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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 433 records · Page 24Linked to original sources

A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection.

An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants.

Cytomegalovirus Infections↗

Aortic aneurysm in a four-year-old child with tuberous sclerosis.

We present a case of aortic aneurysm in a four-year-old child complicated with tuberous sclerosis. We used the same general principles as for adult patients and successfully managed our patient. Our methods included the use of isoflurane plus epidural anaesthesia, dopamine to maintain blood pressure, and induced mild hypothermia to reduce brain metabolism and to prevent spinal cord damage during aortic cross-clamping. Intensive monitoring including EEG was beneficial to the anaesthetic management.

Anesthesia, Epidural↗

A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock.

Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.

Amino Acid Sequence↗

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗

[Clinical study of subglottic carcinoma].

Recently, therapy for laryngeal carcinoma has been becoming established, particularly in the early stage. The prognosis of laryngeal carcinoma is said to be better than that of other head and neck carcinomas. Laryngeal carcinoma is divided into 3 subtypes, supraglottic, glottic and subglottic, according to origin. We analyzed the subglottic carcinomas diagnosed and treated in our department between 1972 and 1990. During that period we treated 515 cases of laryngeal carcinoma, 204 cases of the supraglottic type, 284 cases of the glottic type, and 27 cases (5.2%) of the subglottic type. The 5-year survival rate in subglottic carcinoma was 44% (T1: 83%, T2:55%, T3: 17%, T4: 0%), worse than in the other types of laryngeal carcinoma. We think that there were 2 main reasons for the worse prognosis. The first was their high rate of local recurrence after radiation therapy particularly in the early stage. Although 15 T1 and T2 patients who received full dose (65Gy) radiotherapy had a complete response, 8 patients developed local recurrence. The results of the salvage operation were good in T1 cases, but were followed by death because of metastasis or second recurrence in 2 of the 3 T2 patients. The second reason for the worse prognosis appeared to be metastasis in the advanced cases. Five (50%) T3 and T4 patients developed metastasis to the lung, mediastinum and cervical lymph nodes, resulting in death. Thus, we believe that the main therapy for subglottic carcinoma, except T1, should be surgery to obtain a better outcome, and that adjuvant chemotherapy after irradiation or neck (paratracheal) dissection with total laryngectomy should be performed in advanced cases.

Adult↗

[Effect of oak pollen on patients with birch pollinosis].

The author reviewed 53 cases of birch pollinosis treated in our ENT-clinic between 1990 and 1991. Of interest is the fact that many of these patients complained of typical symptoms in and after June, when birch pollen has usually disappeared. We considered this discrepancy to be attributable to the effects of grass pollen, one of the common causal agents in this period. However, only a few patients tested positive for grass pollinosis. We therefore postulated that cross-reactivity between birch and oak pollen accounted for this phenomenon, because both trees belong to same order, Fagales. A strong correlation between RAST scores for birch and oak pollen was detected, and the oak pollen RAST score was significantly reduced by birch pollen extract in an inhibition test. These findings demonstrated actual cross-reactivity between birch and oak pollen. Birch pollinosis patients in Sapporo therefore have allergic symptoms from March to July.

Cross Reactions↗

[Antineutrophil cytoplasmic antibody (C-ANCA) levels in relation to the treatment of Wegener's granulomatosis].

We assessed the clinical significance of cANCA in relation to the diagnosis and follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the ELISA kit for the detection of cANCA. The NephroScholor C-ANC test for cANCA was revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly less sensitive than the indirect immunofluorescence assay using human neutrophils, which has been in widespread use for the detection of ANCAs. With NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed quantitatively. When conventional immunosuppressive therapy with prednisolone and cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer decreased, and thus it also seemed useful for the follow-up of Wegener's granulomatosis patients. However, a rising ANCA titer during the course of the disease was not always correlated with the occurrence of a relapse as previously reported. Based on these findings, it is not recommended that treatment be changed immediately because of elevation of the ANCA titer alone, and it never seemed too late to increase immunosuppressive therapy, even after a clinical exacerbation was observed. Several treatments other than the conventional immunosuppressive therapy have often been applied for our patients, especially in the limited type of this disease, and these treatments, including sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and cyclophosphamide alone, have often been useful. We conclude that the choice of therapy must depend on the severity or the condition of the individual patient, and this therapeutic policy should reduce unnecessary side effects of potentially toxic drugs.

Adult↗

[Left thoracotomy approach for coronary reoperation].

We experienced reoperative coronary revascularization through a left thoracotomy in 12 patients between June 1992 and June 1994. All patients underwent grafting to the left coronary system except one, who underwent bypass procedure to the atrioventricular branch of the right coronary artery in addition to grafting to the left anterior descending artery, using the pedicled left internal thoracic artery, the gastroepiploic artery as a free graft, or a reversed saphenous vein graft. In one patient, revascularization was accomplished during temporary occlusion of the coronary artery without cardiopulmonary bypass. On the other hand, in 11 patients, cardiopulmonary bypass was used. Coronary bypass procedure was employed under the ventricular fibrillation with hypothermia in those but one, who underwent revascularization under the beating heart with cardiopulmonary support. All patients were hemodynamically stable in postoperative stage, and artificial ventilation time was not prolonged, with a mean time of 15.7 hours. Postoperative morbidity included reexploration for hemorrhage in one patient, convulsion in one, worsening of hemianopsia in one, ventricular arrhythmia in one, and wound complication in one, however, there were no hospital deaths. All patients underwent repeat coronary angiography, which revealed that all grafts were widely patient except one, which had inadequate flow due to diffuse narrowing. Based on these clinical results, we conclude that a left thoracotomy is a useful approach for reoperative coronary bypass procedures to reduce the surgical risk associated with a sternal reentry in properly selected patients.

Adult↗

Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene.

Mucopolysaccharidosis IVA is an autosomal recessive lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. The recent isolation and characterization of cDNA and genomic sequences encoding GALNS has facilitated identification of the molecular lesions that cause MPS IVA. We identified a common missense mutation among Caucasian MPS IVA patients. The mutation was originally detected by SSCP, and successive sequencing revealed an A-->T transversion at nt 393. This substitution altered the isoleucine at position 113 to phenylalanine (I113F) in the 622 amino acid GALNS protein and was associated with a severe phenotype in a homozygote. Compound heterozygotes with one I113F-allele mutation have a wide range of clinical phenotypes. Transfection experiments in GALNS-deficient fibroblasts revealed that the mutation drastically reduces the enzyme activity of GALNS. Allele-specific oligonucleotide or SSCP analysis indicated that this mutation accounted for 22.5% (9/40) of unrelated MPS IVA chromosomes from 23 Caucasian patients, including 6 consanguineous cases. Of interest, the I1e 113-->Phe substitution occurred in only Caucasian MPS IVA patients and in none of the GALNS alleles of 20 Japanese patients. These findings identify a frequent missense mutation among MPS IVA patients of Caucasian ancestry, that results in severe MPS IVA when homoallelic, and will facilitate molecular diagnosis of most such patients and identification of heterozygous carriers. In addition to this common mutation, 10 different point mutations and 2 small deletions were detected, suggesting allelic heterogeneity in GALNS gene.

Base Sequence↗

[Application of microdialysis for pharmacokinetic study in rabbit anterior chamber].

We evaluated a microdialysis technique for analyzing the pharmacokinetics of instilled or orally administered ofloxacin in the anterior chamber of pigmented rabbits. A microdialysis probe was inserted into the anterior chamber and was perfused (2 microliters/min) with Ringer solution using a microinjection pump. Two hours later, 20 microliters of 0.15 and 0.3% ofloxacin was instilled into an eye, or 20 mg/kg of the drug was administered into the stomach through an intubated catheter. Dialysate was then collected every 15 or 20 min for 6 (instillation) or 8 (oral administration) hours. Ofloxacin concentration in dialysates was determined with a HPLC-spectrofluorometry system. Ofloxacin levels in dialysates increased after the instillation in a dose-related manner, reached a maximum at 30 and 45 min, and then decreased gradually with t1/2 of 136 and 114 min after the 0.15% and 0.3% instillation, respectively. After oral administration, ofloxacin levels in dialysates reached a maximum at 120 min and decreased with t1/2 of 175 min. These data suggest the usefulness of microdialysis for pharmacokinetic studies in the anterior chamber, since continuous and stable data can be obtained from each animal.

Animals↗

[Head and neck cancer].

The purpose of this paper is to discuss the recent advances of cancer chemotherapy for head and neck cancer from the viewpoint of survival, focusing on 1) neo-adjuvant chemotherapy, 2) concurrent radiotherapy and chemotherapy, 3) adjuvant chemotherapy, and 4) chemotherapy for palliation. Although neo-adjuvant chemotherapy did not increase survival, it produced a higher rate of organ preservation in some sites such as the larynx and maxilla. Concurrent radiotherapy and chemotherapy form the most promising primary chemotherapy approach to prolong survival of patients with locally advanced resectable and unresectable disease. It is the only systemic approach consistently shown to improve local-regional control and survival in randomized trials. The lack of impact on distant relapse rates, however, suggests that concurrent chemotherapy and radiotherapy should be followed by adjuvant chemotherapy. No survival benefit is evident in adjuvant chemotherapy trials, but some randomized trials including ours produced a significant reduction in the distant relapse rate. As for chemotherapy for palliation, the 5- and 10-year survival were 3.8% and 2.5%, respectively, in patients with local-regional diseases who received chemotherapy for palliation, according to our results. In the patients with distant relapse, the median survival was 10 months, ranging from 2 to 53 months.

Antineoplastic Combined Chemotherapy Protocols↗

[Valvular surgery for the patients 70 years old or older].

From January 1986 to June 1993, twenty one patients aged 70 years or older with valvular heart disease underwent open heart surgery. There were 12 males and 9 females with a mean age of 71.2 years (range 70 to 76). Eight patients were in NYHA class III, and 4 in class IV preoperatively. AVR was performed in 10 patients, MVR, MVR with TAP, OMC, AVR with MAP, DVR with TAP in 4, 4, 1, 1, and 1, respectively. Mechanical and bioprosthetic valves were replaced in 11, and 9 patients respectively. There were 6 early death (4 operative, 2 hospital). Longer duration of cardiopulmonary bypass (p < 0.05) and aortic crossclamp time (p < 0.05) were the risk factors independently for early mortality. Follow-up of 15 hospital survivors was 100% (8 months-7.7 years, mean: 3.2 years) and cumulative follow-up was 47.6 patients years (PY). There was one late death, and one prosthetic valve endocarditis (2.1%/PY). No other valve-related complications was occurred. Actuarial survival rate and freedom from valve-related morbidity at seven years were 83.3%, and 93.3%, respectively. These results show that operative mortality of valvular disease in elderly patients remains high, but the late results is acceptable one. Valve surgery for these elderly patients is reasonably acceptable.

Aged↗

[Multiple systemic embolization from floating thrombus in left atrium].

A 66-year-old woman was referred to our hospital because of cerebral infarction, myocardial infarction and renal infarction. Further examination indicated that she was suffering from mitral valve stenosis with a floating thrombus in the left atrium. She underwent emergency mitral valve replacement and thrombectomy. The thrombus was attached to the left atrium by only four thin and weak strings and removed easily. We think that the thrombus was the precursor of a free-floating ball thrombus without stalk.

Aged↗

[The effects of prostaglandin E1 and epidural anesthesia on peripheral blood flow].

We compared the effects of prostaglandin E1 (PGE1) and epidural anesthesia on peripheral blood flow by laser Doppler tissue flowmetry during lower abdominal surgery. Epidural anesthesia increased the blood flow of the toe, where the sympathetic nerve supply is of the same spinal cord segments as that of pelvic organs. On the other hand, PGE1 could not prevent the decrease of the blood flow of the toe, but increased that of the index finger, which did not receive the nociceptive stimuli from operative site. Thus, the use of epidural anesthesia together with PGE1 is considered to be effective to increase peripheral blood flow.

Abdomen↗

[Problems of commercially available heparinized syringes in measurements of blood gases and electrolytes].

We compared the measured values of blood gases and electrolytes by commercially available heparinized syringes (PZ-II, Quick-lite and QS90) with normal and decreased calcium concentrations. With normal calcium concentration, the measured value of [Ca2+] in PZ-II was significantly less than that in Quick-lite and QS90, seemingly due to contained heparin. With hypocalcemia, the measured values of [Ca2+] in Quick-lite and QS90 were significantly greater than those in non-heparinized syringe. The pH and PO2 decreased, and PCO2 increased as time passed. The [Ca2+] was suggested to be more influenced by heparin than by acid-base balance.

Blood Gas Analysis↗

[O-serotypes, biotypes and antimicrobial susceptibilities of Serratia marcescens isolates from clinical specimens: 4th report].

The clinical isolates of Serratia marcescens in The Showa University Fujigaoka Hospital in the period V during the 3 years from 1991 April to 1994 March were epidemiologically investigated by determining O-antigens, biotypes and antimicrobial susceptibilities. The isolates were collected, while the consumption of beta-lactam antibiotics, new quinolones, and aminoglycosides in the hospital had not changed significantly since 1991. The urease positive O3 strains were predominantly isolated in the period II to IV during the 9 years and 3 months from 1982 January to 1991 April and were more resistant to third generation cephalosporins and the other drugs such as new quinolones and aminoglycosides than the other O-serotype strains. However, the urease negative O14 strains, unlike such O3 strains, were predominantly isolated in the period V and were more resistant to the above mentioned drugs than the other O-serotype strains, indicating that they had higher resistance rates for carbenicillin, latamoxef, ceftizoxime, cefoperazone, cefpirome, tobramycin, dibekacin, gentamicin and fosfomycin than the O3 strains in the period IV during the two years and three months from 1989 January to 1991 March. The hospital wards in which the O14 strains were mainly isolated were the departments of urology, general surgery, orthopedic surgery, haematology, and internal secretion and kidney medicines, corresponding to those in which the isolation number of the O3 strains decreased in the period V. These findings suggest that S. marcescens resident in the hospital inherits multiple drug resistance by changing the biotype and O-serotype.

Anti-Bacterial Agents↗