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Background: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). Conclusions: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6–12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. Clinical trial registration: ClinicalTrials.gov, number NCT01379989. [ABSTRACT FROM AUTHOR]

To prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers' attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p < 0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p < 0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery. [ABSTRACT FROM AUTHOR]

Purpose: The two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.Methods: In total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.Results: Tumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.Conclusion: Tumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC. [ABSTRACT FROM AUTHOR]

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted. [ABSTRACT FROM AUTHOR]

Targeting Poly (ADP-ribose) polymerase 1 (PARP-1) involved in base excision repair (BER) has been shown to be a clinically effective treatment strategy in epithelial ovarian cancer (EOC) defective in homologous recombination (HR). The aim of this study was to evaluate fresh EOC tumor tissue in regard to PAR (Poly (ADP-ribose)) concentration as a surrogate marker for PARP activity and PARP protein expression in archival samples by immunohistochemistry (IHC). The prospective study cohort consisted of 57 fresh tumor samples derived from patients undergoing primary ( n = 38) or interval debulking surgery ( n = 19) for EOC and parallel archival paraffin-embedded tumor samples. PARP activity in fresh frozen tumor tissue was assessed by an enzymatic chemiluminescence assay and PARP protein expression in paraffin-embedded tumor tissue by IHC. No correlation was detected between PARP enzyme activity and PARP staining by IHC ( p = 0.82). High PARP activity was associated with platinum sensitivity both in the entire study cohort ( p = 0.022) and in the high-grade subgroup ( p = 0.017). High PARP activity was also associated with improved progression-free survival (PFS) (32 vs 14 months, log-rank p = 0.009). However, PARP immunostaining pattern was not predictive of patient survival. In conclusion, we present a novel finding of high PARP activity associated with platinum sensitivity and improved PFS in EOC. There was no association between PARP IHC and pharmacodynamic assay, and the correlation of PARP IHC with clinico-pathological characteristics and patient survival was poor. Pharmacodynamic assay rather than IHC seems to reflect better biologically significant PARP. [ABSTRACT FROM AUTHOR]

The food consumption of 38 children newly diagnosed with diabetes aged < 6 years at diagnosis was assessed by 5 day food records. During the 2 year follow up, the proportion of the total energy intake made up of protein decreased from 20% to 18%, that of carbohydrates from 54% to 52%, and that of fat increased from 26% to 30%. The energy intake from sucrose (3%) did not change. In addition, There was a small decrease in the intake of fibre and several vitamins and minerals. One year after diagnosis, the diet of diabetic children was compared with that of 66 age, sex, and social status matched control children. More energy was derived from protein (19% v 15%) and carbohydrates (53% v 50%), and less from fat (28% v 35%), especially from saturated fatty acids (11% v 15%), and sucrose (3% v 16%) in the diet of children with diabetes compared with that of control children. The higher intakes of several vitamins and minerals reflected the higher nutrient density of the diet of children with diabetes. Therefore, the diet of young children with diabetes met the dietary recommendations for subjects with diabetes. Only the protein content of the diet was higher than necessary. [ABSTRACT FROM AUTHOR]

We describe a patient with ovarian carcinoma who presented with cardiac tamponade with subsequently development of cardiac arrest as the initial symptom. After successful resuscitation and pericardiocentesis our patient was given an intrapericardial infusion of bleomycin and there was no recurrence of pericardial effusion at 14 months follow-up. [ABSTRACT FROM AUTHOR]

Two case reports of abdominopelvic actinomycosis associated with an intrauterine device (IUD) are presented. In the first case, the association was difficult to establish and in the second one, a pelvic malignancy was suspected. The diagnosis and treatment of IUD-associated abdominopelvic actinomycosis are discussed on the basis of the present cases and the literature. [ABSTRACT FROM AUTHOR]

A consecutive series of 78 children with transient asymptomatic glucosuria was studied and followed up for up to 7.3 years. The age at presentation was 0.9-17.6 (median 4.6) years. One third of the patients had random blood glucose levels of > 10.0 mmol/l (180 mg/dl). Five patients (6.4%) developed insulin-dependent diabetes mellitus within 2.1 years after the first incident of glucosuria. These patients presented with higher levels of glycaemia than others, and three out of five were positive for islet cell antibodies with a first-phase insulin response < 46 mU/l in all four studied. Of the remaining 73 children, 3 were positive for islet cell antibodies and 12/55 had a first-phase insulin response under 46 mU/l. The insulin response deteriorated in 3 but reverted to normal in 7 patients. CONCLUSION. For a child with transient glucosuria and with presence of islet cell antibodies and a subnormal first-phase insulin response, therapeutic attempts to prevent overt insulin-dependent diabetes mellitus should be considered. [ABSTRACT FROM AUTHOR]

Objective Preoperative evaluation of the depth of myometrial invasion in endometrial carcinoma is challenging. The objective of this study was to evaluate the usefulness of three-dimensional power Doppler angiography (3D-PDA) in this setting. Methods Sonographic and histological data on 100 consecutive cases of endometrial carcinoma were analyzed. The endometrial and myometrial vascular indices VI (vascularization index), FI (flow index) and VFI (vascularization flow index) were calculated by 3D-PDA. The results were compared with a complete surgical staging. Results The mean ( ± SD) age of patients was 67.1 ± 8.8 (range, 33-87) years. Forty-six patients had deep (≥ 50%) myometrial invasion. Eight patients had metastases, seven of them with deep invasion. Three patients were found to have carcinomas of non-uterine origin on histology, and these were excluded from further statistical analysis. The median endometrial and myometrial vascular indices were higher in the group with deep invasion than in the group without. Following multivariable analysis of the indices only the endometrial FI was independently associated with deep invasion (OR, 1.061; 95% CI, 1.023-1.099; P = 0.001). However, a greater endometrial volume was also an independent predictor of deep invasion (OR, 1.109; 95% CI, 1.011-1.215; P = 0.028). Conclusion Our study suggests that endometrial and, to a lesser degree, myometrial vascular indices and endometrial volume correlate with the depth of myometrial invasion in endometrial carcinoma. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background:CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to determine progression.Methods:In all, 976 patients with platinum-sensitive ROC were randomised to carboplatin-paclitaxel (C-P) or carboplatin-pegylated liposomal doxorubicin (C-PLD). CT-scan and CA-125 were performed every 3 months until progression.Results:In all, 832 patients (85%) progressed, with 60% experiencing a first radiological progression, 10% symptomatic progression, and 28% CA-125 progression without evidence of radiological or symptomatic progression. The benefit of C-PLD vs C-P in progression-free survival was not influenced by type of first progression (hazard ratio 0.85 (95% confidence interval (CI): 0.66-1.10) and 0.84 (95% CI: 0.72-0.98) for CA-125 and RECIST, respectively). In patients with CA-125 first progression who subsequently progressed radiologically, a delay of 2.3 months was observed between the two progression types. After CA-125 first progression, median time to new treatment was 2.0 months. In all, 81%of the patients with CA-125 or radiological first progression and 60% with symptomatic first progression received subsequent treatment.Conclusion:CA-125 and radiological tests performed similarly in determining progression with C-PLD or C-P. Additional follow-up with CA-125 measurements was not associated with overtreatment. [ABSTRACT FROM AUTHOR]

Timolol maleate is a non-selective β-adrenoceptor antagonist currently used mainly as an ocular preparation for the treatment of glaucoma and ocular hypertension. Despite the topical administration, ophthalmic timolol causes systemic adrenergic β-blocking because of absorption from the eye into the systemic circulation. Gel formulations of ophthalmic timolol have been developed to reduce systemic absorption and adverse effects in comparison with conventional aqueous solution formulations. Timolol is metabolized by the polymorphic cytochrome P450 2D6 enzyme (CYP2D6). The changes in heart rate (HR) are the most striking effects of the systematically absorbed fraction of ophthalmic timolol, with 0.5 % aqueous formulations presenting larger effects than 0.1 % hydrogel formulations, especially during exercise. Plasma levels of ophthalmic timolol correlate with the changes in HR. Neither 0.5 % aqueous nor 0.1 % hydrogel formulations of timolol have exerted noteworthy effects on systolic (SAP) or diastolic (DAP) arterial pressures, probably because of a compensatory increase in systemic vascular resistance due to the attenuation of HR. Ophthalmic timolol does not exert remarkable effects on pulmonary parameter peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) in non-asthmatic patients. CYP2D6 activity is clearly associated with the pharmacokinetic parameters, particularly when 0.5 % aqueous solution of timolol is used: peak plasma concentration, elimination half-life and area-under-the-curve are highest in CYP2D6 poor metabolizers. Finally, since there is a correlation between the plasma level of timolol and several haemodynamic effects - especially HR in the state of elevated β-adrenergic tonus - the CYP2D6 poor metabolizers may be more prone to bradycardia during treatment with (aqueous) ophthalmic timolol. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of toremifene in the treatment of premenstrual mastalgia. Design Double-blind, placebo-controlled crossover study. Setting Three Finnish general practices from the districts of Satakunta Central Hospital and Tampere University Hospital. Population A total of 62 women aged 25–45 years with premenstrual mastalgia during at least three previous menstrual cycles. Methods Women were randomised to receive toremifene 20 mg daily or placebo from day 15 of the menstrual cycle until menstruation for three consecutive cycles. After a wash-out cycle, the women were crossed over to receive placebo or toremifene for three additional cycles. Main outcome measures Cyclic breast pain relief assessed by visual analogue scale (VAS) score. Quality-of-life scores assessed by a modified 36-item Finnish Depression Scale, with a score ranging from 0 to 108. Acceptability of treatment. Results About 32 women were randomised to receive toremifene first and 30 to receive placebo first. Twenty-nine and 27 participants in the groups treated with toremifene first or placebo first completed the treatment, respectively. There were significant reductions in VAS scores in both groups after three treatment cycles. This was significantly greater in the toremifene-treated group (VAS: 1.8 in the toremifene group and 3.7 in the placebo group, P= 0.004). Treatment effect between treatment cycles was significant ( P= 0.001). Quality of life was similar during the toremifene and placebo cycles. Conclusion This study demonstrates that the antiestrogenic compound, toremifene, is able to relieve premenstrual breast pain without major adverse effects. There was a 64% reduction in median pain scores in the toremifene-treated cycles compared with a 26% reduction in placebo-treated cycles. [ABSTRACT FROM AUTHOR]

Objective: To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT.Methods: An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control.Results: The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported.Conclusions: Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control. [ABSTRACT FROM AUTHOR]

Objective: Two randomized comparative multicenter studies were conducted to establish the endometrial safety and tolerability of a triphasic sequential hormone replacement estradiol valerate/medroxyprogesterone acetate (E2V/MPA) therapy regimen.Methods: Study 1 was a randomized, double-blind, clinical phase III study in 399 postmenopausal women, following parallel-group design with two groups. The duration of study treatment was 12 or 13 cycles of 28 days. A double-dummy technique was used to ensure blinding in the study. The investigational drugs were E2V/MPA triphasic and E2V/MPA biphasic (Diviseq and Divina, respectively; Orion Pharma). In study 2, a total of 341 subjects were randomly allocated by computer into two parallel groups receiving either E2V/MPA or estradiol/norethisterone acetate triphasic (E2/NETA, Trisequens; Novo Nordisk A/S) for 12-13 cycles. The study was an open, clinical phase III trial with a randomized, parallel-group design. Endometrial biopsies combined with transvaginal ultrasound were undertaken before and at the end of treatment during the progestogen phase. Bleeding patterns and symptom control were assessed throughout both studies.Results: E2V/MPA triphasic was found to have similar endometrial effects and bleeding patterns to those with E2V/MPA biphasic and E2/NETA triphasic. Climacteric symptoms were relieved as quickly and effectively as with the two comparator treatments. No adverse drug reactions specific to E2V/MPA triphasic were observed. At the end of the study, the proportions of secretory samples were 67.1% for the combined E2V/MPA triphasic groups, 65.6% for the E2V/MPA biphasic group and 71.6% for the E2/NETA triphasic group. One case of hyperplasia occurred in the E2V/MPA triphasic group. Thus the incidence of hyperplasia for the combined groups was 0.33%.Conclusions: The triphasic E2V/MPA regimen was well tolerated and produced endometrial effects similar to those of the two comparators. Extending estrogen during the so-called treatment-free week with a lower dose of estradiol was effective in controlling vasomotor symptoms. [ABSTRACT FROM AUTHOR]

Background: Quercetin is a flavonoid with a wide range of biological activities. It mainly occurs in plants as glycosides, such as rutin (quercetin rutinoside) in tea. Quercetin and rutin are used in many countries as vasoprotectants and are ingredients of numerous multivitamin preparations and herbal remedies. Objectives: The primary objective was to characterise and compare the absorption and the pharmacokinetics of quercetin from quercetin aglycone and rutin. A secondary objective was to investigate which forms of quercetin are present in plasma. Methods: In this double blind, diet-controlled, two-period cross-over study, 16 healthy volunteers received three different doses of quercetin and rutin orally. The doses corresponded to 8 mg, 20 mg and 50 mg quercetin aglycone. Blood samples were obtained between 0 h and 32 h post-dose. Results: The overall kinetic behaviour of quercetin differed remarkably after ingestion of quercetin aglycone or rutin. The mean area under the plasma concentration–time curve from 0 h to 32 h [AUC(0–32)] and maximum plasma concentration (Cmax) values of the two treatments were similar. However, time to reach Cmax (tmax) was significantly shorter after the quercetin aglycone treatment than after the rutin treatment (1.9, 2.7 and 4.8 versus 6.5, 7.4 and 7.5 h, for doses 1, 2 and 3, respectively). Also, the absorption of quercetin from quercetin aglycone was predictable and inter-individual variation was small. In contrast, after ingestion of rutin, inter-individual variations in AUC(0–32) and Cmax values were considerable and seemed to be associated with gender and use of oral contraceptives. Quercetin and rutin were found in plasma as glucuronides and/or sulfates of quercetin and as unconjugated quercetin aglycone, but no rutin was detected. Conclusions: In clinical trials, studying the effects of quercetin from rutin, bioavailability must be taken into consideration and plasma quercetin concentrations monitored. Whether our results apply to other glycosidic drugs as well, especially other rutosides, should be investigated. [ABSTRACT FROM AUTHOR]

We studied associations of 24-h serum insulin profiles with insulin dose, age, gender, haemoglobin A1c (HbA1c) and C-peptide values, as well as blood glucose profiles in 77 consecutive childrennine aged 2-4, 14 aged 5-8, 26 aged 9-12, and 28 aged 13-17 years-2 years after the onset of insulindependent diabetes mellitus (IDDM). Mean weightbased insulin doses in the four age groups were similar (0.7±0.2 U·kg·day in all); body surface-area-based doses differed. Insulin doses correlated significantly with the 24-h mean and area-under-thecurve (AUC) values, and with mean values at 03.00 hours of serum insulin in the children aged 5-8 and 13-17 years. The mean insulin concentrations of the age groups (95% confidence intervals) increased with age [6.1 (3.8, 9.7), 7.6 (5.9, 9.8), 10.4 (8.6, 12.4), and 14.0 (11.6, 16.8) mU/l; p<0.0002]. The 24-h mean of serum insulin together with HbA concentration predicted 32% of the variation of mean blood glucose concentrations. Of children aged less than 9 years, 50% had insulin values less than 5 mU/l (healthy subjects' lower reference limit), and 14% were of less than 2 mU/l (detection limit of the assay) at 03.00 hours. At 07.00 hours, 82% had insulin values of less than 5 mU/l, and 36% were of less than 2 mU/l, respectively. Some young children had night-time hypoglycaemia with simultaneous hypoinsulinaemia. Insulin profiles correlated poorly with the HbA1c and peak C-peptide values. We conclude that in children the mean and AUC values of serum insulin profiles are age-dependent but C-peptide independent 2 years after the diagnosis of IDDM despite similar weight-based mean insulin doses. Nocturnal and morning hypoinsulinaemia was a frequent finding in the younger children, as was biochemical hypoglycaemia. These findings suggest that insulin kinetics and sensitivity differ markedly in children according to age. [Diabetologia (1995) 38:97-105] [ABSTRACT FROM AUTHOR]

A 9-year-old girl was euthyroid with a small goitre, exophthalmos, scaphocephalic skull, minor sketelal abnormalities, and raised serum thyroid hormone concentrations. Other members of the family did not have goitres and their thyroid hormone levels were normal. From age 3 years the patient was treated for Graves's disease, but after 4 years treatment was stopped because of enlargement of the goitre. Despite increased serum thyroxine (T4), free T4 (FT4), and triiodothyronine (T3), basal serum TSH, and the TSH response to thyrotropin-releasing hormone (TRH) were normal. Pituitary refractoriness was present because full suppression of the TSH response to TRH was achieved only after daily administration of 500 micrograms thyroxine. Urinary excretion of hydroxyproline, and the activity of red cell glucose-6-phosphate dehydrogenase remained normal when excess T4 was administered, demonstrating the tissue resistance to thyroid hormones. Peripheral lymphocytes were found to have nuclear receptors for T3 with normal affinity, but the relatively low binding capacity indicated that the biochemical defect might be a deficiency of nuclear receptor protein. The findings in this patient differ somewhat from previously reported cases of peripheral resistance to thyroid hormones. [ABSTRACT FROM AUTHOR]

The prevalence of IgG class antibodies to endothelial cells (AECA) was studied in 136 young patients with insulin-dependent diabetes mellitus by an enzyme immunoassay using human umbilical cord vein endothelial cells. The patients were divided into four groups according to the time between diagnosis and study and their results were compared with those in control children and blood donors. AECA became progressively more frequent with the duration of diabetes, being 4% in diabetics tested within 2 weeks of diagnosis and reaching 34% after an average disease duration of II 2 years. They were not more common in patients with neuropathy, retinopathy or nephropathy than in patients without these complications, but were associated with co-existing thyroid disease and IgA deficiency. The results suggest that in insulin-dependent diabetes mellitus AECA are associated with co-existing autoimmune disorders but not with diabetic microvascular disease. [ABSTRACT FROM AUTHOR]

Cell samples derived from the thyroid glands of twelve children with juvenile autoimmune thyroiditis (JAIT) were analysed. The cytological findings were those of chronic lymphocytic thyroiditis in eight and suggestive of that disease in four patients. About 86% of the cells infiltrating the thyroid were lymphocytes, 4% were lymphoid blasts, 6% neutrophils and 3% monocytes. Analysis using monoclonal antibodies showed that about 60% of the lymphocytes were T cells and half of the lymphocytes expressed HLA Class II-antigens, T helper cells dominated with a T helper/suppressor ratio of 2-2 in thyroid while the ratio was 12 in peripheral blood, of the thyroid epithelial cells, 80% also expressed HLA class II, The immune activation and immunoglobulin synthesis within the thyroid are discussed. [ABSTRACT FROM AUTHOR]

We have studied the distribution of T and B lymphocytes in the blood and in the thyroid lymphocytic infiltrates (obtained by fine needle aspiration biopsy) in sixteen patients with juvenile autoimmune thyroiditis (JAIT). The same cell populations were also tested for cell-mediated immunity (CMI) to thyroid antigen in the leucocyte migration test (LMT). The relative and absolute numbers of blood T lymphocytes were normal (71-76%), as were the numbers of blood B lymphocytes (19%). The thyroid infiltrate contained 48% B lymphocytes, whereas only 40-44% of the infiltrating lymphocytes were T cells. Half of the JAIT patients showed a positive CMI to thyroid antigen with blood leucocytes, but when thyroid-infiltrating lymphocytes of these patients were tested in the LMT, they were negative. Thus, in contrast to what is generally assumed, we were unable to demonstrate T cell-dominated lymphocytic infiltrates or the accumulation of specifically sensitized T lymphocytes within the thyroid gland in autoimmune thyroiditis. [ABSTRACT FROM AUTHOR]

AIMS: To compare the prevalence of thyroid peroxidase antibodies in 25 children with autoimmune thyroid disorders and in 41 children and young adults with type 1 diabetes, and to test the prevalence of thyrotropin receptor antibodies. METHODS: Two commercially available radioimmunoassays for antibodies to thyroid peroxidase, a commercially available agglutination test of particles coated with thyroid microsomal antigens, and a radioimmunoassay for thyrotropin receptor antibodies were used. Patients and controls were studied. RESULTS: One of the radioimmunoassays detected thyroid peroxidase antibodies not only in all children with autoimmune thyroid disorders and children and young adults with type 1 diabetes and thyroid microsomal antibodies, but also in 20% of healthy control children without microsomal antibodies. With this thyroid peroxidase assay and with microsomal agglutination, 94% of the children with autoimmune thyroiditis, 71% of those with Graves' disease, and over 90% of those with type 1 diabetes and thyroid dysfunction tested positive. In the other radioimmunoassay for thyroid peroxidase antibodies thyroid peroxidase antibody titres in half or more of the children with microsomal antibodies failed to reach the level of positivity given by the producers. Eighty five percent of children with Graves' disease and 71% of those with autoimmune thyroiditis had thyrotropin receptor antibodies but so did 35% of children studied for other endocrinological disorders such as delayed growth or puberty. CONCLUSIONS: Testing patients with well characterised disorders of thyroid function and with other endocrine disorders is important in evaluating the efficacy of new diagnostic tests for thyroid autoantibodies. [ABSTRACT FROM PUBLISHER]

The subrenal capsule assay (SRCA) is used in clinical oncology to assess the sensitivity of individual malignant tumors to various anticancer agents and their combinations. Mitotic indices reflect cancer cell proliferation and have prognostic value in epithelial neoplasms, including ovarian carcinoma. We combined the two tests (SRCA, mitotic index) by evaluating the numbers of mitotic figures per square millimeter of neoplastic epithelium (M/V) in paraffin-embedded tumor samples after SRCA. The M/V index was compared with the tumor size measurement (dTS), which is used in conventional SRCA to predict the drug response. Histology examination showed insignificant changes in the size of tumor transplants due to host reaction but disclosed a number of potential errors in the use of dTS to evaluate transplant growth and drug effects. In our series of 62 patients with advanced ovarian carcinoma the M/V value was superior to the dTS in explaining the clinical response after 6 months as assessed at second-look laparotomy. Patients showing no response had significantly higher M/V values than did those displaying complete or partial responses ( P < 0.033). The use of 6 mitotic figures/mm2 as a limit differentiating responders from nonresponders resulted in an overall predictive accuracy of 79% in the logistic regression analysis. In comparison to the FIGO stage, residual tumor size, and the dTS, the M/V value obtained for the cytostatic combination given to the patient was the single most significant factor predicting the 6-month clinical response. The results indicate that the combined use of the M/V index and SRCA is a promising new approach to prediction of the drug response in ovarian adenocarcinoma. [ABSTRACT FROM AUTHOR]

National cord blood screening for congenital hypothyroidism has operated in Finland with complete coverage since 1980. A low frequency of false positives, 0.08%, was achieved by supplementing the TSH screen with a T4 determination in borderline samples. Among 175188 infants the incidence of (unconfirmed) hypothyroidism was 1/2637. The median age at start of therapy was 6 days. The programme imposed a 2-3 week therapy on the false positive cases. This did not appear to cause any adverse effects. A mechanism for masking congenital hypothyroidism was observed: two athyroid infants were euthyroid at birth because of feto-fetal transfusion. [ABSTRACT FROM AUTHOR]

An abstract of the article "Vascularity measurements in predicting deep invasion in endometrial carcinoma: uterine artery color Doppler and uterine 3D-power Doppler angiography," by S. K. Saarelainen, M. H. Vuento, P. Kirkinen, and J. U. Mäenpää is presented.

Despite considerable progress over the past two decades in the management of advanced ovarian cancer, the majority of patients with this type of malignancy still die from their disease, and the search for new and improved first-line and salvage chemotherapy regimens continues. As part of this work, the antitumour activity and effect on survival of new chemotherapy combinations containing the novel taxane docetaxel are being explored. Dual therapy with docetaxel plus a camptothecin (a topoisomerase inhibitor) has shown promise in second-line treatment, and preliminary data indicate good activity of docetaxel in combination with gemcitabine. Triple-therapy studies have produced mixed results, but encouraging activity has been reported when the anthracycline, epirubicin, is added to docetaxel and carboplatin - sequential therapy with docetaxel, cisplatin and epirubicin is currently being assessed. Combinations of docetaxel, carboplatin and gemcitabine may also be of future interest. Early efficacy and tolerability results with novel combination chemotherapy regimens involving docetaxel thus offer the promise of additional progress in the chemotherapy of advanced ovarian cancer, and further trials should be encouraged.British Journal of Cancer (2003) 89 (Suppl 3), S29-S34. doi:10.1038/sj.bjc.6601498 www.bjcancer.com [ABSTRACT FROM AUTHOR]