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H Iwata

Publications and source records attributed to H Iwata.

At least 55 records · Page 3Linked to original sources
PubMed2002

Systemic administration of interferon-gamma-expressing plasmid reduces late allergic bronchitis in a mouse model of asthma.

Asthma might be caused by a helper T(Th)2 immune response. We hypothesized that the systemic administration of the Th1 cytokines may reduce the Th2 type late asthmatic response (LAR). We examined the effect of the intraperitoneal injection of interferon(IFN)-gamma-expressing plasmid, a Th1 cytokine, or interleukin(IL)-4-expressing plasmid, a Th2 cytokine, at the time of sensitization on a mouse model of asthma induced by ovalbumin in BALB/c mice. We demonstrated that the IFN-gamma-expressing plasmid reduced the LAR, whereas the IL-4-expressing plasmid enhanced the LAR as compared with the saline or plasmid-only treated group. The present study suggests that the systemic administration of IFN-gamma-expressing plasmid may have a modulating ability of Th1/Th2 balance to down-regulate Th2 response by a mutual inhibitory mechanism between Th1 and Th2 cells, leading to the reduction of the LAR.

Animals↗
PubMed2002

Lactic dehydrogenase virus (LDV) infection inhibits allergic eosinophil reaction in the airway.

The effects of interferon (IFN)-gamma induced by virus infection on eosinophil reaction in allergic airway inflammation are not yet clear. We investigated the effects of lactic dehydrogenase virus (LDV) infection, which increases IFN -gamma production with no viral infection or replication in respiratory epithelium, on allergic airway hypersensitivity. LDV infection suppressed antigen-induced eosinophil recruitment into the airway in sensitized mice. IL -5 gene expression in bronchoalveolar lavage (BAL) cells was significantly suppressed in LDV -infected mice compared with uninfected controls. The numbers of total T cells and CD 4+ T cells were significantly reduced in LDV -infected mice compared with controls. The present results suggested that the increase in production of IFN -gamma by viral infection suppresses the eosinophil reaction, and this suppressive effect may be mediated by inhibition of the recruitment of CD 4+ T cell and IL -5 production.

Allergens↗
PubMed2002

Activation of factor IX by erythrocyte membranes causes intrinsic coagulation.

As an extension of our earlier work, procoagulant activity of erythrocyte [red blood cell (RBC)] membrane was examined using biochemical and rheological techniques. Western blot analysis of coagulation factors incubated with erythrocytes (RBCs) showed that only factor IX (FIX) was activated by RBC membranes in the presence of calcium ions. A fluorogenic assay suggested that activated FIX is capable of activating factor X. A preliminary crude extraction of the substance from RBC membranes suggested that a FIX-activating enzyme may be located on the RBC membrane. The initiation of FIX activation by RBCs was enhanced by an elevation in hematocrit. Moreover, the rate of FIX activation by RBCs from normal pregnant women and diabetic patients was much faster than that from normal subjects. In addition, glucose treatment of normal RBCs resulted in the increase in procoagulant activity. It is suggested that FIX activation by RBC membranes may serve as a triggering mechanism for blood coagulation, although further study will be required to clarify the putative FIX activating enzyme on the RBC membrane and to permit more extensive physiological experiments to be performed.

Blood Coagulation↗
PubMed2002

Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis.

We have measured the concentration of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid (SF) from the knees of 49 patients with osteoarthritis (OA) and 79 with rheumatoid arthritis (RA) in order to investigate the correlation between the type of joint disease and level of CD-RAP. The mean concentration of CD-RAP in synovial fluid was significantly higher in OA than in RA. The level of CD-RAP in the group of patients with mild OA was significantly higher than in the moderate or severe groups and that in the group with mild RA was also significantly higher than in the other RA groups and decreased with progression of the disease. Immunohistochemical studies showed expression of CD-RAP in the cytoplasm of chondrocytes in newly-formed fibrocartilage. Since CD-RAP is mainly produced in young and proliferating chondrocytes, our results suggest that the level of CD-RAP in synovial fluid reflects remodelling of articular cartilage and may be used as a marker to estimate objectively the restorative reaction of chondrocytes.

Aged↗
PubMed2002

Characteristics of stress fractures in young athletes under 20 years.

BACKGROUND: With the popularization of organized sports among adolescents and children, the clinical cases of stress fractures in young athletes have increased. This study was carried out to investigate the characteristics of stress fractures in young athletes. METHODS: During the 18-month period between January 1996 and June 1997, new clinical cases of stress fracture due to sports activities were collected from 39 hospitals in Japan. RESULTS: We analyzed 222 stress fractures in 208 athletes under 20 years of age (108 males: 14.4+/-2.2 years, 100 females: 15.2+/-1.5 years). Among these cases, the peak age of occurrence was 16. The most common sport causing stress fracture was basketball. The tibia was the most common location. About 70% of the patients participated in the respective sport for 6 or 7 days per week. High school students trained significantly more often than the primary and junior high school students (p<0.0001). There was a statistically significant difference in the return time to the sport between the cases who visited a hospital within 3 weeks and those who waited for more than 3 weeks after the onset of symptoms (return time, 10.4 vs 18.4 wks). Several cases visited a hospital beyond 8 weeks after the onset of symptoms regardless of the continuous pain of stress fracture, and their recovery was prolonged. CONCLUSIONS: It is important to educate young athletes that continuous pain lasting over 3 weeks is a warning signal to the body, and that early diagnosis leads to early recovery.

Adolescent↗
PubMed2001

A case of clinically and neuropathologically atypical corticobasal degeneration with widespread iron deposition.

A 65-year-old woman was admitted to our hospital for forgetfulness, depression and eccentric behavior that had been first noticed 2 years prior to admission. She showed memory impairment, perseveration and repeated violent actions, but no limb-kinetic apraxia. She died 12 years after the onset of symptoms. At autopsy, the unfixed brain weighed 820 g. Atrophy was circumscribed in the frontal lobe on both sides. The globus pallidus and the caudate nucleus were markedly atrophic and gold yellow in color, and the substantia nigra was strikingly pale. The cortical area showed neuronal loss and status spongiosus of the second and third cortical layers with ballooned neurons. Marked neuronal loss was observed in the dorsomedial nucleus of the thalamus, Meynert basal nucleus and substantia nigra. With Holzer stain, fibrillary gliosis was found to be severe in the frontal lobe, globus pallidus, subthalamic nucleus, hippocampus, dorsomedial nucleus of thalamus, substantia nigra, pontine tegmentum and inferior olivary nucleus. With Bielschowsky-Hirano stain, neurofibrillary tangles were observed in the cortex, hippocampus, substantia nigra, dentate nucleus, subthalamic nucleus, pontine nucleus, the inferior olivary nucleus, dorsomedial nucleus of the thalamus and, to a lesser extent, the neostriatum. Strikingly numerous argyrophilic and tau-positive threads were present in the cerebral white matter. These neuropathological findings corresponded to corticobasal degeneration, but lesions characteristic of progressive supranuclear palsy were also found. Moreover, widespread iron deposition throughout the central nervous system was the most striking finding of the present case. To our knowledge, such a case has not been reported in the literature to date.

Basal Ganglia↗
PubMed2001

Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by application of direct DNA injection method.

CYP3A16 is expressed in the mouse liver specifically during a fetal and puberty life. Functional regions responsible for the transcriptional regulation of the Cyp3a16 gene were identified by an in vivo direct DNA injection into mouse livers followed by a luciferase assay. The results of the deletion analysis of a 5'-flanking sequence suggested the existence of an adult-specific repressor(s) interacting with the Cyp3a16 gene. In addition, a positive regulatory element was assumed to be present in a region from -146 to -56 of the Cyp3a16 gene. A hepatocyte nuclear factor 4 (HNF-4)-binding consensus sequence was found in this region. In fact, HNF-4alpha bound to this sequence as evidenced by a gel mobility shift assay. The role of the HNF-4-binding sequence was further examined by an introduction of mutations in this sequence. The introduction of the mutations resulted in a reduced activity of a luciferase in the assay. These results obtained by an application of the direct DNA injection method suggest that the HNF-4alpha activates the transcription of the Cyp3a16 gene in vivo.

Aging↗
PubMed2001

Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan.

Experimental studies suggest various features of anticancer activity of green tea including inhibitory effect of tumor invasion and metastasis. This study was conducted to examine the association between regular green tea consumption prior to diagnosis and subsequent risk of breast cancer recurrence. The Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) was started in 1988, in which information on lifestyle has routinely been collected from all first-visit outpatients by questionnaire. A total of 1160 new surgical cases of female invasive breast cancers with HERPACC information diagnosed between June 1990 and August 1998 were followed up through December 1999, and the risk (hazard ratio: HR) of recurrence was assessed with reference to daily green tea consumption using a Cox proportional hazard model. During 5264 person-years of follow-up, 133 subjects (12%) were documented to suffer recurrence of breast cancer. A decreased HR for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages. Although careful interpretation is needed, these results suggest the possibility that regular green tea consumption may be preventive against recurrence of breast cancer in early stage cases.

Adult↗
PubMed2001

Association between a polymorphism of the transforming growth factor-beta1 gene and genetic susceptibility to ossification of the posterior longitudinal ligament in Japanese patients.

STUDY DESIGN: A study was conducted to determine the association between polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene and ossification of the posterior longitudinal ligament (OPLL) prevalence. OBJECTIVE: To examine whether the T869-->C polymorphism of the TGF-beta1 gene is associated with genetic susceptibility to OPLL in Japanese subjects. SUMMARY OF BACKGROUND DATA: In the posterior longitudinal ligament, OPLL is associated with abnormal calcium metabolism. Several candidate genes are associated with the prevalence of OPLL. In the ossified matrix and chondrocytes of adjacent cartilaginous areas of OPLL, TGF-beta1 is overexpressed. METHODS: The TGF-beta1 genotype was identified with an allele-specific polymerase chain reaction method in 319 Japanese subjects (46 subjects with OPLL and 273 control subjects). RESULTS: There was a significant association between the T869-->C genotype and the prevalence of OPLL in the cervical spine. Multivariable logistic regression analysis, adjusted for gender, age, height, and body weight, showed that the frequency of the C allele was significantly higher in subjects with OPLL than in control subjects. CONCLUSIONS: The T869-->C polymorphism of the TGF-beta1 gene is a genetic determinant of a predisposition to OPLL, with the C allele representing a risk factor for genetic susceptibility to OPLL in Japanese subjects. Therefore, TGF-beta1 genotyping may be useful in the prevention of OPLL.

Aged↗
PubMed2001

Correlation between the age of pinealectomy and the development of scoliosis in chickens.

STUDY DESIGN: Pinealectomy induces experimental scoliosis in chickens. This study analyzed the correlation between the age at which pinealectomy was performed and the development of scoliosis in chickens. OBJECTIVE: To investigate the differences in the rate or magnitude of scoliosis and the type of curvature in chickens pinealectomized at different times after hatching. SUMMARY OF BACKGROUND DATA: Scoliosis develops in almost all chickens pinealectomized within 3 days after hatching, but there are no data on whether the condition will develop in chickens pinealectomized earlier or later after hatching. METHODS: In this study, 106 female white leghorn chickens were divided into six groups: four pinealectomy groups (pinealectomy was performed 2, 4, 11, or 18 days after hatching in Groups P-2, P-4, P-11, and P-18, respectively), a control group (Group C), and a sham operation group (Group S). Ventrodorsal radiographs of the spine were taken at 4-week intervals until the age of 12 weeks. At 12 weeks, a 1-mL sample of blood was taken from the heart at the middle of the dark cycle, and the serum melatonin concentration was measured by radioimmunoassay. RESULTS: At the age of 12 weeks, scoliosis was present in 63.6% of the chickens in Group P-2, 72.7% in Group P-4, 81% in Group P-11, and 70% in Group P-18, and the Cobb angles in the scoliotic chickens averaged 32.6, 29.8, 23.8, and 22.3 degrees in the respective groups. There were no significant differences in the rate or magnitude of scoliosis and the type of curvature among the pinealectomy groups at the age of 12 weeks. At the age of 12 weeks, the serum melatonin levels at the middle of the dark cycle in the pinealectomized chickens were significantly lower than those of chickens in Groups C and S. However, there were no differences in the serum melatonin levels between scoliotic and nonscoliotic pinealectomized chickens. CONCLUSIONS: Findings from this study show that scoliosis develops in 60% to 80% of chickens pinealectomized within 18 days after hatching, and that scoliotic development is not influenced by the age at which pinealectomy is performed. However, this study suggests that melatonin plays a complicated role in spinal development, inasmuch as the serum melatonin levels after pinealectomy approximated zero. Yet scoliosis did not develop in all pinealectomized chickens.

Aging↗
PubMed2001

Possible association of beta2- and beta3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer.

BACKGROUND: The involvement of beta2-adrenergic receptor (ADRB2) and beta3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. METHODS: A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. RESULTS: Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). CONCLUSION: A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association.

Adult↗
PubMed2001

Subcellular compartment and molecular subdomain of beta-amyloid precursor protein relevant to the Abeta 42-promoting effects of Alzheimer mutant presenilin 2.

Increased production of amyloid beta peptides ending at position 42 (Abeta42) is one of the pathogenic phenotypes caused by mutant forms of presenilins (PS) linked to familial Alzheimer's disease. To identify the subcellular compartment(s) in which familial Alzheimer's disease mutant PS2 (mt PS2) affects the gamma-cleavage of betaAPP to increase Abeta42, we co-expressed the C-terminal 99-amino acid fragment of betaAPP (C100) tagged with sorting signals to the endoplasmic reticulum (C100/ER) or to the trans-Golgi network (C100/TGN) together with mt PS2 in N2a cells. C100/TGN co-transfected with mt PS2 increased levels or ratios of intracellular as well as secreted Abeta42 at similar levels to those with C100 without signals (C100/WT), whereas C100/ER yielded a negligible level of Abeta, which was not affected by co-transfection of mt PS2. To identify the molecular subdomain of betaAPP required for the effects of mt PS2, we next co-expressed C100 variously truncated at the C-terminal cytoplasmic domain together with mt PS2. All types of C-terminally truncated C100 variants including that lacking the entire cytoplasmic domain yielded the secreted form of Abeta at levels comparable with those from C100/WT, and co-transfection of mt PS2 increased the secretion of Abeta42. These results suggest that (i) late intracellular compartments including TGN are the major sites in which Abeta42 is produced and up-regulated by mt PS2 and that (ii) the anterior half of C100 lacking the entire cytoplasmic domain is sufficient for the overproduction of Abeta42 caused by mt PS2.

Alzheimer Disease↗
PubMed2001

Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases.

To identify the amyloid beta peptide (Abeta) 1-42-degrading enzyme whose activity is inhibited by thiorphan and phosphoramidon in vivo, we searched for neprilysin (NEP) homologues and cloned neprilysin-like peptidase (NEPLP) alpha, NEPLP beta, and NEPLP gamma cDNAs. We expressed NEP, phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PEX), NEPLPs, and damage-induced neuronal endopeptidase (DINE) in 293 cells as 95- to 125-kDa proteins and found that the enzymatic activities of PEX, NEPLP alpha, and NEPLP beta, as well as those of NEP and DINE, were sensitive to thiorphan and phosphoramidon. Among the peptidases tested, NEP degraded both synthetic and cell-secreted Abeta1-40 and Abeta1-42 most rapidly and efficiently. PEX degraded cold Abeta1-40 and NEPLP alpha degraded both cold Abeta1-40 and Abeta1-42, although the rates and the extents of the digestion were slower and less efficient than those exhibited by NEP. These data suggest that, among the endopeptidases whose activities are sensitive to thiorphan and phosphoramidon, NEP is the most potent Abeta-degrading enzyme in vivo. Therefore, manipulating the activity of NEP would be a useful approach in regulating Abeta levels in the brain.

Amino Acid Sequence↗
PubMed2001

Analysis of cartilage-derived retinoic acid-sensitive protein in cerebrospinal fluid From patients With spinal diseases.

STUDY DESIGN: The expression of cartilage-derived retinoic acid-sensitive protein (CD-RAP) was measured in cerebrospinal fluid from patients with spinal diseases. OBJECTIVES: To quantify the levels of CD-RAP in human cerebrospinal fluid and to clarify its character. SUMMARY OF BACKGROUND DATA: Cartilage-derived retinoic acid-sensitive protein is a newly discovered, secreted molecule that is expressed during the chondrogenesis phase of endochondral bone formation and in articular cartilage. In recent studies CD-RAP has been detected in the serum of patients with melanoma and breast cancer, and it has been used to monitor tumor activity. However, the function of CD-RAP is unknown, and the expression of CD-RAP in human cerebrospinal fluid has never been reported. METHODS: The concentration of CD-RAP in human cerebrospinal fluid was measured by enzyme-linked immunosorbent assay with antihuman CD-RAP antibodies. Cerebrospinal fluid samples were collected from two groups of patients. Group 1, the control group, consisted of 40 patients: 22 with trauma and 18 with gynecologic diseases. Group 2 consisted of 172 patients with spinal diseases: 5 with meningioma, 5 with neurinoma, 5 with arachnoid cyst, 30 with cervical spondylotic myelopathy, 35 with lumbar disc herniation, 56 with lumbar canal stenosis, and 36 with scoliosis. RESULTS: The concentration of CD-RAP in the control group was 16.5 +/- 8.3 ng/mL. The concentrations of CD-RAP in Group 2 were: 35.3 +/- 14.7 ng/mL in meningioma, 23.5 +/- 7.41 ng/mL in neurinoma, 26.0 +/- 22.2 ng/mL in arachnoid cyst, 41.7 +/- 22.3 ng/mL in cervical myelopathy, 27.8 +/- 14.7 ng/mL in lumbar disc herniation, 36.5 +/- 18.4 ng/mL in lumbar canal stenosis, and 13.4 +/- 7.48 ng/mL in scoliosis. The concentrations of CD-RAP in cervical myelopathy, lumbar canal stenosis, and lumbar disc herniation were significantly higher than in the control group (P < 0.001). CONCLUSIONS: The CD-RAP concentration was low in the control group, whereas it was significantly higher in spinal diseases that cause spinal stenosis. CD-RAP is expressed in cerebrospinal fluid as a result of damage to or stressing of neural structures and could be a marker for spinal diseases.

Adolescent↗
PubMed2001

Osteoclast induction from bone marrow cells is due to pro-inflammatory mediators from macrophages exposed to polyethylene particles: a possible mechanism of osteolysis in failed THA.

Polyethylene debris from joint replacements may be transported in synovial fluid and be phagocytosed by macrophages. The activation and migration of macrophages may play important roles in osteolysis and implant loosening. Tissues from the bone-implant interface do not always contain wear debris, which may mean that osteolysis may not require direct contact with wear debris. We hypothesized that the release of polyethylene debris from the implants induces macrophage activation in the joint space. Then the activated macrophages release humoral factors, such as inflammatory cytokines, into the joint fluid. These cytokines may be transported to the bone marrow tissues around the implants where they stimulate the differentiation of the bone marrow cells into osteoclasts. Finally, the activated osteoclasts resorb the surrounding bone. To test this hypothesis, macrophages were stimulated by polyethylene particles. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay and were increased significantly. To test humoral interaction between macrophages and bone-marrow cells, a co-culture system was used in an in vitro model. With this system, two kinds of cells can be cultured together with humoral contact without the two cell types having to contact each other. We stimulated the macrophages with 5 microm of polyethylene particles and observed whether the bone marrow cells differentiated into the osteoclasts without contact with the macrophages. The numbers of osteoclasts were assessed using tartrate-resistant acid phosphatase (TRAP) staining. The numbers of TRAP-positive cells in the polyethylene particle-stimulated group were higher than in the control group. The ability of the TRAP-positive cells to resorb bone was confirmed by dentine pit formation assay. The results of this study support our hypothesis and suggest that one mechanism of osteolysis in failed joint arthroplasty is the more distant effects of pro-inflammatory cytokine release on osteoclast differentiation and/or activity.

Acid Phosphatase↗
PubMed2001

Relationships of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover and inflammation as revealed by analyses of synovial fluids from patients with rheumatoid arthritis.

OBJECTIVE: To determine interrelationships in matrix turnover in articular cartilage and joint inflammation in rheumatoid arthritis (RA). METHODS: Synovial fluid was obtained from the knees of 63 RA patients; radiographs were evaluated to determine the RA stage. Concentrations of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), the 846 epitope, and the keratan sulfate (KS) epitope of aggrecan, the C-propeptide of cartilage type II procollagen (CPII; biosynthetic marker), the cleavage of type II collagen by collagenase (CIIC; generated neoepitope), and polymorphonuclear leukocyte elastase (PMNE; inflammation marker) were measured by immunoassay. Concentrations of the unsaturated disaccharides of hyaluronic acid (delta di-HA) and the proteoglycan glycosaminoglycan disaccharides of chondroitins 4 and 6 sulfate (delta di-C4S and delta di-C6S) were determined by high-performance liquid chromatography. RESULTS: MMP-3 was markedly increased in RA compared with osteoarthritis. Increases in TIMP-1 in RA were less pronounced and were inversely correlated with MMP-3 levels. CIIC was reduced in RA, as was the release of the KS epitope and delta di-C6S. In contrast, delta di-C4S and the 846 epitope were up-regulated. PMNE levels correlated with the 846 epitope and delta di-C4S, and more strongly with TIMPs 1 and 2. The changes may signify attempts at control of proteolysis in parallel with increased aggrecan turnover, which would favor matrix assembly. PMNE also correlated with MMP-9, and MMP-9 correlated with CPII. The delta di-HA level was decreased in RA and was inversely correlated with CPII and MMP-9 as well as with MMPs 2 and 3. In contrast, delta di-HA was directly correlated with TIMP-1 and the 846 epitope. These observations suggest that HA and PMNs may be involved in the control of proteolysis and cartilage proteoglycan assembly. CONCLUSION: Our observations provide new insights into the complex changes in cartilage turnover and PMN influx in RA joints.

Adult↗
PubMed2001

Acute adrenal failure associated with fluconazole after administration of high-dose cyclophosphamide.

A 63-year-old man received high-dose cyclophosphamide for peripheral blood stem-cell (PBSC) harvest. He received 200 mg fluconazole. On day 3, atrial fibrillation developed with blood pressure declining to 78 mmHg. The rapid adrenocorticotropin (ACTH) test showed blunted adrenal responses. He was suspected as having adrenal failure, and fluconazole was discontinued. The rapid ACTH test became normal on Day 14, and PBSCs were successfully harvested. To clarify the association between adrenal failure and fluconazole, we resumed 400 mg fluconazole on Day 16 and repeated the test on Day 21, which showed blunted adrenal responses. This case demonstrates that prophylactic use of fluconazole can cause adrenal insufficiency.

Adrenal Insufficiency↗