Alterations in gene expression of glutamate receptors and exocytosis-related factors by a hydroxylated-polychlorinated biphenyl in the developing rat brain.

Polychlorinated biphenyls (PCBs), major environmental hormonally active agents, are metabolized into hydroxylated PCBs in the liver to facilitate excretion. Some of hydroxylated PCBs also have potencies disturbing endogenous hormonal activities at least in vitro. Hormonal activities of hydroxylated PCBs raise a possibility of their interfering with normal brain development which is strictly regulated by endogenous hormones. We investigated whether and how prenatal exposure to a congener of hydroxylated PCBs (4-OH-2',3,3',4',5'-penta CB; 4-OH-PCB106) having activities to disrupt thyroid hormone-dependent signals in vitro could perturb normal gene expression in the developing brain in vivo. Pregnant rats were exposed to 4-OH-PCB106 subcutaneously at the dose of 1.0mg/(kgday) from day 7 of gestation to postnatal day 1. Then three brain regions (cerebral cortex, hippocampus and striatum) were obtained from offspring on postnatal day 1 and subjected to further gene expression analyses. Comprehensive analyses of mRNA expression by oligo DNA microarrays and subsequent validations by quantitative RT-PCR revealed that prenatal exposure to 4-OH-PCB106 affected mRNA expression of glutamate receptors as well as that of thyroid hormone-responsive genes in region-specific manners. Concomitantly 4-OH-PCB106 exposure increased mRNA expression of genes related to exocytosis in the three brain regions. These results raise the possibility that prenatal exposure to some hydroxylated PCBs with thyroid hormone-disrupting potencies leads to abnormal brain development via perturbations on the expression of genes involved in glutamatergic neurotransmission.

A case report of a diabetic nephropathy patient with cirrhotic ascites treated by peritoneal dialysis.

A 64-year-old man was admitted because of abdominal fullness, edema and anorexia. He had come to our hospital for treatment of liver cirrhosis and diabetic nephropathy for 1 year. We started diuretics and human albumin intravenous administration. Although the edema disappeared and abdominal fullness improved a little, blood urea nitrogen (BUN) and serum creatinine became elevated, hepatic function deteriorated and he lost his appetite. We consequently started continuous ambulatory peritoneal dialysis (CAPD) in order to control ascites and uremia. Abdominal fullness, appetite and BUN and serum creatinine improved without hepatic function deterioration. It might be important to start CAPD to control ascites although serum creatinine levels might be slightly elevated.

Seroconversion of glutamic acid decarboxylase antibodies in a patient initially diagnosed as having type 2 diabetes mellitus.

A 61-year-old man admitted in July 1998 had suffered from thirst, polydipsia and polyuria for three years. Diet and transient insulin therapy had induced good blood glucose control which was maintained by metformin hydrochloride for a year. Although it worsened, conventional insulin treatment re-implemented good blood glucose control. Glutamic acid decarboxylase antibodies (GAD-Ab) had been negative up to this point. After 8 months, blood glucose levels became elevated. To date, the GAD-Ab has been positive (112-120 U/ml), and the serum and urine C-peptide levels are decreased. Seroconversion of GAD-Ab should be noted in patients initially diagnosed as having GAD-Ab negative type 2 diabetes mellitus.

[Anesthetic management by total intravenous anesthesia with propofol, pentazocine and ketamine].

BACKGROUND: The authors evaluated the efficacy of anesthetic management by total intravenous anesthesia with propofol, pentazocine and ketamine. METHODS: Thirty-five patients for mastectomy were anesthetized by propofol, pentazocine and ketamine. Patients were divided into two groups by age; one is patients under 61 years of age and the others are patients above 61 years. Analysis was made retrospectively. Anesthesia was induced with propofol and ketamine and was maintained with propofol infusion and intermittent administration of vecuronium with 40% oxygen in air. Pentazocine was administrated as a bolus dose before incision. RESULTS: There were no differences in the patient background except age and height between the two groups. After induction of anesthesia, systolic and diastolic blood pressures decreased compared with those before induction in both groups. Systolic and diastolic blood pressures and heart rate increased after tracheal intubation, but the hemodynamics remained stable after the start of surgery. The induction and maintenance doses of propofol were not different between the two groups. Patients above 61 years had smaller dosage of pentazocine compared with those in patients under 61 years. The dosage of ketamine was not different between two groups. Awakening time in about 80% of patients was within 15 minutes and is not different between the two groups. Postoperative pain relief was good in both groups. Incidence of nausea and vomiting was 25% and was not the different between the two groups. CONCLUSIONS: Total intravenous anesthesia with propofol, pentazocine and ketamine would be useful to stabilize hemodynamic state, to obtain rapid recovery and to provide effective postoperative pain relief.

Cyclo (His-Pro) potentiates GABA/ethanol-mediated chloride uptake by neurosynaptosomes.

Cyclo (His-Pro) CHP is a cyclic dipeptide endogenous to the brain of a variety of animal species including man. Administration of exogenous peptide to rodents has been shown to exhibit a variety of biologic activities including, modification of pharmacologic actions of alcohol. Since there are many apparent similarities between the actions of GABA and CHP in modulating alcohol pharmacology, we have examined whether CHP can modulate alcohol potentiation of GABA-receptor-mediated 36Cl-influx in neurosynaptosomes. The results show a further dose-dependent potentiation of 36Cl-influx in neurosynaptosomes by CHP in the presence of GABA and alcohol.

Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure.

A 56-year-old woman with diabetic triopathy, rheumatoid arthritis and chronic renal failure was admitted for severe hypoglycemic coma. Arthralgia had been deteriorating for 6 months. Therefore, 5 mg of prednisolone was administered. Postprandial blood glucose (PPG), however, elevated from 260 to 290 mg/dl, although fasting blood glucose (FBG) levels ranged from 80 to 110 mg/dl. Three months after, 270 mg of nateglinide was given in addition to acarbose. After 2 days, hypoglycemia occurred at 02:00 h. Nateglinide was then decreased to 180 mg (before breakfast and lunch). After 5 days, hypoglycemia re-occurred at 01:00 h. Nateglinide was subsequently decreased to 90 mg before breakfast. The PPG levels ranged from 130 to 150 mg/dl. Hypoglycemia did not occur during the next 2 months. On admission, FBG; 59 mg/dl, fasting immunoreactive insulin; 34 microU/ml, indicated hyperinsulinemic hypoglycemia. We administered 20 g of glucose intravenously, however, hypoglycemia recurred 4 times and 20 g of glucose was then administered. Although the plasma nateglinide level decreased, the nateglinide metabolite, N-[trans-4-(1-hydroxy-1methylethyl)-cyclohexanecarbonyl]-D-phenylalanine levels still had not decreased 29 h after nateglinide administration. Therefore, chronic renal failure appeared to alter the pharmacokinetic parameters of the nateglinide metabolite, which had accumulated by chronic renal failure. The nateglinide metabolite caused severe hypoglycemia in this case.

Insulinoma accompanied by diabetes mellitus.

A 53-year-old type 2 diabetic man was admitted due to spontaneous relatively hyperinsulinemic hypoglycemia. Oral glucose ingestion and arginine tolerance test showed hyperinsulinemic response. Arterial stimulation and venous sampling (ASVS) showed hyperinsulinemic response measured from the splenic artery after calcium gluconate stimulation. Diagnosis was insulinoma in the pancreas feeding from the artery. He has not suffered from spontaneous hypoglycemia since removal of the pancreatic body, tail and spleen. The specimen showed a solitary islet cell tumor. The high homeostasis model assessment of insulin resistance (HOMA-R) levels reflecting insulin resistance and hyperinsulinemic response after operation remained almost unchanged, indicating high insulin resistance and an insulin hypersecreting diabetic patient.

Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis.

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.

Subclinical Cushing's disease accompanied by malignant hypertension and diabetes mellitus.

A 53-year-old woman was admitted because of hypertension and diabetes mellitus. Elevated diastolic blood pressure, hypertensive retinopathy and renal dysfunction indicated malignant hypertension. Adrenocorticotropic hormone (ACTH) and cortisol levels were high although there were no Cushingoid features. One mg dexamethasone administration decreased neither ACTH nor cortisol levels. Brain magnetic resonance imaging revealed a left pituitary tumor (7 mm x 6 mm). Upon removal, the tumor showed positive ACTH staining by immnohistochemistry, and was diagnosed as pituitary ACTH-secreting adenoma (Cushing's disease). Her blood pressure, renal function, blood glucose and hormone levels subsequently improved. Malignant hypertension and deteriorated diabetes mellitus may have been due to subclinical Cushing's disease.

[Intermittent complete left bundle branch block during general anesthesia].

We report a case of intermittent complete left bundle branch block (CLBBB) which occurred during general anesthesia. An 83-year-old female was scheduled for upper lobectomy of the right lung under general anesthesia. Her preoperative 12-lead ECG showed atrial fibrillation and ST-depression in V4-6. Anesthesia was induced with propofol and pentazocine, and maintained with 0.5-1.5% isoflurane, 0-50% nitrous oxide in oxygen under close monitoring and appropriate respiratory management. The operation was performed uneventfully. Several minutes after the end of surgery, on converting her into the supine position from the left lateral decubitus position, widened QRS complexes, later diagnosed as CLBBB, appeared on ECG. At that time, heart rate was 92 beats x min(-1). After the administration of esmolol hydrochloride, heart rate decreased rapidly in a few minutes and ECG returned to normal conduction from CLBBB. We diagnosed this as rate-dependent intermittent CLBBB. Although intermittent CLBBB continued until the next day, the patient was asymptomatic and cardiac enzymes were within normal ranges. The intermittent CLBBB, which occasionally occurs during anesthesia, makes the diagnosis of myocardial ischemia and acute myocardial infarction difficult. The present case suggests that esmolol can be used effectively and safely to distinguish CLBBB as a benign disorder from myocardial ischemia in a patient with CLBBB.

[Successful control of rapid heart rate with atrial flutter by intravenous administration of esmolol in a patient after total correction of the tetralogy of Fallot].

A 30-year-old woman with atrial flutter after surgical correction of tetralogy of Fallot, underwent gynecological procedure under general anesthesia. Because she had been noted to have atrial flutter and heart failure at 8 weeks' gestation, she was scheduled for dilatation and curettage. Chest X-ray film showed cardiomegaly and pulmonary congestive changes. ECG showed atrial flutter with 3:2 atrio-ventricular conduction rate and complete right branch block. She was anesthetized with propofol infused with target-controlled infusion system, fentanyl and 66% of nitrous oxide under close monitoring and appropriate respiratory management. The quantity of hemorrhage was about 850 ml, and hypovolemia was treated with volume infusion and the use of vasoactive drugs. Soon after emergence from anesthesia, atrial flutter with 1:1 A-V conduction (> 230 bpm) occurred suddenly. Esmolol hydrochloride, 30 mg, was administered. Despite the relatively low doses, rapid control of heart rate was possible in a few minutes and the atrial flutter returned to 2:1 conduction. Although atrial flutter had continued until the discharge, tachyarrhythmia was no longer observed and the heart resumed sinus rhythm 3 month after the operation. The present case suggests that esmolol can be used effectively and safely for controling atrial flutter with rapid ventricular response in a patient after surgical correction of tetralogy of Fallot.

Sepsis and gas-forming splenic abscess by Clostridium septicum in a patient with type 2 diabetes.

Clostridium infections are rare but frequently associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 h. These infections are associated with various medical problems including diabetes mellitus. In this report, we describe a unique case of sepsis and a gas-forming splenic abscess caused by Clostridium septicum in a type 2 diabetes patient which was treatable solely with antibiotics.

Metformin use in an obese diabetic patient from weeks 1 to 21 of pregnancy.

A 43-year-old diabetic woman was admitted in the 15th week of her first pregnancy. When HbA1c levels were 8.2%, we began diet therapy and continuous subcutaneous insulin infusion (CSII) therapy. The HbA1c levels subsequently ranged from 6.2 to 6.7%. She was delivered without complications of a healthy male infant (3120g) in the 38th week. Metformin was then administered. Six months later she was diagnosed as being in the 21st week of pregnancy. We changed from metformin to CSII therapy immediately. The HbA1c levels had ranged from 6.0 to 6.4% before the CSII therapy and from 5.8 to 6.6% after the CSII therapy during the entire second pregnancy. A macrosomia delivery (4070g) occurred in the 37th week. Although glycemic control was better during the 2nd pregnancy than the 1st pregnancy, metformin use until the 21st week may have induced macrosomia.

Obstructive sleep apnea syndrome accompanied by diabetes mellitus.

A 66-year-old man with diabetes mellitus was hospitalized with sleeping and dyspnea. Polysomnography determined an apnea hypopneas index (AHI) of 56/hr and that the events occurred in association with continued diaphragm electromyogram activity and thoraco-abdominal wall movement. Obstructive sleep apnea syndrome was then diagnosed and nasal continuous positive airway pressure (nCPAP) (11cmH2O) was set. AHI subsequently became 21/hr. Six months' later, uvulopalatopharyngoplasty (UPPP) for the narrowing middle pharynx was performed and the AHI became 7/hr. After starting nCPAP and UPPP, body weight and insulin resistance had decreased. Treatment for sleep apnea may improve insulin resistance in diabetes mellitus.

Doxapram produces a dose-dependent reduction in the shivering threshold in rabbits.

Dopamine is a thermoregulatory neurotransmitter that provokes hypothermia when injected in or near the hypothalamus. Doxapram stimulates release of dopamine from carotid bodies, but is known to have central effects that are probably, at least in part, similarly mediated. We thus tested the hypothesis that doxapram produces a substantial, dose-dependent reduction in the shivering threshold in rabbits. Twenty-four rabbits, anesthetized with isoflurane, were randomly assigned to 1) saline (control), 2) 0.25 mg x kg(-1) x h(-1) doxapram, or 3) 0.50 mg x kg(-1) x h(-1) doxapram. These doses are within the recommended range for humans. Body temperature was reduced at a rate of 2 degrees to 3 degrees C/h by perfusing water at 10 degrees C through a U-shaped thermode positioned in the colon. Core temperatures were recorded from the distal esophagus. A blinded observer evaluated shivering. Core temperature at the onset of shivering defined the threshold. Data were analyzed with a one-way analysis of variance; P < 0.05 was considered statistically significant. Hemodynamic and respiratory responses were comparable in the groups. The control rabbits shivered at 36.3 degrees +/- 0.3 degrees C, those given 0.25 mg x kg(-1) x h(-1) doxapram shivered at 34.8 degrees +/- 0.5 degrees C, and those given 0.50 mg x kg(-1) x h(-1) shivered at 33.7 degrees +/- 0.6 degrees C. All the shivering thresholds significantly (P < 0.001) differed from one another. The magnitude of this inhibition, if similar in humans, would be clinically important.