The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency.

Hydroxysteroid (17ß) dehydrogenase type 3 (HSD17B3) deficiency causes a disorder of sex development in humans, where affected males are born with female-appearing external genitalia, but are virilized during puberty. The hormonal disturbances observed in the Hsd17b3 knockout mice (HSD17B3KO), generated in the present study, mimic those found in patients with HSD17B3 mutations. Identical to affected humans, serum T in the adult HSD17B3KO mice was within the normal range, while a striking increase was detected in serum A-dione concentration. This resulted in a marked reduction of the serum T/A-dione ratio, a diagnostic hallmark for the patients with HSD17B3 deficiency. However, unlike humans, male HSD17B3KO mice were born with normally virilized phenotype, but presenting with delayed puberty. In contrast to the current belief, data from HSD17B3KO mice show that the circulating T largely originates from the testes, indicating a strong compensatory mechanism in the absence of HSD17B3. The lack of testicular malignancies in HSD17B3KO mice supports the view that testis tumors in human patients are due to associated cryptorchidism. The HSD17B3KO mice presented also with impaired Leydig cell maturation and signs of undermasculinization in adulthood. The identical hormonal disturbances between HSD17B3 deficient knockout mice and human patients make the current mouse model valuable for understanding the mechanism of the patient phenotypes, as well as endocrinopathies and compensatory steroidogenic mechanisms in HSD17B3 deficiency.

Novel epididymal proteins as targets for the development of post-testicular male contraception.

Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the post-meiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags, in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genes in vivo. In this review, we summarize the current knowledge of several epididymal proteins shown either in vivo or in vitro to be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52, and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.

Accuracy of self-reported anthropometric measures - Findings from the Finnish Twin Study.

OBJECTIVE: To determine the accuracy of self-reported height, weight, body mass index (BMI) and waist circumference (WC) compared to the measured values, and to assess the similarity between self-reported and measured values within dizygotic (DZ) and monozygotic (MZ) twin pairs. METHODS: The data on self-reported and measured height, weight and WC values as well as measured hip circumference (HC) were collected from 444 twin individuals (53-67 years old, 60% women). Accuracies between self-reported and measured values were assessed by Pearson's correlation coefficients, Cohen's kappa coefficients and Bland-Altman 95% limits of agreement. Intra-class correlation was used in within-pair analyses. RESULTS: The correlations between self-reported and measured values were high for all variables (r=0.86-0.98), although the agreement assessed by Bland-Altman 95% limits had relatively wide variation. The degree of overestimating height was similar in both sexes, whereas women tended to underestimate and men overestimate their weight. Cohen's kappa coefficients between self-reported and measured BMI categories were high: 0.71 in men and 0.70 in women. Further, the mean self-reported WC was less than the mean measured WC (difference in men 2.5cm and women 2.6cm). The within-pair correlations indicated a tendency of MZ co-twins to report anthropometric measures more similarly than DZ co-twins. CONCLUSIONS: Self-reported anthropometric measures are reasonably accurate indicators for obesity in large cohort studies. However, the possibility of more similar reporting among MZ pairs should be taken into account in twin studies exploring the heritability of different phenotypes.

Characteristics of a 85Kr beta-particle source applied in Series 1 reference irradiations of DIS-1 direct ion storage dosemeters.

Characteristics necessary to specify an ISO 6980 Series 1 reference radiation field were determined for a commercially available 85Kr beta-particle source, using a BEAM EGS4 Monte Carlo code. The characteristics include residual maximum beta energy, E(res), and the uniformity of the dose rate over the calibration area. The E(res) and the uniformity were also determined experimentally, using an extrapolation ionization chamber (EC) and a 0.2 cm3 parallel plate ionization chamber, respectively. The depth-dose curve measured with the EC gave a value 0.62 MeV for the E(res). Series 2 90Sr + 90Y and Series 1(85) Kr beta-particle sources calibrated for H(p)(0.07) at the secondary standard dosimetry laboratory (SSDL) of STUK were used to determine the energy and angular responses of DIS-1 direct ion storage dosemeters. The averaged zero angle H(p)(0.07) responses to the 90Sr + 90Y and 85Kr reference radiations were 135 and 80%, respectively. The responses were normalized to 100%, H(p)(0.07) response to 137Cs photon radiation.

Attention systems and the organization of the human parietal cortex.

Event-related functional magnetic resonance imaging was used to compare activity in the human parietal cortex in two attention-switching paradigms. On each trial of the visual switching (VS) paradigm, subjects attended to one of two visual stimuli on the basis of either their color or shape. Trials were presented in blocks interleaved with cues instructing subjects to either continue attending to the currently relevant dimension or to switch to the other stimulus dimension. In the response switching (RS) paradigm, subjects made one of two manual responses to the single stimulus presented on each trial. The rules for stimulus-response mapping were reversed on different trials. Trials were presented in blocks interleaved with cues that instructed subjects to either switch stimulus-response mapping rules or to continue with the current rule. Brain activity at "switch" and "stay" events was compared. The results revealed distinct parietal areas concerned with visual attentional set shifts (VS) and visuomotor intentional set shifts (RS). In VS, activity was recorded in the lateral part of the intraparietal region. In RS, activity was recorded in the posterior medial intraparietal region and adjacent posterior superior and dorsomedial parietal cortex. The results also suggest that the basic functional organization of the intraparietal sulcus and surrounding regions is similar in both macaque and human species.

Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 north Finland general population birth cohort.

OBJECTIVE: The 1966 North Finland general population birth cohort was studied to determine whether abnormalities during pregnancy, delivery, and the neonatal period are associated with adult-onset schizophrenia. METHOD: The authors included all 11,017 subjects alive in Finland at age 16. For each individual, standardized assessments made during pregnancy, delivery, and infancy were linked to national psychiatric case registers covering the period up to age 28. Subjects with DSM-III-R schizophrenia were identified by using a two-stage screen that included perusal of individual case records. Associations (adjusted odds ratios) between schizophrenia and specific pregnancy, delivery, and neonatal characteristics were calculated. RESULTS: Within this cohort, 76 cases of DSM-III-R schizophrenia arose by age 28 years; 51 (67.1%) of these persons were men. Demographic characteristics and previous obstetric histories of the mothers were similar in the case and unaffected comparison groups, although the former were more likely to have been more depressed than usual during pregnancy. Low birth weight (< 2500 g) and the combination of low birth weight and short gestation (< 37 weeks) were more common among the schizophrenic subjects. Being small for gestational age (< 10th percentile) was not more common. Of 125 survivors of severe perinatal brain damage, six (4.8%) later developed schizophrenia. CONCLUSIONS: The spectrum of adverse outcomes after fetal and perinatal insults unfolded beyond childhood and included adult-onset schizophrenia. The findings have implications for understanding the mechanisms involved in the development of schizophrenia and, possibly, for its prevention.

Pharmacology of antineoplastic agents in pregnancy.

The use of antineoplastic agents in pregnant women poses obvious risks to both the patient and the developing fetus, particularly during organogenesis. While the use of antineoplastics during pregnancy is often unavoidable, the physician may limit the risks by having a clear knowledge of the pharmacology and teratogenic potential of individual agents. Specific physiologic changes in the pregnant patient, such as enhanced renal excretion of drugs, increased or decreased hepatic function, altered gastrointestinal absorption and enterohepatic circulation, altered plasma protein binding, an increase in plasma volume (50%), and creation of a fluid filled 3rd compartment (amniotic fluid) for water soluble drugs may all significantly influence the pharmacology of antineoplastic agents. These physiological changes may effect the pregnant patients ability to absorb orally administered drugs, metabolize drugs to either active or inactive metabolites, and eliminate cytotoxically active drugs. A resulting reduction in concentration x time (C x T) for drug exposure to the maternal system may reduce the efficacy of the antineoplastic agents, while an increase in C x T may expose the patient and her fetus to undue toxicity. The timing of drug administration to gestational age is also a critical factor for some drugs. While many drugs result in adverse effects on the fetus regardless of gestational age, others appear to pose less of a threat if administered beyond the first trimester. This review addresses the pharmacology, pharmacokinetics and the teratogenic potential of individual antineoplastic agents that are commonly used in pregnant patients. The aim of this review is to help the physician select, on a patient specific basis, antineoplastic agents that avoid at least some of the fetal risk involved while maintaining efficacy in the treatment of the patient.

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo.

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.

Improved technique for detection of enhanced green fluorescent protein in transgenic mice.

One of the most exciting recent advances in cell biology is the possibility to use the green fluorescent protein and its various mutated forms as reporter proteins in studies carried out in vitro and in vivo. In the present study, several detection techniques for the enhanced green fluorescent protein (EGFP) were compared in transgenic mice, using fluorescence and confocal microscopy. In addition, different tissue preparation techniques (squash preparations, vibratome sections, frozen sections) were evaluated. As a model we used transgenic mice expressing EGFP under the control of a 5.0-kb fragment of the glutathione peroxidase isoenzyme 5 protein promoter (GPX5-EGFP) or under a 3.8-kb fragment of the cysteine rich protein-1 promoter (CRISP1-EGFP). In the GPX5-EGFP mice, expression of EGFP was observed in the distal part of the caput epididymis, while the CRISP1 promoter directed EGFP expression in the tubular compartment of the testis. Among the various tissue preparation procedures tested, the best morphological and histological preservation, and reproducibility in EGFP detection, were obtained using frozen sections after a slow tissue-freezing protocol developed in the present study. After slow tissue freezing, specimens of testis and epididymis could be stored at -70 degrees C for at least six weeks without any affect on EGFP fluorescence. Hence, the method developed offers the possibility to analyze EGFP fluorescence in tissues several weeks after specimen collection. The sensitivity achieved was equal to that found in immunohistochemistry, applying biotin-streptavidin-FITC detection. Confocal microscopy is known to have the advantage that fluorescence can be detected from cells in different layers. This was found to be important as regards detecting EGFP fluorescence because the fluorescence was destroyed at the cut surfaces of sections produced by either vibratome or cryomicrotome.

Distractible children show abnormal orienting to non-attended auditory stimuli.

Event-related potentials were recorded in response to intermittently presented, non-attended trains of identical auditory stimuli in healthy 9-year-old children. In abnormally distractible children (n =24), the first tone in each train elicited a significantly larger N1 vertex response than in the non-distractible children (n 24), suggesting that increased distractibility may be associated with an abnormally strong cerebral orienting towards non-attended stimuli. A later negativity at around 300 ms, which increases in amplitude with stimulus repetition and may thus reflect the building up of a functional neuronal representation of the stimulus properties, was significantly smaller in the distractible than in the non-distractible children. These findings demonstrate that event-related potential measures may be useful in helping to understand the information processing found in distractible children.

Tamoxifen stimulates in vivo growth of drug-resistant estrogen receptor-negative breast cancer.

An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human breast cancer cell line was grown in culture with and without a noninhibitory concentration (0.5 microM) of tamoxifen for 122 days. Tamoxifen-treated and control cells were inoculated into opposite flanks of nine nude mice, where they produced measurable tumors in every case. Six of the animals were treated with tamoxifen at 500 micrograms/day for 22 days. Although no inhibitory nor stimulatory effect of tamoxifen was seen in vitro, tamoxifen had a clear tumor-growth-stimulating effect in mice. The most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamoxifen therapy, the cells grown in the presence of tamoxifen produced tumors with a mean size of 380 mm2, whereas the cells not pretreated with tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen exposure induces cellular changes that result in tumors that are stimulated to grow faster in mice following tamoxifen treatment.

Topical toremifene: a new approach for cutaneous melanoma?

The distribution of topically applied toremifene (0.5-1 mg/day for 5 days) in the ultraviolet B (UVB)-induced Monodelphis domestica opossum melanoma model was examined. The mean concentration of toremifene measured in the skin was 1200 nmol/g, or > 500 times that detected in any other tissues (blood, brain, liver, testicles, heart, uterus, eyes). In plasma, toremifene could be detected in only one animal of six (0.04 nmol/ml). Intraperitoneal administration of 0.5 mg toremifene daily for 5 days in three female animals resulted in a mean uterus concentration of 22.9 nmol/g, or 400-fold that achieved by topical administration of 0.5 mg/day in three other female Monodelphis (0.05 nmol/g). The cytostatic effect of toremifene was studied in three human melanoma cell lines and three experimental cell lines derived from UVB-induced melanocytic nevi in M. domestica. Toremifene had a cytostatic effect on all cell lines (50% growth-inhibitory concentrations, 5.8-9.6 microM). Topical toremifene administration yields high local concentration with minimal systemic distribution. In addition, toremifene has a cytostatic effect at achievable concentrations in a variety of melanomatous cell lines.

Calibration of a scintillation dosemeter for beta rays using an extrapolation ionization chamber.

A scintillation dosemeter is calibrated for 90Sr/90Y beta rays from an ophthalmic applicator, using an extrapolation ionization chamber as a reference instrument. The calibration factor for the scintillation dosemeter agrees with that given by the manufacturer of the dosemeter within ca. 2%. The estimated overall uncertainty of the present calibration is ca. 6% (2 sd). A calibrated beta-ray ophthalmic applicator can be used as a reference source for further calibrations performed in the laboratory or in the hospital.

Calculation of beta-ray dose distributions from ophthalmic applicators and comparison with measurements in a model eye.

Dose distributions throughout the eye, from three types of beta-ray ophthalmic applicators, were calculated using the EGS4, ACCEPT 3.0, and other Monte Carlo codes. The applicators were those for which doses were measured in a recent international intercomparison [Med. Phys. 28, 1373 (2001)], planar applicators of 106Ru-106Rh and 90Sr-90Y and a concave 106Ru-106Rh applicator. The main purpose was to compare the results of the various codes with average experimental values. For the planar applicators, calculated and measured doses on the source axis agreed within the experimental errors (<10%) to a depth of 7 mm for 106Ru-106Rh and 5 mm for 90Sr-90Y. At greater distances the measured values are larger than those calculated. For the concave 106Ru-106Rh applicator, there was poor agreement among available calculations and only those calculated by ACCEPT 3.0 agreed with measured values. In the past, attempts have been made to derive such dose distributions simply, by integrating the appropriate point-source dose function over the source. Here, we investigated the accuracy of this procedure for encapsulated sources, by comparing such results with values calculated by Monte Carlo. An attempt was made to allow for the effects of the silver source window but no corrections were made for scattering from the source backing. In these circumstances, at 6 mm depth, the difference in the results of the two calculations was 14%-18% for a planar 106Ru-l06Rh applicator and up to 30% for the concave applicator. It becomes worse at greater depths. These errors are probably caused mainly by differences between the spectrum of beta particles transmitted by the silver window and those transmitted by a thickness of water having the same attenuation properties.

Dosimetry of beta-ray ophthalmic applicators: comparison of different measurement methods.

An international intercomparison of the dosimetry of three beta particle emitting ophthalmic applicators was performed, which involved measurements with radiochromic film, thermoluminescence dosimeters (TLDs), alanine pellets, plastic scintillators, extrapolation ionization chambers, a small fixed-volume ionization chambers, a diode detector and a diamond detector. The sources studied were planar applicators of 90Sr-90Y and 106Ru-106Rh, and a concave applicator of 106Ru-106Rh. Comparisons were made of absolute dosimetry determined at 1 mm from the source surface in water or water-equivalent plastic, and relative dosimetry along and perpendicular to the source axes. The results of the intercomparison indicate that the various methods yield consistent absolute dosimetry results at the level of 10%-14% (one standard deviation) depending on the source. For relative dosimetry along the source axis at depths of 5 mm or less, the agreement was 3%-9% (one standard deviation) depending on the source and the depth. Crucial to the proper interpretation of the measurement results is an accurate knowledge of the detector geometry, i.e., sensitive volume and amount of insensitive covering material. From the results of these measurements, functions which describe the relative dose rate along and perpendicular to the source axes are suggested.

Dose characteristics of in-house-built collimators for stereotactic radiotherapy with a linear accelerator.

Dose characteristics of a stereotactic radiotherapy unit based on a standard Varian Clinac 4/100 4 MV linear accelerator, in-house-built Lipowitz collimators and the SMART stereotactic radiotherapy treatment planning software have been determined. Beam collimation is constituted from the standard collimators of the linear accelerator and a tertiary collimation consisting of a replaceable divergent Lipowitz collimator. Four collimators with isocentre diameters of 15, 25, 35 and 45 mm, respectively, were constructed. Beam characteristics were measured in air, acrylic or water with ionization chamber, photon diode, electron diode, diamond detector and film. Monte Carlo simulation was also applied. The radiation leakage under the collimators was less than 1% at 50 mm depth in water. Specific beam characteristics for each collimator were imported to SMART and dose planning with five non-coplanar converging 140 degrees arcs separated by 36 degrees angles was performed for treatment of a RANDO phantom. Dose verification was made with TLD and radiochromic film. The in-house-built collimators were found to be suitable for stereotactic radiotherapy and patient treatments with this system are in progress.

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

PIP: Gynecologists accepted 288 women aged 30-49 from six different clinics in Finland into a clinical trial of a new biphasic oral contraceptive (OC) containing natural estradiol and cyproterone acetate (manufactured by Leiras Oy, Turku, Finland). They aimed to determine the contraceptive efficacy, safety, cycle control, and acceptability of this OC. 24% of the women smoked cigarettes. Gastrointestinal upset in one woman led to failure to take the fourth and fifth tablets at the beginning of the second treatment cycle. She became pregnant (pregnancy rate = 0.35%). 9.3% and 13.3% of women missed pills at the 3-month and 12-month follow-up visits, respectively. 95% of the women had serum progesterone values lower than 9 nmol/l, indicating ovulation suppression. OC use reduced excessive menstrual bleeding (30% before study vs. 3% after 13 cycles; p 0.0005). It also reduced dysmenorrhea (14% vs. 2%; p 0.0005). No one had any serious side effects. The minor side effects (breast tension, edema, headache, and depression) subsided with time. The 12-month continuation rate was 63%. The main reason for discontinuation was side effects (25.9%). Total serum cholesterol and HDL-cholesterol levels did not change significantly, while serum triglyceride levels increased from 0.92 to 1.14 mmol/l (p = 0.02). Even though serum potassium and creatinine levels changed significantly, the 13-month levels fell within the normal range. These findings show that this new OC is an effective contraceptive for premenopausal women. The absence of adverse effects on the blood coagulation system and lipoprotein metabolism make this new OC safe for smokers.

Transdermal oestrogen replacement therapy in a Finnish population.

In an open, multicentre study, transdermal administration of oestradiol (E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and 83.5% sweating before therapy, only 5.7% and 11.8%, respectively, reported these symptoms at the end of the trial. Furthermore, 97.6%, 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patients completing the treatment, of whom 78% were willing to continue the treatment after the trial. These results show that transdermal administration of E2 is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermal treatment to be superior to their previous oral replacement therapy.

Subepithelial space in otitis media.

The role of the subepithelial space (SES) has not received sufficient attention in assessing pathogenesis, pathology, and therefore, clinical diagnosis and treatment of the various forms of otitis media (OM). Temporal bones from patients with OM were classified as cases of acute purulent (POM), serous (SOM), mucoid or secretory (MOM), or chronic otitis media (COM). Controlled morphometric studies were made of cellular components of the SES, along with studies of the epithelium and middle ear space. Corollary studies of biochemistry, cellular components, and prostaglandins (PGs) were done on fluid from the human middle ear. Middle ear effusions (MEE) from animal models of SOM, MOM, and POM were analyzed biochemically. Findings are surprising in that the SES was more actively involved in all forms of OM than had been thought, especially in MOM and COM. Implications are discussed.

Intracavitary irradiation of endometrial cancer of large uteri using a two-phase afterloading technique.

A specific intracavitary two-phase technique was developed for irradiation of endometrial cancer located in uteri with a large uterine cavity. In this technique an insertion catheter (external diameter 9 mm) was used for the introduction and precise location of the treatment catheter (external diameter 6.4 mm). During the first phase of the therapy, one lateral half of the uterine body was irradiated. Thereafter the positions of the catheters were changed by 180 degrees, followed by irradiation of the other lateral half of the uterine body. Using a wax phantom and extirpated uteri as models, we observed that the dose distributions followed the uterine shape and the calculated doses in the radiographs. Clinical observations from 34 patients treated so far, and followed-up for periods of 3 months to 6 years, prove that this method yields similar results to those observed in previous studies employing the Heyman packing method or afterloading techniques with a one-source tandem in the intracavitary irradiation of endometrial cancer.