One-time umbilical cord milking after cord cutting has same effectiveness as multiple-time umbilical cord milking in infants born at <29 weeks of gestation: a retrospective study.

OBJECTIVE: To compare two strategies to potentiate the effects of placental transfusion in infants born at <29 weeks of gestation. STUDY DESIGN: Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth. RESULT: There was no significant difference in the probability of not needing a transfusion during the hospital stay (P=0.75) and the mean number of RBC transfusions given within the first 21 days of life (1.1±1.8 for the one-time umbilical cord-milking group vs 0.7±1.2 for the multiple-time umbilical cord-milking group, P=0.48). CONCLUSION: One-time umbilical cord milking after umbilical cord cutting had similar beneficial effects to multiple-time umbilical cord milking before umbilical cord cutting in very premature infants.

Initial experience using Sivelestat to manage preterm labor with a bulging fetal membrane in pregnant women.

Intrauterine infection and inflammation are recognized as major contributors to the onset of preterm labor. We describe two cases of severe preterm labor with bulging membrane that were treated by intravenous injection of Sivelestat, a neutrophil elastase inhibitor. Ritodrine hydrochloride and magnesium sulfate were intravenously administered for tocolysis, and ampicillin was provided as an antibiotic. Urinary trypsin inhibitor (UTI) was administered transvaginally. Sivelestat was infused intravenously at 4.8 mg kg(-1) day(-1) through the maternal vein. No side effects were observed. Levels of interleukin (IL)-6 and IL-8 in amniotic fluid decreased, and gestations were prolonged without complications for >1 week. Two healthy infants were delivered. Our experience suggests that multidrug therapy with Sivelestat offers a new therapeutic strategy for preterm labor, but further investigations of the indications, administration period and dosage are required.

Blood pressure and urine output during the first 120 h of life in infants born at less than 29 weeks' gestation related to umbilical cord milking.

OBJECTIVE: To investigate the effects of umbilical cord milking on cardiopulmonary adaptation in very low birth weight infants. PATIENTS AND METHODS: This study was the secondary analysis of a randomised control study of the effect of umbilical cord milking in premature infants. Forty singleton infants born between 24 and 28 weeks' gestation were randomly assigned to groups in which the umbilical cord was clamped either immediately after birth (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Blood pressure, heart rate, urine output, fluid intake, and ventilatory index values in both groups were measured during the first 120 h after birth. RESULTS: There were no significant differences in gestational age or birth weight between the two groups. The initial haemoglobin value was higher in the milked group (mean (SD) 16.5 (1.4) g/dl in the milked vs 14.1 (1.6) g/dl in the control; p<0.01). During the first 12 h, blood pressure was significantly higher in the milked group. Urine output in the milked group was higher than that in the control group during the first 72 h. There were no significant differences in heart rate, water intake, or ventilatory index values between the groups. CONCLUSION: Umbilical cord milking may facilitate early stabilisation of both blood pressure and urine output in very low birth weight infants.

Hemodynamic changes in two patients with retinal circulatory disturbances shown by fluorescein angiography using a scanning laser ophthalmoscope.

PURPOSE: To assess hemodynamic changes in two patients with severely affected retinal circulation. METHODS: A 62-year-old man with central retinal artery occlusion and a 46-year-old woman with branch retinal vein occlusion were studied by fluorescein angiography with a scanning laser ophthalmoscope (SLO). Fluorescein angiography with SLO revealed hypofluorescent clumps of different sizes and hyperfluorescent dots in large retinal vessels. The velocities of the hypofluorescent clumps were calculated between two points on the same vessel, and movements of the hypofluorescent clumps and the hyperfluorescent dots were investigated. RESULTS: The velocities of the hypofluorescent clumps were slow and varied in the same vessel. The velocities of the hypofluorescent clumps increased at the sites with narrow calibers. The hypofluorescent clumps occasionally changed size in the bloodstream. The hypofluorescent clumps flowed along the walls of retinal vessels. Distance between consecutive hypofluorescent clumps was wide. Some vessels filled with hypofluorescent clumps were also detected. Rolling hyperfluorescent dots were seen in fluorescent plasma. CONCLUSIONS: The hypofluorescent clumps were concluded to be packed erythrocytes and the hyperfluorescent dots corresponded to leukocytes and platelets moving in the vessels. Fluorescein angiography with SLO is a useful method for evaluating hemodynamic changes using the hypofluorescent clumps in severely affected retinal circulation.

[Patient compliance and the quality of life are well maintained in weekly paclitaxel and carboplatin therapy for advanced gynecologic cancers in Japanese women].

OBJECTIVES: To assess patient compliance and efficacy of a combination chemotherapy consisting of weekly administration of paclitaxel and carboplatin for gynecologic malignancy in Japanese women. METHODS: Fourteen ovarian and three uterine cancer patients received 80 mg/m2 of paclitaxel (paclitaxel) and AUC 1.5 to 2.0 of carboplatin weekly. The toxicity was evaluated and patients' QOL was tested. RESULTS: Neutropenia higher than grade 3 were observed in 29.4%. Four patients received G-CSF support. Grade 1 neurotoxicity was seen in 76.5% of patients. Evaluation of QOL by EORTC-QLQC30 showed significantly better tolerance of a weekly than monthly regimen. Three out of four patients with lung metastasis showed complete disappearance of the lesions. One patient with stage IIIb cervical cancer underwent postchemotherapy-hysterectomy and a complete pathological response was confirmed. The overall response rate was 64.7% including patients previously treated with platinum based multidrug regimens. CONCLUSIONS: A weekly paclitaxel and carboplatin regimen was well tolerated by Japanese women. The regimen was active in over 60% of cases and it also appeared active in multidrug resistant cases.

A case of rapidly growing ovarian squamous cell carcinoma successfully controlled by weekly paclitaxel-carboplatin administration.

BACKGROUND: Primary squamous cell carcinoma of the ovary is uncommon and has a poor prognosis. Because of its rarity, the effective postoperative treatment is unknown. We describe a remarkable response of this tumor to weekly paclitaxel-carboplatin administration. CASE: A 53-year-old woman had rapidly growing primary squamous cell carcinoma of the ovary that metastasized to the abdominal wall and transverse colon after maximum cytoreductive surgery. The tumor was resistant to primary chemotherapy with cisplatin, vincristine, mitomycin C, and bleomycin. A combination of paclitaxel and carboplatin was used for second-line chemotherapy and was repeated every week. The patient tolerated the chemotherapy well and demonstrated a pathological complete response in the abdominal metastases following the five courses of chemotherapy. CONCLUSION: Weekly paclitaxel-carboplatin administration may be a safe and effective treatment for advanced and rapidly growing ovarian squamous cell carcinoma with primary resistance to chemotherapy.

Comparison between histopathologic findings and indocyanine green angiographic findings in Lewis rats with experimental autoimmune uveoretinitis.

PURPOSE: Recently, indocyanine green angiography (IA) was used to examine chorioretinal circulation in posterior uveitis in humans, and abnormal IA findings were reported. However, choroidal pathologic examination in conjunction with these abnormal IA findings has rarely been done. Experimental autoimmune uveoretinitis (EAU) is a model for posterior uveitis in humans. The purpose of this study was to correlate abnormal IA findings in Lewis rats with EAU with pathologic findings. METHODS: Eleven male Lewis rats were immunized with bovine S-antigen in complete Freund's adjuvant with Bordetella pertussis. After immunization, IA was performed by using a scanning laser ophthalmoscope. Eyes with abnormal IA findings were enucleated and examined histopathologically. RESULTS: Demonstrated leakage from retinal vessels at the initial stage of disease; a decrease of background fluorescence and of the number of moderate and large vessels of the choroid, and leakage from choroidal vessels at the progressive stage; and hypofluorescent areas at the late stage. Histopathologic examination at the initial, progressive, and late stages revealed inflammation of the inner layers of the retina, a large number of inflammatory cells in the thickened retina and choroid, and impaired choroidal capillaries, respectively. CONCLUSION: Since a correlation between pathologic findings and IA findings was demonstrated in Lewis rats with EAU, IA may be useful for evaluating the severity of uveitis in humans.

Indocyanine green angiographic findings in 3 patients with traumatic hypotony maculopathy.

PURPOSE: Little is known about the choroidal circulation in human eyes with ocular hypotony. Recently, indocyanine green angiography (IA) became a useful method for examining choroidal circulation. The present study using IA was designed to determine choroidal circulatory disturbances in patients with traumatic hypotony maculopathy. METHODS: Indocyanine green angiography was performed on 3 consecutive patients (3 eyes) with traumatic hypotony. One patient underwent IA using an infrared fundus camera only during the hypotony stage. The other 2 patients underwent IA using a scanning laser ophthalmoscope before and after recovery of intraocular pressure (IOP). RESULTS: During the hypotony stage, IA revealed multiple hypofluorescent spots in many parts of the fundus, sector hypofluorescent areas, dilatation, and tortuosity of the choroidal vessels in the posterior pole. These findings had not been detected by fluorescein angiography. After surgical treatment, IOP returned to the normal range and visual acuity improved. Indocyanine green angiography showed improvement of the sector hypofluorescent areas, and dilatation and tortuosity of choroidal vessels in the posterior pole. However, most of the hypofluorescent spots and regional delay of choroidal filling remained. CONCLUSIONS: Indocyanine green angiography revealed that choroidal circulatory disturbances occurred during the hypotony stage and that some remained during the recovery stage.

Changes in purine metabolism and production of oxygen free radicals by intermittent partial umbilical cord occlusion in chronically instrumented fetal lambs.

OBJECTIVE: Undetected umbilical-cord compression has been suggested to be implicated in unexplained fetal brain damage. We tested the hypothesis that the generation of oxygen-free radicals (OFRs) during intermittent partial umbilical cord occlusion might play a causal role in antenatal CNS injury. METHODS: Using 7 established chronically instrumented fetal lambs, intermittent partial occlusion of the umbilical circulation was produced according to the method of Clapp et al. for 1 of every 3 minutes for 2 hours. A microdialysis probe was implanted in the fetal brain white matter. Normal saline was infused, and the perfusate obtained at 2 micrograms/ min. Hypoxanthine (HX), xanthine (XA), and inosine-5-monophosphate (IMP) concentrations in the perfusate and blood samples obtained from fetal jugular veins were assayed by HPLC. Concurrently, the perfusate, which contained superoxide produced in the brain, when mixed with cypridina luciferin analogue extracorporally, caused chemiluminescence that in 4 cases was measured by a highly sensitive electronic fluorescence detector. RESULTS: (1) HX, XA, and IMP concentrations in the blood and perfusate were higher than in the control during the intermittent partial occlusion of the umbilical circulation period and returned to control levels during the recovery period. (2) The residual chemiluminescence of perfusate revealed that the intermittent partial occlusion of the umbilical circulation level was about 100% higher than the control level, and during the recovery period the level returned to the control level. (3) The chemiluminescence during the intermittent partial occlusion of the umbilical circulation period was inhibited by infusion through the fetal jugular vein of 1 micron polyethylene glycol conjugated superoxide dismutase. CONCLUSION: During the intermittent partial occlusion of the umbilical circulation period the fetal brain tissue releases a large amount of OFRs, and a portion of these might be synthesized by the increased conversion of HX to XA. This phenomenon might play an important role in the etiology of fetal brain injury.

Ameloblastoma of the mandible metastasizing to the orbit with malignant transformation. A histopathological and immunohistochemical study.

We report here a case of ameloblastoma of the mandible with multiple local recurrences and metastasis to the orbit. The patient was a 63-year-old Japanese woman with visual disturbance of her right eye. Diagnostic imaging revealed a mass occupying the right orbital apex with partial intracranial involvement. She had been surgically treated for mandibular ameloblastoma 27 years previously, and the tumour had recurred three times in the past 5 years. The orbital tumour and recurrent ameloblastomas were investigated histopathologically and immunohistochemically. The tumour changed in morphology as it recurred, from follicular ameloblastoma without atypia to apparent malignant tumours disclosing undifferentiated or squamoid features. On immunohistochemical analysis, staining for cytokeratin was positive in the squamoid cells but not in the undifferentiated cells. Both histopathologically and immunohistochemically, the orbital tumour was almost identical to the undifferentiated recurrent tumour. The orbital tumour was distinct from the primary site or sites of recurrence of ameloblastoma, and we concluded that the mandibular ameloblastoma underwent malignant transformation with multiple recurrences and finally metastasized to the orbit.

Effect of magnesium sulfate treatment on neonatal bone abnormalities.

OBJECTIVE: It has been reported that neonatal bone abnormalities occur as a result of long-term intravenous magnesium administration (MgSO4) to pregnant women. The purpose of this retrospective study was to evaluate the frequency of such abnormalities and the clinical background of both mothers and neonates. PATIENTS AND METHODS: We reviewed maternal (114 cases) and neonatal (139 cases) charts from all pregnant women who received intravenous MgSO4 administration for preterm labor and preeclampsia between June 1, 1992, and May 31, 1994. All chest X-ray films were obtained within 48 h after birth and reviewed by a doctor who was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the proximal humerus were considered as abnormal. The subjects were divided into affected (group 1 and 1a) and unaffected (group 2 and 2a) groups. Neonates born to pregnant women given no MgSO4 at the same period, were considered as control. RESULTS: The total number of bone abnormalities in the offspring of mothers receiving MgSO4 amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2 of 101 cases. In the control group bone abnormalities were not observed (p < 0.05). Significant differences were found between groups 1 and 2 in the gestational ages at the start of MgSO4 administration and at delivery, and in the total duration of administration and doses of MgSO4. Also, cases of multiple pregnancy and pregnancy complicated with impaired glucose tolerance were more prevalent in group 1. According to the results obtained from 139 neonates, cases showing low Apgar and high magnesium score and those receiving respiratory support were more noticeable in group 1a (15 cases). CONCLUSIONS: The gestational ages and the total doses of MgSO4 in pregnant women were the main factors related to the onset of neonatal bone abnormalities, but other factors also have a possible bearing on the condition. In addition, the cases with onset of bone abnormality seemed to be associated with symptoms attributable to hypermagnesemia of neonates.

Nitric oxide and endothelin 1 during postnatal life.

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

[Evaluation of 5-FU, leucovorin, etoposide, and cisplatin (FLEP) chemotherapy by hepatic artery injection in the treatment of multiple liver metastases from gastric cancer].

We performed FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide, and cisplatin) by hepatic artery injections for three patients with multiple liver metastases from gastric cancer, and two of three resulted in partial response (PR). We presented two PR cases. Case 1 is a 57-year-old male with multiple liver metastases from gastric cancer. Distal partial gastrectomy with regional lymphadenectomies were carried out, and an injection port was implanted in the hepatic artery. We performed FLEP chemotherapy from 16 days after the operation. Liver metastases subsided and resulted in PR after 3 months by CT scan. He is now healthy and working for 15 months after the operation. Case 2 was a 49-year-old female with multiple liver metastases from gastric cancer. Total gastrectomy with regional lymphadenectomies was carried out. We performed FLEP chemotherapy by hepatic artery injections from 21 days after the operation. The response of chemotherapy resulted in PR by CT scan, and she is now healthy and has been working for 11 months after the operation. Thus, this form of chemotherapy may be useful for patients with multiple liver metastases from gastric cancer.

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs.

OBJECTIVE: Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. STUDY DESIGN: Eleven trials of arginine vasopressin infusion (40 to 160 mIU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 micrograms). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. RESULTS: Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. CONCLUSION: These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns.

Variable fetal heart rate decelerations and electrocortical activities.

OBJECTIVE: The purpose of this study was to examine the influence of fetal behavioral states on baroreflex-mediated, variable fetal heart rate decelerations caused by umbilical cord occlusion. STUDY DESIGN: Five chronically instrumented fetal lambs were subjected to intermittent partial umbilical cord occlusion for 1 minute every 3 minutes, lasting 2 hours. Fetal behavioral states determined by electrocorticogram and heart rates by electrocardiogram were monitored continuously during these experiments. RESULTS: The fetuses exhibited an alteration between low- and high-voltage electrocorticogram states. Both the depth and width of the variable fetal heart rate decelerations were greater during high-voltage than during low-voltage electrocorticogram. CONCLUSION: Amplitude and duration of variable fetal heart rate decelerations are affected by fetal behavioral states.

[A study on the detection of Helicobacter pylori in children with gastric and duodenal diseases].

Infection of Hellcobacter pylori (H. pylori) in the gastric mucosa is said to participate in the pathogenesis of gastric and duodenal ulcers as well as gastritis. The detection rate of H. pylori in tissue specimens endoscopically taken from adult patients with these diseases was 75.2% (408/542). In affected children (2-15 yrs), on the other hand, 27 biopsies were performed in 22 cases but the initial positive rats was as low as 45.5%. According to the diagnosis, it was 75% for acute gastric mucosal lesion (AGML), 50% for duodenal ulcer, 33% for duodenitis, and 38% in seemingly normal children. When changes in the detection rate of H. pylori was examined after administration of H2 blocking antiulcer agents, it was found to very case by case, e.g. changed in individual disease stages or completely or reoccurrence disappeared.

[A study on the integration of fetal behavior and the development of association between parameters evaluated].

To evaluate the development of the fetal behavioral state with reference to the association of the fetal parameters we selected, we simultaneously monitored fetal heart rate (FHR), fetal movement (FM), fetal eye movement (FEM) and fetal breathing movement (FBM). These various parameters were monitored with 2 ultrasonographic real time scanners and a doppler device to monitor fetal movement. We assessed the convergence and integration of these four parameters to evaluate the association rate (AR). FHR with a variation in excess of 3 min. was interpreted as the active phase (A), and reduced variation in excess of 3 min. as the inactive phase (I). When FM and FEM were observed in the 1 min. window of A, we labeled this A3, and when FBM was present in more than 10% of the 1 min. window, we labeled it A4. A3/A = AR-A3% and A4/A = AR-A4% was calculated. A similar calculation was done for I, without FM and FEM in the 1 min. window of I (I3) and when FBM was present less than 10% of 1 min. (I4), allow derivation AR-I3% and AR-I4%. A discrete separation of synchrony in A and asynchrony in I can be seen to develop as the fetus matures, and we feel that this may be a valuable tool in the evaluation of fetal central nervous system development in utero.

Intermittent sinusoidal heart rate pattern in vagotomized fetal lambs.

OBJECTIVES: Our aims were to investigate the relationship between the dose of arginine vasopressin and the pattern and duration of arginine vasopressin-induced sinusoidal fetal heart rate and to elucidate the correlation between intermittent sinusoidal heart rate and fetal sleep cycle. STUDY DESIGN: Sinusoidal heart rate pattern was induced by intravenous arginine vasopressin infusion at doses from 2 to 78 mlU/min into 11 chronically instrumented fetal lambs with bilateral cervical vagotomy. Appearance and frequency of sinusoidal heart rate, intermittent sinusoidal heart rate, and persistent sinusoidal heart rate were observed along with fetal tracheal pressure and electrooculogram. RESULTS: Intermittent sinusoidal heart rate response to low, medium, and high doses of arginine vasopressin appeared in 73.3%, 50.0%, and 33.3% of experiments, respectively. Intermittent sinusoidal heart rate appeared more frequently than persistent sinusoidal heart rate with lower doses (p < 0.02). When intermittent sinusoidal heart rate was induced, the incidence of sinusoidal patterns significantly increased during non-rapid-eye-movement sleep in comparison with rapid-eye-movement sleep (p < 0.01). CONCLUSIONS: Appearance of sinusoidal heart rate seems to be related to the dose of arginine vasopressin infused. Appearance of sinusoidal heart rate is also influenced by fetal sleep cycle; sinusoidal heart rate is more likely to appear during non-rapid-eye-movement sleep than during rapid-eye-movement sleep. These results support the hypothesis that persistent sinusoidal heart rate correlates with severity of stress.

[Current alteration of Helicobacter pylori in gastro-duodenal diseases].

The current alteration of the detection rate of Helicobacter pylori (H. pylori) on mucous membranes of the stomach has been surveyed and reviewed for 49 cases of gastro-duodenal diseases. The survey has been conducted for 3 years and an endoscopic examinations have been performed 2-8 times. On the first visit, the diagnosis can be made endoscopically, and H2 blockers and another agents were used as therapeutic drugs. The detection rate was 67.3% (33 cases) for positive cases and positive reaction cases, while the rate was 32.6% (16 cases) in negative cases and negative reaction cases. Among them, the most commonly observed disease was atrophic gastritis, followed by duodenal ulcer, and acute gastric mucous lesions (AGML). Peptic ulcer was not seen. After administration of H2 blockers and anti-ulcer agents, the H. pylori-detection rate was found to fluctuate according to the diseases and alterations in the morbidity period. Some cases indicated the disappearance of H. pylori in accordance with the improvement of the lesion site.