Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.     

Resuscitation and circulatory support using extracorporeal membrane oxygenation for fulminant pulmonary embolism

Fulminant pulmonary embolism (PE) with circulatory collapse is associated with a high mortality rate due to acute right ventricular failure and hypoxia. Immediate and appropriate resuscitation and circulatory support in the perioperative period is mandatory to prevent sudden death. Extracorporeal membrane oxygenation (ECMO) was recently introduced for extracorporeal life support in patients with circulatory collapse and has provided an excellent outcome. We report on the effectiveness of ECMO support for fulminant PE. Seven patients were placed on veno-arterial ECMO for circulatory collapse caused by fulminant PE refractory to conventional treatment. After resuscitation, all patients underwent pulmonary angiography, and thrombolytic therapy was administered in all 7 patients under ECMO support. Three patients who did not improve by thrombolysis underwent embolectomy with standard cardiopulmonary bypass. Two thrombolysis and 2 surgery patients were weaned from bypass and survived. The duration of support ranged from 18-168 h (mean = 67.8 +/- 67.1 h), with maximum bypass flow rates of 2.0-4.5 (mean = 3.5 +/- 0.9). There were no device-related complications during support. In total, 4 patients (57%) were successfully weaned from support and discharged from the hospital in good condition. All patients who survived required prolonged support (27, 82, 151, and 168 h). We conclude that resuscitation and circulatory support using ECMO can be effective, life-saving measures in cases of circulatory collapse caused by fulminant PE.     

Subjective and functional results after total gastrectomy: prospective study for longterm comparison of reconstruction procedures

Background: Many reconstruction procedures have been developed in efforts to resolve patients' complaints after total gastrectomy. However, there have been few reports of longterm comparisons between reconstruction procedures, especially with regard to the prevention of duodenal food passage. This study was undertaken to compare the longterm subjective and functional results among Roux-en-Y esophagojejunostomy (R-Y), R-Y with pouch (P-Y), and jejunal interposition with pouch (P-I) after total gastrectomy. Methods: Consecutive patients requiring curative total gastrectomy were enrolled in this prospective study by the envelope method. Results: Hospital stay was longer following a P-I than an R-Y or a P-Y. Over 50% of R-Y patients complained of heartburn, and 20% of R-Y patients showed dumping syndrome throughout the postoperative period, with this rate being significantly different from rates in the other two groups. P-Y patients complained of early satiety in the late postoperative period, while P-I patients complained of early satiety in the early postoperative period. The nutritional index in P-I patients was higher than those in patients with the other two procedures. Gastrointestinal and hepatobiliary dual scintigraphy (GHDS) showed that the rate of bile reflux with an R-Y was relatively high after surgery. Food reflux with a P-Y was increased (9.4% to 11.1%), but with a P-I food reflux was decreased at 3 years after surgery (13.3% to 9.9%). Patients with a P-Y had a faster recovery of body, weight in the early postoperative period; however, at 5 years after operation, body weight recovery with a P-I was greatest. Conclusion: Reconstruction should be performed with pouch formation after total gastrectomy with curative intent. Received: March 7, 2002 / Accepted: September 26, 2002 Acknowledgments This study was partly supported by the University of Tsukuba Research Project. Offprint requests to: S. Adachi     

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.     

Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by α-tocopherol supplementation

Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by ⁵¹Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral α-tocopherol (α-Toc) supplementation (100 mg/day), NK cell activity had normalised. When α-Toc supplementation was interrupted for 16 weeks, NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16⁺ CD 56⁻ fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of α-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. Conclusion These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16⁺ CD56⁻ NK cells and that this abnormality is reversible with α-Toc supple‐mentation. Received: 30 January 1996 and in revised form: 19 November 1996 / Accepted: 22 November 1996     

A double-blind randomised controlled trial of the effects of medroxyprogesterone acetate on bone density of women taking oestrogen replacement therapy

Objective To assess the effects of medroxyprogesterone acetate on bone density in women who have had a hysterectomy
Design Randomised, double-blind, placebo-controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an adjunct to oestrogen therapy.
Participants One hundred and twenty-three women, aged 18 to 45 years and currently receiving daily oestrogen, who presented at a university-based rheumatology practice.
Interventions The women were randomly assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo daily beginning on day 15 of each month for one year. Forty-one women were randomised into each group.
Main outcome measure The primary outcome measurement was the percentage of change from baseline in bone mineral density of the lumbar spine (L2–L4). Secondary outcome measures included differences in femoral neck bone density, cholesterol and triglyceride levels between groups.
Results At one year, change in bone mineral density did not differ between either the treatment or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to statistically significant reductions in very low density lipoprotein cholesterol, total triglycerides, and very low density lipoprotein triglycerides when compared with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically significant reduction in high density lipoprotein cholesterol, high density lipo-protein-2 cholesterol, and high density lipoprotein-2 triglycerides.
Conclusions Medroxyprogesterone acetate at either dose as an adjunct to oestrogen did not improve bone mineral density at one year when compared with placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids. Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein cholestrol and therefore may increase cardiovascular risk.     

Tumor lysis syndrome in widely metastatic small-cell lung cancer

Tumor lysis syndrome is a rare complication of nonhematologic malignancies that results from massive necrosis of neoplastic cells after chemotherapy. This syndrome consists of life-threatening metabolic derangements, including severe hyperphosphatemia, hyperkalemia, hyperuricemia, and hypocalcemia, and may result in renal failure and death if not recognized early and treated appropriately. We report a case of tumor lysis syndrome after induction chemotherapy in a patient with widely metastatic smallcell lung cancer. This case emphasizes the importance of awareness and early treatment of this syndrome.     

Allelotype and replication error phenotype of small cell lung carcinoma

Allelotype and replication error (RER) phenotype analyses were performed to clarify the pathogenetic significance of inactivation of tumor suppressor genes and genomic instability in the genesis and progression of small cell lung carcinoma (SCLC). We examined 37 cases of SCLC for loss of heterozygosity (LOH) and microsatellite instability at 49 loci on all 39 nonacrocentric chromosomal arms. LOH was frequently (>70%) detected on chromosomes 3p (29/32, 90.6%), 5q (15/21, 71.4%), 13q (25/26, 96.2%), 17p (22/25, 88.0%), and 22q (24/33, 72.7%). Frequent LOH (>70%) on these loci was observed even among seven cases of stage I tumors. The incidence of LOH on all 39 nonacrocentric chromosomal arms was not significantly different between primary tumors and metastases. These results suggest that inactivation of multiple tumor suppressor genes accumulates relatively early during progression of SCLC and it may be responsible for clinically and biologically aggressive phenotype of SCLC. RER was observed in 6/37 (16.2%) of SCLC, however, RER at multiple loci was observed only in two cases. Therefore, it was indicated that genomic instability is uncommon, but might play a role in the genesis of a small subset of SCLC.      

Assessment of proliferating cell nuclear antigen immunostaining in parotid tumors

We evaluated the prognostic value of immunostaining proliferating cell nuclear antigen (PCNA) by using a monoclonal antibody (PC10) in patients with parotid tumors. Twenty-seven cases were studied. Immunohistochemical studies were carried out on paraffin-embedded tissues from the patients, and the PCNA index was calculated as the percentage of positively staining tumor cells. The PCNA index ranged from 0.1 to 65.3%. We divided the 27 lesions into three groups histologically: group A with benign pleomorphic tumors (11 cases), group B with low-grade malignant tumors (5 cases), and group C with high-grade malignant tumors (11 cases). The mean PCNA index was 0.7% in group A, 2.0% in group B, and 23.1% in group C. The clinical data revealed a significantly higher local tumor recurrence and mortality rate in group C than in groups A and B. We conclude that PCNA may be used as an important indicator for determining clinical prognosis in parotid tumors. Received: 26 July 1997 / Accepted: 28 October 1997