[Nursing diagnosis and clinicians' competency].
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Biomedical subjects
Publications and source records attributed to Y Kuroda.
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Thirty-nine patients with brain metastasis from breast cancer who were treated in our hospital between 1978 and 1992 and followed up until November 1995 were reviewed. The initial diagnosis of brain metastasis and follow-up were made by MRI and/or CT. Extracranial metastases were found in 90% of the patients and were the cause of death in 89%. Treatments included surgery alone in 2 patients (group S) surgery plus postoperative radiotherapy in 8 (group SR), radiotherapy alone in 28 (group R) and conservative therapy in 1 (group C). Radiotherapy of up to 40Gy to the whole brain was carried out, but was performed in only 75% of patients in group R. The overall median survival was 5.4 months with a 1-year survival rate of 23% and a two-year rate of 10%. In patients treated with over 40Gy, the survival time for radiotherapy alone was 5.1 months, with a 1-year survival rate of 9.5%; relief of specific neurologic symptoms was noted in 80%. The longest survival was noted in a patient with a single brain metastasis, who, to date, has survived for five years and two months following 60Gy of irradiation. Patients with the following clinical conditions should have a good prognosis: (1) no further metastases in other sites, or well controlled if existing, (2) no symptoms of NF (neurological function: RTOG) or slight, and improved NF by treatment, (3) surgical candidate, (4) good response to initial treatment on CT or MRI. Despite a bad prognosis in general, brain metastasis from breast cancer can be treated affirmatively, if these clinical conditions are fulfilled.
Progressive rubella panencephalitis (PRP) is a slow virus infection of the central nervous system. PRP was first reported in 1974, and fewer than 20 cases have been reported since then. All patients were male who were between the ages of 8 and 21 years at onset, and most had signs of congenital rubella syndrome. Although PRP may exhibit clinical features resembling SSPE, the age at onset is much older and the clinical course is more benign. The main neurological features of PRP are dementia, cerebellar ataxia, and seizures. Increases in antirubella antibody titer and IgG are found in the CSF and diffuse atrophy of the brain with ventricular dilatation may be found on MRI. The pathomechanism of PRP remains unclarified.
Prion diseases are characterized by the accumulation of prion protein(PrP) with abnormal configuration in the brain. PrP itself is a host gene-encoded glycoprotein composing cell membrane, and the PrP detected in prion diseases is its isoform. The function of normal PrP is not fully understood but may play a preventing role in the cell death mechanism. In human, prion diseases are divided into two types, hereditary (autosomal dominant) type and sporadic one. In hereditary prion diseases, 16 different pathogenic mutations of the PrP gene have been discovered and each mutation exhibits distinguishable clinical pictures. In sporadic prion diseases such as Creutzfeldt-Jakob disease(CJD) the abnormal PrP is highly infectious. Although routes of transmission are not clarified in most CJD cases, there are reports of iatrogenic CJD and, recently, 14 cases of atypical CJD probably transmitted from bovine spongiform encephalopathy. The mechanism of replication of the abnormal PrP, however, remains unknown in CJD.
For the purpose of local control and breast conservation, intraarterial infusion chemotherapy combined with radiotherapy has been indicated in patients with locally advanced breast cancer both in primary and recurrent cases. The present series, evaluated during the past 4 years, consisted of 15 patients 35-83 years of age, with invasive ductal carcinoma, including 10 with primary breast cancer (stage IIIb: 1; IV: 9) and 5 with postoperative recurrence (stage IIIb: 2, IV: 3). Intraarterial chemotherapy is started, basically infusing ADM 50 mg, MMC 10 mg and CDDP 50 mg into the internal thoracic and/or subclavian artery 1-3 times, followed by reduction surgery (quadrantectomy: 4, wide resection: 2) and radiotherapy to the breast, supraclavicular, parasternal and cervical regions according to tumor extent. Local response after arterial infusion was CR: 2, PR: 10, NC: 3 (response rate: 73%). The response rate of distant metastases after arterial infusion was 73%. Of 10 patients with primary breast cancer, recurrence was noted in 1. Breast conservation was successful in 8 of 10 patients. One of them, in stage IIIb, has survived for 4.5 years with no evidence of disease and with breast conservation. Five patients with postoperative recurrence showed CR with no recurrence after intraarterial chemotherapy and radiotherapy. Acute skin reaction occurred in 6 patients, and was especially frequent in patients with postoperative recurrence (4 of 5). According to these results, combined therapy affords breast conservation even in patients with locally advanced breast cancer, and improves patient's QOL in stage IV.
To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) of infant and cord blood (CB). The results were compared with those in bone marrow (BM) CD34+ cells. The final purity of the CD34+-enriched fraction from PB, CB, and BM, based on FACS analysis, was 88 +/- 14%, 73 +/- 13%, and 68 +/- 19% (mean +/- SEM), respectively. Cells were then cultured for 96 hours with supernatant containing the vector in the presence of interleukin (IL)-3, IL-6, and stem cell factor (SCF). The average efficiency of gene transfer into mobilized PB (n = 5) or CB CD34+ cells (n = 6) was significantly higher than that into BM CD34+ cells, as measured by G418-resistant colony-forming units for granulocyte/macrophage (CFU-GM; 59% or 58% vs. 39%; p < 0.05) and PCR-positive CFU-GM (83% or 79% vs. 53%; p < 0.05). When the evaluation was made in an LT culture system with irradiated allogeneic marrow stroma, these efficiencies were, respectively, 74% or 61% vs. 34% (p < 0.005 or < 0.02) for G418-resistant CFU-GM at week 5 of long-term culture, and 88% or 83% vs. 63% (p < 0.05) for PCR-positive CFU-GM. Fluorometric examination was performed for cell-cycle analysis before and after culture, and the results showed that the fraction of cycling cells was largest in freshly prepared BM (18%), whereas only a small portion of PB (4.6%) and CB (2%) was cycling. However, this value was 17% in BM, 22% in PB, and 13% in CB after culture. These results suggest that mobilized PB from small children and CB cells are suitable and realistic targets for clinical gene therapy and that tandem transduction procedures can be achieved by combining CB and PB.
BACKGROUND: A novel system of complete portal venous isolation and charcoal haemoperfusion (PVI-CHP) has been developed in an attempt to increase dose intensity while minimizing the systemic toxicity of the cytotoxic agent during intra-arterial chemotherapy of the pancreas. METHODS: Mongrel dogs were given doxorubicin (3 mg kg-1), infused over a 5-min period via the splenic artery, together with PVI-CHP (group 1; n = 5) or without PVI-CHP (group 2; n = 5). Plasma doxorubicin concentrations were determined in serial samples obtained from the inlet and outlet of the CHP filter and in samples obtained from the left jugular vein (systemic levels) for up to 30 min after initiation of drug infusion. Subsequently, specimens were obtained from the pancreas, liver and heart to determine tissue doxorubicin levels. RESULTS: The mean(s.d.) peak systemic concentration of doxorubicin in group 1 was 0.78(0.03) microgram ml-1, significantly lower than that in group 2 of 3.49(1.15) micrograms ml-1 (P < 0.01). The peak concentration of doxorubicin in group 1 was significantly lower (more than 90 per cent) than that before filtration (P < 0.01). Tissue doxorubicin concentration in the pancreas was similar in both groups. However, concentrations in the liver and heart were significantly lower in group 1 than in group 2 (P < 0.05). CONCLUSION: These results indicate that PVI-CHP can produce a significant reduction in systemic drug exposure and may allow dose intensification during intra-arterial chemotherapy for the pancreas.
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A 61-year-old-male with local advanced inoperable cervical esophageal cancer (squamous cell carcinoma, T4N1M0 stage III) was treated by concurrent radiochemotherapy. A dose of 50.6 Gy/46 Fr/36 days and one course each of CDDP-5-FU and nedaplatin-5-FU were delivered safely. Radical surgery could be performed thereafter because of the good tumor response. Pathological CR was obtained in metastatic cervical lymph nodes and almost total necrosis in primary cancer. Concurrent radiochemotherapy produced a significant improvement in this case of advanced cervical esophageal cancer.
A 41-year-old woman was admitted to the hospital because of diarrhea followed by progressive weakness of all extremities and dysphagia. On neurological examination, she showed facial diplegia, bulbar palsy, flaccid quadriplegia, and absence of all deep tendon reflexes in addition to Laségue's sign. The Campylobacter jejuni Penner type 4 was isolated from the culture of stool. The test of anti-GM1b antibody (IgG) was positive in the serum. The protein content was elevated in the cerebrospinal fluid without pleocytosis. The studies of motor nerve conduction velocity showed a pattern of the axonal neuropathy. This is a case of Guillain-Barré syndrome presenting with the axonal neuropathy possibly due to the immune response directed to GM1b which is triggered by the Campylobacter jejuni Penner type 4 infection.
We herein report a case of multiple colonic liver metastases treated with repeated percutaneous isolated liver chemoperfusion of cisplatin under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) as an inductive treatment. The patient was a 70-year-old man who underwent curative resections for metachronous rectal and descending colonic cancer in 1979 and 1995, respectively. During outpatient follow-up, he showed increases of serum CEA level. An abdominal CT study demonstrated multiple low-density lesions in the bilateral lobes of the liver, indicating colonic liver metastases. The patient had a total of 2 treatments with percutaneous isolated liver chemoperfusion of cisplatin (total dose, 500 mg) under HVI.CHP. His post-treatment course was uneventful without side effects, including leukopenia and renal dysfunction. Serum CEA levels showed a sharp decrease to 160 ng/ml 3 months after treatment from the pretreatment value of 1,064 ng/ml. CT scan 3 months after treatment revealed remarkable tumor regression along with liquefaction of liver tumors, showing a partial response. These results suggested that repeated percutaneous isolated liver chemoperfusion of cisplatin under HVI.CHP is a potent inductive treatment for patients with multiple colonic liver metastases.
We herein evaluated the efficacy of combined use of sodium thiosulfate (STS) in isolated liver chemoperfusion of cisplatin (CDDP) under complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 5), CDDP (4 mg/kg) + STS (4 g/body) and group II (n = 5), CDDP (4 mg/kg). In both groups, CDDP was intraarterially administered for 20 minutes under HVI.CHP. In addition, in group I, STS infusion was administered for 20 minutes via the outlet side of CHP filter. The adsorption rates of free and total CDDP of CHP filter were in a range of 50-80%, and the rates in group I were higher than in group II. At all sampling points, the AUC (microgram.min/ml) of free CDDP was not different between the two groups. However, the AUC of total CDDP at postfilter [group I: 35.3 +/- 2.7 (mean +/- SD); group II: 63.5 +/- 21.5] and systemic serum (group I: 24.9 +/- 8.6, group II: 43.5 +/- 13.5) was significantly lower in group I than in group II (p < 0.05). The cumulative amounts of urinary excretion of CDDP (microgram/kg) were 39.5 +/- 12.1 and 13.5 +/- 9.3 in groups I and II, respectively, showing a significant increase in group I (p < 0.01). These results indicated that the use of STS in percutaneous isolated liver chemoperfusion of CDDP under HVI.CHP could further reduce systemic toxicities of CDDP, by increasing CDDP filter extraction of CHP filter and urinary CDDP excretion.
To compare the metabolic consequences of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), glycemic control and energy metabolism were evaluated in 18 children displaying IDDM and 19 NIDDM adult patients. With rising concentrations of fasting blood glucose (FBG), hemoglobin A1C and free fatty acid, the percentage of the ratio of resting energy expenditure (REE) to predicted REE expressed as %REE increased and the respiratory quotient (RQ) decreased. The linear regression between RQ and FBG showed the same gradient in IDDM and NIDDM although the RQ in IDDM was always 0.07 lower than that in NIDDM given various FBG concentrations. Those patients whose RQ values were less than 0.7, indicating ketone body production, included 8 (44%) IDDM and 2 (11%) NIDDM patients. These results may explain the relatively greater manifestation of ketoacidosis in IDDM.
We present two siblings with vitamin B6-nonresponsive homocystinuria due to a deficiency of cystathionine beta-synthase who had different levels of methionine in the blood during the neonatal period, even though they had the same genetic defect. One of them was missed in the screening of newborns for homocystinuria. Special care should be taken in screening neonates for homocystinuria using the blood level of methionine.
To clarify how synthesized ATP is utilized to maintain cellular integrity during preservation by the two-layer method, we examined the effect of ouabain, inhibitor of ATP dependent Na+/K+ pump, on ATP tissue levels, graft weight, and vascular endothelial cells during 48 hr preservation by the two-layer method and pancreatic tissue perfusion and graft survival after transplantation in a canine model. Ouabain treatment did not affect ATP production but prevented its utilization by the sodium pump, and actually significantly increased ATP levels and decreased the weight loss of the graft. In addition, ouabain caused a significant increase of nuclear trypan-blue staining in vascular endothelial cells and a significant decrease of pancreatic tissue perfusion at reperfusion. Consequently, the grafts did not survive. We conclude that the two-layer method allows sufficient synthesis of ATP to drive the sodium pump and maintains membrane integrity of parenchymal cells and vascular endothelial cells, thus extending the period of preserved pancreatic viability.
The purpose of this study was to measure directly tissue oxygen tension (PO2) of the ischemically damaged pancreas graft during preservation by the two-layer (University of Wisconsin solution/perfluoro-chemical) method at 20 degrees C using Clark-type polarographic oxygen electrodes and to make clear the relationship of tissue PO2 and ATP levels during preservation and graft survival after transplantation in a canine model. During warm ischemia, tissue PO2 and ATP were dramatically decreased. Tissue PO2 continued to decrease, and tissue ATP levels were not elevated during simple storage in oxygenated University of Wisconsin solution at 20 degrees C. On the contrary, during preservation by the two-layer method at 20 degrees C, tissue PO2 promptly increased and reached about 50% of the preprocurement level at 30 min of preservation. Then, tissue PO2 was maintained this level throughout the preservation period. Tissue ATP levels were still low in the first 1 hr, but after that tissue ATP increased in a time-dependent manner. Consequently, the two-layer method at 20 degrees C could restore the viability of pancreas damaged by warm ischemia during 3- and 5-hr preservation. We conclude that the ischemically damaged pancreas grafts were oxygenated, and tissue ATP was increased during preservation by the two-layer (University of Wisconsin solution/pefluorochemical) method at 20 degrees C. Consequently, the graft was resuscitated and survived after transplantation.
The antimutagenic effects of green tea catechins, (-)-epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg) on induction of 6-thioguanine (6TG)-resistant mutations induced by 4-nitroquinolin 1-oxide (4NQO) were found in cultured Chinese hamster V79 cells. The antimutagenic activity of catechins was found only when cells were post-treated with catechins during the mutation expression time after treatment with 4NQO, and not found by simultaneous treatments with 4NQO and catechins. This bioantimutagenic activity of catechins were not observed in ethyl methanesulfonate (EMS)-induced mutations. This suggests that the antimutagenic effects of catechins may act intracellularly as bio-antimutagenic blocking agent or suppressive agent. These catechins had no effects on the cytotoxic activity of 4NQO in V79 cells, whether catechins were used in simultaneous treatment with or in post-treatment after 4NQO. This indicates that the antimutagenicity and anticytotoxicity to 4NQO may be caused by different mechanism(s).
Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of mesangial matrix (MM) accumulation in human and experimental glomerulonephritis. To clarify molecular mechanisms responsible for pathological MM deposition, we examined the effect of TGF-beta on the production of beta1 integrins and on adhesion function of rat mesangial cells (MC). In immunoprecipitation experiments using [35S]methionine-labeled MC, stimulation of MC with TGF-beta for 48 h resulted in an increase in the synthesis of alpha1beta1 (collagen/laminin receptor) and alpha5beta1 (fibronectin receptor) integrins accompanied by increases in the synthesis of their ligands, collagen type I (collagen I), and fibronectin. A time-dependent increase in beta1, alpha1 integrin subunit mRNA peaking 48 h after exposure to TGF-beta was shown by Northern blot analysis. After 48 h of treatment with TGF-beta, MC displayed significant increases in adhesion to fibronectin, collagen I, and laminin as compared to untreated MC. Anti-beta1 antiserum significantly inhibits MC adhesion to fibronectin, collagen I, and laminin. Anti-alpha1 subunit antibody very strongly inhibited adhesion to collagen I and laminin, but not to fibronectin. Synthetic peptides containing RGD sequences specifically blocked adhesion to fibronectin. These data suggest that TGF-beta may promote MM deposition by increasing MC synthesis of both matrix proteins and beta1 integrins which facilitate binding of these proteins to the MC surface and thus enhance their incorporation into MM.