Clinicopathological study of intrapelvic cancer spread to the iliac area in lower rectal adenocarcinoma by serial sectioning

BACKGROUND: The role of iliac lymphadenectomy in surgery for rectal cancer remains unknown. Detailed clinicopathological data on lateral cancer extension may be needed to determine the true role of this procedure. METHODS: Seventy consecutive patients with low rectal cancer who underwent systematic iliac lymphadenectomy between 1991 and 1995 were reviewed. The iliac area was divided into five regions: (1) middle rectal root, (2) internal iliac, (3) obturator, (4) common iliac and (5) external iliac. Iliac lymph nodes that were cancer-free based on conventional pathological examination were serially sectioned at 100-microm intervals and re-examined for occult microscopic involvement. RESULTS: Occult microscopic foci were detected in five (7 per cent) of the 70 patients, and the overall incidence of lateral cancer spread was 24 per cent (17 of 70). Among patients without other sites of distant metastasis or circumferential involvement of the margin, the 5-year survival rate of those with lateral spread was 35 per cent. Although the prognosis of patients with cancer involving multiple iliac regions was poor, three of six patients with metastasis to only a single region were alive without disease at 3 years. CONCLUSION: Surgeons should be aware of the possibility of localized lateral spread, including microscopic metastasis, when determining the optimum procedure for iliac lymphadenectomy in patients with rectal cancer.     

Successful treatment of acute renal failure in a patient with essential mixed cryoglobulinemia using prednisolone and cryofiltration

We report a case of acute renal failure associated with cryoglobulinemic glomerulonephritis. The patient, a 49-year-old woman, was referred to our hospital because of acute nephritic syndrome. After admission, she developed oliguria, and hemodialysis was instituted. Renal biopsy was performed and the specimens showed moderate endocapillary proliferation, large deposits filling the capillary lumen ("intraluminal thrombi"), and a double-contoured appearance, which are typical morphologic features of cryoglobulinemic glomerulonephritis. Immunoelectrophoresis showed a monoclonal increase of IgM kappa. On the basis of these findings, we diagnosed type II essential mixed cryoglobulinemia. Cryofiltration was performed with oral administration of prednisolone. Following the start of therapy, the patient's renal function gradually improved. Because of severe hypoproteinemia, cryofiltration was discontinued after three sessions. However, renal function recovered and was maintained with prednisolone only. This case shows that acute oliguric renal failure caused by cryoglobulinemic glomerulonephritis can be reversible if immunosuppressive therapy, together with plasmapheresis in more severe cases, is instituted promptly.     

Serosurvey of wild rodents for Rickettsioses (spotted fever, murine typhus and Q fever) in Java Island, Indonesia

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8–51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0–4.8%, p < 0.01). The antibody positive rates against SFGR and murine typhus in rats captured in Jakarta were significantly higher than those in rats captured in Boyolali (p < 0.01). In this survey, all species of rats had antibodies against SFGR, indicating that the 4 species of tested rats (R. norvegicus, R. rattus, R. exulans, R. tiomanicus) were infected with SFGR and that SFGR may infest the whole of Java Island. Most of the rats that were antibody-positive against murine typhus were captured in Jakarta. Therefore, R. norvegicus and R. rattus are likely to be important hosts of murine typhus in Jakarta. The antibody-positive rates against SFGR and murine typhus in rats captured in the dry season were significantly higher than those in rats captured in the rainy season. This may coincide with the active periods of ticks and fleas in Indonesia.     

A physical performance battery assessing low/high extremity functional fitness in older Japanese women

The aim of this study was to establish a physical performance test battery to assess the wide variation of functional fitness in older Japanese women. The criteria for sampling low/high extremity functional fitness were the amount of physical activities that older women perform on a regular basis and the distance they could move by foot. Seventeen tests related to the activities parallel to daily living (APDL) were completed for 178 women, aged 60 to 91 years. Principal component analysis of the 17 performance tests in the reference group (n = 140) yielded 5 components accounting for 63.5% of the total variance. Fourteen test items were heavily loaded on the 1st principal component, so that 31.4% of the total variance was accounted for by this component. Considering these results as well as test-retest reliability, kurtosis, and skewness of each item, the following four items were selected as a combination of test battery: (X1) repetition of the bicipital flexion/extension, (X2) walking around two cones and sitting on a chair, (X3) moving beans with chopsticks, and (X4) functional reach. Principal component analysis was again applied to these four variables so as to obtain the first principal component score of each person. As a result, the following equation was drawn: the first principal component score = 0.063X1 - 0.055X2 + 0.098X3 + 0.042X4 - 2.65. The scores averaged 0.68 +/- 0.27 for the exercise group (n = 19) (those who played croquet or other similar sports activities consistently twice or more a week); and -0.76 +/- 0.55 for the sedentary group (n = 19) (those who did no exercise and confined their activities to the home). Biserial correlation coefficient as an index of criterion-related validity was 0.67 (P < 0.05) between the scores in the exercise and sedentary groups. These results indicate that a wide range of functional fitness among older Japanese women can be assessed by the four tests.     

Genetic background determines the nature of immune responses and experimental immune-mediated blepharoconjunctivitis (EC)

PURPOSE: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in Lewis rats by immunization with ovalbumin (OVA) in complete Freund's adjuvant (CFA) or aluminum hydroxide [Al(OH)3]. To investigate the affect of genetic factors on the susceptibility of EC, we tested different strains of rats for the development of EC. METHODS: Lewis and Brown Norway (BN) rats were immunized once with 100 microg of OVA in CFA or Al(OH)3. Three weeks later they were challenged with OVA in eye drops; 24 hours after the challenge they were sacrificed and their eyes, blood, and lymph nodes were harvested for histological studies, measurement of OVA-specific antibodies (IgG, IgG1, IgG2a, IgE), and proliferation or cytokine assay, respectively. ELISA was used to detect OVA-specific IgG; passive cutaneous anaphylaxis was used for detecting IgE. RESULTS: EC, OVA-specific IgG, and cellular immunity were induced in Lewis rats by using either adjuvant, whereas IgE was not produced by either adjuvant. In contrast, IgE was produced in BN rats using either adjuvant, whereas cellular immunity was evoked only when CFA was used. Less cellular infiltration as well as cellular proliferation was detected in BN rats immunized with Al(OH)3. In both strains, Al(OH)3 induced a higher IgG1/IgG2a ratio than did CFA. More interferon-gamma by stimulation with OVA was noted in Lewis rats compared to BN rats, whereas interleukin-4 was detected only in BN rats. CONCLUSIONS: The severity of EC evaluated by cellular infiltration was dependent on OVA-specific cellular immunity. Genetic background is more important than adjuvants in determining the nature of EC and immunity.     

Antibiotic-induced endotoxemia in a patient with endogenous endophthalmitis

PURPOSE: The aim of the study is to describe a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia. METHODS: The human leukocyte antigen (HLA) typing of peripheral leukocytes was studied by lymphocytotoxicity technique. Histological and immunohistochemical studies of paraffin embedded specimen were conducted. RESULTS: Findings of HLA typing revealed positive reaction for B 51, Cw 3, DR 8, DR 11, DQ 3. The vitreous body of an eviscerated eye was occupied by the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and Sudan black staining positive foamy cells, including melaniferous phagocytes, identified as CD 68 positive macrophage. CONCLUSION: It is suggested that antibiotic-induced endotoxemia of a patient with septic endogenous endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA and endotoxin activated macrophages may release cytokines, followed by fibrin formation and subsequent granuloma.     

In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system.

1. The aim of the present study is to characterize the role of the P2X receptor in spinal nociceptive processing in vivo. We investigated the mechanisms of the P2X receptor agonist alpha,beta-methylene ATP (alpha,betameATP)-induced modulation of acute nociceptive signalling in mouse spinal cord. 2. Intrathecal administration of alpha,betameATP produced a significant and dose-dependent thermal hyperalgesic response. This response was completely blocked by intrathecal pretreatment with the non-selective P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and the selective P2X1, P2X3 and P2X2-3 receptor antagonist, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). Pretreatment with alpha,betameATP 15, 30 and 60 min prior to administration of a second dose of alpha,betameATP diminished the alpha,betameATP-induced thermal hyperalgesia. 3. A potent agonist for the P2X1 receptor, beta,gamma-methylene-L-ATP, did not show the hyperalgesic response, indicating that the P2X1 receptor is not involved in the spinal nociceptive pathway. 4. In fura-2 experiments using mouse dorsal root ganglion (DRG) neurons, alpha,betameATP (100 microM) increased intracellular Ca2+ ([Ca2+]i). This was not produced by a second application of alpha,betameATP. The same DRG neurons also showed a marked [Ca2+]i increase in response to capsaicin (3 microM). 5. Intrathecal pretreatment with the Ca2+-dependent exocytosis inhibitor, botulinum neurotoxin B, abolished the thermal hyperalgesia by alpha,betameATP. Furthermore, thermal hyperalgesia was significantly inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonopentanoate (APV), dizocilpine and ifenprodil. 6. These findings suggest that alpha,betameATP-induced thermal hyperalgesia may be mediated by the spinal P2X3 receptor subtype that causes unresponsiveness by repetitive agonist applications, and that alpha,betameATP (perhaps through P2X3 receptors) may evoke spinal glutamate release which, in turn, leads to the generation of thermal hyperalgesia via activation of NMDA receptors.     

Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.

Endogenous serotonin (5-hydroxytryptamine, 5-HT)-mediated regulation of dopamine release in the rat prefrontal cortex was pharmacologically characterized using in vivo microdialysis. To increase synaptic 5-HT availability, a selective 5-HT uptake inhibitor fluoxetine was applied via the dialysis probe. Local perfusion of fluoxetine (30 and 100 microM) increased dopamine levels in a concentration-dependent manner. The fluoxetine (100 microM)-induced increases in dopamine release were abolished by pretreatment with the 5-HT(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide] ) (10 and 100 microM). The facilitation of dopamine release was also prevented by selective inactivation of the mRNA encoding 5-HT(6) receptors using antisense oligonucleotides techniques. These findings suggest that not only 5-HT(1B) receptors but also 5-HT(6) receptors are associated with the endogenous 5-HT-mediated facilitation of dopamine release. In other words, 5-HT(6) receptors may play, in part, a significant role in the functional interaction between the dopaminergic and serotonergic neuronal system in the rat prefrontal cortex.     

A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection.

The pharmacokinetics, toxicity, and activity of KNI-272, a transition state inhibitor of HIV-1 protease, was assessed in a phase I trial. After an initial phase in which the pharmacokinetics were assessed, 37 patients with AIDS or symptomatic HIV infection and 100-400 CD4 cells/mm3 were entered in an escalating dose study. KNI-272 was administered four times daily for up to 12 weeks. Oral bioavailability ranged from 22 to 55% and was not appreciably different in the fasting and post-prandial state. The dose limiting toxicity was hepatic transaminase elevation; this could be reduced by escalating the dose over 4 weeks. When administered this way, the maximum tolerated oral dose was 40 mg/kg per day. At the highest two tolerated doses (26.4 and 40 mg/kg per day), there was some evidence of an anti-HIV effect with median decreases of 0.2-0.3 log10 copies/ml plasma HIV RNA; these decreases persisted through 7-8 weeks of treatment. There was an upward trend in the CD4 count at the 40 mg/kg per day dose but not at other doses. Additional studies focused on approaches to improve the therapeutic index of KNI-272 may be warranted.     

Evidence of cross-link formation of vitreous collagen during experimental ocular inflammation

Purpose: To determine the mechanisms of vitreous changes during ocular inflammation. Methods: We investigated vitreous changes, with special emphasis on collagen, in an experimental model of ocular inflammation induced by intravitreal injection of endotoxin (Escherichia coli) in rabbits. Results: Inflammation caused gel contraction and loss of elasticity, accompanied by release of a water-like liquid from the gel, and increases in the amount of insoluble material and highmolecular-weight components of vitreous collagen, presumably due to extensive cross-links of the collagen molecules. Those changes were partially inhibited by intravitreal injection of superoxide dismutase. Conclusions: The crosslinks of vitreous collagen may promote vitreous gel contraction and release of a water-like liquid from the gel. Superoxide anion may play a role in this process.