Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

A new strategy for management of retroperitoneal tumors with supradiaphragmatic vena caval thrombi

A new surgical technique to treat retroperitoneal tumors with supradiaphragmatic vena caval invasion is described. In this technique, hepatic warm ischemia can be avoided with reversed hepatic outflow through the portal vein and neither hypothermic circulatory arrest nor cardiopulmonary bypass is necessary using centrifugal blood pump-driven bypass.     

Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets

We examined the effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion by isolated rat islets of Langerhans. Culture of islets for 24 h in the presence of 10(-6) M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. Similarly, the rates of proinsulin biosynthesis were not altered in islets incubated in 10(-4)-10(-9) M IAPP and 5.5 mM glucose, nor was the rate of conversion of proinsulin to insulin changed at 10(-6) M IAPP. Addition of 10(-5) M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rate; however, the secretion of newly synthesized proinsulin and insulin was not affected. These data indicate that it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.     

Two cases of thyroid metastases from renal cell carcinoma]

The identification and diagnosis of thyroid metastases from renal cell carcinoma are rare in living patients in spite of more frequent incidence during autopsy. We reported two cases of thyroid metastases from renal cell carcinoma. In both cases, histological examination revealed metastasis from renal cell carcinoma and negative immunohistological stain for thyroglobulin ruled out primary thyroid carcinoma.     

Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in the pediatric field. Pediatric Study Group for Imipenem/Cilastatin Sodium

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in a joint study in the pediatric field by a study group consisting of investigators at 16 institutions. The results were summarized below. Pharmacokinetic studies Peak plasma concentrations of MK-0787/MK-0791 were 27.7-190.0/28.3-216.4 micrograms/ml at doses of 10/10-50/50 mg/kg administered by a 30 or 60-minute drip infusion. The above findings proved that dose response was clearly observed. Over a period of 6 or 7 hours, the urinary excretion of MK-0787 and MK-0791 totaled 54.2-88.0% and 53.6-89.0% of the dose administered, respectively. Plasma half-lives of MK-0787 and MK-0791 in the beta-phase were 0.87-1.05 hours and 0.59-0.95 hour, respectively. The cerebrospinal fluid (CSF) levels of MK-0787 in patients with purulent meningitis were 2.0-14.4 micrograms/ml; however, the penetration rate of the drug into the CSF was relatively poor in patients with normal meninges. Clinical study Clinical efficacy was evaluated in 283 patients. In 112 patients the daily dosage ranged from 30/30 mg/kg to 59/59 mg/kg, and in 138 patients it ranged from 60/60 mg/kg to 99/99 mg/kg. The maximum dose administered was 222/222 mg/kg. The drug was administered either 3 or 4 times per day. The clinical efficacy rate was 92.5% among 187 patients with identified etiologic pathogens. The drug was effective in 3 out of 4 patients with purulent meningitis and in 7 out of 10 patients with septicemia. The clinical efficacy rate was 96.7% in 90 patients with respiratory tract infection (pneumonia, lung abscess, etc.), 96.5% in 57 patients with urinary tract infection, 90.9% in 11 patients with SSTI. The clinical efficacy rate in those with no identified etiologic pathogen was 97.0% among 101 patients. Bacteriologically, the eradication rate for S. aureus was 87.9% of 33 isolates. Comprehensively, the eradication rate for Gram-positive bacteria was 94.7% of 75 isolates. The eradication rate for P. aeruginosa was 87.5% of 8 isolates. Including these strains, the eradication rate for Gram-negative bacteria was 90.3% of 134 isolates. The MK-0787/MK-0791 exhibited an eradication rate of 91.9% among a total of 211 Gram-positive and Gram-negative bacteria including anaerobes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Terminal sequences of the replicative form of RNA of the Japanese encephalitis virus

The 5' and 3' terminal sequences of the replicative form (RF) of RNA of a flavivirus, the Japanese encephalitis (JE) virus, strain Ja0ArS982, have been determined by in vitro labelling and mobility shift analysis. The plus strand sequence was 5'AGAAGUUUAUCUGUGUGAA...UCUOH3', while the minus strand sequence was 5'AGAUCCUGUGUUCUUCCUCA...UCUOH3'. These sequences were similar to those of West Nile (WN) virus being identical in 12 nucleotides at the 5'terminal of the minus strand, and in the 5'terminal dinucleotides, 5'AG3'. Somewhat more internal hexanucleotides 5'CUGUGU3' are conserved among 3 flaviviruses, the JE, WN, and yellow fever viruses.     

Fetal stabilization for antenatally diagnosed diaphragmatic hernia

BACKGROUND/PURPOSE: Infants with congenital diaphragmatic hernia have pulmonary hypoplasia resulting in persistent pulmonary hypertension of neonates (PPHN), which is the main contributor to both high mortality and morbidity. The pulmonary artery bed in patients with congenital diaphragmatic hernia (CDH) is underdeveloped and is very sensitive to slight stimuli. It is, therefore, vital to avoid any factors that might increase pulmonary vascular resistance during the perinatal treatment of these patients. Recently, fetal anesthesia for perinatal stabilization in patients with CDH has been reported. However, the efficacy of this method remains controversial. The aim of this study is to analyze the benefits of fetal stabilization using fetal anesthesia in patients with CDH. METHODS: The authors have seen 9 cases of antenatally diagnosed CDH and attempted fetal stabilization. The indication for fetal stabilization was a lung thoracic ratio of less than 0.2, without any severe associated anomalies. The protocol for fetal stabilization was (1) monitoring the fetal respiratory movement and heart beat by ultrasonography, (2) the administration of morphine (20 to 30 mg) and diazepam (5 mg) to the mother, (3) the confirmation of any interruptions in fetal movement followed by a cesarean section, (4) pancuronimum (0.5 mg) was given through the umbilical vessels, (5) intubation before clamping of the umbilical cord, and (6) high-frequency oscillatory ventilation (HFO) without bagging. RESULTS: The lung-thratic ratio (LTR) was between 0.06 to 0.17 (average, 0.10+/-0.04). Operation was performed in 7 of 9 patients at between 2.5 and 27 hours after birth. The overall survival rate was 66.7% (6 of 9). All of the patients who underwent operation within 5 hours after birth survived. CONCLUSIONS: Perinatal stabilization using fetal anesthesia was found to be effective in preventing PPHN and shortening the period of preoperative stabilization. It also improved the survival rate of patients with severe CDH.