T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR Vα-Vβ genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption

Human epidermis contains a phenotypically heterogeneous population of T cells. No information, however, is available regarding the TCR repertoire of these T cells and their relevant physiologic and pathologic functions in vivo. To this end, T cells were prepared from the lesional epidermis in two patients with fixed drug eruption (FDE) and their phenotype, function and TCR repertoire were examined in parallel. Both epidermal T cells, termed FDE-1 and -2 cells, respectively, expressed αβ TCR, but displayed some phenotypic heterogeneity. These T cells were induced to display cytolytic activity by ligation of the CD3/TCR-αβ complex. Comparative analyses of TCR Vα and Vβ expression in the epidermal T cells and the paired peripheral blood lymphocytes (PBL) by quantitative polymerase chain reaction (PCR) demonstrated that the epidermal T cells, but not the paired PBL, utilized a very limited range of Vα and Vβ genes. These results indicate that some expansion or preferential migration of epidermal T cells that recognize a restricted set of antigens expressed within the epidermis could occur in situ following ingestion of the causative drug. The persistence of these epidermal T cells in FDE lesions suggests their pathologic role in a drug-induced flare.     

Hypertrophic cardiomyopathy in Noonan syndrome

Noonan syndrome, a well-known multiple congenital anomalies syndrome, is frequently accompanied by cardiovascular diseases including hypertrophic cardiomyopathy (HCM). The incidence of HCM in Noonan syndrome is approximately 20–30% and one-third of cases reveal ventricular outflow obstruction. HCM in Noonan syndrome is occasionally associated with a congenital heart defect, whereas classic HCM seldom accompanies cardiac malformations. Asymmetric septal hypertrophy and symmetric septal hypertrophy (concentric hypertrophy) can be observed both in HCM with Noonan syndrome and in classic HCM. but apical hypertrophy has not been reported in Noonan syndrome yet, although it appears in classic HCM. Congestive heart failure is the major cause of death in patients with HCM in Noonan syndrome, but cases of sudden death have also been reported. The histopathologic findings of ventricular myocardial tissue in HCM with Noonan syndrome are similar to those in classic HCM.     

Effect of Low Dose Aspirin on Augmented Piasminogen Activator Inhibitor Type 1 Activity in Patients with Permanent Pacemakers

To clarify the activity states of coagulation and fibrinolysis in patients with a permanent pacemaker, we studied 29 patients more than 4 months after operation. They were divided into a single pacemaker lead group (S, n = 14) and a double lead group (D, n = 15). Prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, tissue-type plasminogen activator (tPA) activity, plasminogen activator inhibitor type-1 (PAI-1) activity, and platelet aggregation were measured and compared to those in an age-matched control group (C, n - 7). The effects of low dose aspirin (81 mg/day) in the patients (n = 21) were also studied 2 weeks after administration. PAI-1 activity in groups S and D was significantly higher than that in the group C (53.5 ± 36.5, 86.8 ± 59.2 ng/ mL vs 19.4 ± 7.2 ng/mL; P < 0.01 and P < 0.005). Platelet aggregation induced by collagen was slightly higher in groups S and D than group C. Other parameters were not significantly different. In the patients, low dose aspirin significantly suppressed collagen induced platelet aggregation (71.8 ± 20.3% vs 41.7 ± 28.3%; P < 0.005), but not PAI-1 activity. tPA activity was increased significantly by the low dose aspirin administration (3.94 ± 1.85 ng/mL vs 2.48 ± 1.19 ng/mL; P < 0.005). Thus, PAI-1 activity in patients with a permanent pacemaker is elevated, and the activity is not suppressed by low dose aspirin unlike the platelet aggregation.     

Bile acids inhibit tumour necrosis factor α-induced interleukin-8 production in human colon epithelial cells

To clarify the regulatory mechanism of the production of various inflammatory mediators by intestinal epithelial cells, the effect of bile acids (tauroursodeoxycholate, TUDC; taurochenodeoxycholate, TCDC; and taurocholate, TC) on the cytokine-induced production of interleukin (IL)-8 in a human colon epithelial cell line (HT-29) was examined. HT-29 cells were incubated for 24 h in a culture medium containing tumour necrosis factor α (TNFα; 1 ng/mL) and/or interleukin (IL)-1 β (1 ng/mL) in the presence or absence of bile acids. The IL-8 concentration in the medium was measured by an enzyme-linked immunosorbent assay. The binding assay of TNFα was performed using [125I]-TNFα (100 pmol/L). Interleukin-8 production during incubation with TNFα was markedly reduced in the presence of 0.5 and 1 mmol/L TUDC, 0.5 and 1 mmol/L TCDC and 0.5 and 1 mmol/L TC, by 56, 85, 86, 91, 37 and 70%, respectively. The IL-8 production during incubation with IL-1ß was not significantly reduced in the presence of these bile acids. The specific binding of TNFα to cells was inhibited 33, 47, and 14% by 1 mmol/L TUDC, TCDC and TC, respectively. These findings suggest that bile acids inhibit TNFα-induced IL-8 production by the colonic cells. The suppression may be partly due to inhibition of TNFα binding to the cells by bile acids.     

Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co-administration of erythromycin

Abstract A case of repetitive hallucinations during treatment with a therapeutic dosage of triazolam (0.25 mg/day) and nitrazepam (5 mg/day) is presented. The patient suffered from acute pneumonia and chronic renal failure. Such non-psychotic symptoms as anxiety, tremor and depressed feeling were observed initially. However, after co-administration of erythromycin (600 mg/day), visual hallucinations and abnormal bodily sensations developed repeatedly after each administration of triazolam or nitrazepam. This report suggests that benzodiazepine hypnotics even at a therapeutic dosage with co-administration of erythromycin causes serious psychotic symptoms in vulnerable patients with physical complications.     

Plasma Proteins Case Report: Massive Bone Marrow Necrosis with Polyclonal Hypergammaglobulinemia and Blue Toe Syndrome

Massive bone marrow necrosis was rare, and most of these cases were accompanied with malignant disease. We report a case that was thought to be idiopathic massive bone marrow necrosis. It was a 58 y.o. male who was admitted because of blue toe syndrome and hypergammaglobulinemia. We tried to detect malignant diseases with computed tomography and gallium scintigraphy, and infectious diseases with bacterial culture and viral antibodies, but all of them were negative. Pancytopenia and bone marrow necrosis was not improved, and he had died after 5-month hospitalization. Autopsy revealed massive bone marrow necrosis and bone marrow fibrosis after necrosis, but malignant or infectious diseases were not detected. It may be diagnosed as idiopathic massive bone marrow necrosis.     

Continuous Intravenous Administration of l-(2-Tetrahydrofuryl)-5-Fluorouracil [FT] by Intravenous Hyperalimentation (IVH) -- Stability of FT in IVH Solution and Tumor Levels of 5-Fluorouracil (5-FU) --

The continuous intravenous administration of l-(2-tetrahydrofuryl)-5-fluorouracil(FT) to colorectal cancer patients was studied in regard tothe stability of FT in intravenous hyperalimentation (IVH) solutionsand tumor levels of 5-fluorouracil (5-FU). FT was very compatiblewith IVH solutions, because the decomposition of FT in IVH solutionwas very low, 3%. High levels of 5-FU, which is an active metaboliteof FT, were obtained in the tumors, averaging 0.369 mcg/g. Theratios of 5-FU levels in the tumor to those in serum and normaltissues were 13.6 and 3.7. respectively. The difference in 5-FUlevels between normal tissues and the tumors was statisticallysignificant (P<0.01). Therefore, continuous intravenous administrationof FT should be widely used to treat patients with colorectalcancer, as the method of administration of antitumor agents.     

Clinical impact of tamsulosin on generic and symptom-specific quality of life for benign prostatic hyperplasia patients: Using international prostate symptom score and Rand Medical Outcomes Study 36-item Health Survey

AIM: To examine the efficiency of alpha1-blocker treatment on disease-specific and generic quality of life (QOL) in men with clinically diagnosed benign prostatic hyperplasia (BPH), the improvement of QOL scores with International prostate symptom score (I-PSS) and Rand Medical Outcomes Study 36-item Health Survey (SF-36) was prospectively analyzed. METHODS: A total of 68 newly diagnosed patients with symptomatic BPH that satisfied all inclusion and none of the exclusion criteria were prospectively recruited. All patients received 0.2 mg/day of tamsulosin for 12 weeks. All patients underwent pretreatment documentation of lower urinary tract symptoms (LUTS) and assessment of symptom-specific QOL. Symptoms and general health-related QOL (HRQOL) were assessed using the I-PSS and SF-36, respectively. Also, other objective variables, such as prostate volume, maximal urinary flow and postvoid residual urine volume, were evaluated. RESULTS: After 12 weeks, decrease in I-PSS was 27% compared with baseline (from 16.4 +/- 7.18 to 11.9 +/- 7.56). All questionnaires in the I-PSS showed improvement after tamsulosin treatment and the I-PSS QOL score was improved from 4.51 +/- 1.14 to 3.17 +/- 1.38 (P < 0.0001) at 12 weeks after tamsulosin administration. In intragroup comparisons of HRQOL scores with age-gender adjusted SF-36 Japanese national norms, three SF-36 subscales (bodily pain, BP; social function, SF; and mental health, MH) were worse in the BPH group aged over 70 years, while younger BPH groups aged <70 had better mean SF-36 physical function (PF) scores compared with age-gender adjusted Japanese national norms. In the BPH group with a prostatic volume > or =20 mL, three mean SF-36 scales (BP, SF and MH) were significantly improved after tamsulosin treatment. It is noteworthy that these SF-36 subscales were identical to those observed to worsen in the older BPH group compared to Japanese national norms. CONCLUSIONS: Treatment with tamsulosin for symptomatic BPH patients is associated with significant improvement in the generic HRQOL, in addition to disease-specific QOL and symptoms, at 3 months after drug administration. In particularly, for generic HRQOL with SF-36, tamsulosin treatment can efficiently improve three mean SF-36 subscales (BP, SF and MH) that are decreased in older BPH patients.     

Suppressive Therapy for Radiation-Associated Nodular Thyroid Disease: Double-Blind Study With T3 and Desiccated Thyroid

A thyroid screening program for individuals who had irradiationto the head and neck areas was started at Roswell Park MemorialInstitute in February 1977 and by June 1979, 1,071 patientswere seen in the clinic. Three hundred and ninety-six patientswere found to have palpable abnormalities of the thyroid, andfollowing pretreatment evaluation, suppressive therapy withtriiodothyronine (T3) (50 µ/day) or DT (desiccated thyroid)(1 20 mg/day) was administered in a double-blind fashion. Twohundred fifty patients with nodular disease completed 6 mo oftreatment and are analyzed in this paper. Pretreatment thyroidfunction tests showed that two patients had hypothyroidism witha high thyroid-stimulating hormone (TSH) and a low thyroxinelevel. A high incidence of thyroid autoantibodies was also notedand surgical findings confirmed a high incidence of chronicthyroiditis. Complete disappearance of the nodules was seenin 29% of the patients, and in addition, 38% of the patientswere seen to have significant shrinkage of the nodules, indicatingthat radiation-associated thyroid nodules were as sensitiveto the thyroactive agents as nonirradiated nodular thyroid disease.There was little difference in the response rate between T3and DT. Both agents suppressed circulating TSH levels to anunmeasurable level in 76% of the patients. There was no correlationbetween scan findings and response rates. Thyroid carcinomawas found in 19% of the patients who underwent surgery; althoughall were well-differentiated carcinomas, two-thirds of the patientsalready had evidence of dissemination and/or invasion suggestingthe aggressive nature of postirradiation thyroid carcinoma.     

COMPARISON OF 3 SURGICAL APPROACHES TO LAPAROSCOPIC ADRENALECTOMY: A NONRANDOMIZED, BACKGROUND MATCHED ANALYSIS

PURPOSE: To clarify the characteristics of surgical approaches to laparoscopic adrenalectomy we performed background matched analysis of clinical outcomes of the 3 approaches. MATERIALS AND METHODS: From February 1992 to July 2000 we performed 118 laparoscopic adrenalectomies in 115 patients with adrenal tumors. For these operations we used the anterior transperitoneal approach in 46 patients, the lateral transperitoneal approach in 32 and the lateral retroperitoneal approach in 40. RESULTS: To exclude the learning curve effect we eliminated our initial 20 patients treated with the anterior transperitoneal approach. To allow background matching of the 3 groups we also excluded 14 patients with tumors more than 5 cm., 6 who underwent conversion to open surgery and 1 patient who required 5 days of bed rest for retroperitoneal hematoma caused by bleeding from a trocar port. The final analysis included 16, 25 and 36 cases managed via the anterior transperitoneal, lateral transperitoneal and lateral retroperitoneal approach, respectively. Average operative time was significantly shorter for the lateral transperitoneal approach. Postoperative recovery was not significantly different in the lateral transperitoneal and lateral retroperitoneal groups. Postoperative complications included mild paralytic ileus in 2 patients and shoulder tip pain, probably peritoneal irritation due to carbon dioxide insufflation and bowel preparation, in 4 in the transperitoneal groups. Our results imply that the easiest procedure is the lateral transperitoneal approach but the lateral retroperitoneal approach is slightly less invasive. CONCLUSIONS: Although it is important to remember that this study was not a prospective randomized trial and, thus, had from certain biases, we believe that if a tumor is more than 5 cm. and/or the surgeon is not yet skilled in laparoscopic adrenalectomy, the lateral transperitoneal approach is the most suitable method. If the surgeon has performed at least 20 operations, the adrenal tumor is unilateral and the lesion is less than 5 cm., the lateral retroperitoneal approach seems to be more suitable because of its minimally invasive nature. The lateral retroperitoneal approach is also preferred in patients with a history of upper abdominal surgery. With improvements in technique and new instruments the time required for the lateral retroperitoneal approach has been significantly decreased.