Pathological analysis of umbilical cord ulceration associated with fetal duodenal and jejunal atresia.

Umbilical cord ulceration is a serious complication of fetal intestinal atresia. To elucidate the relationship between fetal intestinal atresia and umbilical cord ulceration grade, we pathologically examined umbilical cords in 15 duodenal and 5 jejunal atresia cases and 28 control cases. Microscopic examination of the umbilical cords of patients with intestinal atresia revealed high-grade ulceration and a significant increase in macrophage numbers (P = 0.0087). Transudation of red blood cells was not associated with any specific clinical diagnosis, but was seen in all high-grade ulceration cases. It is suggested that clinical symptoms become apparent following gradual pathological changes.

Urinary 2,5-dichlorophenol as biological index for p-dichlorobenzene exposure in the general population.

The relationship between exposure to p-dichlorobenzene (p-DCB) and urinary excretion of 2,5-dichlorophenol (2,5-DCP), the major metabolite of p-DCB, was examined to evaluate the usefulness of the metabolite as a biological index for low-level exposure of p-DCB in the general population. Personal exposure concentrations of p-DCB and concentrations of 2,5-DCP excreted in the urine of 119 adults living in Osaka were determined. Airborne p-DCB was collected for 24 h by passive gas sampling tubes packed with charcoal. The tubes were exchanged every 12 h. The sampling was started immediately after the subject woke up in the morning (7 A.M.). The collected p-DCB was desorbed with toluene and measured using a gas chromatograph with an electron capture detector (GC-ECD). On the other hand, the first morning urine samples were collected at the endpoint of airborne p-DCB sampling (7 A.M. the next morning). The urine samples were hydrolyzed with concentrated sulfuric acid. 2,5-DCP in the hydrolysates was extracted with n-hexane and measured by GC-ECD. Both p-DCB and 2,5-DCP were detected in more than 99% of the air and urine samples, respectively, from the participants. The median of p-DCB exposure concentrations for 24 h was 2.5 ppb, with a maximum concentration of 33.3 ppb. The median of urinary 2,5-DCP concentrations was 0.39 mg/g creatinine, with the maximum concentration of 3.32 mg/g creatinine. The regression line between the urinary 2,5-DCP concentration (y) and the p-DCB exposure concentration (x) was y = 0.080 x + 0.181, with the Pearson correlation coefficient of 0.81 (p < 0.001), demonstrating a strong association between these measurements. Consequently, urinary 2,5-DCP should be suitable as an index for monitoring low-level exposure of p-DCB in the general population.

Simulation of air-bag impact on post-radial keratotomy eye using finite element analysis.

PURPOSE: To determine the physical and mechanical conditions of an impacting air bag that causes corneal rupture in a post-radial keratotomy (RK) eye using a simulation model of the human eye. SETTING: Numerical simulation study on a computer. METHODS: The simulations were performed by a computer using the finite element analysis program PAM-CRASH (Nihon ESI). The air bag was set to impact the surface of a post-RK eye with 4, 6, or 8 corneal incisions at various velocities. Strain on the corneal tissue including scarred incisions exceeding 9.0% was assumed to indicate the possibility of corneal rupture. RESULTS: At a medium velocity of 30 m/s, corneal rupture was likely to occur. At an air-bag impact velocity of 40 m/s, 3 of 4, 5 of 6, and 8 of 8 incisions were likely to rupture in the case of 4-, 6-, and 8-incision procedures, respectively, leading to likely globe rupture in all situations. Lacerations extended beyond the incisions and involved the intact cornea at a velocity of 40 m/s. If the corneal tissue strength reduction was increased to 90%, most incisions were likely to rupture at impact velocities greater than 35 m/s in all incision procedures. CONCLUSIONS: The results could partly reflect a reported case of globe rupture after RK and suggest that severe ocular trauma can be caused in the post-RK eye by air bags at ordinary impact velocities.

Effect of adrenal and ovarian androgens on type 4 follicles unresponsive to FSH in immature mice.

The present study investigates the physiological significance of dehydroepiandrosterone, dehydroepiandrosterone sulfate, T, androstenedione (Delta(4)), dihydrotestosterone (DHT), estrone (E1), and E2 on recombinant human FSH- (rhFSH) resistant type 4 follicles obtained from immature mice. Type 4 follicles of a diameter of 100-120 microm with one or two granulosa cell layers around the oocyte and an intact basal lamina with theca cells were isolated from the ovaries of 11-d-old BDF-1 mice and cultured with medium alone (control) or with dehydroepiandrosterone, dehydroepiandrosterone sulfate, T, Delta(4), DHT, E1, or E2 at concentrations ranging from 1 x 10(-11) to 1 x 10(-7) M for 4 d. We examined the mean diameters of type 4 follicles, levels of immunoreactive (IR)-inhibin, and E2 and progesterone in the culture media on day 4. In addition, we evaluated follicular cell proliferation by immunofluorescence staining with 5-bromo-2'-deoxyuridine. All tested androgens significantly increased the diameter of type 4 follicles in a dose-dependent manner without the production of IR-inhibin and E2. The nuclei of granulosa cells in type 4 follicles cultured with all tested androgens exhibited intense 5-bromo-2'-deoxyuridine-positive staining, compared with those of controls. In contrast, neither E1 nor E2 had any stimulatory effects. The stimulatory effects of T, Delta(4), or DHT were inhibited by an AR antagonist in a dose-related fashion but not by an aromatase inhibitor. Furthermore, all tested androgens had a synergistic effect with rhFSH on follicular growth and the production of IR-inhibin and E2. These results demonstrated that neither adrenal nor ovarian androgens are arteriogenic but that they stimulate type 4 follicles unresponsive to rhFSH and augment the responsiveness of these follicles to rhFSH.

The posterior inferior cerebellar artery arising from the extracranial segment of the internal carotid artery via the hypoglossal canal without an interposed segment of the basilar artery: a persistent primitive hypoglossal artery variant.

The authors present a rare case of a persistent primitive hypoglossal artery (PHA) variant ending in the posterior inferior cerebellar artery (PICA) without an interposed segment of the basilar artery and describe briefly the possible embryogenesis of this anomaly.

Inhibitory action of leptin on early follicular growth differs in immature and adult female mice.

In order to investigate the action of leptin on early follicular growth, preantral follicles, 95-115 microm in diameter were mechanically isolated from the ovaries of BDF1 hybrid immature (11-day-old) and adult (8-wk-old) mice, and cultured for 4 days in vitro. Follicular growth was assessed by daily changes in follicular diameter and by the amount of estradiol and immunoreactive (IR)-inhibin released into the culture medium at Day 4. Preantral follicles from immature mice showed a significant development in follicular growth as a result of stimulation by GH (1 mIU/ml), insulin-like growth factor (IGF)-I (100 ng/ml) + FSH (100 mIU/ml), and GH (1 mIU/ml) + FSH (100 mIU/ml). Although leptin at concentrations of 1-1000 ng/ml did not have any significant effect on follicular growth stimulated by IGF-I or GH, it significantly inhibited follicular growth in a dose-related manner when follicles were stimulated by IGF-I + FSH and GH + FSH, respectively, suggesting that leptin attenuated the additive effect of FSH. On the other hand, preantral follicles from adult mice were cultured in the presence of FSH, and FSH-dependent follicular growth was inhibited by leptin in a dose-related manner. Because FSH stimulates cAMP production, we investigated the involvement of cAMP in the inhibitory mechanisms of leptin. Preantral follicles from immature and adult mice were cultured in the presence of either 8-Br-cAMP or forskolin. Both 8-Br-cAMP and forskolin significantly increased follicular diameter and hormone secretion in both immature and adult mice. However, 8-Br-cAMP and forskolin-stimulated follicle growth and hormone secretion were significantly inhibited in immature mice by coadministration of leptin, whereas growth of preantral follicles from adult mice was not inhibited by addition of leptin to cultures. These results indicate that leptin causes an inhibitory effect on the early follicular development of both immature and adult mice, but the inhibitory mechanisms of leptin are different.

A case of tracheobronchopathia osteochondroplastica diagnosed by fiberoptic bronchoscopy upon removal of an aspirated crown.

Tracheobronchopathia osteochondroplastica (TO) is a relatively rare benign disease, around 300 and 130 cases have been reported in English and Japanese literature, respectively. Most of the cases have been diagnosed incidentally at autopsy. Due to the widespread use of fiberoptic bronchoscopy (FOB), the number of cases diagnosed upon examination is increasing. Here, we report a case of a 72 year-old man with a history of crown aspiration, who was diagnosed as TO upon removal of a foreign body using FOB. The diagnosis of TO and the removal of an aspirated crown by FOB are discussed.

[Actual conditions of occupational health administration of small-scale enterprises in Japan: (II). Occupational health controls for hazardous and musculo-skeletally stressful working factors].

In order to clarify the actual condition of occupational health management for hazardous and musculo-skeletally stressful work factors in small-scale enterprises (SSEs) in Japan, a questionnaire survey was conducted in an area near Osaka city. The hazardous work factors examined were dust, organic solvents, lead, specified chemical substances, anoxia, noise, hand-arm vibration, ionizing radiation, high and low temperatures, and high air pressure. The musculo-skeletally stressful work factors examined were VDT work, prolonged standing, unnatural postures, handling of heavy weights, and stress on neck, shoulders and arms. The number of SSEs that replied to the questionnaire was 765 (recovery rate: 69.3%). Enterprises with noise, dust, hand-arm vibration and organic solvents numbered 14.0%, 10.7%, 6.9% and 6.4%, respectively, and those with other hazardous factors numbered less than 3%. Special medical examinations and working environment measurements for hazardous factors were conducted in 0.0% to 26.7% and 0.0% to 13.3%, respectively, of the enterprises. Working environment controls were conducted in 0.0% to 40.2%. Enterprises with prolonged standing and VDT work, were 42.0% and 35.8%, whereas those with other stressful factors were approximately 30%. Special medical examinations for musculo-skeletally stressful factors were conducted in 3.0% to 5.1% of the enterprises, and work controls were conducted in 20.4% to 25.3%. Non execution of the special medical examinations and working environment measurements were mainly due to "lack of knowledge of the law (19.7% and 30.2%)" and "lack of time to perform (16.0% and 23.3%)". Non execution of the controls for the hazardous work factors was due to "lack of knowledge as to how to control (9.0%)", "high costs (7.4%)", "lack of time to perform (6.4%)" and "absence of a suitable adviser (5.9%)". Non execution of the controls for stressful work factors was due to "lack of knowledge as to how to control (15.6%)" and "lack of time to perform (10.2%)". Consequently, as a result of the survey, it was suggested that it is necessary to enlighten the employers of SEEs as to the importance of occupational health controls. It is also necessary to propose low-cost, feasible control methods.

Effects of recombinant human FSH (rhFSH), urinary purified FSH (uFSH), and hMG on small preantral follicles and tertiary follicles from normal adult and androgen-sterilized female mice.

OBJECTIVE: To examine the stage-specific follicular response to recombinant human FSH (rhFSH), urinary FSH (uFSH), and hMG preparations. SETTING: In vitro follicle culture. INTERVENTION(S): Small preantral and tertiary follicles isolated from adult normal BDF-1 mice and androgen-sterilized mice were cultured with rhFSH, uFSH, and hMG for 4 days. MAIN OUTCOME MEASURE(S): Follicular diameter. Immunoreactive inhibin, E2, and progesterone concentrations in cultured medium. RESULT(S): The minimal effective dose of rhFSH, uFSH, and hMG for the follicular growth of small preantral follicles from normal mice was 10 mIU/mL, 1 mIU/mL, and 0.1 mIU/mL, respectively. For tertiary follicles from normal mice, the minimal effective dose of rhFSH, uFSH, and hMG was 10 mIU/mL, 10 mIU/mL, and 1 mIU/mL, respectively. The minimal effective dose of hMG for the follicular growth of small preantral follicles from androgen-sterilized mice was 0.01 mIU/mL, and that of rhFSH and uFSH on tertiary follicles from androgen-sterilized mice was 1 mIU/mL and 10 mIU/mL, respectively. No significant increase was found in the follicular diameter of the tertiary follicles from androgen-sterilized mice as a result of stimulation by hMG, but an hMG dose of >10 mIU/mL produced a significant increase in progesterone secretion. CONCLUSION(S): Human menopausal gonadotropin preparation acts detrimentally on follicles from androgen-sterilized mice by increasing the sensitivity of small preantral follicles to FSH and by inducing the luteinization of tertiary follicles.

Morphological assessment of the effect of growth hormone on preantral follicles from 11-day-old mice in an in vitro culture system.

The present study was carried out to verify that the cells attached to the outside of the basement membrane of mechanically isolated follicles are theca cells and to evaluate the effect of growth hormone (GH) on these cells. Preantral follicles, 100-140 micrometer in diameter, were mechanically isolated from 11-day-old BDF1 hybrid immature mice, divided randomly into two groups, and cultured in vitro. One group was treated with 0.1% collagenase immediately after mechanical isolation in an attempt to remove theca cells attached to the outside of the basement membrane. The other group was untreated. Morphological examination revealed that 86.1% of mechanically isolated follicles before collagenase treatment had at least one theca cell around the basement membrane on the single section. However, after collagenase treatment no theca cells remained on the basement membrane of the follicles. Androstenedione secretion as a result of stimulation by 100 ng/ml hCG was significantly higher in the culture medium of the follicles with theca cells than in those of collagenase-pretreated follicles (p < 0.0001), indicating that the cells attached to the outside of the basement membrane were actually functional theca cells, not interstitial cells. To elucidate the effect of GH on theca cells, preantral follicles cultured in the presence of 1.0 mIU/ml GH were morphologically examined. Preantral follicles mechanically isolated from immature mice showed significant proliferation of not only granulosa cells but also theca cells in the presence of GH. In particular, theca cells, which remained dotted on the basement membrane in a small number just after isolation, proliferated and finally formed complete layers after the culture with GH. This is the first report that GH induced the proliferation of theca cells to form morphologically complete layers around the preantral follicle from 11-day-old mice.

Genomic structure and promoter analysis of the ecto-phosphodiesterase I gene (PDNP3) expressed in glial cells.

PDNP (phosphodiesterase I/nucleotide pyrophosphatase) is one of a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. PDNP possesses ATPase (EC 3.6.1.3) and ATP pyrophosphatase (EC 3.6.1.8) activities. Mammalian PDNP consists of three closely related family proteins (PDNP1, -2, and -3), and they are expressed in different cell types and at different developmental stages. Rat PDNP3 is expressed in a subset of immature glial cells and in the alimentary tract. Human PDNP3 is expressed in glioma cells, prostate, and uterus, but not in the alimentary tract. We have cloned genomic DNA containing the whole coding region of the human PDNP3 gene and determined its exon-intron structure. The human PDNP3 gene spans over 60 kb and is organized into 25 exons and 24 introns. We determined the nucleotide sequence of the 5'-flanking region of human and rat PDNP3 genes. The upstream region of both species lacks a canonical TATA box and contains a putative binding site for CCAAT enhancer-binding proteins near the transcription start site. Promoter activity analysis of the 5'-flanking region revealed that the sequence around the CCAAT box is required for its transcriptional activity in 9L rat glioma cells. A gel shift assay demonstrated that 9L nuclear extract contains proteins that bind to this region.

Evaluation of small internal mammary lymph node metastases in breast cancer by MRI.

PURPOSE: In breast cancer, diagnosis of a small internal mammary lymph node (IMLN) metastasis of less than 10 mm in size has been difficult. Our purpose was to retrospectively evaluate MRI findings of small IMLN metastases in comparison with dissected IMLNs. METHODS: We studied 43 dissected IMLNs (range 2-12 mm, mean 4.512+/-2.763 mm) in 16 women with breast cancer (15 primary, and 1 recurrent). MRI examinations were performed using a 1.5 Tesla scanner (200FX; Toshiba, Tokyo, Japan) to obtain noncontrast T1-weighted SE images (TR/TE; 500/15 or 400/15ms), with a slice thickness of 5 mm on coronal images, 10 mm or 7 mm on sagittal images, FOV 15x15 cm, matrix 256x256, using a surface coil with patients in the supine position. MR images were evaluated regarding the major diameter and shape and margin of each node. RESULTS: Regarding the presence of IMLN metastases, there was a significant difference between nodes with a major diameter of 5 mm or more and those of less than 5 mm (p<0.05). Using the size-based criterion (defining< or =5 mm as positive), MRI had 90.7% accuracy, 93.3% sensitivity, and 89.3% specificity. There were no significant differences in the shape-or margin-based criterion. CONCLUSIONS: MRI was useful in diagnosing small IMLN metastases, using a size-based criterion.

A comparative study on transforming growth factor-beta and activin A for preantral follicles from adult, immature, and diethylstilbestrol-primed immature mice.

Both transformation growth factor-beta (TGFbeta) and activin belong to the TGFbeta superfamily, and each receptor is structurally related. We have shown that the action of activin A on folliculogenesis is different in immature and adult mice, so it is of interest to study whether TGFbeta has such an action on follicular development. The effect of TGFbeta on folliculogenesis was studied in isolated preantral follicles from immature, adult, and diethylstilbestrol (DES)-primed immature mice and was compared with that of activin A. TGFbeta caused a significant increase in follicular diameter and estradiol and immunoreactive inhibin secretion in adult mice in a dose-related manner, but did not affect the size of preantral follicles from immature mice. Activin A, on the other hand, caused a significant increase in the size of follicles from immature mice, but did not change the size of preantral follicles from adult mice. TGFbeta enhanced the effect of FSH, whereas activin A completely blocked the action of FSH on preantral follicles from adult mice. Such a specific action of TGFbeta and activin A was age dependent because preantral follicles obtained from 28-day-old mice, compared with those from 11- and 56-day-old mice, showed an intermediate reaction to TGFbeta and activin A. DES pretreatment of 11- and 28-day-old mice caused an enhanced response to FSH, but this response was completely inhibited by TGFbeta. These results indicate that both TGFbeta and activin A have proliferative action and cytodifferentiative action on granulosa cells, but the action of each is age dependent and opposite in direction. In conclusion, although both TGFbeta and activin A belong to the same family, and each receptor is structurally related, both share a specific role in early folliculogenesis before and after puberty.

Estimation of absorption of trihalomethanes and carbon tetrachloride in low-level exposure by inhalation pharmacokinetic analysis in rats.

Inhalation pharmacokinetics of the environmental contaminants chloroform, bromodichloromethane, chlorodibromomethane, and carbon tetrachloride were evaluated, and their absorption amounts were estimated in rats to obtain fundamental data for risk assessment of chronic low-level exposures. Measured amounts of the substances were injected into a closed chamber system in which a rat had been placed, and the concentration changes in the chamber were examined. The pharmacokinetics of the substances were evaluated on the basis of the concentration-time courses using linear or nonlinear compartment models. The metabolic elimination amounts at various exposure concentrations were extrapolated using the estimated pharmacokinetic parameters. With exposure to chloroform, the fraction of the elimination amount at 1 ppb exposure (low concentration) against the exposure concentration was estimated to be 1.1 times higher than the fraction at 10 ppm exposure (high concentration). With exposure to low concentrations (1 ppb), extrapolation showed that more chloroform (0.33 nmol/h/kg) was absorbed by the rats than chlorodibromomethane (0.11 nmol/h/kg), bromodichloromethane (0.072 nmol/h/kg), and carbon tetrachloride (0.053 nmol/h/kg). Our findings revealed differences in the absorption amounts among the substances for the same exposure concentrations.

Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage.

The purpose of the present study was to investigate 1) whether activin A can cause primary follicles to become dormant at the resting stage, and 2) the role of the secondary follicle on follicular growth of primary follicles. Preantral follicles (100-120 microm in diameter) harvested from adult mice and cultured in in vitro follicle culture system showed a significant increase in size and estrogen and inhibin secretion in response to FSH, but the administration of activin A blocked the effect of FSH. Withdrawal of activin A not only restored the follicular response to FSH but also enhanced the effect of FSH, indicating that the action of activin A is to cause small preantral follicles to become dormant at the preantral stage. To investigate the role of secondary follicles in early folliculogenesis, small preantral follicles were cocultured with secondary follicle (300-350 microm in diameter) in the presence of FSH. The secondary follicle showed a significant increase in follicular diameter as a result of stimulation by FSH, but the small preantral follicles did not increase in size. After removal of the secondary follicle, however, the small preantral follicles commenced follicular growth, indicating that the growth of small preantral follicles is suppressed by the secondary follicle. Administration of the activin binding protein follistatin caused a significant increase in follicular diameter of both small preantral and secondary follicles as a result of stimulation by FSH. These results have suggested that secondary follicles cause primary follicles to become dormant at the resting stage by secreting activin.

[Actual conditions of occupational health activities in small-scale enterprises in Japan: system for occupational health, health management and demands by small-scale enterprises].

In order to clarify the real conditions of occupational health services (OHS) in small-scale enterprises (SSEs) in Japan, we analyzed questionnaires recovered from 765 SSEs in the area of a city neighboring Osaka City (recovery rate, 69.3%). The SSEs included 358 SSEs with 1 to 4 workers (46.8% of total SSEs), 203 with 5 to 9 (26.5%), 163 with 10 to 29 (21.3%) and 41 with 30 to 49 (5.4%). The main types of businesses were manufacturing (374, 48.9% of total SSEs), wholesale/retail trade/restaurants (153, 20.0%), community, social and personal services (132, 17.3%) and construction (72, 9.4%). Health examinations were performed in 47.7% of SSEs. The reason for the lack of examinations were "shortage of time" (33.3% of SSEs lacking health examination) and "employees do not want to be examined" (28.1%). Some health promotion measures were conducted in 29.2% of SSEs. Health examination (59.0% of SSEs), health promotion (36.5%), measure of mental health (25.9%) and information service for employers and employees (25.5%) were demanded by SSEs as OHS. Financial subsidies and economical incentives were demanded by 46.4% and 28.8% of SSEs, respectively. Regional occupational health center in this area was poorly known among SSEs (8.2%), but health examination (48.4%), information service (37.5%), assessment of work method and advice to improve (19.8%) and environment measurement (12.4%) are demanded of the center by SSEs.

A case of ganglioneuroma with fatty replacement: CT and MRI findings.

We report a rare case of posterior mediastinal ganglioneuroma with fatty replacement together with its appearance on CT and MRI and suggest adding this entity to the differential diagnosis of fat-containing posterior mediastinal masses.

[Load on the low back of teachers in kindergartens].

In order to evaluate the load on the low back of teachers in kindergartens, basic activity and working posture were analyzed for four teachers by means of video recording. The trunk inclination angle (TIA) was also measured continuously during full workshifts for 12 kindergarten teachers by means of an inclination monitor. The kindergarten teachers spent 67% of the workshift on activities in contact with children, "indoor group childcare", "indoor free playing", "outdoor childcare", "preparation and clearing away" and "help and care", and did not take a recess during the workshift. They spent 36% of the workshift in three working postures with the load on the low back, "standing bent forward", "squatting" and "kneeling". Cumulative time at a TIA of 20 degrees or more represented 43% of the workshift. The frequency of trunk-lifting from severe bending forward (TIA > 45 degrees) was 95 times/hr on average. A comparison of the kindergarten teachers and nursery teachers in 4-5 year age classes showed that the time distributions of basic activities were generally similar to each other. Although the time distributions of working postures were also similar, time spent "standing bent forward", "squatting" and "kneeling" was longer in the kindergarten teachers than in the nursery teachers. Cumulative time at a TIA of 45 degrees or more was significantly longer in the kindergarten teachers. Although the frequency of trunklifting was not significantly different, the kindergarten teachers tended to lift their trunk more frequently. The present study found that the load on the low back was considerably great in the kindergarten teachers.

A comparative study of fixed-dose, step-down, and low-dose step-up regimens of human menopausal gonadotropin for patients with polycystic ovary syndrome.

OBJECTIVE: To compare the efficacy and safety of the fixed-dose, the step-down, and the low-dose step-up regimens of hMG for women with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized study. SETTING: Gunma University School of Medicine, Maebashi, Japan. PATIENT(S): Thirty-seven women with PCOS. INTERVENTION(S): The fixed-dose, the step-down. and the low-dose step-up regimens were administered. MAIN OUTCOME MEASURE(S): The number of growing follicles and serum hormone levels. RESULT(S): Serum FSH levels on the day of hCG administration were significantly higher in the fixed-dose regimen group than in the step-down and the low-dose step-up regimen groups, and the number of growing follicles (> or =11 mm) in the low-dose step-up regimen group was significantly smaller than in the fixed-dose regimen group. On the 7th day after hCG administration, the maximal diameter of the ovaries in the low-dose step-up regimen group was significantly smaller than in the fixed-dose and the step-down regimen groups, and the risk of excessive ovarian enlargement (> or =70 mm) was significantly lower in the low-dose step-up regimen group than in the fixed-dose regimen group. CONCLUSION: The low-dose step-up regimen of hMG for patients with PCOS may be the safest protocol among the three stimulation regimens for reducing multiple follicular development.