[Antibiotics-associated colitis--Clostridium difficile colitis].
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Biomedical subjects
Publications and source records attributed to T Inamatsu.
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The leucocyte adhesion molecule-1 (LAM-1) is the human homologue of the murine peripheral lymph node homing receptor, MEL-14, and might play a crucial role in neutrophil localization at inflammatory sites. We have reported previously that recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates or enhances several neutrophil functions in vivo, as well as in vitro. To further explore the possible role of G-CSF in inflammation we studied the effect of rhG-CSF on the surface expression of LAM-1 on human neutrophils, both in vitro and in vivo. The expression of LAM-1 by human neutrophils was investigated by indirect immunofluorescence using flow cytometry and monoclonal antibodies anti-Leu-8 and TQ1. A whole blood analysis was performed to minimize in vitro manipulation. Most circulating human neutrophils expressed LAM-1 on the cell surface. Brief exposure of neutrophils to rhG-CSF in vitro decreased the surface expression of LAM-1. rhG-CSF down-regulated neutrophil LAM-1 expression in a time- and dose-dependent manner. Neutrophils from healthy volunteers and from patients who were receiving rhG-CSF exhibited a decreased expression of LAM-1 after rhG-CSF administration, and the expression thereafter returned or overshot the pretreatment level after stopping rhG-CSF administration. These findings indicate that rhG-CSF down-regulates the surface expression of LAM-1 on human neutrophils in vivo, as well as in vitro, and G-CSF might participate in neutrophil-endothelial cell interaction in inflamed tissue.
The metabolism and clinical safety of the pivalic acid-containing antibiotic S-1108, an orally active pro-drug cephalosporin, were investigated to assess the clinical effects, with special emphasis on the influence of carnitine consumption in 15 patients with various infectious diseases receiving S-1108 three times a day at a 300- or 600-mg total daily dose for 3 to 7 days. The free carnitine concentrations in plasma were greatly reduced to approximately 65% of pretreatment levels, and the plasma pivaloylcarnitine (the main metabolite of pivaloyloxymethyl ester) concentrations were increased during the 200-mg (three times a day) regimens but returned to the pretreatment levels within 3 to 5 days after the cessation of treatment. In three elderly patients with declining renal function (creatinine clearance rate, 31 to 50 ml/min), the acylcarnitine/free carnitine ratio increased from 0.1 to 0.4 up to 0.7 to 1.5 at day 5 during the 7-day treatment, showed a tendency to decrease, and then returned to the pretreatment ratio 4 days after discontinuation of the drug. The degree of free carnitine reduction and increase of the acylcarnitine/free carnitine ratio depended mostly on the dose and the duration of S-1108 treatment. The increased acylcarnitine/free carnitine ratio in elderly patients was due to reduction of the free carnitine concentration in plasma and mainly to the retardation of nontoxic pivaloylcarnitine excretion. This study indicated that there was a decrease in free carnitine levels in plasma, but there were no clinical symptoms or adverse effects associated with carnitine reduction in patients during the 7-day multiple administration of S-1108.
During the last 50 years, there have been changes in the types of infectious diseases causing death in Japan. Endemic diseases have decreased and nosocomial infection during the therapeutic course of various diseases have increased. Progress of various new medical technology for cancer therapy and transplantation are supported by developed infection control, and the target of microbiological tests has changed from endemic organisms to resident organisms. To manage infectious diseases, clinicians collect considerable information. Microbiological tests are only one part and sometimes are used to assess therapeutic results. In this situation, microbiological tests sometimes only reconfirm or guide changes in therapeutic strategy if the initial empiric therapy was inappropriate. Then, well designed statistical data are necessary for appropriate empiric therapy. Surveillance of hospital infection is another important role of the microbiological laboratory. To improve the functioning of the microbiological laboratory, we need not only automatic and rapid systems, but also effective communication with clinicians to respond to their needs with clinically useful data.
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Peripheral blood mononuclear cells were obtained from people ranging in age from newborn to 102 years old and analyzed by dual color flow cytometer in terms of number and percentage of various subsets of T cells, B cells and natural killer cells (CD3, 4, 5, 8, 11b, 19, 20, 21, 25, 29, 45RA and 56). Numbers of T cells (CD3+ or CD5+ cells) significantly declined at the 3rd decade as compared with those of younger people, stayed at a relatively constant level between the 3rd and the 7th decade and gradually declined thereafter. In T cell subsets, both CD4 and CD8 positive positive cells decreased with age, but a decrease was more pronounced in the latter, showing an age-related increase of CD4/CD8 ratio. The most interesting finding was a contrasting age-change in two subsets of CD4+ T cells; i.e. a subset of suppressor inducer T cells (CD4+CD45RA+ naive cells) decreased with age, while a subset of helper inducer T cells (CD4+CD29+ memory cells) increased with age. CD20+ B cells also decreased with age in a manner similar to that observed in T cells. Natural killer cells (CD56) showed an increase in numbers with age. The relationship between these changes in various subsets of peripheral blood leukocytes and the age-related decline in immune functions has been discussed.
The Working Party for Legionellosis headed by the Japanese Ministry of Health and Welfare processed to standardize the diagnostic procedures for Legionella pneumonia, as the first step to clarify the actual occurrence of patients with this respiratory disease. All the clinical data were collected and analysed on the 28 culture-confirmed patients in Japan during the past 11 years, from 1980 through 1990. The 28 patients were distributed throughout Japan, from Hokkaido to Kyushu. Out of 28 patients, 18 were community-acquired and 10 were nosocomially infected. In 8 of 18 community-acquired patients, any significant underlying disease was not observed. Though it was dominant in the age group in their 60s & 70s, victims were distributed in adults over 20 years of age and even in a new born baby. Only 5 out of 28 patients recovered successfully. From the autopsy findings, in 5 out of the remaining 23 expired patients, Legionella pneumonia seemed to be successfully treated, but other disease or other bacterial pneumonia put an end to the patients. The results of clinical laboratory tests and the efficacy of antibiotics to Legionella pneumonia were essentially the same as those reported in the literature.
We analyzed the initial and follow-up chest radiographs of 28 patients with culture-positive Legionella pneumonia, and developed a scoring system to quantitate the severity of radiological findings for pneumonia. Intrapulmonary shadows were observed on the initial chest radiograph in 26 patients, but pleural effusion was noted in only one. In one patient the initial chest radiograph had probably been obtained too early to reveal any pulmonary change. Alveolar shadows were noted on the initial radiograph in 21 (81%) patients, and interstitial shadows in 5 (19%). In ten (38%) patients shadows were present in both lung fields. Shadows were prominent in the middle and lower lung fields. A cavity was noted in only one patient, and pleural effusion was also noted at some time during the clinical course in 19 (70%). A large amount of pleural effusion was observed in four patients. The average pneumonia severity score was 3.3 in the 9 patients who survived, and 5.1 in the 17 who died (p > 0.05). The mortality rate was 53% in the 17 patients with pneumonia severity score of 5 or less and 89% in the 9 patients with a score of 6 or more (p > 0.05). Twelve patients died within one week after the initial chest radiograph was obtained. There were no differences among patients with community-acquired infection with or without underlying disease and those with nosocomial infection in characteristic and extension of shadow, presence of pleural effusion, or pneumonia score. The chest radiograph of Legionella pneumonia include bilateral shadow findings characteristic, pleural effusion and rapid progression of shadow, and are clinically useful for diagnosis.
In order to elucidate the frequency of hyperbilirubinemia associated with sepsis in the elderly, as well as in clinical and histological characteristics, a total of 117 autopsy cases with sepsis were analyzed retrospectively. Based on the clinico-pathological findings, 48 cases with primary hepato-biliary, cardiac, hematological and shock complications, were excluded because these disorders were thought to affect liver function tests. Four cases out of the remaining 69 cases, 5.8% of the total, showed hyperbilirubinemia above 2 mg/dl (average 4.1 mg/dl), which was thought to be associated with sepsis itself. In these 4 cases, disproportionately high levels of blood total bilirubin were characteristic compared to changes of GOT, GPT, LDH, ALP and gamma-GTP levels. Blood culture of these 4 cases revealed Gram-negative organisms in 3 cases and Gram-positive in 1 case. Histological findings of the liver included cholestasis, Kupffer cell hyperplasia and cell infiltration in the sinusoid and portal areas, however these findings were mild and nonspecific. It is important to recognize the presence of hyperbilirubinemia associated with sepsis in order to properly treat febrile elderly patients with hyperbilirubinemia.
A case of flunarizine hydrochloride (FZ)-induced severe urinary retention and meteorism which resulted from sphincter spasm of the urinary bladder and the anus is presented. An 81-year-old female had received 10 mg/day FZ orally for 12 months before hypokinesia and general fatigue developed. Physical examination revealed slight rigidity of the extremities, abdominal distention and spasm of the anal sphincter muscle. Laboratory examinations showed uremia (BUN 88 mg/dl, Creatinine 16.8 mg/dl) and abdominal X-ray demonstrated marked distention of the small and large bowels. Renal failure improved within 2 days after massive urination using a urethral catheter. Abdominal distention was improved by the ileus and anal tubes. The difficulties of urination and defecation and decreased mobility of the extremities were resolved one month after the cessation of FZ. No organic changes were detected in urinary, intestinal and neurological systems by cystoscopy, CT, MRI and gastrointestinal fiberscopy. Serum concentration of FZ was 42.5 ng/ml on admission but decreased slowly to 17.9 ng/ml 80 days later. Serum half life was calculated to be 55 days which was 3 times longer than that healthy younger volunteers.
A case of splenic tuberculosis is reported. The patient was a 79-year-old man who was admitted to the Tokyo Metropolitan Geriatric Hospital because of high fever and loss of body weight. Several finger-tip sized superficial lymph nodes were palpable in bilateral inguinal regions. The intermediate PPD skin test was positive. However, there was no evidences of active tuberculosis on the chest roentgenogram. The computed tomogram of the abdomen showed moderate enlargement of the spleen with multiple low density areas and several swollen lymph nodes in the para-aortic region. Although a lymph node of the inguinal region was resected for the pathologic examination, it showed no specific changes. In order to obtain a final diagnosis, laparotomy was performed. The spleen was markedly enlarged and nodular in appearance. No abnormal findings were observed in the other abdominal organs. Splenectomy was carried out. Numerous yellowish nodules, varying from 0.1 to 5 cm in diameter, were observed on the cut surface of the resected spleen (20 x 20 x 8 cm, 700 g). The bacteriologic examination revealed acid-fast bacilli. The fever subsided after splenectomy and following antituberculous therapy. Recently, isolated tuberculosis of the spleen has become very rare. Since 1965, only six cases in five reports can be found in the English, French and German literature. The present case is considered to be one such very rare cases of tuberculosis. Although splenic tuberculosis is rare at the present time, splenic tuberculosis should be included in the differential diagnosis of fever of unknown origin with splenomegaly.
Historically, various types of antibiotic-associated diarrhea have been recognized. In the 1950-1960s, multi-resistant Staphylococcus aureus was implicated to be major cause of antibiotic-associated diarrhea, especially pseudomembranous enterocolitis. In the late 1970s, a new type of antibiotic-associated diarrhea, which is characterized by pseudomembranous colitis and lack of fecal multi-resistant S. aureus, usually following lincosamide administration, was recognized. Many studies have revealed the pathogenic roles of Clostridium difficile in these patients. Recent emergence of methicillin resistant S. aureus (MRSA) provokes another type of antibiotic-associated diarrhea. We have tried to isolate S. aureus and C. difficile from 150 faecal samples of patients with antibiotic-associated diarrhea. S. aureus alone was isolated from 32 (21.3%) samples. C. difficile alone was isolated from 51 (34.0%) samples, and, both were detected in 23 (15.3%) samples. 90.9% of S. aureus were MRSA. Comparing the clinical features of these cases, patients with both C. difficile and MRSA showed more serious clinical features. The patients who had undergone laparotomy were accompanied by shock and meteorism, more often than patients without laparotomy. The management of antibiotic-associated diarrhea due to MRSA is discussed.
Wide spread of MRSA infection in geriatric hospitals indicated two important problems which must be resolved. One is how we can eradicate MRSA in the elderly, and the other is how we can control cross infections of MRSA within the hospital. The presence of infected decubital ulcers in the elderly make it difficult to answer these problems. Usually, MRSA and Pseudomonas aeruginosa which is isolated from decubital ulcers act as colonizers on the surface of granulated wounds but do not contribute to clinical symptoms. However, these colonizers can be the source of cross infection toward other debilitated patients. The actual management for decubital ulcer infected by MRSA are discussed from the above viewpoints.
Bacterial meningitis is one of complications in the elderly with neurosurgical procedures. In an attempt to find the clinical features of this complication we analyzed 10 cases, which were found in 30 cases of the bacterial meningitis in Tokyo Metropolitan Geriatric Hospital from 1972 to 1989. The patients were 4 males and 6 females, 52-86 years old (the mean, 69). While 2 Enterococcus species were isolated after craniotomy, Staphylococci were common pathogens (4 S. aureus, 4 S. epidermidis and 1 P. aeruginosa) in patients with shunt infection. Most of these patients lacked typical manifestations of meningitis except the fever. Symptoms occurred long after surgery with little abnormality in the data of serum and cerebrospinal fluid. However, blood cultures were positive in 75% of the cases. Removal of the infected catheter was effective in the cases of shunt infection.
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We report a 77-year-old woman with Guillain-Barré syndrome following Campylobacter jejuni infection. She was admitted complaining of mild weakness in the left leg. Seven days before, she had severe diarrhea, which continued several days. After admission, the weakness soon worsened resulting in tetraparesis, and the respiration became so impaired that she was supported by the artificial ventilator. Deep tendon reflexes were absent in four limbs, and no sensory disturbance was noted. CSF contained the protein as low as 20.4 mg/dl in concentration; no pleocytosis was seen. Muscle action potentials evoked by the stimulation of nerves were markedly reduced in amplitude, but conduction velocity along the nerve was decreased mildly. Campylobacter jejuni was detected by bacterial culture of the stool; the antibody was positively raised against this bacteria in serum. By 90 hospitals days, she was restored to spontaneous respiration.