and 7% (2-13%), respectively. Triglyceride levels increased with hormone therapy and decreased with simvastatin (p < 0.001), while there was little change with the combination (effect of combined therapy vs. simvastatin, p = 0.002; vs. hormone therapy, p < 0.001). Both hormone therapy and combined therapy reduced lipoprotein(a) similarly (-23% and -14%, respectively, p = 0.078). Simvastatin had no effect on lipoprotein(a) levels. CONCLUSION: For postmenopausal women with hypercholesterolemia, use of a statin in combination with continuous combined oral estrogen and progestin therapy can result in a more cardioprotective lipoprotein-lipid profile than that achieved with either therapy used alone.

Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women.

BACKGROUND: Postmenopausal estrogen therapy has favorable effects on serum lipoproteins in women with normal serum lipid levels, but the effect of combined estrogen and progestin therapy on lipoproteins in women with hypercholesterolemia has not been determined, nor has it been directly compared with the effect of conventional lipid-lowering therapy. METHODS: In a randomized crossover trial, we studied 58 postmenopausal women with fasting serum total cholesterol levels greater than 250 mg per deciliter. Each woman received simvastatin (10 mg daily) for eight weeks and postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens daily, along with 5 mg of medroxyprogesterone acetate daily) for eight weeks, with an eight-week washout period between the two treatment phases. RESULTS: At base line, the mean (+/-SD) cholesterol values were as follows: total cholesterol, 305+/-39 mg per deciliter; high-density lipoprotein (HDL) cholesterol, 62+/-19 mg per deciliter; and low-density lipoprotein (LDL) cholesterol, 217+/-39 mg per deciliter. For total cholesterol, the mean decrease with hormone therapy was 14 percent (95 percent confidence interval, 11 to 16 percent) and the mean decrease with simvastatin was 26 percent (95 percent confidence interval, 23 to 29 percent). For LDL cholesterol, the mean decrease was 24 percent (95 percent confidence interval, 20 to 28 percent) with hormone therapy and 36 percent (95 percent confidence interval, 32 to 40 percent) with simvastatin. The effect of simvastatin was significantly greater than that of hormone therapy (P<0.001). HDL cholesterol increased similarly with hormone therapy (mean increase, 7 percent; 95 percent confidence interval, 2 to 12 percent) and simvastatin (mean increase, 7 percent; 95 percent confidence interval, 4 to 10 percent). Triglyceride levels increased with hormone therapy (mean increase, 29 percent; 95 percent confidence interval, 15 to 42 percent) but decreased with simvastatin (mean decrease, 14 percent; 95 percent confidence interval, 8 to 20 percent). Lp(a) lipoprotein decreased with hormone therapy (mean decrease, 27 percent; 95 percent confidence interval, 20 to 34 percent), but not with simvastatin. CONCLUSIONS: In postmenopausal women with hypercholesterolemia, therapy with estrogen plus progestin has beneficial effects on lipoprotein levels. Hormone therapy may be an effective alternative to treatment with simvastatin, especially in women with normal triglyceride levels.

Posture and gastro-oesophageal reflux: a case for left lateral positioning.

AIM: Prone posture is often recommended for symptomatic gastroesophageal reflux in young infants, but prone positioning has been associated with sudden infant death. The aim of this study was thus to establish the optimal alternative posture for reducing reflux. METHODS: 24 infants (< 5 months) with symptomatic gastro-oesophageal reflux were studied prospectively with 48 h pH monitoring. They were randomly assigned to one of the 24 permutations of the four positions (supine, prone, right, left). During the first 24 hours the infant was held horizontally, and then the permutation was repeated at 30 degrees head elevation, giving a total of eight study segments for each infant. Data were edited to remove all time when the infants were not in the prescribed positions. Results were evaluated using analysis of covariance. RESULTS: Gastro-oesophageal reflux expressed as reflux index (mean % (SEM)) was significantly less in the prone and left lateral positions (6.72 (1.06) and 7.69 (1.03) respectively) than in the supine and right lateral positions (15.33 (2.33) and 12.02 (1.38); p < 0.001). Head elevation did not affect any variables significantly. CONCLUSIONS: Head elevation may not always be of clinical value. The left lateral position is a suitable alternative to prone for the postural management of infants with symptomatic gastro-oesophageal reflux.

Effects of FSH on serum immunoreactive inhibin levels in the luteal phase of the menstrual cycle.

OBJECTIVE: FSH causes a dose-related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase. DESIGN: Normal volunteers were treated with a single injection of LH-free FSH (Metrodin, 150 units) or saline as control, during the early, mid- or late luteal phase of the cycle, with subsequent hormone measurements. PATIENTS: The 21 volunteers were aged 19-29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1-4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the midluteal phase, 5-9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase. MEASUREMENTS: Oestradiol (E2), progesterone (P), and INH were measured by previously described radio-immunoassays. RESULTS: In both the early and mid-luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid-luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid-luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P. CONCLUSIONS: It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.

Do infants of depressed mothers cry more than other infants?

OBJECTIVE: This study compared the crying behaviour of infants of depressed and non-depressed mothers at 3 and 6 months of age. METHODOLOGY: Twenty-nine depressed and 44 non-depressed mothers, their infants and partners participated in this study. Mothers were asked to complete 24-hour diaries of the amount their infants cried for 1 week. RESULTS: The diurnal variations in crying patterns of infants of depressed and non-depressed mothers were not significantly different. However, infants of depressed mothers were found to cry significantly more in total per day than infants of non-depressed mothers at 3 months of age, but not at 6 months. The results could not be explained by differences in infant temperament. CONCLUSION: Maternal depression may be a contributory factor to infant crying at 3 months of age.

Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

BiliBlanket phototherapy system versus conventional phototherapy: a randomized controlled trial in preterm infants.

OBJECTIVE: This study compares the use of standard overhead fluorescent phototherapy units with the BiliBlanket a woven fibreoptic pad which delivers high intensity light with no ultraviolet or infrared irradiation in the treatment of jaundice in preterm infants. METHODOLOGY: We chose to study infants between 800 and 2500 g, with strict criteria for commencing and ceasing phototherapy. Serum bilirubin levels were followed at 12-24 h intervals until 24 h after cessation of phototherapy. Infants were allocated at random to receive either conventional phototherapy or the BiliBlanket. RESULTS: There were 24 infants in the conventional group and 20 in the BiliBlanket group. Mean duration of phototherapy was compared and was 44 h for the conventional group versus 42 h for the BiliBlanket group. CONCLUSIONS: We have shown that the BiliBlanket is as effective as conventional phototherapy and was well accepted by nursing staff and parents.

The effect of the Myo device on the gingival health in orthodontic patients.

The purpose of the present investigation was to determine the effectiveness of the Myo in reducing plaque and gingivitis development in orthodontic patients using a single-blind, cross-over design. Thirty subjects were randomly assigned to experimental and control groups. All subjects continued their customary oral hygiene procedures. In addition, the experimental group was instructed to chew on the Myo for four minutes, twice each day. Plaque Index and Gingivitis Index were assessed each time the subjects attended their scheduled orthodontic appointment. The patients failed to demonstrate any significant reduction in plaque and gingivitis development when the Myo was introduced as an additional oral hygiene measure. Some soft tissue injuries were found.

Serum inhibin during lactation: relation to the gonadotrophins and gonadal steroids.

OBJECTIVE: The aims of the study were to describe the changes in serum immunoreactive inhibin (INH) during normal lactation and to examine the relations between INH, oestradiol (E2) and follicle stimulating hormone (FSH), particularly during the first weeks post partum. DESIGN: Blood samples were obtained from normally lactating women for hormone measurements at daily intervals until discharge from hospital, and subsequently at weekly intervals until the resumption of menses, or one year post partum. SUBJECTS: Eighteen breast feeding women aged 27-36 years volunteered for the study. MEASUREMENTS: INH, FSH, luteinizing hormone (LH), prolactin (PRL), E2, and progesterone (P4) were measured by standard radioimmunoassays. Non-linear modelling was used to quantify the hormone patterns observed. RESULTS: Hormone levels were compared with those found in the follicular phase of the normal menstrual cycle. Levels of INH fell rapidly in the first week post partum and remained at the lower end of the follicular phase range for the period of study, rising only just prior to resumption of menses. E2 fell more slowly, into the follicular phase range, reaching the lower end of that range only at about approximately 100 days post partum. FSH levels were suppressed initially below the follicular phase range, commencing to rise 4.7-24 days post partum, reaching a plateau high in the follicular phase range 17.5-53 days post partum, and subsequently showing a slow decline. Human chorionic gonadotrophin (hCG), initially measured because of its cross-reactivity in the LH assay, fell rapidly post partum and LH remained in the low follicular phase range for several weeks. PRL fell slowly throughout and was still elevated at 150 days post partum, while P4 fell very rapidly and was less than 1 nmol/l until just prior to first menses. CONCLUSIONS: Inhibin levels fall rapidly post partum and remain low until close to the time of resumption of follicular activity and menses. The post partum rise in serum FSH appears to be much more closely related to falling oestradiol levels than to the very early and rapid fall in inhibin. Oestradiol thus appears to be the predominant negative feedback factor influencing FSH secretion during the post partum period. The low inhibin levels may allow FSH to rise to levels high in the follicular phase range under the predominant negative feedback control of oestradiol. Inhibin levels do not appear to be a suitable marker of returning fertility.

Determinants of forearm mineral density and its correlation with fracture history in women.

In order to evaluate the role of single photon absorptiometry (SPA) in the prediction of osteoporotic fracture risk, 1935 women, referred for measurement of forearm mineral density (FMD) at the distal radial site, were studied by questionnaire in a cross-sectional design. There was no significant decline in FMD until the age of 47, after which there was a linear decline with age of about 1.2% per year. There was no relationship between age and FMD, or forearm mineral content (FMC), in premenopausal women. There was a fall in FMD with the number of years since menopause, after correcting for the effects of age, of approximately 0.5% per year. Body weight was positively correlated with FMC in postmenopausal women. The duration of exposure to hormone replacement therapy (HRT) was positively correlated with FMD, and the magnitude of this effect was reduced the longer the delay between the onset of the menopause and the commencement of HRT. There was no significant association of FMD with calcium intake, weight-bearing exercise, tobacco or alcohol consumption, or family history of osteoporosis. FMD was significantly lower in postmenopausal women who reported fractures after the age of 25, after correcting for age and years postmenopause. In conclusion, a low FMD is predictive of a past history of fractures and may therefore be capable of predicting future fracture risk.