Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy

Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluoro-octanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17-37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography-electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples (range, < 0.5 to 2.3 ng/mL, 4 of 15). Our results revealed a high correlation between PFOS concentrations in maternal and cord blood (r2 = 0.876). However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs. Key words: cord blood, fluorinated organic compounds, human, PFOA, PFOS, PFOSA, pregnancy.     

Properties of utricular and saccular nerve-activated vestibulocerebellar neurons in cats

Properties of otolith inputs to vestibulocerebellar neurons were investigated in 14 adult cats. In the vestibular nuclei, we recorded single-unit activities that responded orthodromically after stimulation of the utricular and/or saccular nerves and antidromically after stimulation of the cerebellum (uvula-nodulus and anterior vermis). Descending axonal projections to the spinal cord were also examined by antidromic stimulation of the caudal end of the C1 segment. Forty-seven otolith-activated neurons that projected to the uvula-nodulus were recorded. Thirteen (28%) of the 47 neurons received convergent inputs from the utriculus and sacculus. The remaining 34 (72%) vestibular neurons were non-convergent neurons: 18 (38%) received utricular input alone, and 16 (34%) received saccular input alone. Most (35/47) vestibulocerebellar neurons were located in the descending vestibular nucleus and only one of these projected to the spinal cord. Seven of the 47 vestibulocerebellar neurons were located in the lateral vestibular nucleus and most of these neurons projected to the spinal cord. The remaining neurons were located in group X (two neurons) and the superior vestibular nucleus (three neurons). In a different series of experiments, 37 otolith-activated vestibular neurons were tested to determine whether they projected to the uvula-nodulus and/or the anterior vermis. Nineteen of the 37 neurons projected to the anterior vermis, 13/37 projected to the uvula-nodulus, and 5/37 projected to both. The utricular and/or saccular nerve-activated vestibulocerebellar neurons projected to not only the uvulanodulus, but also to the anterior vermis. In summary, the results of this study showed that vestibular neurons receiving inputs from the utriculus and/or sacculus projected to the cerebellar cortex. This indirect otolith-cerebellar pathway terminated both in the anterior lobe and in the uvula/nodulus.     

Chronological T‐wave alternation before and after the onset of arrhythmogenic right ventricular cardiomyopathy

Identification of arrhythmogenic right ventricular cardiomyopathy (ARVC) during childhood is challenging due to the lack of specific ECG manifestation. We report chronological ECG alteration before several years of the ARVC onset in two affected children. Their ECG at the age of 6 years was almost normal for their age, and their chronological ECGs exhibited inversion of T wave in inferior leads, which are typical for ARVC, developed at younger age than that in precordial leads. In addition, the leftmost T‐wave inversion in the precordial lead shifted toward the left in our patients, which is a sharp contrast to its physiological transition.     

Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethylnitros-amine followed by partial hepatectomy and unilateral nephrectomy

Sequential observations were carried out on the induction ofpreneoplastic lesions in the liver and the kidney. Rats wereinitially given N-ethyl-N-hydroxyethylnitrosamine (EHEN) intheir drinking water (0.1%) for 3 days (Group 1), 1 week (Group2) or 2 weeks (Group 3) or tap water (Group 4). Rats in Groups1 – 3 were subjected to partial hepatectomy and unilateralnephrectomy (right side) 2 weeks after the end of EHEN treatment.Rats from these groups were killed in week 10, 20, 30 and 40of the experiment. In the liver, the effect of EHEN in the inductionof -glutamyltranspeptidase (-GT) positive foci and hyperplasticnodules (HN) was clearly dependent on the length of treatment.The preneoplastic lesions increased with the lapse of observationtime. Changes measured as number of -GT positive foci were 10–40times greater than those measured as HN, especially among thesmall size range. Values for changes in Group 1 given 0.1% EHENfor 3 days were very low, indicating that this dose is closeto the threshold. Two rats with hepatocellular carcinoma inGroup 3 given EHEN for 2 weeks survived until week 40. In thekidney, tubular epithelial proliferations composed of cellswith slightly basophilic cytoplasm and slightly atypical nucleiwere tentatively named atypical cell foci (ACF). EHEN inducedACF, renal cell adenomas and renal cell carcinomas. The increasein the induction of ACF was dependent on the length of observationperiod but not on the length of treatment. Even though controlrats (not treated with EHEN) also had ACF, their quantitativevalues were far less than the groups given EHEN and killed atweek 40, indicating that a large number of ACF were inducedby EHEN. Therefore, EHEN is good for experimental inductionof preneoplastic lesions in the liver and kidney of rats. Theexperimental schedule for Groups 1 and 2 could be used as ashort-term screening test for promoters and the schedule forGroup 3 as an assay for inhibitors.     

Indication for the use of an interposed graft during portal vein and/or superior mesenteric vein reconstruction in pancreatic resection based on perioperative outcomes

Purpose

Combined portal vein and/or superior mesenteric vein (PV/SMV) resection with pancreatic resection sometimes leads to prolonged survival for patients with pancreatic cancer. In this study, we evaluated perioperative outcomes of patients with PV/SMV reconstruction and considered indications for the use of a graft during this procedure.

Methods

We performed PV/SMV resection with pancreatic resection in 128 patients, including 14 using grafts. Complications associated with PV/SMV reconstruction and harvesting venous grafts and reconstructed PV/SMV patency during follow-up were assessed.

Results

Of the 128 patients, 5 underwent total pancreatectomy, 99 pancreaticoduodenectomy, and 24 distal pancreatectomy. In the 14 patients who underwent PV/SMV reconstruction with grafts, the grafts were harvested from the external iliac vein (EIV) in 10 patients and internal jugular vein (IJV) in the other 4. Five patients (3.9 %) had an intraoperative or postoperative acute thrombus or stenosis of reconstructed PV/SMV after direct end-to-end anastomosis. However, PV/SMV patency was excellent after reconstruction using grafts. There were no significant differences in other complications between groups with and without the use of grafts. Three patients (30 %) with EIV grafts had postoperative leg edema, and one of them required analgesics until his death because of leg pain caused by compartment syndrome, whereas no patients with IJV grafts had complications associated with sacrificing veins.

Conclusions

Depending on the length and/or position of the removed PV/SMV segment, interposed graft may be required for reconstruction in some patients, and the use of graft vein, particularly using IJV, is an appropriate procedure that is not associated with any complications.     

Effects of bathing immediately after birth on early neonatal adaptation and morbidity: A prospective randomized comparative study

OBJECTIVE: Because the risks and benefits of early bathing of newborn infants are not well established, we investigated the effects of bathing immediately after birth on rectal temperature, respiratory rate, heart rate, blood pressure, percutaneous arterial blood oxygen saturation (SpO2) and early neonatal morbidity. METHODS: The study was designed as a randomized prospective comparative study in the neonatal care unit of a university hospital. A total of 187 healthy term and near-term newborn infants, who were delivered vaginally without asphyxia, between January and December 1997 were the study subjects. We compared findings in newborns who were bathed 2-5 min after birth (n = 95) with those of a control group (n = 92) who received dry care instead. Groups were comparable with respect to gestational age, birthweight, male: female ratio, Apgar score and umbilical blood pH. Rectal temperature was measured with an electronic thermometer immediately before the intervention bathing or dry care and at 30 min and 1, 2, 3, 8 and 12 h after birth. Heart rate, respiratory rate, systolic and diastolic blood pressure and SpO2 were measured at 1, 2, 8 and 12 h after birth. The incidence of early neonatal morbidity, including hyperbilirubinemia and gastrointestinal and respiratory problems, was also compared. RESULTS: Rectal temperature changed over time postnatally in both groups (P < 0.0001, ANOVA) and there was a significant difference in rectal temperature between groups (P< 0.0001, ANOVA). Mean (+/- SEM) rectal temperature at 30 min after birth (i.e. approximately within 20 min after intervention) was significantly higher in the bathed group than in the control (dry care) group (37.30 +/- 0.06 is 37.00 +/- 0.05 degrees C, respectively; P = 0.000022). Respiratory rate, heart rate, blood pressure and the ratio of the number of infants with SpO2 90-94% and 95-100% did not differ significantly between the two groups. The incidence of early neonatal morbidity, including vomiting, acute gastric mucosal lesion, polycythemia, need for tube feeding, phototherapy and oxygen therapy, also did not differ between the two groups. CONCLUSIONS: Early bathing, minutes after birth, did not appear to adversely affect the adaptation of healthy full-term and near-term newborn infants.     

Time- and Dose-dependent Induction of Invasive Urinary Bladder Cancers by N-Ethyl-N-(4-hydroxybutyl)nitrosamine in B6C3F1 Mice

A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcino-genesis was performed in male B6C3F₁mice maintained ad libitum on tap water containing 0.025% EHBN for 4, 12, 20, 28 and 36 weeks. A total of 81 invasive tumors, comprising 55 smiamous cell carcinomas (SCCs) (68%), 25 transitional cell carcinomas (TCCs) (31%) and 1 adenocarcinoma (1%) were found. Of these, 23 (22 SCCs and 1 TCC) demonstrated invasion to the prostate, 3 metastasized to the lung, and 2 spread by peritoneal seeding. The anaplastic grade and extent of invasion of the SCCs significantly exceeded those of the TCCs. The results suggested a histogenetic pathway from simple dysplasia through papillary or nodular dysplasia and/or carcinoma in situ to eventual development of invasive carcinomas     

Aortic pressure augmentation as a marker of cardiovascular risk in obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.     

ENDOSCOPIC COAGULATION THERAPY IS USEFUL FOR IMPROVING ENCEPHALOPATHY IN CIRRHOTIC PATIENTS WITH GASTRIC ANTRAL VASCULAR ECTASIA

Background: Gastric antral vascular ectasia (GAVE) is an uncommon but treatable cause of chronic gastrointestinal bleeding often associated with severe cirrhosis. Efficacy of endoscopic treatment is well known; however, long‐term outcome after endoscopic treatment is not clear. Methods: We studied 16 cases of GAVE patients with liver cirrhosis that were endoscopically treated using heater probe unit or argon plasma coagulator. Endoscopic finding of GAVE and clinical finding of hepatic encephalopathy in particular was evaluated after endoscopic therapy. Results: After endoscopic ablation therapy, mucosal vascular lesion of GAVE and rebleeding occurred in four patients during follow up; however, re‐treatment was effective and long‐term hemostasis was achieved. Moreover, a case report herein revealed the effectiveness of endoscopic therapy on hepatic encephalopathy of GAVE patients with cirrhosis. In the follow‐up study of 13 patients of GAVE with cirrhosis that suffered from encephalopathy, the coma level of nine patients was improved after endoscopic therapy. Conclusion: Endoscopic treatment, such as heater probe coagulation and argon plasma coagulation therapy, are effective and useful for long‐term follow up. Also, the beneficial effect of endoscopic therapy on hepatic encephalopathy for GAVE with cirrhosis encourages us to find and treat the mucosal lesion intensively to improve the quality of life of such patients.     

Different effects on inhibition of cardiac hypertrophy in spontaneously hypertensive rats by monotherapy and combination therapy of adrenergic receptor antagonists and/or the angiotensin II type 1 receptor blocker under comparable blood pressure reduction.

To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1 receptor blockers (ARBs) have different abilities to attenuate progressive cardiac hypertrophy despite their comparable lowering of blood pressure, we compared the effect of these agents alone or in combination on hypertensive cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were divided into 7 groups. Single administration of doxazosin, atenolol, or losartan, or half-dose combinations of these drugs were given orally for 6 weeks. The control group did not receive any drugs. The heart weight-to-body weight ratio (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide (BNP) and left ventricular BNP mRNA expression were measured after 6-week administration. Blood pressure did not differ among the drug-treated groups, all of which showed lower blood pressure than the control group. The HW/BW and LVMI of the drug-treated groups, except the doxazosin group, were lower than in the control group. Moreover, the LVMI values of the groups receiving losartan were significantly lower than those in the groups without losartan (p < 0.05). Plasma BNP of the drug-treated groups was lower than that in the control group (p < 0.05). The left ventricular BNP mRNA expression of the drug-treated groups, except the doxazosin group, was lower than that in the control group. The atenolol group showed a higher level of BNP mRNA than the groups receiving losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB had the strongest attenuating effect on the development of hypertensive cardiac hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more effective in combination than as monotherapies in SHR.