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Biomedical subjects

Y Kitahara

Publications and source records attributed to Y Kitahara.

At least 19 recordsLinked to original sources
PubMed2006

A case of amelogenesis imperfecta, cleft lip and palate and polycystic kidney disease.

OBJECTIVE: Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders characterized by developmental abnormalities of tooth enamel. The AI is also seen as part of multi-organ abnormalities, e.g. with cone-rod dystrophy, hypothalamo-hypophyseal insufficiency and renal failure. The present patient with AI and nephrocalcinosis exhibited a phenotype different from previous cases with renal failure. To highlight the characteristics of this rare case, extensive analysis that included histological, biochemical and genetic examinations was performed. PATIENT: The present Japanese male patient exhibited dentition with AI and bilateral cleft lip and palate. Ground sections of his extracted tooth showed that it was hypomaturation-type AI, unlike previous cases with nephrocalcinosis were hypoplastic-type. He showed nephrocalcinosis and hematuria at 15 years of age but these symptoms appeared to be secondary to polycystic kidney disease. He showed skeletal Class II pattern with a retrognathic profile and retroclined incisors of both arches. A dolicofacial appearance was seen with an enlarged gonial angle. Biochemical makers including serum alkaline phosphatase, parathyroid hormone, calcitonin, calcium, and phosphate, were all in the normal range. Sequence analysis of the genes encoding amelogenin and enamelin, which are known to be responsible for hypoplastic-type AI, did not reveal any mutations. Since mouse null mutant of homeobox transcription factor, Msx2, exhibits a phenotype resembling AI, the human homolog of this gene, MSX2, was sequenced. There was a missense mutation of T447C that resulted in the conversion of methionine to threonine at 129.

Adult↗
PubMed2004

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development.

Acid Phosphatase↗
PubMed2004

Role of early insulin secretion in postglucose-loading hyperglycaemia and postfat-loading hyperlipidaemia: comparing nateglinide and glibenclamide for acute effects on insulin secretion in OLETF rats.

AIM: The aim of this study was to clarify the role of an early insulin secretion in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats with visceral obesity was performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading. METHODS: Fasting rats were given 50 mg/kg of NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then immediately given oral glucose 1 g/kg. RESULTS: An acute increase in insulin levels in portal blood peaked at 15 min in the NAT group, while insulin levels in the GB group continued to increase significantly after 60 min. Glucose levels in peripheral blood were significantly lower in the NAT group at 30 and 60 min and in the GB group at 120, 180 and 270 min after glucose loading, compared with those in the vehicle group. Subsequently, fasting rats were given NAT, GB or vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute increase in insulin secretion was seen with NAT, peaking at 30 min, while TG, chylomicron and very low-density lipoprotein levels after fat loading were shown to be significantly lower with NAT than with vehicle. However, the continued insulin secretion observed with GB led to no significant decrease in TG levels after fat loading. In addition, lipoprotein lipase mRNA expression in adipose tissue increased significantly 120 min after NAT administration in comparison with baseline. This increase was not noted with GB administration. CONCLUSION: Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.

Adipose Tissue↗
PubMed2004

Concentration of clarithromycin and 14-R-hydroxy-clarithromycin in plasma of patients with Mycobacterium avium complex infection, before and after the addition of rifampicin.

Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

Aged↗
PubMed2003

Development of a novel mouse osteoclast culture system including cells of mandibular body and erupting teeth.

Osteoclasts are multinucleated cells with the specialized function of resorbing calcified tissues. These cells develop from hemopoietic cells of the monocyte-macrophage lineage with the support of osteoblasts/stromal cells. Tooth eruption is a vertical movement of teeth via creation of an eruption pathway in and through the alveolar bone. The precise cellular and molecular determinants of tooth eruption are not yet clear, and a cell culture system that can reproduce the activity of osteoclast formation during tooth eruption is expected to be a useful tool to clarify the mechanism of eruption pathway formation. To this end, mandibular bodies, including incisors and molars, were isolated from 9- to 11-day-old mice undergoing active tooth eruption. Primary cells were obtained from mandibular bodies by enzymatic digestion and cultured in alphaMEM containing 15% FBS without any cytokine or growth factor or hormone in the culture (AFT culture, for alveolar bone, dental follicle, and tooth). A progressive increase in the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells was observed in AFT culture. The osteoclastic cells generated were immunopositive for cathepsin K and calcitonin receptor, and formed resorption pits when cultured on dentine slices. Parathyroid hormone-related protein (PTHrP), expressed by the enamel organ of tooth, is reported to be an essential factor in creation of the eruption pathway. To verify this point, cells were isolated from mandibular bodies from which all teeth and dental follicles had been removed and cultured similarly (A culture, for alveolar bone). Osteoclastic cells were not formed and PTHrP production was hardly detected in the medium of A culture, in contrast to the high level of PTHrP in AFT culture. Since our previous study demonstrated that neonatal homozygous PTHrP-knockout mice show impaired osteoclastogenesis around tooth germs, AFT culture was performed by using this sample to examine whether this culture system can reproduce the status of osteoclastogenesis observed in vivo. The result showed that none of the osteoclastic cells were generated from cells of homozygous mice. We here report a novel mouse osteoclast culture system that reproduces the activity of osteoclast formation around erupting teeth without addition of any cytokine or growth factor or hormone to the medium. Histological examination of various transgenic and mutant mice now offers valuable findings on studies of tooth eruption and the present culture system using these animals would be a powerful tool in clarifying the cellular and molecular mechanisms of eruption pathway formation.

Animals↗
PubMed2002

Disturbed tooth development in parathyroid hormone-related protein (PTHrP)-gene knockout mice.

Parathyroid hormone-related protein (PTHrP) is involved in epithelial-mesenchymal cell interactions during development of various tissues and organs. Tooth germ development is a classical model for this interaction. In tooth germs, PTHrP is expressed in the enamel organ (epithelial component), whereas its major receptor, the type I PTH/PTHrP receptor is expressed in cells of the alveolar bone and dental follicle (mesenchymal components). To clarify the role of PTHrP during fetal tooth germ development, PTHrP gene-knockout mice were used for histochemical and ultrastructural analysis. In wild-type mice, osteoclastic cells were aligned predominantly in the inner aspects of the alveolar bone surrounding the developing tooth germs throughout the late embryonic (after embryonic, 17.5 days) and neonatal animals examined. In contrast, osteoblasts were predominant in corresponding areas of fetal homozygous PTHrP-gene knockout mice with only occasional osteoclasts. In such areas, cell-free surfaces showing cement line-like tartrate-resistant acid phosphatase (TRAP) reactions were frequently observed. In neonatal homozygous mice, bone spicules were often shown to penetrate and/or compress the enamel organ and caused partial destruction of the tooth germs. Osteoclasts were few in number in the inner aspects of the alveolar bone, and had poorly developed ruffled border. No morphological abnormality was noted in cells of the tooth germs proper. On bone surfaces away from developing tooth germs, functional osteoclasts with structural features similar to those in wild-type mice were observed in homozygous mice. These observations suggest that PTHrP is required to maintain an appropriate spatiotemporal arrangement of bone cells and osteoclast function, which are necessary for the normal development of tooth germ and alveolar bone encasing the tooth germ. The observation also demonstrates that PTHrP deficiency affects the structure and function of osteoclasts exclusively those located in the vicinity of the growing tooth germ.

Acid Phosphatase↗
PubMed2001

Expression of chloride channel, ClC-5, and its role in receptor-mediated endocytosis of albumin in OK cells.

By using Western blot and RT-PCR analyses, the expression of ClC-5, a member of the ClC family of voltage-gated chloride channels, and its mRNA was detected in OK cells. The effect of chloride channel inhibitors on receptor-mediated endocytosis of albumin was examined in OK cells and compared to that of vacuolar H(+)-ATPase inhibitors. Accumulation of fluorescein-isothiocyanate (FITC)-albumin, a receptor-mediated endocytosis marker, was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a chloride channel inhibitor, in a concentration-dependent fashion. In contrast, uptake of FITC-inulin, a fluid-phase endocytosis marker, was not affected by NPPB. Other chloride channel inhibitors, 4,4'-diisothiocyanatostilbene-2-2'-disulfonic acid and diphenylamine-2-carboxylic acid, also inhibited FITC-albumin uptake. NPPB, as well as a vacuolar H(+)-ATPase inhibitor bafilomycin A(1), caused a decrease in the affinity and in the maximal velocity of FITC-albumin uptake. These results suggest that chloride channel, most likely ClC-5, plays an important role in the receptor-mediated endocytosis of albumin in OK cells.

Albumins↗
PubMed2001

A case of late onset cardiac amyloidosis with a new transthyretin variant (lysine 92).

A new transthyretin (TTR) variant (lysine 92), which causes late onset cardiac amyloidosis, is described in a 71-year-old man. The patient at first had syncope due to ventricular tachycardia and was admitted our hospital. Typical findings of cardiac amyloidosis were observed by echocardiography, and a diagnosis of systemic amyloidosis was made by rectal biopsy. The man died approximately 3 years and 6 months after first admission, with gradually worsening congestive heart failure. Pathological examination showed prominent amyloid deposits in the heart and the vascular wall of many organs including the liver, pancreas, kidney, lung, and gastrointestinal tracts. Amyloid protein of transthyretin type was indicated by immunohistochemical study, and DNA sequencing identified a novel mutation in the transthyretin gene encoding 92 glutamine --> lysine. A polymerase chain reaction-induced mutation restriction analysis with a mismatched antisense primer showed that the patient was heterozygous for the TTR Lys92 allele.

Adult↗
PubMed2001

The effects of anesthetics on cortical spreading depression elicitation and c-fos expression in rats.

The effects of anesthetics on the generation of cortical spreading depression (CSD) were investigated. Volatile anesthetics halothane, isoflurane, sevoflurane (0.5, 1.0, and 2.0 MAC), and the intravenous anesthetic pentobarbital were studied. Cortical spreading depression was induced by 3M-KCl applied to a surface of brain cortex for 30 minutes. Direct current (DC) potential was recorded, and the number, amplitude, and duration of CSDs were observed. With increasing concentrations of each volatile anesthetic, there was a dose-related reduction in CSD frequency but not in CSD amplitude. At 2.0 MAC of sevoflurane the suppression of CSD was less than with the other volatile anesthetics. In addition, the influence of anesthetics on expression of c-fos mRNA was investigated. Additional animals anesthetized by isoflurane or sevoflurane were studied. Five CSDs were elicited by electric stimulation (0.5 mV, 1 second) in each animal. In situ hybridization with 35S-labeled oligonucleotides was used to evaluate the level of c-fos mRNA. The expression of c-fos was observed in the hemisphere in which CSD was elicited, but there was no difference in expression of c-fos among the groups. We conclude that volatile anesthetics can induce suppression of CSD elicitation in a dose dependent manner, but that at high concentrations sevoflurane is significantly less effective than other volatile agents. Pentobarbital has the least effect on KCl-induced CSD. These data suggest that the choice of anesthetics can impact the results of studies examining membrane depolarization and the ionic changes initiated by CSD.

Anesthetics↗
PubMed2001

Parathyroid hormone-related protein is required for normal intramembranous bone development.

It is well established that parathyroid hormone-related protein (PTHrP) regulates chondrocytic differentiation and endochondral bone formation. Besides its effect on cartilage, PTHrP and its major receptor (type I PTH/PTHrP receptor) have been found in osteoblasts, suggesting an important role of PTHrP during the process of intramembranous bone formation. To clarify this issue, we examined intramembranous ossification in homozygous PTHrP-knockout mice histologically. We also analyzed phenotypic markers of osteoblasts and osteoclasts in vitro and in vivo. A well-organized branching and anastomosing pattern was seen in the wild-type mice. In contrast, marked disorganization of the branching pattern of bone trabeculae and irregularly aligned osteoblasts were recognized in the mandible and in the bone collar of the femur of neonatal homozygous mutant mice. In situ hybridization showed that most of the osteoblasts along the bone surfaces of the wild-type mice and some of the irregularly aligned osteoblastic cells in the homozygous mice expressed osteocalcin. Alkaline phosphatase (ALP) activity and expression of osteopontin messenger RNA (mRNA) in primary osteoblastic cells did not show significant differences between cultures derived from the mixture of heterozygous mutant and wild-type mice (+/? mice) and those from homozygous mutant mice. However, both mRNA and protein levels of osteocalcin in the osteoblastic cells of homozygous mutant mice were lower than those of +/? mice, and exogenous PTHrP treatment corrected this suppression. Immunohistochemical localization of characteristic markers of osteoclasts and ruffled border formation did not differ between genotypes. Cocultures of calvarial osteoblastic cells and spleen cells of homozygous mutant mice generated an equivalent number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear and multinucleated cells and of pit formation to that of +/? mice, suggesting that osteoclast differentiation is not impaired in the homozygous mutant mice. These results suggest that PTHrP is required not only for the regulation of cartilage formation but also for the normal intramembranous bone development.

Adenosine Triphosphatases↗
PubMed2001

[Radiological assessment of the structural relationship between the trachea and the innominate artery in physically disabled and scoliotic children].

Studies were made on the physically disabled and scoliotic children who underwent tracheostomy. The purpose was to clarify factors that might lead to the tracheo-innominate artery fistula, by use of three-dimensional helical CT (3 DCT). In a case of right scoliosis, the tracheo-innominate artery fistula may be caused by the left-ward displacement of the trachea from the vertebra, having the innominate artery ride over the trachea and compressing it. In a case of the physically disabled and scoliotic children, there may be more compression on the trachea by the innominate artery along with the worsening scoliosis. Therefore, we consider it necessary to examine the structural relationship between the trachea, the vertebra, and the innominate artery periodically by 3 DCT.

Adolescent↗
PubMed2001

[Pulmonary Mycobacterium Kansasii infection in the southern area of Fukuoka prefecture].

Cases of pulmonary infection caused by Mycobacterium kansasii (Mk) in our hospital located at the mid-northern area of the Kyushu district, which is in the southern part of Fukuoka prefecture were evaluated. Mk infection is not so rare in other areas of Japan, such as Tokyo and Kinki district, however, there has been no published report on the disease from the Kyusyu district. Therefore, the frequency and the clinical features of our cases of Mk infection were analyzed. During 17 years from 1982 to 1998, there were 14 patients of Mk infection out of 241 nontuberculous mycobacteriosis (NTM). There were 595 patients of culture-positive pulmonary tuberculosis without prior treatment (Tbc). The proportion of Mk/Tbc was 2.4% and that of Mk/NTM was 5.8%. During the period A (from 1982 to 1994) the ratio of Mk/Tbc was 5/462 (1.1%), while on the other side that of Mk/Tbc during the period B (from 1995 to 1998), it was 9/133 (6.8%), which was significantly (P < 0.01) higher compared with that in the period A. Although the patients of Mk infection in our hospital had been rare until 1994, from the results mentioned above, it was considered that the frequency of Mk infection in our hospital has increased to some extent since 1995. One of the characteristics in our cases was that the ratio of female (42.9%) was relatively high. All the female patients were considered to be compromised hosts. The results of the drug resistance tests were consistent with the other reports in our country. By the combination treatment including rifampicin as the major drug, the negative conversion of culture were obtained within 2 months in all our cases.

Adult↗
PubMed2000

[Evaluation of CT appearance of Mycobacterium avium complex infection--comparison with bronchiectasia].

We compared computed tomographic pictures (CT) of primary pulmonary mycobacterium avium complex (MAC) infection with bronchiectasia (BE). These patients were examined during the period from 1988 to 1996. There were 51 patients of pulmonary MAC infection group (13 males and 38 females) with a mean age of 67.5 years and 27 patients of BE group (8 males and 19 females) with a mean age of 53.9 years. The results were as follows: 1. In both groups, bronchiectasis was most commonly found in the middle lobe and in the lingula. In pulmonary MAC infection group, 38 patients (74.5%) had bronchiectasis in the middle lobe, and 40 patients (78.4%) had them in the lingula. In BE group, 18 patients (66.7%) had them in the middle lobe and in the lingula respectively. In the lower lobe, bronchiectasis of BE group was observed more frequently. And in pulmonary MAC infection group, 15 patients (29.4%) had bronchiectasis in the central zone, 42 patients (82.4%) had them in the intermediate zone, and all 51 patients had them in the peripheral zone. On the other hand, in BE group, 18 patients (66.7%), 27 patients (100%) and 21 patients (77.8%) had them in the central zone, in the intermediate zone and in the peripheral zone respectively. Bronchiectasis of pulmonary MAC infection was observed in peripheral zone more frequently than that of BE group. 2. By the type of bronchiectasis, saccular bronchiectasis was observed more frequently in BE group than in pulmonary MAC infection group. 3. Nodules were seen in pulmonary MAC infection group significantly more than in BE group. They were seen in 96% of lobes with bronchiectasis, and 50% of lobes without bronchiectasis in pulmonary MAC infection group. It was thought that the bronchiectasis with nodules predominantly in the peripheral zone was a characteristic CT finding of primary pulmonary MAC infection. As this finding was different from that of BE, it is suggested that primary pulmonary MAC infection caused this type of bronchiectasis.

Aged↗
PubMed2000

[Comparison of chest CT findings between suspected and definite cases of primary pulmonary M. avium complex infection].

It is very difficult to treat pulmonary infection with MAC, because we have few effective drugs against this organism. In this situation, an early diagnosis and treatment are very important to manage this disease. We evaluated chest CT scans of the primary pulmonary MAC infection which had no underlying lung diseases and no immunocompromised diseases such as HIV infection. We defined suspected cases of pulmonary MAC infection as cases in which abnormal features of chest CT scans were recognized but frequency of detection of organisms of MAC did not fulfil the diagnostic criteria for atypical mycobacteriosis according to Japanese Mycobacteriosis Research Group of the National Chest Hospitals. CT scans of suspected cases were compared with the definite cases. Results obtained were as follows: 1. In classification by CT scans of primary pulmonary MAC infection, the proportion of localized type and diffuse type was the same both in suspected and definite cases. In localized type, more tuberculosis-like pattern was seen in definite cases. 2. In suspected cases, characteristic features of CT scans of primary pulmonary MAC infection were recognized in the same frequency as in definite cases. 3. In pulmonary tuberculosis-like type, definite cases showed more cavitary lesions than suspected cases. These results showed that a careful long term follow-up of suspected cases with frequent bacteriological tests of sputum and chest CT scannings was important for early diagnosis of primary pulmonary MAC infection.

Aged↗
PubMed1999

Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of the sea krait, Laticauda semifasciata.

A phospholipase A2 (PLA2) inhibitor was purified from the blood plasma of a sea krait, Laticauda semifasciata, by sequential chromatography on Sephadex G-200, Mono Q, and Phenyl Sepharose columns. The purified inhibitor was found to be the same type as the PLA2 inhibitors, named PLIgamma, that had been purified from the blood plasma of the Thai cobra Naja naja kaouthia [Ohkura et al. (1994) Biochem. Biophys. Res. Commun. 200, 784-788] and Chinese mamushi Agkistrodon blomhoffii siniticus [Ohkura et al. (1997) Biochem. J. 325, 527-531]. Like other PLIgammas, the L. semifasciata inhibitor (LsPLIgamma) inhibited equally all of the PLA2s investigated including Elapid venom PLA2s (group I), Crotalid and Viperid venom PLA2s (group II), and honeybee PLA2 (group III). The LsPLIgamma was a 100-kDa glycoprotein composed of two distinct subunits, LsPLIgamma-A and LsPLIgamma-B, with an approximate molar ratio of 2:1. The amino acid sequences of the two subunits were determined by alignment of the peptides obtained by lysyl endopeptidase, endoproteinase Asp-N, and staphylococcal V8 protease digestions. LsPLIgamma-A and LsPLIgamma-B were composed of 182 and 181 amino acid residues, respectively; and the former subunit was a glycoprotein containing one asparagine-linked sugar chain at the position 157. The sequences of LsPLIgamma-A and LsPLIgamma-B showed 65 and 74% homology, respectively, to those of the corresponding subunits of N. naja kaouthia PLIgamma, and had two tandem patterns of cysteine residues, characteristic of the urokinase-type plasminogen activator receptor (uPAR) and members of the Ly-6 superfamily.

Amino Acid Sequence↗
PubMed1999

[Anesthetic management for pericardial fenestration in a hypertrophic cardiomyopathy (HCM) patient with massive pericardial effusion].

A 65 year-old male with HCM had progressively increased pericardial effusion. He also had atrial fibrillation (af), cardiac systolic dysfunction and chronic renal failure needing hemofiltration. Pericardial fenestration was carried out to improve diastolic function. Anesthetic management with fentanyl plus low-dose propofol infusion and postoperative analgesia with epidural morphine were effective for hemodynamic stability to prevent myocardial depression and to control ventricular response to atrial fibrillation. Intraoperative trans-esophageal echocardiography (TEE) monitoring was very useful for fluid therapy, inotropic support and estimation of systolic and diastolic function.

Aged↗
PubMed1999

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

Adult↗