Cerebral blood flow measurement of severely head-injured patients during mild hypothermia.

In 14 patients with severe head injury, the cerebral blood flow (CBF) during mild hypothermia therapy was measured. Their Glasgow Coma Scale scores on admission were 8 or less and the intracranial pressures were greater than 20 mmHg despite conventional therapy. The CBF was measured with two-level stable xenon CT techniques. And in 11 patients, the cerebral metabolic rates for oxygen (CMRO2) was also calculated. All cases were divided into two groups according to the outcome at discharge by using the Glasgow Outcome Scale, good outcome group in 6 and poor outcome one in 8. The values of mean CBF and CMRO2 of each group were 25.6 +/- 6.6 vs 24.4 +/- 6.4 ml/100 g/min and 1.26 +/- 0.45 vs 0.79 +/- 0.31 ml/100 g/ml, respectively. There were no statistically significant differences between both groups. Single CBF measurement during this therapy may not be helpful as a factor of prognosis evaluation in patients with severe head injury.

Topological and functional characterization of the N-glycans of soybean (Glycine max) agglutinin.

Soybean agglutinin (SBA), is a noncovalently bound tetramer comprised of four identical subunits having a single N-glycan chain, Man9GlcNAc2, that is known to be essential for regeneration of the functional tetrameric structure from unfolded subunits. In this study, SBA was found to have strong affinity for concanavalin A, indicating that the N-glycans are extensively solvent-exposed. The susceptibilities of the N-glycans to alpha-mannosidase and endo-beta-N-acetylglucosaminidase revealed that their distal areas have nonreducing ends embedded among the subunits, whereas their proximal regions are solvent-exposed. Endo-beta-N-acetylglucosaminidase-digested SBA was unable to retain its conformation and gradually unfolded. Periodate-oxidized SBA, whose N-glycans closely correspond to the invariant pentasaccharide core, tended to dissociate into the subunits, but permitted to stay as folded monomers. This SBA species was capable of refolding from unfolded subunits but unable to form the functional tetramer. It seems probable that the proximal regions of the N-glycans function in the formation and stabilization of the subunit conformation, whereas the branches outside the invariant cores stabilize the tetrameric structure.

Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis.

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.

Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques. METHODS: Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR. RESULTS: Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea. CONCLUSION: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.

[Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition associated with multicentric Castleman's disease].

We report a case of a 65-year-old man presenting with multicentric Castleman's disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion with fibrillary deposits. The lesion was characterized by highly organized ultrastructual deposits that were negative for Congo-red stain and for immunoglobulin, light chain and C3. Thus, this renal lesion was considered histologically to be fibrillary glomerulonephritis presenting by light microscopy as mesangiocapillary glomerulonephritis. To our knowledge, among the limited number of cases of renal lesion associated with MCD ever reported, this is the first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6 (IL-6), known as an indicator of MCD activity and as an autocrine growth factor for mesangial cells, was chronologically measured. Augmentation of urinary IL-6 simultaneously with that of extra renal symptoms of MCD and associated renal disease may indicate an underlying role of this cytokine in the present case. Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is derived from extrarenal lymphonodi, and not to an in situ product of the glomeruli. However, it may have been related to glomerular injury.

Source of reactive oxygen species in anti-Thy1 nephritis.

In proliferative glomerulonephritis, both macrophages and mesangial cells generate reactive oxygen species (ROS), contributing to the development of glomerular injury. We have attempted to determine which cell produces ROS during anti-Thy1 nephritis (ATN) in rats. The generation of ROS was studied using luminol amplified chemiluminescence (GCL) on isolated glomeruli. Immunohistochemical studies used avidin-biotin complex (ABC) to label macrophages and mesangial cells. Immediately after ATN induction, mesangiolysis and infiltration with ED-1 positive cells (referred to as macrophage) was noted with a peak at day 1. After day 4, mesangial proliferation appeared with a decrease of the ED-1 positive cells and a prominent increase of PCNA positive cells (regarded as mesangial cells). In the early phase of ATN, GCL, reflecting ROS generation, increased along with the appearance of ED-1 positive cells. GCL subsequently decreased as mesangial cells increased. This suggested that macrophage were the principal participants in ROS generation in the early phase of ATN although mesangial cells cannot be completely disregarded in the generation of ROS and development of glomerular injury.

Ultrastructural background of albuminuria in rats with passive Heymann nephritis.

BACKGROUND: Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria. METHODS: The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats. RESULTS: Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups. CONCLUSIONS: Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.

Atrophy and maldevelopment of the ipsilateral cerebral hemisphere after acute subdural hematoma in infants.

Among nine infants aged less than 4 years with acute subdural hematoma admitted between 1980 and 1991, five required evacuation of a hematoma. Eight of them survived longer than 1 month and the remaining patient who had a hematoma removal died 3 days postoperatively. The four infants who required evacuation of a hematoma and survived longer than 1 month had prolonged hemispheric swelling ipsilateral to the hematoma lasting for 2 weeks postoperatively. Intracranial pressure was higher than 25 mm Hg during this period. Diffuse high density was observed in the affected hemisphere in one patient 12 days after injury, which was assumed to be hemorrhagic infarction. Subsequently, these four infants developed atrophy of the cerebral hemisphere ipsilateral to the hematoma. The pathophysiology of the atrophy of the cerebral hemisphere ipsilateral to the acute subdural hematoma is discussed.

Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer.

In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer.

[Pelvic hyperthermochemotherapy combined with surgery for rectal cancer].

In an attempt to prevent local recurrence, intraoperative pelvic hyperthermochemotherapy (IOPHC) was performed in combination with curative surgery for rectal cancer. One hundred twenty-three patients were divided into four groups: A, 8 patients without nodal involvement (n0) and given IOPHC; B, 22 with nodal involvement (n+) and given IOPHC; C, 47 n0 and no IOPHC; D, 46 n (+) and no IOPHC. Local recurrence developed in one patient in group A (12.5%), 3 in group B (13.6%), 5 in Group C (10.6%), and 16 in Group D (34.8%), respectively. Thus, the rate of local recurrence in group B was low compared to that of Group D, even through there was no statistical difference (p = 0.11). IOPHC may be one option for limiting local recurrence after surgical resection of rectal cancer.

Clinicopathologic characteristics and survival of elderly patients with gastric cancer.

From 1980 to 1991, Japanese patients aged over 49 years with gastric cancer underwent gastric resection in our hospitals. For various studies, two groups, 35 patients over 79 years (advanced age group) and 884 patients aged 50-79 years (mature age group) were prepared. A retrospective study was done with special reference to clinicopathological features and the prognosis. There were no differences in clinicopathological characteristics between the two groups, except for operative procedures and the size, histology and vascular involvement of the primary tumor. The survival rate for the advanced age group was higher than that for the mature age group, with a significant difference at p = 0.00556. However, the postoperative morbidity rate was 48.6% in the advanced age group compared with 5.1% in the mature age group. The most frequent complications were respiratory-related, that is, atelectasis, pneumonia or aspiration pneumonia. Based on these data, advanced age is not a contraindication for resection of a gastric cancer, but patients with serious pulmonary and/or cardiac diseases would not be candidates.

Low serum aminotransferase activity in patients undergoing regular hemodialysis.

Of 150 patients undergoing regular hemodialysis (HD), 14 (9.3%) and 12 (8.0%), respectively, showed low serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). An investigation was conducted to elucidate the underlying mechanisms in 20 patients with low serum AST and/or ALT activity. Fifty-five percent of the patients with low aminotransferase activity manifested serum levels of pyridoxal phosphate (PLP) that were lower than normal. Serum PLP levels correlated neither with AST nor with ALT activity. Oral administration of vitamin B6 to the cases with low aminotransferase activity resulted in an increase in pre-hemodialysis aminotransferase activity. Addition of vitamin B6 in vitro to the sera from the patients with low aminotransferase activity did not increase the values when the added vitamin B6 was within the physiological range, but did increase when added in larger (pharmacological) amounts. However, aminotransferase activity increased, but PLP levels remained unchanged when these values were compared before and after HD. On the other hand, guanase being within the normal range in all cases studied, did not change after HD. Although our study does not correlate with vitamin B6 deficiency, but rather with some uremic substance(s) which interfere(s) with the enzyme reaction as a cause of low aminotransferase activity, the fact that less than 10% of our patients showed low AST and/or ALT points to the latter possibility, suggesting the need of further study.

Comparative clinicopathologic features of early gastric cancer in young and older patients.

BACKGROUND: The clinicopathologic features of advanced gastric cancer have been analyzed in young or older patients; however, with regard to early gastric cancer, it remains unknown whether the features differ between young and older patients. Reported here is an analysis of clinicopathologic characteristics in young and in older patients. METHODS: This study is based on a retrospective review of 25 patients less than 40 years of age with early gastric cancer and of 64 patients more than 70 years of age with early gastric cancer. These patients were treated from 1977 through 1991. RESULTS: Because in the older group there were early double cancers in three patients and quadruple cancers in one, 70 early cancers were present in these 64 patients. Although the young group included a larger percentage of women, the ratio of mucosal cancer to submucosal and the incidence of nodal metastasis did not differ between the groups. Poorly differentiated adenocarcinoma was detected in 13 (52%) of the 25 younger patients, whereas in the older group it was present in 6 cancers (8.6%) alone. The number of metastatic nodes and extent of nodal metastasis were more severe in the young group, but survival rates did not differ between the groups. The depressed type of lesion was present in all patients in the young group, whereas it was only 41 of 70 cancers in the older group. CONCLUSIONS: These findings suggest that early gastric cancer in young adults has aggressive features as based on the histologic pattern, in particular with cancer invasion into the submucosal layer. For these patients nodal extirpation and postoperative adjuvant chemotherapy should be performed in an attempt to prevent lymphatic or hematogenic metastases.

Peritumoral edema in meningioma: a contrast enhanced CT study.

The propagation of extravasated contrast medium around 6 supratentorial meningiomas with peritumoral white matter of low density (PWL) of Lanksch II-III was investigated by repeated CT scanning at 4 h intervals, following a 1 h drip infusion of 200 ml of Iopamidol. The volume of the expanding peritumoral contrast enhancement was calculated according to a method previously described. By calculating the increase in volume from the first to the second scan, and from the second to third, we derived the rate of edema formation as well as the resolution rate of edema in the PWL. The surface area of the entire tumor (TS) and area of tumor surface facing the PWL (LS) were calculated by summating the surface areas of all CT slices, each area of which was derived from the measured length of the entire circumference of the tumor and circumference of the tumor facing the PWL, respectively, multiplied by the slice thickness of 0.5 cm. The volume of PWL, edema formation rate of entire tumor, and tumor volume x LS/TS were well correlated with each other. We concluded that the severity of peritumoral edema in meningiomas depends on the size of the tumor and the extent of tumor surface contact with the PWL.

High colloid oncotic therapy for contusional brain edema.

We investigated whether prolonged high colloid oncotic therapy for two weeks can suppress contusional brain edema. Eighteen patients with cerebral contusion were randomly divided into two groups of patients receiving high oncotic pressure (HOP; 26-30 mmHg) treatment and those receiving normal oncotic pressure (NOP; 22-26 mmHg) treatment. Oncotic pressure was maintained for two weeks with administration of a 25% albumin solution with additional use of furosemide. Edema volume was calculated by summation of all measured low-density areas in each CT slice multiplied by 1.0 cm of slice of thickness. We expressed contusional brain edema volume as a percent increase based on each patient's initial CT. The mean percent increase of contusional brain edema in the NOP group was significantly higher than that in the HOP group at 9-15 days (208.9% and 14.0%, respectively) and 16-25 days (188.8% and 10.0%, respectively). There were no complications such as heart failure or renal failure during treatment. All the patients in the HOP group recovered with minimal or no neurological deficit. On the other hand, 30% of patients in the NOP group remained in poor condition. With frequent measurement of oncotic pressure and adjustment of fluids and electrolytes, continuous oncotic therapy for two weeks effectively and safely reduced contusional brain edema.

High colloid oncotic therapy for brain edema with cerebral hemorrhage.

We examined the effectiveness of high colloid oncotic pressure (COP) therapy to suppress and/or reduce brain edema associated with putaminal hemorrhage of patients whose clinical grades were grade 3 or 4a classified according to the Japanese neurological grading for putaminal hemorrhage. In the treated group of 11 patients, 25% albumin solution was intravenously administered (50-100 ml/day) with additional use of furosemide (20-40 mg/day) following hematoma removal. The serum COP was maintained at 25-30 mmHg for 2 weeks. In the untreated group of 11 patients, the COP therapy was not applied following hematoma removal. The serum COP was 20-25 mmHg for 2 weeks thereafter. During the 2-week observation period, serum osmolality, electrolyte, and hematocrit levels did not significantly differ between the two groups. The midline structure shift on CT of the treated group was 4.5 mm, which was significantly smaller than that of the untreated group (p < 0.05). The numbers of patients either in the vegetative state or death were 0 and 3, respectively, in the treated and the untreated groups. We concluded that high COP therapy for 2 weeks following hematoma removal was effective to suppress and/or reduce brain edema associated with putaminal hemorrhage, and that this therapy could be continued for 2 weeks without systemic complications.

Hyperthermia-induced antitumor activity in human gastric cancer cells serially transplanted into nude mice.

Hyperthermia-induced antitumor activity was assessed histopathologically and findings related to transplantation of human gastric cancer into nude mice were examined. Fragments of human gastric cancer were incubated at 37 degrees C to 47 degrees C for various durations of time, then were evaluated either histologically or with regard to delay in tumor growth and the rates of transplantation into nude mice. Fragments exposed to 39 degrees C for 30 min to 120 min and 41 degrees C for 30 min did not differ from findings in the controls concerning tumor growth and transplantability. In the case of 41 degrees C for 60 min or more, the rates of transplantation decreased significantly and there was a delay in tumor growth. At 43 degrees C for 120 min, 45 degrees C for 30 and 60 min, and 47 degrees C for 15 to 60 min, transplantability was nil. In the groups with a delay in tumor growth, there were irreversible changes in nucleic and cytoplasmic components, and in 6 groups with no evidence of transplantability, complete destruction of the glandular structure, pyknosis and karyorrhexis as well as disappearance of the cytoplasm occurred in almost all cases. Thus, the thermal dose of 43 degrees C for 120 min seems to be the minimally effective one for hyperthermia-induced tumoricidal activity.