Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100mg/m², IV_Y day 8), Adriamycin (30mg/m², IV_Y days 1,2), teniposide (75 mg/rn², IV, day 1), cyclophophamide (300 mg/m², po, days one to five), Oncovin (1.4 mg/m², IV: maximum 2 mg, days 8,15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m², IV, day 1), Adriamycin (50 mg/m², IV, day 1), Oncovin (1.4 mg/m² IV: maximum 2 mg, day 1) and prednisolone (100 mg, PO, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p 0.0001), mucositis (p= 0.002) and infections (p= 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification. (Aust NZ J Med 1992; 22: 123–128.)     

Characterization of a benzyladenine binding-site peptide isolated from a wheat cytokinin-binding protein: sequence analysis and identification of a single affinity-labeled histidine residue by mass spectrometry

A wheat embryo cytokinin-binding protein was covalently modified with the radiolabeled photoaffinity ligand 2-azido-N6-[14C]benzyladenine. A single labeled peptide was obtained after proteolytic digestion and isolation by reversed-phase and anion-exchange HPLC. Sequencing by classical Edman degradation identified 11 of the 12 residues but failed to identify the labeled amino acid. Analysis by laser photodissociation Fourier-transform mass spectrometry of 10 pmol of the peptide independently confirmed the Edman data and also demonstrated that the histidine residue nearest the C terminus (underlined) was modified by the reagent in the sequence Ala-Phe-Leu-Gln-Pro-Ser-His-His-Asp-Ala-Asp-Glu.     

Effect of 6-hydroxydopamine lesions of the amygdala on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement

Bilateral six-hydroxydopamine (6-OHDA) lesions were placed in the amygdala of rats self-administering cocaine (1.5 mg/kg per injection i.v.) under a progressive ratio schedule of reinforcement. Post-lesion access to three doses of cocaine (1.5, 0.75 and 0.37 mg/kg per injection i.v.) revealed a lesion effect only at the highest dose. At this dose, the lesion caused a significant increase in breaking point. No change in the breaking point was produced at the lower two doses. The biochemical results show a significant reduction in dopamine and DOPAC levels within the amygdala and an increase in dopamine within the NACC. In contrast, noradrenaline and serotonin (5-HT) levels were unaffected by the lesion in any of the dissected areas. These results demonstrate that no specific effect on cocaine reinforcement was produced by 6-OHDA lesions of the amygdala. The possibility that the lesion may have attenuated the anxiogenic qualities of the high dose of cocaine is discussed.     

Complex I,Iron, and ferritin in Parkinson's disease substantia nigra

Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples.     

The correction of BMD measurements for bone strontium content.

Strontium ranelate (SR) is a new oral treatment for osteoporosis associated with large increases in bone mineral density (BMD) compared with alternative therapies such as bisphosphonates. Much of the BMD increase during SR treatment is a physical effect caused by the increased attenuation of X-rays due to the accumulation of strontium in bone tissue. The aim of this study was to assess the contribution made by bone strontium content (BSC) to the overall BMD increase by evaluating the percentage F of the BMD change explained by the physical presence of strontium in bone. A value of F less than 100% would provide evidence of the anabolic effect of SR as an additional factor contributing to the overall BMD increase. Studies of mixtures of strontium hydroxyapatite (SrHA) and calcium hydroxyapatite (CaHA) scanned on a variety of dual-energy X-ray absorptiometry (DXA) systems show that a 1% molar ratio of SrHA/(CaHA+SrHA) causes a 10% overestimation of BMD. The correction of spine BMD measurements for the physical effects of strontium depends on knowledge of 2 further factors: (1) bone biopsy measurements of iliac crest BSC and (2) the ratio R of BSC at the DXA site to BSC at the iliac crest measured in animal studies. We used clinical trial data and values of R(spine) measured in studies of monkeys and beagle dogs to determine values of F(spine) for 1, 2, and 3 yr treatment with SR. Based on the average value of R(spine) approximately 0.7 for male and female monkeys, we found values for F(spine) approximately 75-80% for 1, 2, and 3 yr of treatment. Using the value of R(spine) approximately 1.0 from the beagle study gave values of F(spine) approximately 100%. Although values of F(spine) as low as 40% are possible, we conclude that the most likely figure is 75% or greater. However, it is apparent that there are large uncertainties in the correction of BMD results for the effect of bone strontium and that the most important of these is the inference of BSC values at DXA scan sites from measurements of iliac crest bone biopsy specimens.     

Bilateral Mid-Diaphyseal Femoral Stress Fractures in the Elderly

Abstract Background: Osteoporosis is characterized by low bone density and poor bone mineralization. Mid-diaphyseal stress (insufficiency) fractures of the femur caused by osteoporosis are rare. The symptoms of these lesions are vague and confusing. The physician must be alert to the possibility of femoral shaft stress fractures when evaluating an elderly patient complaining of back, hip or leg pain. Case Study: A 72-year-old osteoporotic female patient with bilateral mid-diaphyseal stress fractures of the femur is reported. The diagnosis of femoral shaft stress fracture in the elderly is very difficult when based on physical findings and plain radiography only. A magnetic resonance imaging (MRI) scan or nuclear scintigraphy is necessary for early diagnosis. In the described case, the patient had an excellent result after surgical treatment with intramedullary nails. Conclusion: MRI or nuclear scintigraphy must be obtained to exclude the possibility of femoral shaft stress fractures in the elderly. In the absence of contraindications, surgery is the best solution for this kind of lesion.     

Transplantation for myocarditis: a controversy revisited.

Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide, approximately 45% of all heart transplants are performed for IDC and up to 8% for myocarditis. Early reports suggested that survival after transplantation for myocarditis was poor and patients had an increased risk of rejection. More recently, larger case series suggest that overall survival after transplantation for myocarditis is similar to survival after transplantation for other causes. However, certain disorders, including cardiac sarcoidosis and giant cell myocarditis (GCM), require heightened surveillance for post-transplantation disease recurrence. We present the case of a 42-year-old man with recurrence of GCM 8 years after transplantation and review the literature on the role of cardiac transplantation for patients with myocarditis.