Osteosarcoma occurring in osteogenesis imperfecta

We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Suramin inhibits DNA damage in human prostate cancer cells treated with topoisomerase inhibitors in vitro

Suramin, a highly sulfonated drug, has been reported to be effective against several human malignancies in vitro and in vivo, and currently is undergoing clinical trials against prostate tumors. The biochemical and molecular mechanisms for suramin's antiproliferative activity are not clear. In order to define the biochemical basis for its antitumor activity and to enhance suramin's chemotherapeutic potential while decreasing its toxicity, we have examined interactions of suramin with topoisomerase I and 11 and several clinically active anticancer drugs against the human prostate (PC3 and LNCaP) cancer cell line. While etoposide, m-AMSA, camptothecin, and SN-38 (the active metabolite of CPT-11) were active in killing prostate cells as single agents, combinations of suramin and these agents were antagonistic against these cells. We found that suramin inhibited activities of purified topoisomerase I and II in vitro as measured by relaxation and cleavage assays. Further studies indicated that suramin also inhibited the drug-induced DNA damage in vitro and in isolated nuclei. These findings indicate that combinations of suramin with topoisomerase inhibitors, for example, VP-16, m-AMSA, or CPT, may not be beneficial to patients receiving suramin-containing chemotherapy. © 1993 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America

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A Double-Blind Controlled Study of Clinical Efficacy of Maprotiline and Amitriptyline in Depression

A multiclinic double-blind controlled study was performed on the effects of MAP in both inpatients and outpatients with AMT as control drug.

• 1 Subjects consisted of 41 male and 45 female patients suffering from various types of depression. MAP was assigned to 42 cases and AMT to 44 cases. Of these patients, 14 MAP cases and 10 AMT cases were subsequently dropped for a variety of reasons to obtain 28 MAP cases and 34 AMT cases as evaluable.
• 2 The global improvement ratings were compared and found not significantly different for any week between the two treatments.
• 3 The global improvement ratings by the characteristic features of patients did not show any significant difference in any items studied between the two treatments.
• 4 The symptomatic improvement ratings (on the Hamilton R.S. for assessment by the physician) indicated that AMT was more effective on “anxiety (psychic).”
• 5 The symptomatic improvement ratings (on the Beck self-assessment scale by the patient) indicated that MAP was more effective on “work” and AMT on “pathos”, “feeling of satisfaction”, “withdrawal” and “loss of libido.”
• 6 During the treatment period, 74.3 percent of the MAP group and 76.9 percent of the AMT group of patients showed some side effects or accompanying symptoms, with no significant difference recognized between the two treatments. Itemwise, however, the incidence of tremor was significantly lower (p-=0.06) in the MAP group. Moreover, the MAP group tended to be less liable to such anti-cholinergic side effects as dry mouth, constipation, trouble of accommodation, urinary disturbance and palpitation.
• 7 On the basis of the above findings, it is concluded that MAP is as effective against depression as AMT and less liable to the anticholinergic side effects. It is, therefore, a very useful antidepressant.

     

Effects of sodium and temperature on tension in isolated canine coronary artery

The effects of sodium and temperature on tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the strength of tension was inversely related to the Na concentration. At 37°C, the tension was significantly increased at 70mEq·l ^–1 Na and below. The tension was gradually suppressed by lowering of the temperature from 37°C to 10°C. At 10°C, tension did not developed significantly at Na concentrations between 127mEq·l ^–1 and 12mEq·l ^–1.It was concluded that the decrease in Na concentrations increased the tension of the canine coronary artery and the lowering of temperature supressed the tension inducted by the decrease in Na concentrations.(Yoshida K, Fujii Y, Ina H, et al.: Effects of sodium and temperature on tension in isolated canine coronary artery. J Anesth 5: 56–59, 1991)     

Investigation of the pathogenesis of glaucoma capsulare with special discussion of α1Lp and Cp in aqueous humor

The aqueous humor proteins of exfoliation syndrome were studied qualitatively by crossed immunoelectrophoresis and compared with normal controls. Two kinds of macromolecules (₁-lipoprotein and ceruloplasmin) were detected more frequently in exfoliation syndrome than in the normal controls. ₁Lp was detected in eight of ten patients with exfoliation syndrome, but in none of the eight controls. Cp was detected in seven of ten patients with exfoliation syndrome, but in only one of the eight controls.The presence of these macromolecules in the anterior chamber suggests high permeability of vessels in the exfoliation syndrome. This interpretation is also supported by the fact that neovascularization is sometimes present in the iris of the exfoliation syndrome.In the aqueous humor from a patient with diabetic retinopathy, ten kinds of aqueous humor proteins were identified.     

Gastric Acidity following Pancreaticogastrostomy with Pylorus-preserving Pancreaticoduodenectomy

Pancreaticogastrostomy (PG) has been reintroduced and employed occasionally as a useful alternative to pancreaticojejunostomy (PJ) after Whipple resection or pylorus-preserving pancreaticoduodenectomy (PPPD). Although the physiologic alteration in the stomach is important for the correlation between gastric and pancreatic functions, the actual intragastric pH profile after PG is still unclear. This study was conducted to investigate the physiologic changes in gastric pH and serum gastrin and secretin levels before and after PPPD reconstructed with PG (PPPD-PG) in humans. Twenty-four hour continuous intragastric pH and serum gastrin and secretin levels in the fasting state were examined in 25 patients who had undergone PPPD-PG. No peptic ulcer was detected after the operation. After PG, serum gastrin and secretin levels were unchanged. Twenty-four hour gastric pH monitoring revealed two distinct patterns during the nocturnal period before the operation: patients with acid-type secretion (n= 11) exhibited a persistent acid pH, whereas those with alkaline-type secretion (n= 14) had cyclic variations between an acid and an alkaline pH value. After PG, in both acid- and alkaline-type patients, median pH and percentages of time that the gastric pH was less than 4 (% pH < 4) and more than 6 (% pH > 6) did not change, and circadian pH patterns also remained unchanged. These results suggest that PPPD-PG has little influence on gastric acidity, and the neurohumoral relation between the stomach, duodenum, and pancreas is preserved after PG. Therefore, physiologically, PG can be recommended as a reconstructive procedure after PPPD.     

Long-term survival after radical resection of advanced pancreatic cancer

A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection for pancreatic cancer is alive 8 yr after surgery. Originally, computed tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had infiltrated the portal vein, but grew expansively, so there was neither biliary obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes were seen within cancer cell nests on routine histopathology. We performed immunostaining for CD8, and found that a large number of the lymphocytes were CD8⁺ T cells. The patient’s prognosis was considered poor because the tumor was large and had infiltrated the portal vein. We suspect that long-term survival may be related to the response of CD8⁺ T cells to the cancer.