Recurrence of thyrotoxicosis after attack of allergic rhinitis in patients with Graves' disease.

Graves' disease is frequently aggravated during antithyroid drug therapy; however, little is known of its aggravating factors. We studied 83 patients with Graves' disease who were euthyroid for at least 6 months under antithyroid maintenance therapy, and we examined the relationship between thyrotoxicosis relapse, attack of allergic rhinitis, and peripheral eosinophil increase. Forty-one patients showed thyrotoxicosis relapse; of these, 22 (54%) showed peripheral eosinophil increase, and 14 (34%) had attacks of allergic rhinitis. In the remaining 42 patients without thyrotoxicosis relapse, only 4 (10%, P < 0.001) showed an increase in peripheral eosinophils, and only 3 (7%, P < 0.01) had allergic rhinitis. Recurrence of thyrotoxicosis was observed with the increase in serum levels of TSH-receptor antibodies and increase in eosinophils 2 months after the attack of allergic rhinitis. Three patients with seasonal allergic rhinitis showed thyrotoxicosis relapse at the same time of year within 2 consecutive years. Our findings indicate that allergic rhinitis can be an aggravating factor of Graves' disease and suggest that the preceding increase in peripheral eosinophils can be a predictive indicator of recurrence of thyrotoxicosis during antithyroid drug therapy.

Thioperamide, a histamine H3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats.

BACKGROUND: Whether or not peptide YY (PYY)-induced hyperphagia is modified by the histaminergic system in the brain is not yet known. METHODS: We investigated the effect on feeding of intracerebroventricular (ICV) administration of a specific histamine H3 receptor antagonist prior to ICV administration of PYY in rats. RESULTS: PYY (1, 3, and 10 micrograms/10 microL) strongly induced feeding behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced by 3 micrograms/10 microL of PYY was equal to that induced by a 16-hour fast. The ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-microgram dose of PYY. CONCLUSIONS: These results suggest that the effect of PYY on appetite is different than that induced by fasting and may involve a histaminergic mechanism.

Centrilobular nodules correlate with air trapping in diffuse panbronchiolitis during erythromycin therapy.

BACKGROUND: Low-dose erythromycin therapy improves airflow limitation and airway inflammation in patients with diffuse panbronchiolitis (DPB). However, to our knowledge there has been no study to determine whether physiologic improvement during erythromycin therapy correlates with radiologic findings. STUDY OBJECTIVE: To clarify whether improvement in pulmonary function correlates with specific changes on chest CT. DESIGN: The relationship between five CT findings and five pulmonary function parameters was evaluated before and 3 months after low-dose erythromycin therapy in 24 patients with DPB retrospectively. RESULTS: After erythromycin therapy, the predicted percentage of vital capacity (%VC; 87.0 +/- 3.07% vs 98.9 +/- 3.39%; p = 0.00006) and 50% of the maximum midexpiratory flow rate of FVC (1.41 +/- 0.26 L/s vs 1.61 +/- 0.27 L/s; p = 0.03) significantly increased, and the residual volume/total lung capacity ratio (RV/TLC%; 44.5 +/- 1.93% vs 40.7 +/- 1.83%; p = 0.0019) significantly decreased, but the FEV(1) to FVC ratio and 25% of the maximum expiratory flow rate of FVC did not. In five CT findings, centrilobular nodules (3.7 +/- 0.4 vs 1.5 +/- 0.3; p = 0.0001), peripheral bronchiolar wall thickness (3.8 +/- 0.3 vs 2.6 +/- 0.4; p = 0.0007), and peripheral bronchiolectasis (2.8 +/- 0.3 vs 2.2 +/- 0.4; p = 0.0058) had significantly improved, whereas low attenuation area and central bronchiectasis had not. There were positive correlations of improved scores of centrilobular nodules with improved %VC (r = 0.58, p = 0.0062) and RV/TLC% (r = 0.64, p = 0.0022). CONCLUSIONS: Decreased air trapping in DPB correlates with an improvement of centrilobular nodules, which reflects the obstructive lesions of bronchioles during the erythromycin therapy.

A novel surgical glue composed of gelatin and N-hydroxysuccinimide activated poly(L-glutamic acid): Part 1. Synthesis of activated poly(L-glutamic acid) and its gelation with gelatin.

Although fibrin glue has been widely used as a surgical adhesive, its components, fibrinogen and thrombin, obtained from human blood are not completely free from the risk of virus infection due to acquired immune deficiency and hepatitis. Recently, we have reported that a polymer pair composed of gelatin and poly(L-glutamic acid) (PLGA) promptly forms a gel and can firmly bond to soft tissues when crosslinked with the aid of water-soluble carbodiimide (WSC). The present study was undertaken to design a new PLGA-gelatin glue without using WSC. Two kinds of PLGA with molecular weights of 71 and 22 kDa were employed to prepare N-hydroxysuccinimide (NHS) activated derivatives. The NHS-activated PLGA could be synthesized at high yields and was found to be stable for an extended time without losing the ability to crosslink with gelatin when stored under a dry-cold condition. This NHS-activated PLGA could spontaneously form a gel with gelatin in an aqueous solution within a short time, comparable to a commercial fibrin glue, when gelation was allowed to proceed at pH 8.3. The NHS-activated PLGA prepared from PLGA with the molecular weight of 22 kDa could be readily dissolved at high concentrations and its ability to form a gel was maintained for more than 10 min when an acidic 8% NHS-activated PLGA solution was used. The bonding strength of PLGA gelatin glues with natural tissue was higher than that of fibrin glue. These findings strongly suggest that this combination of gelatin and NHS-PLGA is very promising as a surgical adhesive and may possibly replace fibrin glues prepared from human blood components.

Thioperamide, a histamine H3 receptor antagonist, suppresses NPY-but not dynorphin A-induced feeding in rats.

Whether or not neuropeptide Y (NPY)-induced feeding in rats is influenced by the histaminergic system in the brain was investigated by intracerebroventricular (i.c.v.) administration of a selective histamine H3 receptor antagonist prior to i.c.v. administration of NPY. NPY (10 microg/10 microl) strongly induced feeding in sated rats during the light phase of the day. Dynorphin A1-17 (10 microg/10 microl), a kappa-opioid agonist, and rat pancreatic polypeptide (rPP, 30 microg/10 microl) also stimulated ingestive behavior in sated rats, but food intake in both cases was less than that induced by NPY. Thioperamide maleate, a specific histamine H3 receptor antagonist (408.5 microg/10 microl) reduced the feeding response to NPY by 52% (P < 0.0001), but not to dynorphin A1-17 and rPP. Thioperamide at i.c.v. doses of 40.8-408.5 microg/10 microl had no effect on food intake in sated rats. These results suggest that the thioperamide may have a specific effect on NPY receptor-mediated neuronal systems related to feeding.

Outcome of clonal hemophagocytic lymphohistiocytosis: analysis of 32 cases.

We studied the impact of clonality, determined by analysis of Epstein-Barr virus genome termini, T-cell receptor genes and clonal chromosomal abnormality, on the clinical outcome in 32 patients with hemophagocytic lymphohistiocytosis (HLH). Of the cases studied, 23 cases were EBV-clonal, 15 cases were TCR-clonal and 7 cases were cytogenetically clonal. Thirty patients were treated with immuno-chemotherapy and/or multiagents' chemotherapy and 4 received bone marrow transplantation. All 7 cases, in which cytogenetically abnormal clones were identified, were fatal (3-year survival by Kaplan-Meier analysis; 14%, 95%CI: 0-40%). None of these 7 cases received bone marrow transplantation. On the other hand, the 3-year survival of 23 clonal EBV-positive HLH cases including 4 cytogenetically abnormal cases was 64 % (95%CI: 42-84%), while that of 15 TCR-clonal cases was 53% (95%CI: 26-78%). Our observations suggest that cytogenetically abnormal cases are at extremely high risk, requiring intensive immuno-chemotherapy followed by prompt and timely allogeneic bone marrow transplantation.

Acetylcholinesterase-containing neurons in the striatum, septum and hippocampus of the rat in embryonic culture and adult in situ.

Neurons of the rat brain, of either adult in situ or embryonic culture, have been studied by using a sensitive method for acetylcholinesterase (AChE) histochemistry. In the culture system, incubated for 6-18 days, AChE-positive neurons were found in tissues originating from the striatum and septum, but not in those from the hippocampus. These positive somata were morphometrically analyzed in terms of the cell size, i.e. the lengths of the major axis (Lmax) and the minor axis (Lmin) in cultured dishes of the striatum and septum; the mean Lmax was 20 and 22 microns, respectively. In in situ adult brain sections, a similar morphometric examination of AChE-positive neurons gave comparable results to those obtained in the culture system. An evaluation of both in vitro and in vivo through the histogramatical analysis revealed that the striatum contained more than two populations of AChE-positive cells differing in cell size. In contrast, a major single peak of Lmax was detected in the histogram of the septum. In both cases of striatum and septum in in situ adult brain, sagittal sections show larger size of Lmax, indicating that AChE-positive neurons are arranged in the sagittal direction. In studies on electrophysiological properties of large striatal cells in culture, both acetylcholine and glutamate induced changes in the membrane potential and/or the frequency of excitatory postsynaptic potential, while dopamine induced much smaller responses.

Platelet hypoaggregability in rats exposed to SART stress (repeated cold stress).

A prolongation of bleeding time accompanied by thrombocytopenia and abnormalities in coagulation-fibrinolysis systems has been observed in laboratory animals exposed to a chronic form of environmental stress induced by severe fluctuations of air temperature, known as SART (specific alternation of rhythm in temperature) stress. In order to clarify the hemostatic profile under SART stress in more detail, the present study examined platelet aggregability in vitro as well as in vivo in stressed rats. During exposure to stress, thrombocytopenia developed from day 5, and remained up to at least day 14. In vitro aggregation of platelets stimulated by ADP or collagen was markedly decreased in stressed rats, compared with unstressed rats. Furthermore, stressed rats exhibited in vivo hypoaggregability of platelets, as estimated by the magnitude of the drop in circulating platelet counts following intravenous injection of ADP and collagen. Protein and cholesterol content in platelets remained constant after stress exposure. These results indicate that SART-stressed rats exhibit platelet dysfunctions in addition to thrombocytopenia. Considering the previous findings, the hemostatic system under SART stress appears to show a general tendency toward hemorrhage.

Crucial role of serum human chorionic gonadotropin for the aggravation of thyrotoxicosis in early pregnancy in Graves' disease.

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and is closely associated with postpartum recurrence of stimulative thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), was responsible for this early aggravation, the respective TSA due to TSAb or hCG was evaluated by a highly sensitive cAMP accumulation assay using FRTL-5 cells. TSA was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG concentration, and was abolished completely by the pretreatment of serum sample with the solid-phase hCG antibody coupled with Sepharose 4B. The model serum samples of Graves' disease with pregnancy were made by the mixture of normal pregnant and Graves' sera, and their TSA were reduced by the pretreatment with the solid-phase hCG antibody, just corresponding with the reduction in hCG-induced TSA. TSA of early pregnant sera in 20 patients with Graves' disease decreased significantly but were still positive even after the pretreatment with the hCG antibody. Serial changes in TSAb and hCG-induced TSA were measured in 5 of these 20 pregnant patients. hCG-induced TSA increased associated with the increase in free thyroxine, while TSAb did not show striking change in early pregnancy. These data indicate that (1) respective TSA due to TSAb or hCG can be measured distinctively by using the solid-phase hCG antibody and (2) hCG plays a crucial role in the aggravation of Graves' thyrotoxicosis in early pregnancy.

Separation of perfluoroalkylsulfinic acids and perfluoroalkylsulfonic acids by ion-exclusion chromatography.

Ion-exclusion chromatography has been successfully applied to the separation of a number of perfluoroalkylsulfinic acids and perfluoroalkylsulfonic acids. The separation of various perfluoroalkylsulfinic and perfluoroalkylsulfonic acids, with different alkyl groups, was investigated on a polymethacrylate-based, weakly acidic, cation-exchange resin (TSK gel OApak-A) in the H+-form and using conductimetric detection. When water was used as the eluent, these perfluoroalkylsulfinic and perfluoroalkylsulfonic acids could not be resolved. When an aqueous solution of benzoic acid and o-phthalic acid was used, the separation of each of these acids occurred. In order to improve their separation, the effect of the addition of methanol and 2,2,2-trifluoroethanol, as organic modifiers, was also investigated.

Behavioral characteristics of SART-stressed mice in the forced swim test and drug action.

SART-stressed (repeated cold-stressed) mice exhibited shortened immobility time in forced swimming tests, and a time-dependent increase in the duration of immobility time of stressed mice was less compared to unstressed mice. These changes were blocked by diazepam and alprazolam without influence on the immobility time of unstressed mice. The shortening of immobility time caused by SART stress was inhibited by repeated pretreatment with imipramine and mianserin, but not by a single dose. In contrast, neither single nor repeated administrations of lithium carbonate had effect on the immobility time of SART-stressed mice. The SART stress technique may be a potential model to investigate the relationship between stress and depression with complex symptoms like excessive emotion- and anxiety-related depression.

Clinical features and therapeutic outcomes of 65 patients with acromegaly at Tokyo Women's Medical University.

OBJECTIVE: The purpose of this study was to survey the clinical characteristics, complications, and therapeutic outcome in patients with acromegaly. PATIENTS AND METHODS: The clinical features of 65 patients with acromegaly (31 males, 34 females; mean age: 50+/-2 yr.) who were admitted to Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. RESULTS: The retrospective analysis revealed that the diagnosis of acromegaly was preceded by approximately 8.1+/-1.1 years of signs and symptoms of the disease. Forty-six of the 65 patients (71%) had macroadenomas, 16 (25%) had microadenomas, and the remaining three had empty sella. The rate of biochemical cure or remission was 81% for microadenoma (13/16), 64% for macroadenoma without extrasellar extension (9/14), and 13% for macroadenoma with cavernous sinus extension (2/15). Eighteen (28%) patients had impaired glucose tolerance (IGT) and 32 (49%) had diabetes mellitus (DM). After treatment for acromegaly, glucose metabolism was analyzed again in 38 patients, and it improved in 26 patients with IGT or DM. Twenty-five of 65 patients (38%) had hypertension. Of 26 patients who underwent barium enema or colonoscopy, 10 had colonic polyps and 4 had colon cancer. CONCLUSION: This study suggests that long-term excessive growth hormone (GH) secretion causes many complications. Therefore, awareness of the early symptoms and signs of acromegaly and long-term careful management of complications, along with therapy to reduce serum GH/insulin-like growth factor (IGF)-I levels, are important for patients with acromegaly.

[A clinicopathological study of two respirator-aided long-survival cases of amyotrophic lateral sclerosis].

We reported two respirator-aided 10-year-survival male patients with sporadic amyotrophic lateral sclerosis (ALS). Their ages at onset were 54 and 52, clinical features common in both cases, the durations to tracheotomy 32 months and 27 months respectively, and the durations for respiratory support over 8 years in both cases. There were normal external ocular movement, normal pelvic sphincter function, normal sensory system and no bed sores throughout 10 years of illness. The brain weighted 1,295 g in case 1 and 1,430 g in case 2, being normal macroscopically. The spinal cord was slightly wasted with atrophic anterior roots. The histopathological study demonstrated the typical pattern of ALS in spite of the prolonged survival with artificial respiration. Neuronal loss and gliosis of the motor nuclei in the spinal cord and brainstem were more striking than those of the natural course. Neither hypertrophic astrocyte, central chromatolysis nor neuronophagia was observed. This finding suggested inactive condition of the degeneration. The pattern of white matter degeneration in the cord indicated some pallor of anterior and lateral columns, severe pallor of pyramidal tracts and intact posterior column and spinocerebellar tracts. The giant pyramidal cells in the precentral gyrus were lost in both cases. Pyramidal degeneration was traceable up to the cerebral peduncles in the case 2 and undetectable in that portion in the case 1. On the other hand, the extraocular muscle nuclei, the Onuf's nuclei, the dorsal motor nucleus of the vagus nerve, intermediolateral and Clarke's nuclei were relatively preserved, though no cell count was done in Clarke's nuclei and Onuf's nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

[Weber's syndrome of ischemic vascular origin--a clinical and neuroradiologic study].

A series of 4816 patients with cerebrovascular disease have undergone CT and/or MRI examinations over the last 25 years at the Higashi Nagoya National Hospital and the Nagoya National Hospital. Of these, we experienced 5 cases (4 men and 1 woman) of Weber's syndrome: two cases were resulted from cerebral embolism and three from cerebral thrombosis. All of the patients had left hemiparesis and right oculomotor palsy. On full investigation, complete unilateral external and internal oculomotor palsy was seen in two patients, while the remaining three patients showed pupillary sparing. The patients with complete oculomotor palsy presented with left hemiparesis as the initial symptom. In addition to oculomotor palsy and crossed hemiparesis, two patients had paralysis of the face and one patient had tongue muscle on the opposite side of the lesion and disorders of sensation. Positive Babinski's sign was found in four of the five patients. In one patient with unilateral glossoplegia on the side of hemiparesis, CT or MRI revealed a limited low-density or low signal intensity (T1) area in the inner part of the crus cerebri, and in the other patient who also had hemihypesthesia, the low-density or low-signal intensity (T1) area expanded into the dorsal midbrain. We would like concluded that the frequency of Weber's syndrome was very low though this syndrome was well celebrated, and the careful clinical observation of the neurological features of affected patients guided to the obvious site of lesion in the midbrain.

[Effects of glycerol on local cerebral glucose utilization and local cerebral blood flow of hypoxic rats].

Effects of a continuous infusion of glycerol on the hypoxic rat were assessed by measurements of local cerebral glucose utilization and local cerebral blood flow using the quantitative autoradiographic 1-[C-14]-2-deoxyglucose and [C-14]-iodoantipyrine techniques, respectively. Local cerebral glucose utilization of the hypoxic rat was decreased in most of cerebral structures except for the amygdala, septal nucleus and the white matter. Local cerebral glucose utilization of the hypoxic rat treated with glycerol was recovered to the pattern of normal control, although glucose utilization of the nucleus raphe and locus ceruleus was accelerated. Cerebral blood flow of the hypoxic rat was elevated in almost of all measured structures. In particular, blood flow in the substantia nigra and locus ceruleus was increased significantly. The pattern of local cerebral blood flow of the hypoxic rat treated with glycerol was more analogous to that of normal control than of hypoxic rat without treatment. It is suggested that glycerol has beneficial effects by elevating local cerebral glucose utilization inhibited and decreasing local cerebral blood flow overshot on the hypoxic condition.

[A case report of metastatic colonic carcinoma in the liver effectively treated by long-term, ambulatory and continuous, intra-hepatic-arterial infusion of 5-fluorouracil using disposable multi-day-type infusor].

A 42-year-old female was diagnosed as having sigmoid colonic carcinoma with multiple metastases in the liver. Following sigmoid colectomy and descending colostomy, a catheter was inserted from the right gastroepiploic artery to the proper hepatic artery. From the day of surgery 5-Fluorouracil was administered in doses of 250 mg/day continuously through a catheter over the 2-month period of hospitalization. After the patient was discharged, 250 mg/day of 5-Fluorouracil was administered at home using Vaxter Infusor according to a regimen of 10-day continuous infusion and subsequent 4-day rest. Five months after the initial operation, the serum CEA level decreased dramatically, and CT scan of the liver revealed the complete disappearance of the metastases. The patient underwent a second operation in which the colostomy was closed, and she is doing well at this writing. This case suggests that long-term, ambulatory, continuous and intra-hepatic-arterial infusion of 5-Fluorouracil can be a very effective treatment not only in reducing the hepatic metastases but also in improving the quality of life of patients with colonic carcinoma.

Biological significance of phospholipids in the rat stomach--from the viewpoint of electron microscopy.

The structures of gastric phospholipids (PLs) were further confirmed by employing an improved fixative and fixation method. PLs were detected on the free surface of superficial mucous epithelial cells and epithelial cells of the foveolar crypts. PLs were also detected inside superficial mucous cells and epithelial cells of the foveolar crypts. The gastric PLs were secreted through a merocrine-like mechanism. Apocrine-like secretion of PLs was also observed in some electron microscopic images. PLs were observed in the intercellular and intracellular secretory canaliculi of parietal cells and also in the rest of the parietal cytoplasm. The above findings indicated the localization of PLs on the surface of the gastric lumen and in the gastric mucosa, and suggested that, similar to gastric glycoproteins, gastric PLs play an important role in the gastric mucous barrier and mucosal barrier.