Damage accrual related to pregnancies before and after diagnosis of systemic lupus erythematosus: a cross-sectional and nested case-control analysis from a lupus registry.

OBJECTIVE: The objective of this study was to evaluate the chronic damage associated with pregnancies before and after the diagnosis of systemic lupus erythematosus (SLE). METHODS: Using childbearing-aged female SLE patient data registered at the Okayama and Showa University Hospitals, a nested case-control analysis was performed to investigate the relationship between pregnancy and chronic damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: Pregnancy occurred in 22 patients before and 13 patients after the diagnosis of SLE in 104 eligible patients. Live births occurred in 82% (33/40) and 50% (9/18) of the pregnancies before and after the diagnosis of SLE, respectively. After matching age and disease duration, 33 case patients with chronic damage (SDI ≥ 1) and 33 control patients without chronic damage (SDI = 0) were selected. Hypertension was more frequent in cases than in controls (48% vs. 24%, p = 0.041). Pregnancies before and after the diagnosis of SLE were comparable between cases and controls (before the diagnosis: nine case patients and eight control patients; after the diagnosis: three case patients and five control patients; p = 1.00). Even after adjusting for hypertension using multivariate analysis, the pregnancies before and after the diagnosis were not significant predictors for chronic damage (odds ratio = 1.48 (95% confidence interval 0.33-6.65)), p = 0.60 of the pregnancy before the diagnosis; odds ratio = 0.78 (95% confidence interval 0.13-4.74), p = 0.78 of the pregnancy after the diagnosis). CONCLUSION: Pregnancies, either before or after the diagnosis of SLE, did not show any differences in chronic damage. Our results help alleviate fears regarding childbearing in female patients with SLE and their families.

Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus.

OBJECTIVE: Serologically active clinically quiescent (SACQ)-SLE is a subtype of systemic lupus erythematosus (SLE); most SACQ-SLE patients relapse. Although complement and/or anti-dsDNA level fluctuations during SACQ status are reportedly not useful for predicting relapse, they might be useful in specific clinical settings. We aimed to assess the correlation between future relapse and progressive reductions in serum complement levels following remission in patients with hypocomplementemia . METHODS: We retrospectively reviewed patients aged ≥15 years who were treated with ≥20 mg/day of prednisolone for remission induction. After achieving remission, the patients treated with prednisolone tapered to ≤15 mg/day without relapse and followed by hypocomplementemia (first hypocomplementemia point) were analyzed. The primary outcome was the relapse during the first 24 months. RESULTS: Seventy-six patients were enrolled; 31 (40.8%) relapsed. A ≥10% reduction after the first hypocomplementemia point in serum C3, C4, and CH50 levels was found in 10, 21, and 16 patients, respectively. Hazard ratios (95% confidence intervals) for relapse were 2.32 (0.92-5.12) for serum C3 levels and 2.46 (1.18-5.01) for serum C4 levels. Progressive reductions in serum C3 and C4 levels had relatively high specificity (93.3% and 82.2%) but limited sensitivity (22.6% and 41.9%) for predicting relapse. However, simultaneous progressive reduction in C3 levels and increase in anti-dsDNA antibody levels had the highest specificity (97.8%), and simultaneous progressive reduction in C4 levels or increase in anti-dsDNA antibody levels had the highest sensitivity (71.0%). CONCLUSION: Simultaneous progressive reductions in complement levels and increases in anti-dsDNA antibody levels may indicate future relapse SACQ-SLE patients.

Salvage chemoradiotherapy for locally advanced esophageal carcinomas.

'Salvage chemoradiotherapy (CRT)' was introduced in 2005 to treat thoracic esophageal carcinomas deemed unresectable based on the intraoperative findings. The therapeutic concept is as follows: the surgical plan is changed to an operation that aims to achieve curability by the subsequent definitive CRT. For this purpose, the invading tumor is resected as much as possible, and systematic lymph node dissection is performed except for in the area around the bilateral recurrent nerves. The definitive CRT should be started as soon as possible and should be performed as planned. We hypothesized that this treatment would be feasible and provide good clinical effects. We herein verified this hypothesis. Twenty-seven patients who received salvage CRT were enrolled in the study, and their clinical course, therapeutic response, and prognosis were evaluated. The patients who had poor oral intake because of esophageal stenosis were able to eat solid food soon after the operation. The radiation field could be narrowed after surgery, and this might have contributed to the high rate of finishing the definitive CRT as planned. As a result, the overall response rate was 74.1%, and 48.1% of the patients had a complete response. No patient experienced fistula formation. The 1-, 3-, and 5-year overall survival rates were 66.5%, 35.2%, and 35.2%, respectively. Salvage CRT had clinical benefits, such as the fact that patients became able to have oral intake, that fistula formation could be prevented, that the adverse events associated with the definitive CRT could be reduced, and that prognosis of the patients was satisfactory. Although the rate of recurrent nerve paralysis was relatively high even after the suspension of aggressive bilateral recurrent nerve lymph node dissection, and the rate of the progressive disease after the definitive CRT was high, salvage CRT appears to provide some advantages for the patients who would otherwise not have other treatment options following a non-curative and residual operation.

Shortening of distal motor latency in anode distal stimulation.

OBJECTIVE: Distal motor latency (DML) is shortened when the anode is held distally instead of the cathode by increasing the stimulus intensity. The objective of this study was to clarify the mechanism responsible for this shortening. METHODS: In seven healthy subjects, compound muscle action potential (CMAP) was obtained from the thenar muscle by bipolar stimulation of the median nerve at the wrist, and the intensity at which the first motor units were stimulated was defined as the threshold. Bipolar stimulation with extended interpole distance was employed to identify the generating site of the CMAP and F-wave. RESULTS: The shortening of DML was dependent on the stimulus intensity and threshold. For the low threshold condition, the CMAP generating site was replaced from the proximal cathodal pole to the distal anodal pole by increasing the stimulus intensity. The generating site of the F-wave remained at the proximal cathodal pole irrespective of stimulus intensity. CONCLUSIONS: Replacement of the generating site results in the shortening of DML. When the F-wave is recorded after being induced by anode distal stimulation, CMAP should not be simultaneously evaluated. SIGNIFICANCE: This study clarified the generation sites of CMAP and the F-wave when induced by anode distal stimulation.

The effects of peripheral nerve injury of the masseteric nerve on the levels of calcium binding proteins and neuropeptide Y, and their correlation in the mesencephalic trigeminal nucleus of the rat.

Combined retrograde neuronal tracing with FluoroGold (FG) and a double immunofluorescence method was performed to examine the effects of peripheral nerve injury of the masseteric nerve (MassN) on the levels of two calcium binding proteins (CaBPs), parvalbumin (PV) and calbindin D28k (CB), and neuropeptide Y (NPY) in the mesencephalic trigeminal nucleus (MesV) in the rat. In the normal MesV, many medium- to large-sized unipolar PV-like immunoreactive (-IR) cells were detected through the entire rostrocaudal extent, but CB-IR cells were rarely observed. No NPY-IR cells were observed in the normal MesV. The distributions of these three neurochemical markers in the MesV contralateral to the transection of Mass were almost identical to those observed in the normal MesV. Four days following transection and application of FG to the MassN, approximately 52% (572/1104) and 38% (414/1104) of FG-labeled cells (FG cells) in the MesV displayed PV-like immunoreactivity (-LI) and NPY-LI, respectively; Approximately 24% (265/1104) of FG cells showed both PV-LI and NPY-LI. Approximately 47% (265/572) of FG cells with PV-LI showed NPY-LI or 64% (265/414) of FG cells with NPY-LI displayed PV-LI. Fourteen days following transection and application of FG, the percentage of FG cells with PV-LI significantly decreased to 36% (365/1024) compared to that observed 4 days post-injury; approximately 44% (448/1024) of FG cells displayed NPY-LI; approximately 38% (141/365) of FG cells with PV-LI showed NPY-LI and approximately 31% (141/448) of FG cells with NPY-LI displayed PV-LI. In contrast, FG cells showing CB-LI were very rare on 4 days (1%; 15/1182) or 14 days (1%; 16/1085) following MassN transection. The present results indicate that the levels of PV in the MesV decreased 14 days following the MassN injury compared to those observed 4 days post-injury and rapid induction of NPY in the injured MesV neurons, and that the correlation between CaBP and NPY in the MesV following the MassN transection is different from that observed in the trigeminal ganglion, which is equivalent to the MesV, following peripheral nerve injury of the inferior alveolar nerve.

Calbindin D28k-like immunoreactivity in the gustatory epithelium in the rat.

The distribution of calbindin D28k (CB)-like immunoreactivity (-LI) in the gustatory epithelium was examined in the adult rat. In the circumvallate and foliate papillae, CB-like immunoreactive (-IR) nerve fibers were observed in the subgemmal region, and some of these penetrated the taste buds. Two or three spindle-shaped gustatory cells displayed CB-LI in each taste bud of these lingual papillae; the immunoreactivity was restricted to the cytoplasm. In the fungiform papilla, CB-IR nerve fibers were detected in the subgemmal region, but no CB-IR cells were observed in the taste buds of the fungiform papillae. In the taste buds of the incisive papillae, many CB-IR intragemmal nerve fibers were observed, but no apparent CB-IR cells were detected. In the soft palate, CB-IR nerve fibers associated with the taste buds were also observed, but no CB-IR cells were detected in the taste buds. The present findings indicate that CB-IR gustatory cells were only localized in the taste buds in the posterior lingual papillae (circumvallate and foliate papillae), but not in the taste buds in other gustatory epithelium.

Myelin basic protein in the cerebrospinal fluid of patients with brain tumors.

We measured the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with various kinds of tumors, including malignant tumors, using radioimmunoassay. The CSF had been obtained by lumbar puncture through an Ommaya reservoir or a shunt device placed in the lateral ventricle. The level of MBP was high (> 4 ng/ml) in the patients with meningeal dissemination of malignant tumors, but in those who showed a good response to chemotherapy and/or radiation, it decreased or returned to the normal level, with improvement on the computed tomography and magnetic resonance imaging, cytological, general CSF, and neurological findings. Of seven malignant gliomas without CSF dissemination, six showed an elevated level of MBP before selective intra-arterial chemotherapy with a combination of etoposide and cisplatin administered via a microcatheter placed at A1, M1, P1-P2, and the basilar top. All CSF specimens obtained during the period of the intra-arterial chemotherapy showed an abnormally high (> 4 ng/ml) level of MBP that exceeded the prechemotherapy level. The MBP level decreased or returned to normal in the patients with a good response to chemotherapy after intra-arterial chemotherapy. In some patients with multiple metastatic brain tumors, the MBP level was elevated before treatment and returned to normal after treatment (surgical removal, chemotherapy, and/or irradiation) in all except one. Thus, there was a clear correlation between the timing of treatment and changes in imaging studies and MBP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein gene-product 9.5 in developing mouse circumvallate papilla: comparison with neuron-specific enolase and calcitonin gene-related peptide.

The present study was made to investigate the ontogeny of protein gene-product 9.5 (PGP 9.5)-like immunoreactivity (-LI) in the developing mouse circumvallate papilla (CVP), and its distribution was compared to that of neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP). In adult CVP, PGP 9.5-LI was observed in the subgemmal nerve plexus; some thin PGP 9.5-like immunoreactive (-IR) nerve fibers penetrated taste buds and apical epithelium. PGP 9.5-LI was also observed in the spindle-shaped cells in taste buds, and a small number of round- or oval-shaped ganglionic cells in the lamina propria. The distribution of NSE-LI was comparable to that of PGP 9.5-LI. CGRP-LI was observed in the nerve fibers only; distribution of CGRP-IR nerve fibers was similar to that of PGP 9.5-IR nerve fibers, although the number of CGRP-IR nerve fibers was smaller than that of PGP 9.5-IR nerve fibers. At least six developmental stages were defined with regard to the developmental changes in the distribution of PGP 9.5-LI from embryonic day (E) 12 to adulthood: Stage I (E12-13)-a dense nerve plexus of PGP 9.5-IR nerve fibers was detected in the lamina propria beneath the core of newly-formed papilla. Stage II (E14-16) - thin PGP 9.5-IR nerve fibers penetrated the apical epithelium, and a few round-shaped cells in the apical epithelium also displayed PGP 9.5-LI. Stage III (E17-18) - thin PGP 9.5-IR nerve fibers penetrated the inner lateral epithelium of the trench. Stage IV [Postnatal day (P) 0-3] - many PGP 9.5-IR nerve fibers penetrated the outer lateral epithelium of the trench; later in this stage, taste buds appeared. Stage V (P5-10) - a small number of PGP 9.5-IR cells in the taste buds appeared, and their number increased gradually. Stage VI (P14-adult) - the number of PGP 9.5-IR taste cells increased and reached the adult level, while the number of PGP 9.5-IR nerve fibers decreased. The development of NSE-LI was similar to that of PGP 9.5-LI. CGRP-IR nerve fibers were detected at E12 in the lamina propria, and the development of the intraepithelial CGRP-IR nerve fibers was similar to that of PGP 9.5-IR nerve fibers. The present results indicate that invasion by nerve fibers of the epithelium of lingual papillae occurs in a complex manner, and that these nerve fibers may participate in the formation of the taste buds.

MR imaging of oculomotor nerve neurilemmoma.

The authors present a proved case of neurilemmoma arising from the oculomotor nerve in which MR imaging, including enhancement by gadopentetate dimeglumine, dynamic study and three-dimensional gradient echo images, provided much more precise definition of the tumor.

Positive correlation between blood cyclosporin A level and severity of gingival overgrowth in rats.

Cyclosporin a is a drug used to control rejection of organ transplantation and autoimmune diseases; however, it has also been implicated in gingival overgrowth. The present study investigates the relationship between severity of gingival overgrowth and blood cyclosporin A (CsA) levels in Fischer rats treated orally with CsA. Thirty-six 15-day-old male rats were divided into six experimental groups and given powdered rat chow containing 0, 50, 100, 200, 300, and 400 micrograms CsA/g diet ad libitum for 40 days. At the end of the 40-day treatment period, whole blood samples were collected from each rat for assessment of CsA levels. The rats were then sacrificed and the gingival sulcus depth (pseudopocket) around mandibular molars measured to estimate gingival overgrowth. The blood levels of CsA in rats increased with increasing amounts of CsA provided in their food. A 100% incidence in gingival overgrowth was induced in all the rats treated orally with CsA. The overgrowth was more severe in buccal than in lingual gingiva. A significantly positive correlation was found between gingival sulcus depth and the blood CsA level (rs = 0.914, P < 0.0001; Spearman's correlation coefficient by rank). On histological examination, the overgrown gingiva consisted of a thickened epithelial layer and an accumulation of subepithelial fibrous connective tissue components without marked distortion of their proportion.

Viscoelastic properties of canine temporomandibular joint disc in compressive load-relaxation.

The present study was designed to investigate the mechanical properties and load-relaxation of these discs in compression. Eight discs were used for the experiments. Compression was applied to specimens up to the specified strain, and a series of load-relaxation tests was conducted on each specimen from 0.25% strain to 2.0% strain with 0.25% intervals. The load-relaxation was monitored over a period of 2 min. The elastic moduli of the canine articular discs were 30.9 and 15.8 MPa at t = 0 and 120 sec, respectively, and the discs exhibited near-linear elastic characteristics at each time within a 2-min period. At all strains, the time-dependent load-relaxation curves showed that the load decreased markedly for the initial 30 sec, after which it levelled off after 120 sec with a steady nonzero level. This relaxation feature can be well represented by Kelvin's model. It is concluded that the canine temporomandibular joint disc can be represented as a linear viscoelastic material, and that it plays an important part as a stress absorber under compression.

Changes in the biomechanical properties of the rat interparietal suture incident to continuous tensile force application.

This study was designed to investigate the relation between the biomechanical behaviour of rat interparietal sutures and expansion forces placed on them. Thirty-five 4-week-old rats were divided into four groups, a control group and three experimental groups subjected to mechanical expansion of the interparietal sutures with a tensile force for 15, 30 and 50 h. After expansion, the parietal bones, including the interparietal suture, were dissected as specimens for tensile tests. Under tension, the relaxed stress-strain plots in the control group could be better fitted by a power of 2.00, and the relaxed moduli were 0.64 and 4.51 MPa at the lower and the higher applied strains, respectively. An initial fall in the relaxed moduli at 15 h of expansion was followed by an increase over time. It is therefore suggested that the biomechanical behaviour of the interparietal sutures is influenced by the duration of an external force.

Effects of tensile forces on the expression of type III collagen in rat interparietal suture.

The aim was to investigate the direct contribution of mechanically induced stress to synthesized type III collagen in the interparietal suture. Twenty 4-week-old male rats were used as experimental animals. An activated expansion spring was placed across the interparietal suture. After expansion, the parietal bones including the suture were dissected and immunostained for type I and III collagens. Also, a three-dimensional model of the interparietal suture was developed to analyze stress during expansion. The localization of type III collagen in the suture was dependent upon the duration of expansion. Although the control suture exhibited no or little reactivity for type III collagen, it was observed as early as 15 h of expansion in the cambial layers, and was distributed throughout the suture at 50 h of expansion. The time-dependent distribution of type III collagen was fully consistent with that of tensile stresses calculated by the use of a three-dimensional finite-element model. It was concluded that the increases in tensile stress are associated with the synthesis of type III collagen in the suture.

Calbindin D28K-like immunoreactive nerve fibres in the predentine of rat molar teeth.

Immunoelectron-microscopy was applied to reveal the existence of nerve fibres and terminals showing calbindin D28k (CB)-like immunoreactivity (IR) in the rat molar tooth pulp. In the root pulp, thick, smooth-surfaced CB-IR nerve fibres were in bundles accompanying the blood vessels. In the coronal pulp, the fibres arborized repeatedly and extensively. CB-IR nerve fibres had a predominantly thick, smooth-surfaced appearance, though parts appeared thin and beaded. Occasionally some thin, varicose CB-IR nerve fibres ran along the odontoblasts, penetrating into the predentine alongside the dentinal tubules. They could be traced for approx. 10-20 microns into the predentine from the pulp-predentine border. Immunoelectron-microscopy revealed that only some of the nerve terminals in the predentine showed CB-IR, and that predentinal CB-IR nerve terminals were located close to the odontoblast processes. No synaptic structures were observed between them. The presence of CB-IR nerve terminals in the predentine suggests that many, if not all, CB-IR nerve fibres could be nociceptors. The CB could be involved in Ca2+ homeostasis during the activation of nociceptors.

Involvement of prostaglandin E-like material in the purgative action of rhein anthrone, the intraluminal active metabolite of sennosides A and B in mice.

Intracaecal administration of rhein anthrone, the intraluminally active metabolite of sennosides A and B, to mice quickly induced severe diarrhoea. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor, indomethacin, and PGE2 antagonist, SC-19220, prevented the onset of diarrhoea induced by rhein anthrone, but the PGE2 antagonist polyphoretin phosphate (PPP) showed only a weak inhibitory effect. Rhein anthrone stimulated the production of PGE-like material only in the colon and its large intestinal propulsive activity was depressed by indomethacin and SC-19220, but not by PPP which suggests that the release of PGE-like material has some role in its purgative action.

Suppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in rats.

Rhein anthrone (12.48 mg kg-1) produces watery and mucoid diarrhoea approximately 20 min after intracaecal administration to rats. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor indomethacin (10 mg kg-1, i.p.) only delayed and did not completely block the onset of the induced diarrhoea. Rhein anthrone stimulated PGE2 release into the rat colonic lumen and the increased release was depressed by indomethacin. Rhein anthrone also accelerated large intestinal transit and this acceleration could be partly inhibited by indomethacin, which was probably responsible for the delay in the onset of diarrhoea. Indomethacin prevented the enhanced water, K+ and mucus secretion and the reduced Na+ absorption in the colon which were induced by rhein anthrone. The net water secretion could not be reversed to net absorption and the mucus secretion was only slightly depressed by indomethacin. Thus, our findings suggest that other mechanisms, together with the PG-dependent mechanism, are involved in the purgative action of rhein anthrone in rats.

Prostaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein anthrone, the active metabolite of sennosides A and B, in the mouse colon.

Rhein anthrone, the active metabolite of sennosides A and B, stimulated PGE2 release into the mouse colonic lumen. At 6.24 mg kg-1, it decreased net water and Na+ absorption significantly in the case of water, but could not reverse the net absorption in mouse ligated colon, although it enhanced net K+ secretion. Pretreatment with indomethacin diminished the effects of rhein anthrone except on K+ net secretion. Rhein anthrone or PGE2 markedly stimulated mucus secretion and synthesis in mouse ligated colon. The enhanced mucus secretion and synthesis induced by rhein anthrone were significantly suppressed by pretreatment with indomethacin. Our results have shown that the colonic secretion of water and electrolytes mediated by PGE2 is partly involved in the rhein anthrone-induced diarrhoea but that in mice, the mucoid diarrhoea induced by rhein anthrone results mainly from PGE2-mediated mucus synthesis and secretion in the colon.

The Japan Home-health Apparatus Industrial Association: investigation of home-use electronic sphygmomanometers.

The Japanese Home-health Apparatus Industrial Association is an official independent organization comprising ten departments. That concerned with home electronic sphygmomanometers, which has seven participants from different Japanese manufacturers, has already undertaken and is currently involved in various activities related to voluntary standards for performance validation and quality assurance. Because Japanese companies form a large proportion of manufacturers, these activities are important in terms of autonomic regulation. Although many improvements have been made to home electronic sphygmomanometers, some problems still remain unresolved, especially in terms of measurement reliability and easy operation by lay people. Another aspect of the department's work relates to making proposals on major validation standards, such as those of the Association for the Advancement of Medical Instrumentation, the British Hypertension Society and Comité Européen de Normalisation (CEN). Clinical validation should be discussed in order to define a more accurate standard method of measurement using auscultation and more appropriate criteria that are unaffected by primary blood pressure variation.

Selective intra-arterial chemotherapy with a combination of etoposide and cisplatin for malignant gliomas: preliminary report.

We administered selective intra-arterial chemotherapy consisting of a combination of etoposide and cisplatin to 20 patients with malignant glioma (seven with recurrent and six with enlarged tumors after initial treatment, and seven newly diagnosed patients). Evaluation of efficacy was based on computed tomographic and magnetic resonance imaging findings. In the process of establishing a safe technique for superselective intra-arterial chemotherapy, we encountered cerebrovascular accidents in two patients (after etoposide in one and after etoposide plus cisplatin in the other). In these two cases, 100 mg/m2 of etoposide and 100 mg/m2 of cisplatin were delivered via the horizontal segment of the middle cerebral artery (M1) or the tip of the basilar artery, with the infusion time reduced to 20 minutes. Thereafter, the etoposide was diluted, and the doses of both drugs were reduced to 80 or 50 mg/m2, and finally to 60 mg/m2, and both were infused over 60 minutes. In addition, for prevention of local spasm, papaverine hydrochloride and nicardipine were given via the same catheter at 5-minute intervals during administration of etoposide and cisplatin. No complications developed in the later cases. Thereafter, selective intra-arterial infusion of etoposide and cisplatin into the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, or the basilar artery for malignant gliomas in the basal ganglia, internal capsule, and brainstem--a procedure generally considered risky in terms of potential complications--was performed safely, with tolerable side effects. Computed tomography and magnetic resonance imaging indicated improvement in 13 patients, including four whose tumors completely disappeared. This method of intra-arterial chemotherapy may be useful as an adjuvant treatment for malignant glioma.

[Penetration of potassium clavulanate/ticarcillin sodium into cerebrospinal fluid in neurosurgical patients].

Concentrations of potassium clavulanate (CVA) and ticarcillin sodium (TIPC) in the plasma and cerebrospinal fluid (CSF) of patients after neurosurgical intervention were determined at various times after a 1-hour drip infusion (3.2-g dose). Patients whose blood-brain barriers were supposed to be maintained in almost a normal condition were selected. CSF was obtained through a catheter placed in the anterior horn of the lateral ventricle in all the patients. Maximum plasma levels (micrograms/ml) of 57.6 to 384.0 with an average of 169.7 (TIPC) and 0.41 to 26.2 with an average of 6.1 (CVA) were achieved at the termination of infusion. The maximum CSF levels (micrograms/ml) were 0.61 to 18.8 (TIPC) and 0.1 to 6.81 (CVA) with mean values of 4.5 and 1.2, respectively. Plasma half lives (T1/2) (minute) were 24 to 93 (TIPC) and 32 to 227 with mean values of 58 and 127, respectively. The mean values of the CSF half lives (minute) were 237 (TIPC) and 113 (CVA). The ratios (%) of CSF levels to plasma levels in maximum concentration (Cmax), AUC (area under concentration curve) and half life (T1/2) were calculated. Cmax ratios were 0.2 to 29.2 (TIPC) and 1.4 to 69.8 (CVA) with mean values of 4.4 and 22.8, respectively. AUC ratios were 0.3 to 23.5 (TIPC) and 1.1 to 70.2 (CVA) with mean values of 4.3 and 22.4, respectively. T1/2 ratios were 1.3 to 18 (TIPC) and 1.1 to 4.3 (CVA) with mean values of 5.5 and 2.3, respectively. These values indicate that CVA/TIPC may be classified into a group of antibiotics with good penetration into the CSF.