PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

Summary Acute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.     

Sensitive Detection of p53 Gene Mutations in Esophageal Endoscopic Biopsy Specimens by Cell Sorting Combined with Polymerase Chain Reaction Single-strand Conformation Polymorphism Analysis

For the rapid and sensitive detection of p53 gene mutations in esophageal endoscopic biopsy specimens, we combined cell sorting with the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations in exons 5–8 of the p53 gene were investigated by FCR-SSCF analysis using 10³ sorted nuclei obtained from each endoscopic biopsy specimen of 16 patients with esophageal cancer. DNAs extracted from their respective surgical specimens were investigated by a conventional method of PCR-SSCP analysis. Mutations in the biopsy specimens were detected in 6 of the 12 aneuploid tumors but in none of the 4 diploid tumors. After tumor cell enrichment by cell sorting, one mutation in exon 8 became apparent, which could not be detected from the surgical specimen by a conventional method of PCR-SSCP analysis. This method should improve the sensitivity of detecting p53 gene mutations, and provides additional information concerning the DNA ploidy pattern in the tumors.     

Prevalence and patient's consciousness of tinea pedis and onychomycosis]

Epidemiological studies on tinea pedis and onychomycosis have been performed across Europe and East Asia. The prevalence of these conditions was 20%, respectively, and it increased with advancing age, more men than women had fungal infection of the feet. The prevalent predisposing factors were sports participation, average temperature, and family history of tinea pedis. The predisposing diseases were hypercholesterolemia, cardiovascular disease, diabetes mellitus, and osteoarticular disease. We conducted an epidemiological investigation to determine the prevalence and circumstances of untreated and unsuspected tinea pedis and onychomycosis. The results showed that the prevalence of occult athlete's foot was 25%, and that 59% of those cases were complicated by tinea unguium. The characteristics of patients with occult athlete's foot included a higher proportion of men and a tendency toward a low clinical score together with a high severity score. In the patient background, a strong correlation was observed between a positive KOH test result and characteristics such as past history of tinea pedis and/or onychomycosis, age, disposition of toes, and predisposing disease, as well as the type of shoes worn daily. We suspected that a patient's local and systemic conditions affected each other, creating good conditions for tinea pedis and onychomycosis so that the prevalence has increased. More understanding of occult athlete's foot will lead to prevention and improvement in treatment and diagnosis.     

The role of natural killer T cells in host defense to cryptococcal infection--a bridge from innate to acquired immunity]

Cryptococcosis is an opportunistic fungal infectious pathogen in immunocompromised patients with acquired immunodeficiency syndrome and hematological malignancies. The host defense to this pathogen is mediated mostly by cellular immunity. Th1-type cytokines including IFN-gamma, IL-12 and IL-18 play a pivotal role in this process. Recently, innate immunity mediated by NK, NKT and gammma-delta-T cells has garnered much attention from investigators. NKT cell has been identified as a particular cell population which recognizes glycolipids and participates in the development of tumor immunity and autoimmune diseases. In the present review, the accumulating knowledge on the roles of NKT cells in host defense to infectious pathogens are summarized with our own data on cryptococcal infection.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Inhibition of HIV-1 replication and syncytium formation by synthetic CD4 peptides

Summary Only one peptide of CD₄ (amino acid residues 70–132) among 16 synthetic peptide fragments selectively inhibited HIV-1 replication and HIV-1-induced syncytium formation. Several smaller peptides within this region did not show any activity, except for the peptide (86–132) which showed somewhat lower activity.     

Phenytoin desensitization monitored by antigen specific T cell response using carboxyfluorescein succinimidyl ester dilution assay

We evaluated drug-specific T cell responses in a patient with refractory partial seizures and paroxysmal kinesigenic choreoathetosis successfully treated with clinical desensitization to phenytoin. Drug-induced lymphocyte transformation test before desensitization was negative with a stimulation index of 130%. The frequencies and cytokine-producing phenotypes of phenytoin-specific T cells were examined simultaneously by using a carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Before desensitization, the proportion of CFSElow CD4+ cells in whole CD4+ was 3.09%; 13.6% of CFSElow CD4+ cells were stained with anti-interferon gamma antibody. After desensitization, phenytoin-specific CFSElow CD4+ cells decreased to background level. These results indicate that CFSE dilution assay will be useful for the diagnosis and monitoring of drug hypersensitivity.