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Biomedical subjects

N Manabe

Publications and source records attributed to N Manabe.

At least 19 recordsLinked to original sources
PubMed2007

Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression.

The proto-oncoproteins ETS1 and growth factor independent-1 (GFI1) are implicated in cell growth and differentiation in various types of cells, and their deregulated expression is involved in malignant transformation. Here, we report that ETS1 and GFI1 interact and affect gene expression through their cross-talk. Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner. However, in the Bax promoter where the Ets- and Gfi-binding sites (EBS and GBS) are adjacent, ETS1 and GFI1 cooperatively reduced activation. Site-directed mutagenesis on the EBS and GBS of the Bax promoter showed that both binding sites were necessary for full repression. Chromatin immunoprecipitation analyses confirmed that an ETS1-GFI1 complex formed on the Bax promoter even when either EBS or GBS was mutated. Introduction of small interfering RNA against ETS1 and/or GFI1 enhanced endogenous Bax gene expression. Our results suggest that the interaction between ETS1 and GFI1 facilitates their binding to specific sites on the Bax promoter and represses Bax expression in vivo.

Binding Sites↗
PubMed2006

The usefulness of transabdominal ultrasound for the diagnosis of lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal bleeding is a frequent cause of hospitalization, but diagnostic methods for this condition are not fully established. Transabdominal ultrasound is a widely accepted diagnostic tool in bowel diseases. AIM: To evaluate the usefulness of transabdominal ultrasound for lower gastrointestinal bleeding. METHODS: We reviewed the medical records of consecutive patients who underwent transabdominal ultrasound as the first diagnostic procedure for acute haematochezia during the period June 1999 to June 2004. The study group comprised 111 patients and all underwent colonoscopy thereafter. Detection and diagnosis of lower gastrointestinal bleeding by ultrasonographic examination were evaluated by comparing the ultrasound diagnosis with the colonoscopic findings and final diagnosis. RESULTS: The bleeding site was localized by colonoscopy in 90 of the 111 patients (81%). The bleeding site was localized by ultrasound in 59 of the 90 patients (66%). When the bleeding site was in the rectum, ultrasonographic detectability was 30% (10/33); ultrasonographic detectability was 82-100% when the bleeding site was elsewhere. Rectal bleeding and diverticular bleeding were difficult to diagnose by ultrasound, but for the other diseases, diagnosis by ultrasonographic examination was possible in 91-100% of cases. CONCLUSIONS: Ultrasonographic examination may be an effective screening method for lower gastrointestinal bleeding.

Colon↗
PubMed2006

A novel strategy for preventing human CD8+ cytotoxic T lymphocyte-mediated cytotoxicity against pig endothelial cells by overexpression of pig cellular FLICE-like inhibitory protein (c-FLIP) gene.

Human CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity in xenograft recipients is an important obstacle for successful xenotransplantation of pig organs into humans. In our previous study, we demonstrated that xenocytotoxicity of human CD8+ CTL detrimental to pig endothelial cells (PEC) is mediated mainly by the Fas/FasL apoptotic pathway. Furthermore, we developed new methods to prevent this CTL killing by extracellular remodeling using overexpression of human decoy Fas antigen and membrane-bound human FasL on pig xenograft cells. The cellular FLICE-inhibitory protein (c-FLIP), a caspase-8 inhibitor that lacks the cysteine domain, is a negative regulator of death receptor-mediated apoptosis. c-FLIP proteins exist as long (c-FLIP(L)) and short (c-FLIPs) splice variants, both capable of protecting cells from death receptor-mediated apoptosis. In this report, we have demonstrated that both pig c-FLIPs and pig c-FLIP(L) significantly inhibit human CD8+ CTL-mediated xenocytotoxicity toward stably transfected PEC, although the expression level of pig Fas antigen on cell surface was not changed. These data suggested that intracellular remodeling with overexpression of pig c-FLIP in xenograft cells may decrease the innate cellular responses against xenografts, facilitating long-term xenograft survival.

Animals↗
PubMed2005

Famotidine prevents canine gastric blood flow reduction by NSAIDs.

AIM: To investigate the effect of famotidine on gastric blood flow reduction induced by diclofenac sodium, a common non-steroidal anti-inflammatory drug in Japan, using laser Doppler flowmetry in the canine stomach. METHODS: The gastric mucosal blood flow was measured by laser Doppler flowmetry in 15 healthy male beagles before and 60 min after the administration of diclofenac suppository (1.0 mg/kg) into the rectum. The examination was done in a crossover, single-blinded fashion. All dogs underwent both famotidine (0.5 mg/kg) and placebo (saline) injection simultaneously with the administration of diclofenac. In addition, the tissue concentration of prostaglandin E2 was measured. RESULTS: The blood flow decreased by 18.3 +/- 9.1% in the gastric body, by 26.3 +/- 8.1% in the antrum in the placebo group after the administration of diclofenac sodium, while the decreases seen were significantly smaller in the famotidine group: 3.2 +/- 12.6% in the gastric body and 7.9 +/- 16.5% in the antrum (P = 0.001 for the gastric body, P = 0.0034 for the antrum). Conversely, the percentage of mucosal prostaglandin E2 concentration decrease in each group did not show a significant difference. CONCLUSION: Famotidine alleviates the reduction of gastric blood flow induced by diclofenac sodium. Further, not only mucosal prostaglandins but also gastric acid may play an important role in non-steroidal anti-inflammatory drugs-induced gastric microcirculatory disturbance.

Animals↗
PubMed2004

Sonographic detection of longitudinal ulcers in Crohn disease.

BACKGROUND: The purpose of this study was to investigate the characteristic sonographic features, such as focal disappearance of the wall stratification sign (FD sign), of longitudinal ulcers in patients with Crohn disease (CD). METHODS: A total of 545 sonographic examinations of patients with Crohn disease (n = 166), ulcerative colitis (n = 196), bacterial colitis (n = 78), ischemic colitis (n = 63), pseudomembranous colitis (n = 32), Behçet's disease (n = 7), and collagenous colitis (n = 3) were extracted. The sonographic findings were compared with those of a barium contrast study, colonoscopy, and resected specimens. In transverse views of the bowel segment, wall stratification was investigated. The FD sign was defined as the disappearance of the layered structure observed in a single portion of the bowel circumference. Prevalence of the FD sign was investigated for each disease. RESULTS: Eighty lesions (76 CD, 1 ulcerative colitis, 2 ischemic colitis, 1 Behçet's disease) with active single longitudinal ulcers were detected by barium contrast study and endoscopy. Among them, the FD sign was detected by ultrasonography (US) in 73 lesions (91.3%). No lesions with the FD sign were found by US without radiological or endoscopic findings of longitudinal ulcers. An in vitro study (water-immersion method) of resected specimens revealed that the FD sign reflected the focal destruction of wall stratification caused by the deep longitudinal ulceration. CONCLUSIONS: Ultrasonographic findings of FD sign are correlated with the existence of deep longitudinal ulcers, which are most frequently found in CD. US is a useful diagnostic modality for detecting longitudinal ulcers in patients with CD.

Adolescent↗
PubMed2003

Augmented cytoplasmic Smad4 induces acceleration of TGF-beta1 signaling in renal tubulointerstitial cells of hereditary nephrotic ICGN mice with chronic renal fibrosis; possible role for myofibroblastic differentiation.

The Institute of Cancer Research (ICR)-derived glomerulonephritis (ICGN) mouse is a hereditary model animal for nephrotic syndrome with chronic renal tubulointerstitial fibrosis. In most fibrotic diseases, myofibroblastic differentiation is considered to play crucial roles in pathogenesis of fibrosis and is dominantly regulated by the transforming growth factor (TGF)-beta1 signaling system. To reveal the pathogenic mechanism of chronic renal fibrosis in ICGN mice, we examined the expression and localization of TGF-beta1 signal transducer proteins (TGF-beta receptor-I and -II, Smad2/3 and Smad4) in kidney sections and in primarily cultured tubulointerstitial fibroblasts (TIFs). In kidneys of ICGN mice, many tubulointerstitial cells were differentiated to myofibroblastic cells and were alpha-smooth muscle actin (alphaSMA)-positive. The numbers of alphaSMA-positive TIFs prepared from kidneys of ICGN mice (ICGN-TIFs), but not those of ICR control mice (ICR-TIFs), increased during cell culture. No significant differences in production or activation of TGF-beta1 between ICGN-TIFs and ICR-TIFs were seen by enzyme-linked immunosorbent assay. In vitro transcriptional reporter assay for TGF-beta1 and Western immunoblotting for TGF-beta1 signal transducers showed no notable differences in the expression levels of TGF-beta receptor-I or -II or Smad2/3 between these TIFs. However, augmented cytoplasmic Smad4 protein in ICGN-TIFs, but not ICR-TIFs, seemed to cause hypersensitivity against TGF-beta1, and the eventual nuclear localization of Smad2/3-Smad4 complex was increased in ICGN-TIFs. Thus, the abnormal cytoplasmic augmentation of Smad4 induces acceleration of TGF-beta1 signaling in the renal tubulointerstitial cells of ICGN mice.

Animals↗
PubMed2003

Long-term observation of reflux oesophagitis developing after Helicobacter pylori eradication therapy.

BACKGROUND: Development of reflux oesophagitis after Helicobacter pylori eradication therapy has been reported, but the prognosis is not well known. AIM: To evaluate the prognosis of patients with reflux oesophagitis that developed after eradication therapy by long-term observation. METHODS: Forty-five patients who developed reflux oesophagitis after successful H. pylori eradication therapy were followed up prospectively. All 45 patients were followed up by endoscopy more than 3 years after onset of reflux oesophagitis (3-year follow-up group) and nine were followed up more than 5 years after onset (5-year follow-up group). Endoscopic observations were performed yearly or when upper gastrointestinal symptoms recurred. Reflux oesophagitis was graded according to the Los Angeles Classification System. Presence of gastro-oesophageal reflux symptoms and medication of proton pump inhibitors, H2-blockers or prokinetics were investigated at final endoscopy. RESULTS: All patients were classified as grade A or B at initial endoscopy. At final observation, the grade of reflux oesophagitis improved in 35/45 (78.8%) patients from the 3-year follow-up group and 7/9 (78.8%) patients from the 5-year follow-up group. Reflux oesophagitis progressed from grade A to B in only four (8.9%) patients from the 3-year follow-up group and in no patients in the 5-year follow-up group. No patient progressed to grade C or D. Gastro-oesophageal reflux symptoms were seen in 12 patients (26.7%) from the 3-year follow-up group and four patients (44.4%) from the 5-year follow-up group. Among them, medication was needed continuously in only six (13.3%) and two (22.2%) patients, respectively. CONCLUSIONS: Reflux oesophagitis, which develops after H. pylori eradication therapy, rarely becomes a long-term clinical problem among patients who complete therapy successfully.

Amoxicillin↗
PubMed2003

Autonomic nerve dysfunction is closely associated with the abnormalities of esophageal motility in reflux esophagitis.

BACKGROUND: While reflux esophagitis (RE) is often associated with esophageal motility dysfunction, the causes of this abnormal motility are not well understood. The aim of our study was to assess the relationship between esophageal motility and autonomic nerve dysfunction by comparing 14 healthy control subjects (11 M, 3 F; mean age, 56.4 years) with 26 patients with RE (19 M, 7 F; mean age, 60.4 years). METHODS: According to results of esophageal manometry, subjects with RE were assigned to group I (RE with esophageal motility dysfunction, n = 12) or group N (RE without motility dysfunction, n = 14). Autonomic neuropathy was assessed by measuring the heart rate coefficient of variation at rest (CVR-R), the Valsalva ratio for the R-R interval, the systolic blood pressure response to mental calculation, and the antral contractile response to modified sham feeding (MSF). RESULTS: CVR-R at rest was lower in group I (2.08 +/- 0.18) than in group N (3.80 +/- 0.44; P < 0.05). The frequency of antral contractile response to MSF per 3-min interval over 15 min was significantly lower in group I than in either group N or controls. The 15-min integrated antral contractile response, taken as the area under the contraction time curve, was much lower in group I (13.2 +/- 6.2) than in controls (55.6 +/- 9.2; P < 0.01). CONCLUSIONS: We conclude that esophageal motor dysfunction in some patients with RE may result from autonomic dysfunction.

Adult↗
PubMed2003

Expression and activity of Apaf1 and caspase-9 in granulosa cells during follicular atresia in pig ovaries.

Apoptosis in granulosa cells plays a crucial role in ovarian follicular atresia, but the intracellular regulating mechanism, especially the mitochondrion-dependent apoptosis signalling pathway, is still largely unknown. This study examined whether the mitochondrial pathway is associated with granulosa cell apoptosis during atresia in pig ovaries. Both mRNAs of caspase-9 and apoptotic protease-activating factor 1 (Apaf1), which are major signal transducing components in the mitochondrial pathway, were detected in granulosa cells in healthy, early atretic and progressed atretic follicles by RT-PCR. No changes in the expression of Apaf1 mRNA were seen during follicular atresia, but the expression of caspase-9 mRNA increased during atresia. Apaf1 protein was steadily detected in granulosa cells prepared from healthy, early atretic and progressed atretic follicles by western blot analysis, but high expression of the precursor of caspase-9 (procaspase-9) was detected only in granulosa cells of healthy follicles. Decreased procaspase-9 protein was demonstrated during follicular atresia. Proteolytic activity of caspase-9 increased during atresia, in agreement with the diminution of procaspase-9 protein. Intensive expression of caspase-9 mRNA was demonstrated in the granulosa cells of early atretic and progressed atretic follicles but not in those of healthy follicles. These results indicate that the mitochondrial signalling pathway, which is mediated by Apaf1 and caspase-9, plays a crucial role in determining the fate of granulosa cells during atresia in pig ovaries.

Animals↗
PubMed2002

Long-term rebamipide therapy improves Helicobacter pylori-associated chronic gastritis.

We investigated an antiinflammatory effect of rebamipide [2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid], a gastroprotective agent, in H. pylori-associated gastritis. Eighty-six patients with H. pylori-positive chronic gastritis were enrolled: 53 were treated with rebamipide (300 mg daily for 12 months) and 33 served as controls. Significant decreases in mononuclear cell infiltration into the antrum and corpus were noted in the rebamipide treatment group (before vs after, 1.42 +/- 0.15 vs 1.02 +/- 0.15; P < 0.01 and 1.60 +/- 0.15 vs 1.21 +/- 0.14; P < 0.05, respectively). Levels of infiltrating neutrophil were also decreased in the antrum (before vs after, 0.98 +/- 0.14 vs 0.70 +/- 0.13; P < 0.05) and were associated with a decrease in iNOS production. Sera from patients treated with rebamipide showed a significant decrease in gastrin (276.3 +/- 58.3 pg/ml vs 173.0 +/- 34.2 pg/ml; P < 0.05), whereas no change was observed in the control group. These suggest that long-term rebamipide treatment improved histologic gastritis and decreased serum gastrin levels in H. pylori-associated gastritis.

Alanine↗
PubMed2002

Evaluation of esophageal motility by endosonography using a miniature ultrasonographic probe in patients with reflux esophagitis.

BACKGROUND: Although there are several established methods used to evaluate esophageal motility, none allows for direct observation of esophageal wall motion. Esophageal dysmotility is thought to contribute to reflux esophagitis (RE). The aim of this study was to evaluate esophageal wall motility by endosonography using a miniature ultrasonographic probe (MUP) in patients with RE. METHODS: The subjects consisted of 10 healthy controls (10 men with a mean age of 31.5 years) and 9 patients with RE (4 men and 5 women with a mean age of 51.5 years). High-frequency endoluminal sonography was performed using a 20-MHz transducer through a 16F gastric tube to evaluate esophageal wall motion. Four sonographic phases of an esophageal peristaltic sequence were identified. In the resting phase, the esophageal wall was in direct contact with the transducer. In the passive distention phase, the esophageal lumen was stretched maximally; in the contraction phase, it contracted; and in the relaxation phase, it returned to baseline. The baseline thickness of the muscle layers of the esophageal wall was measured at rest. The width decreased during the passive distention phase, increased and reached a maximum during the contraction phase, and returned to baseline during the relaxation phase. RESULTS: The contractility index of the circular smooth muscle (CSM) in the distal esophagus and of the longitudinal smooth muscle (LSM) in the proximal esophagus were significantly lower in patients with RE. The duration of contraction in the distal esophagus was significantly longer in RE. CONCLUSIONS: We used a MUP to demonstrate abnormalities in esophageal wall motility in patients with RE. We conclude that the MUP is a potentially useful technique for evaluating esophageal dysmotility.

Adult↗
PubMed2001

Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a common skeletal dysplasia characterized by disproportionate short stature, early-onset osteoarthrosis, and dysplasia of the spine, epiphysis, and metaphysis. Multiple epiphyseal dysplasia (MED) is a similar but less severe disorder characterized by dysplasia of the epiphysis. Both disorders are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. COMP mutations cluster in a region of the gene that encodes calmodulin-like repeats (CLRs) and correlate closely with disease severity. Typically, mutations in exon 13 that composes the seventh CLR produce severe PSACH phenotypes, whereas mutations found elsewhere in the gene produce mild PSACH or MED phenotypes. We have identified a PSACH patient carrying a novel mutation in exon 18 of COMP that composes the C-terminal globular domain. This mutation produced a severe PSACH phenotype with marked short stature and deformities of the spine and extremities. Our results extend the range of disease-causing mutations within the COMP gene and demonstrate the importance of the additional domain of COMP protein in its in vivo function.

Achondroplasia↗
PubMed2001

Connection between B lymphocyte and osteoclast differentiation pathways.

Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another osteoclast differentiation pathway closely connected with B lymphocyte differentiation. Recently the TNF family molecule osteoclast differentiation factor/receptor activator of NF-kappaB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating osteoclast differentiation. We demonstrate that B-lymphoid lineage cells are a major source of endogenous ODF/RANKL in bone marrow and support osteoclast differentiation in vitro. In addition, B-lymphoid lineage cells in earlier developmental stages may hold a potential to differentiate into osteoclasts when stimulated with M-CSF and soluble ODF/RANKL in vitro. B-lymphoid lineage cells may participate in osteoclastogenesis in two ways: they 1) express ODF/RANKL to support osteoclast differentiation, and 2) serve themselves as osteoclast progenitors. Consistent with these observations in vitro, a decrease in osteoclasts is associated with a decrease in B-lymphoid cells in klotho mutant mice (KL(-/-)), a mouse model for human aging that exhibits reduced turnover during bone metabolism, rather than a decrease in the differentiation potential of osteoclast progenitors. Taken together, B-lymphoid lineage cells may affect the pathophysiology of bone disorders through regulating osteoclastogenesis.

Aging↗
PubMed2001

Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures.

We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. elegans atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607--3614]. Together with the fact that aPKC and a mammalian PAR-3 homologue, aPKC-specific interacting protein (ASIP), colocalize at the tight junctions of polarized epithelial cells (Izumi, Y., H. Hirose, Y. Tamai, S.-I. Hirai, Y. Nagashima, T. Fujimoto, Y. Tabuse, K.J. Kemphues, and S. Ohno. 1998. J. Cell Biol. 143:95--106), this suggests a ubiquitous role for aPKC in establishing cell polarity in multicellular organisms. Here, we show that the overexpression of a dominant-negative mutant of aPKC (aPKCkn) in MDCK II cells causes mislocalization of ASIP/PAR-3. Immunocytochemical analyses, as well as measurements of paracellular diffusion of ions or nonionic solutes, demonstrate that the biogenesis of the tight junction structure itself is severely affected in aPKCkn-expressing cells. Furthermore, these cells show increased interdomain diffusion of fluorescent lipid and disruption of the polarized distribution of Na(+),K(+)-ATPase, suggesting that epithelial cell surface polarity is severely impaired in these cells. On the other hand, we also found that aPKC associates not only with ASIP/PAR-3, but also with a mammalian homologue of C. elegans PAR-6 (mPAR-6), and thereby mediates the formation of an aPKC-ASIP/PAR-3-PAR-6 ternary complex that localizes to the apical junctional region of MDCK cells. These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells.

Actins↗
PubMed2001

Spondylar dysplasia in type X collagenopathy.

BACKGROUND: The type X collagen gene (COL10A1) is currently known as the disease-causing gene of metaphyseal dysplasia type Schmid (MDS), whereas a mutation of COL10A1 has been reported to cosegregate with a disease phenotype of mild spondylometaphyseal dysplasia (SMD) in a Japanese family. OBJECTIVE: To elucidate whether or not spondylar dysplasia is common in patients with mutations of COL10A1. MATERIALS AND METHODS: We re-evaluated the radiological manifestations in six patients with mutations of COL10A1, who had been previously reported as having MDS. RESULTS: Two of six patients showed mild platyspondyly in infancy and early childhood. In both patients, the spondylar dysplasia tended to normalize with age, but mild alterations of the vertebral bodies persisted, even into late childhood. The other radiological manifestations of both patients were identical to those of MDS. CONCLUSION: Our observation suggests that mild spondylar dysplasia may not be uncommon in MDS.

Bones of Upper Extremity↗
PubMed2001

Dynamic changes in protein components of the tight junction during liver regeneration.

The construction of the hepatocyte tight junction is one of the most important events during liver regeneration leading to the reorganization of the bile canaliculi and the repolarization of hepatocytes after cell division. To understand this event at the molecular level, we examined the expression of tight junction proteins by Western blot analysis and their cellular localization by immunofluorescence microscopy in regenerating rat liver after two-thirds hepatectomy. The levels of tight junction components such as claudin-3, ZO-1 and atypical protein kinase C (PKC)-specific interacting protein (ASIP) increased two- to three-fold over control levels in coordination with a peak 2-3 days after partial hepatectomy, whereas occludin levels remained unchanged. The bile canaliculi outlined by tight junction components and actin filaments reveal significant morphological changes from 2-3 days after partial hepatectomy. During this period, claudin-3/ZO-1 and ASIP/ZO-1 were nearly co-localized, whereas occludin was locally reduced or almost absent on the bile canaliculi outlined by ZO-1 staining. The uncoupled localization of F-actin and tight junction components was often observed. The function of hepatocytes, as revealed by the serum bile acids level, was distorted temporally at an early stage of regeneration but mostly restored 3 days after partial hepatectomy. These observations suggest that the de novo construction of tight junctions proceeds mainly 2-3 days after partial hepatectomy in parallel with the cell polarization required for hepatocyte function. However, the complete normalization of the composition of the tight junction components, such as occludin and the association with F-actin, requires additional time, which may support the regeneration of fully polarized normal hepatocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Urinary tract infection in neurogenic bladder.

The most frequent medical complication in patients with neurogenic bladder dysfunction is urinary tract infection (UTI). In the acute phase of neurogenic bladder, aseptic intermittent catheterization should be applied. After this phase, patients are subject to UTIs leading to febrile diseases. In the chronic phase of neurogenic bladders, febrile infections are often accompanied with hypertonic bladder. Some causes or symptoms prior to febrile attack are recognized in many of the cases. Antimicrobial chemotherapy has to be started in time without delay. Newer generation cephalosporins and carbapenems may shorten the febrile period. We report our experience with 229 patients treated between January 1993 and December 1998.

Acute Disease↗