Systemic fusariosis after a preparative regimen including thiotepa, VP-16 and busulfan used for blood stem cell transplantation in Hodgkin's disease.

Fusarium infection is rare but important infection after bone marrow transplantation (BMT). A 27-year-old man developed systemic fusarial infection following severe skin damage probably caused by high-dose thiotepa administration. Systemic fusariosis rapidly progressed to a variety of organs despite antifungal treatment, and he finally died of this infection on day 75. Considering that this organism usually invades via damaged skin and that the penile lesion was the first manifestation of systemic fusariosis in this patient, careful examination of the skin might be helpful for early diagnosis of fusarial infection. His clinical course provided us with an important clue for diagnosis of fusarial infection.

Sickness absence due to mental disorders in Japanese workforce.

This study was conducted to elucidate sickness absence due to mental disorders in Japanese companies. Data on sickness absence taken for seven consecutive days or more at eight companies (total number of employees: 44,816) was used for the analysis. Diagnosis of mental disorders was based on medical certificates prepared by physicians. The frequency of absence due to all diseases and mental disorders was 3.0% and 0.3%, respectively. The proportion of frequency absence due to mental disorders compared to that for all diseases was 9.4%. Figures for absence prevalence were almost the same as those for frequency absence. The average length of absence due to mental disorders and non-mental disorders was 119.5 days and 47.3 days, respectively. Rate of absence days due to mental disorders compared to that for all diseases was 21.0%. Percent of sickness absenteeism was 0.4%. In one company, the proportion of frequency absence and rate of absence days due to mental disorders compared to those for all diseases had an increasing tendency over the last six years.

[Pituitary apoplexy with hypercreatinekinasemia].

A 59 year-old female with hypercereatinekinasemia associated with pituitary apoplexy was presented. The patient showed headache, nausea, vomiting and pyrexia. On admission, slight nuchal rigidity and photophobia were observed. However all the cranial nerves were intact; neither ophthalmoplegia nor visual defect were observed. Cerebrospinal fluid analysis revealed an elevated protein concentration of 164 mg/dl. There were 157 cells/mm2 (30% neutrophils). Skull X-P disclosed the ballooning of the sella turcica. CT scan, endocrinological examination and angiography lead us to the diagnosis of pituitary apoplexy. By the sphenoidal approach necrotic tissue with a little chromophobe adenoma were removed. No haematoma was detected. The isozyme pattern of serum CK showed 100 percent MM type. Serum CK concentration reached as high as 2502 IU/l on the fifth day from the onset of the symptom and then normalized in 12 days. Though the cause of the hypercreatinekinasemia uncertain, the similar pattern of hypercreatinekinasemia is known in the acute stage of cerebrovascular accident, and it is more often observed in thalamic hemorrhage. We assumed that the hypercreatinekinasemia in our case was caused by hypothalamic irritation, which lead hyperpermeability of sarcolemma and leakage of the enzymes of muscle origin.

Concentration of levofloxacin in cervical mucus and its clinical effects on cervicitis.

An investigation was made on the concentration of levofloxacin (LVFX) in cervical mucus and its clinical effects on cervicitis. The results were as follows: 1) The concentrations of orally administered LVFX in the cervical mucus of 110 subjects were determined by HPLC. During 1-4 hour after the administration the mean concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g, which was higher than the serum level. The transfer of LVFX to the cervical mucus was almost the same as that to other genital organs. 2) When LVFX was given to 102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was evaluated with clinical improvement, the clinical efficacy rate of LVFX was 72/102 (70.6%). Significant bacteriological effects were observed in 70/73 (95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%). 3) The administration LVFX did not cause any subjective or objective side effects and any abnormalities were not detected in the laboratory test done in this study. These results demonstrate that LVFX can be sufficiently transferred to the cervical mucus for the treatment of cervicitis due to the infection of C. trachomatis etc.

[A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor (G-CSF)].

A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor (G-CSF) is reported. The patient was a 75-year-old female with the chief complaint of appetite loss. Abdominal ultrasonography and abdominal computed tomography revealed left renal pelvic tumor. Left radical nephrouretrectomy was performed. The histopathological report showed Bellini duct carcinoma. Immunohistochemical staining using the anti-G-CSF antibody showed positive staining in the cancer cells. Preoperatively, the white blood cell count and serum G-CSF concentration were elevated to 34,100/microliter and 334 pg/ml respectively. After operation these values became normal. However, these values were elevated again and CT scan revealed a left pulmonary metastasis 3 months after the operation. In spite of chemotherapy, she died of brain metastases 7 months after the operation.

[Management of medical practice at home].

We present here how medical practice is managed at the patients home. Medical care at home is conducted in conjunction with a variety of professionals who provide health care in the community. The use of computers allows us to easily download information, and transfer it from the clinic to community services. Fluid replacement, total parenteral nutrition, palliative treatment of pain in cancer patients, management of urethral catheters, and other skills that are carried out at home would be stated.

Mechanism of the onset of puberty, with special reference to the dynamics of the hypothalamic gonadotropin releasing factor and pituitary gonadotropin.

PIP: In vivo and in vitro studies of the dynamics of hypothalamic FSH-RF, LH-RF, PIF, and anterior pituitary FSH, LH, and prolactin during the process of sexual maturation were carried out in female Wistar-starin rats. Around the time of vaginal opening there was a wide fluctuation of hormonal values. The peak of FSH content in the anterior pituitary was on Day 25 after birth, LH peaked on Day 40, and prolactin on Day 45. Addition of crude HE (hypothalamic extract) of 20-45 day old female rats to the incubation fluid of anterior pituitary glands resulted in a rise of FSH and LH activity in the culture fluid. The greatest increase of FSH activity was seen on the addition of HE of 20-day-old rats. LH increased most on hte addition of HE in 35-day-old rats and prolactin decreased on the addition of HE in 45-day-old rats. The relationship between anterior pituitary FSH, LH, and prolactin contents and hypothalamic RF and IF is suggested.^ieng

[A simplified method for measuring the binding capacity of sex hormone-binding globulin in human serum and its clinical application (author's transl)].

A simple and reliable method for determining the binding capacity of the sex hormone-binding globulin (SHBG-BC) in human serum is described. The principle of this method is to saturate the SHBG binding sites with dihydrotestosterone (DHT) and measure the amount of SHBG-bound steroid. Endogenous steroids are initially removed from the serum samples by adsorption on dextran-coated charcoal. The samples are subsequently equilibrated with a mixture of known amount of tritium-labeled and unlabeled DHT. The unbound steroid is removed by dextran-coated charcoal incubated at 4 degrees C, and the mass of bound DHT is determined from the known specific activity of the added steroid. The intraassay and interassay coefficient of variation of this assay method is less than 6.2% and 7.5%, respectively. Forty serum samples can be assayed in duplicate in a working day. The mean values of SHBG-BC, expressed as microgram DHT bound per 100ml serum, were 1.56 +/- 0.33 (SD) in 6 adult men aged 20 approximately 40 and 2.05 +/- 0.75 in 37 adult women aged 20 approximately 36. Higher levels (1.75 +/- 0.40) were found in 10 older men aged 65 approximately 80. In contrast, SHBG-BC (1.80 +/- 0.30) in postmenopausal women (ages 52 approximately to 62) was lower than that in the reproductive age group of women. No significant variations in SHBG-BC were observed during the normal menstrual cycle. The levels of SHBG-BC rose progressively in pregnancy to 9 approximately 10 times those in the normal non-pregnant women. In 4 women with polycystic ovarian disease and 2 hirsute women, SHBG-BC levels were lower (means: 1.63 and 0.75, respectively), while patients with 1st and 2nd grade amenorrhea showed levels similar to those in the reproductive women.

[Effects of several estrogenic compounds on serum corticosteroid-binding globulin (CBG) and the estrogen thresholds for increasing CBG (author's transl)].

The effects of several estrogen substances--alone, or in combination with norgestrel--on serum CBG in humans are reported in this paper. CBG was measured by a modified charcoal adsorption technique. Daily oral doses of Premarin, from 0.3 to 2.5mg, were given to healthy postmenopausal women for 14 days. Dose-dependent increases in CBG-BC were observed. Ovral, which contains ethinylestradiol and norgestrel, also induced significant increases in the levels of CBG-BC. Similar results were seen with Lo Ovral, but it had less influence than Ovral. When given alone, daily for 21 days, norgestrel had no effect on CBG-BC. The maximum rise of serum CBG-BC was found after 10 days of the daily doses of Ovral, and then the levels remained quite constant during the period of treatment. Exogenous estrogens of other types also caused increases in CBG-BC. The response of CBG to exogenous estrogens is of use in comparing the estrogen potencies of the compounds. CBG-BC levels remained constant throughout the menstrual cycle in five normal women despite fluctuating levels of estradiol which reached peaks of 190 approximately 430 pg/ml. In pregnant women and in HMG-treated women, however, serum levels of CBG-BC increased beginning when estradiol levels were greater than 1 ng/ml.

Involvement of prolactin in the control of follicular maturation.

This study was designed to explore the role of prolactin (PRL) in the modulation of follicular growth and steroidogenesis. An ovarian perifusion technique was used to determine the effect of PRL on steroid production by ovarian tissue. Immature female rats were injected with 5 IU pregnant mare's serum gonadotropin to induce follicular maturation. After 40 h rats were killed, ovaries removed, and follicles dissected out. Follicles were divided into two groups (small, less than or equal to 4 mm; large, greater than or equal to 5 mm in diameter), cut into fine fragments, and perifused for 6 in the presence or absence of ovine PRL (100 or 1,000 ng/ml). In the group of small follicles, either of the PRL doses reduced the ability of follicular tissues to convert androgen to estrogen. HCG-induced production of progesterone by small follicles was also suppressed by higher doses of PRL. On the other hand, in the group of large follicles, PRL showed no effects on the aromatization and progesterone release by the follicular fragments. These results suggest that the small immature follicle is more sensitive to the inhibitory action of PRL on steroidogenesis and folliculogenesis. Thus it is possible that PRL may have a modulatory role in follicular growth and maturation and, consequently, in the selection of ovulatory follicle.

Lack of inhibitory effect of exogenous prolactin on ovarian responsiveness to gonadotropins in the rat.

Attempts were made to elucidate the possible antigonadotropic action of PRL at the ovarian level. Immature female rats of Wistar strain were injected subcutaneously with PMS (5-10 i.u.) at 0900 h on day 23 of age, followed an intraperitoneal injection of HCG (5-10 i.u.) at 1400 h on day 25. In all animals treated with PMS-HCG, ova were found in the oviducts when examined at 0900 h on day 26 of age. Rat PRL was administered either at various doses (1.0-20 micrograms/day) in the morning (0800 h) between day 23-25 or at 5 micrograms/day for 10 days prior to HCG injection. The ability of exogenous gonadotropins to induce ovulation and weight gain of the ovary were not affected by this PRL treatment. In animals injected with PMS, significant rises in serum estradiol-17 beta levels were observed 48 h later. This PMS-induced increase in the estrogen concentration was also not affected by the treatment with various doses of PRL. From these results, it seems likely that exogenously administered PRL may be unable to suppress the ovarian responsiveness to gonadotropins by direct action on the ovary.

Further evidence that prolactin controls the prepubertal sexual development in the female rat.

To assess the role of prolactin (PRL) in the puberty onset and the ovarian aromatase activity, hyper- and hypoprolactinemic conditions were induced by treating chronically prepubertal female rats with PRL and bromocriptine, respectively. Injection of rat PRL (5 micrograms, twice daily) from day 20 onward advanced the day of vaginal opening. By contrast, the suppression of PRL release by bromocriptine, which was provided in the drinking water at a concentration of 40 micrograms/ml, caused a significant delay in the age of occurrence of vaginal opening. This bromocriptine-induced delayed puberty was prevented by the concomitant administration of exogenous PRL, suggesting that the effect of bromocriptine is exerted through its suppressive effect on the endogenous PRL release. The in vitro release of estradiol by the ovaries from 30-day-old rats treated with PRL was found to be higher than that from the control animals, when the ovaries were perifused for 6 h with an excess of androstenedione. On the other hand, the ovaries perifused in the presence of androgen produced less estradiol in the bromocriptine-treated rats than in their controls. It appears, therefore, that PRL is more likely related to the aromatase activity in the maturing ovary. These results suggest that PRL may be one of the factors that regulate the timing of puberty onset by influencing the aromatase activity in the ovary.

[Evaluation of hypothalamic-pituitary function in amenorrheic women by utilizing the combined clomiphene-GnRH test (author's transl)].

Hypothalamic-pituitary function in 62 women with amenorrhea syndrome was evaluated by comparing the response of gonadotropin to GnRH stimulation before and after clomiphene treatment. Each woman was initially tested with an intramuscular injection of 100 microgram GnRH, and then ingested 150 mg of clomiphene daily for 5 consecutive days followed by GnRH test. Fourteen out of 29 patients with 1st grade amenorrhea showed increased baseline LH, FSH and estradiol, and slightly decreased net responses of LH to GnRH after clomiphene administration, indicating that positive and negative estrogen feedback for gonadotropin release is functioning. In contrast, 8 patients with 2nd grade amenorrhea (17 cases) showed an increase in LH net responses after Clomid treatment. In 5 patients, however, clomiphene induced the increase in baseline LH and FSH values and the decrease in the LH release in response to GnRH as seen in the 1st grade amenorrheic patients. These 5 patients ovulated on that clomiphene dosage. One patient with PCO also had a barely significant decrease in LH responses to GnRH following clomiphene administration, with slightly increased baseline gonadotropins. With one exception, all the 5 patients with primary amenorrhea showed no or poor LH responses to GnRH. Following clomiphene administration, no change in either baseline gonadotropine levels or pituitary responsiveness to GnRH was observed in 4 patients, suggesting that a hypothalamic-pituitary defect appeared most likely to be present. The two patients with streak gonad had significantly high responses to GnRH injection and further increase in the responses following clomiphene administration, accompanied by a slightly decreased baseline gonadotropin levels. On the other hand, in hyperprolactinemic amenorrhea syndrome individual response to GnRH before and after clomiphene use was quite variable. It is likely that this group includes the patients with various pathologic states of the hypothalamic-pituitary system. Thus, syndrome and in diagnosing the degree and the site of the defect.

Maturation of negative and positive estrogen feedback in the prepubertal female rat.

The development of estrogen feedback system on gonadotropin release during sexual maturation in female rats was studied. Animals (Wistar strain rats) were divided into 6 groups according to their ages; 10, 15, 20, 25, 30, and 35 days. Both LH and FSH levels in serum increased significantly in response to ovariectomy in all age-groups studied when measured one week postoperatively, though in the rats aged 10-15 days the increase in FSH following castration was only slight. In rats older than 25 days, the postcastration gonadotropin rise, calculated as a percent increase from the basal figure, decreased gradually with increasing age. Ovariectomized rats injected with estradiol benzoate (EB, 5 micrograms/100 g BW) showed significantly lower levels of both LH and FSH than those in castrated controls. However, the inhibitory action of EB on postcastration gonadotropin output was found to be relatively less effective in rats older than 25 days. Ovariectomized rats primed with EB were again injected with a 2nd dose of EB (5 micrograms/100 g BW) at noon 3 days after priming. The 2nd EB injection induced a significant rise in LH 6 h later in 30- and 35-day-old, though not in younger, animals. On the other hand, the FSH response to EB was markedly enhanced during days 15-25 of age. These results indicate that the estrogen negative feedback action on gonadotropin release is already operating in female rats at a very early age, and that the brain sensitivity to estrogen decreases slightly during the late prepubertal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

[A double adsorption technique for the determination of corticosteroid-binding globulin in human serum (author's transl)].

Despite the widespread use of many different estrogenic compounds in hormonal contraception and estrogen replacement, in the human a simple test for comparing the potencies of the compounds is lacking. Many of the estrogenic compounds are difficult to measure, and animal studies may not relate directly to those done on humans in terms of potency. Corticosteroid-binding globulin (CBG) in human serum has been known since 1958 to increase in response to estrogen administration, and the degree of its elevation has been shown to be closely dose-related and reasonably sensitive. Therefore, CBG represents a biological parameter that provides for the specific quantal analysis of estrogenicity in the human. In this paper a simple and reliable method for the determination of the cortisol-binding capacity of CBG (CBG-BC) in human serum is described. The procedure is based on the amount of cortisol required to saturate the CBG binding sites. All endogenous steroids are initially removed from the serum by adsorption on dextran-coated charcoal (DCC). A mixture of a known amount of unlabeled and labeled cortisol is added to the sample in order to saturate the "stripped" binding sites of CBG. The unbound cortisol is removed by DCC at 4 degrees C, and the supernatant represents the total cortisol-binding capacity of the serum sample. To distinguish between cortisol-binding to CBG and to albumin, "stripped" serum is heated for 30 min at 60 degrees C, the temperature which does not influence cortisol binding by albumin but which does inactivate CBG. The samples are subsequently equilibrated with a mixture of labeled and unlabeled cortisol. The free cortisol is removed by DCC and the bound cortisol remaining in the supernatant is designated as the albumin-bound cortisol. Thus, CBG-BC is assayed by a double adsorption technique as differential binding to native and heat-inactivated serum. The cortisol determined by this method corresponds to CBG-bound cortisol, and CBG-BC is expressed as micrograms of cortisol bound per 100 ml serum. The precision and accuracy of the method were found to be good. The values of CBG-BC obtained by this method were 14.9 +/- 1.9 (SD) microgram/100ml in adult men and 16.0 +/- 1.8 microgram/100ml in adult women. Daily serum samples in five women revealed no significant variations in CBG-BC throughout the normal menstrual cycle despite fluctuating levels of serum estradiol. CBG-BC was also found not to vary significantly with age. In pregnancy, however CBG-BC increased significantly.

Turner's syndrome--review of the literature with reference to a successful pregnancy outcome.

A 30-year-old Japanese female with Turner's syndrome had become pregnant and delivered a normal male infant by cesarean section. Her menarche was at age 14, and secondary sex characteristics developed normally. She had some features of Turner's syndrome, and cytogenetic studies from peripheral blood lymphocytes and several tissues revealed only 45,XO karyotype without evidence of mosaicism. To our knowledge, she is only the thirteenth case of monosomy X to achieve pregnancy. A review of the literature indicates a high incidence of fetal wastage and increased chromosomal errors in the offspring of women with a 45,XO cell line with or without mosaicism.

An acute increase in serum prolactin does not modify gonadotropin release in female rats.

Attempts were made to find out whether hyperprolactinemia has an effect on the hypothalamo-pituitary response to estrogen feedback and LHRH stimulation. Adult female rats of Wistar strain were ovariectomized and received subcutaneous injection of 20 micrograms estradiol benzoate (EB) 3-4 weeks later (day-0). A second injection of 20 micrograms EB, when administered at noon on day-3, induced a highly significant increase in serum LH (p less than 0.001 vs. basal values), but not FSH, estimated at 1800 h on the same day. This EB-promoted LH release was not altered by pretreatment with rat PRL (5 micrograms/day), which was administered subcutaneously daily in the morning (1100 h) between day-1 and day-3. No statistical difference in the serum LH concentration was found when compared with the values for the control animals pretreated with 0.9% saline alone. Serum gonadotropins 15 min after LHRH administration (100 ng/100 g BW) in 32-day-old female rats were not statistically different between the animals pretreated with 5 micrograms PRL, which was given subcutaneously daily (at 0800 h) for 3 days, and the controls pretreated with 0.9% saline. These results suggest that an acute increase in serum PRL may not exert a negative effect on the gonadotropin release induced by estrogen feedback and LHRH stimulation.

Biomechanical analysis of effects of foot placement with varying chair height on the motion of standing up.

Individual experience reveals that posterior foot placement enables one to stand up easily from a chair. However, the way in which foot placement affects this motion has not been investigated in detail. This study was performed to examine the effects of foot placement in the initial stage of the dynamics of standing up from a chair. Subjects wearing light-emitting diode markers and surface electrodes stood up from a chair over force plates, and ground reaction force, joint angle, and muscle activity were measured. The motions required to stand up from chairs 30, 40, or 50 cm in height were analyzed with anterior, vertical, and posterior foot placement. With anterior foot placement, the forward-acceleration components of the ground reaction force were recorded with simultaneous and long-sustained activity of the muscles in order to shift the center of gravity of the body forward even more after lift-off. Our findings indicate that the distance between the center of gravity and the point of application of ground reaction force at lift-off are critical factors in the standing-up motion, and that chairs should be of adequate height as well as having sufficient space under the seat to permit the backward movement of the lower legs.

Cholinergic and serotonergic neural links and the inhibitory effects of hippocampus, lateral amygdala and central gray matter on gonadotropin release.

Effects of electrical stimulation of the hippocampus (HPC), lateral amygdala (1-AMYG) and midbrain central gray matter (CG) on the release of ovulatory gonadotropin were examined using proestrous Wistar rats with or without pretreatment with reserpine, atropine or p-chlorophenylalanine (PCPA) at such dosage that had been confirmed not to block ovulation. Electrical stimulation of the HPC, 1-AMYG or CG under light ether anesthesia just before the critical period prevented a rise in serum LH, FSH and prolactin levels at 18:00. Pretreatment with atropine (200 mg/kg body wt, sc) was effective to abolish this inhibitory effect of the HPC stimulation on the release of LH and FSH, whereas reserpine treatment (1mg/kg body wt, ip) did not affect the effect. The inhibitory effect of the 1-AMYG or CG stimulation on LH and FSH release was abolished by treatment with PCPA (150 mg/kg body wt, ip), while neither atropine nor reserpine had any effect. The inhibitory effect of the HPC stimulation on the release of these hormones was also blocked by PCPA treatment. In regard to the prolactin release, it was inhibited by the stimulation of the HPC, 1-AMYG or CG in both the non-treated rat and in the atropine or PCPA-treated one, while in the reserpine-treated rat it was not inhibited but rather was facilitated by these stimulations. It was assumed that the normal maintenance of both cholinergic and serotonergic neural links for the expression of the HPC inhibition on ovulatory LH, FSH and prolactin secretion and that of serotonergic link for the expression of the 1-AMYG or CG inhibition are needed. The inhibitory action on prolactin release changed into facilitation under the depletion of monoamines, but the mechanism is unknown.