Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.     

Biocompatibility of two apatite cements

The incidence of HIV-associated tuberculosis has been increasing worldwide since the beginning of the AIDS epidemic, and is expected to increase even further during the foreseeable future, especially in developing countries. There is no doubt now that, in the presence of HIV infection, new-onset tuberculous infection progresses rapidly to clinically significant disease and the likelihood that latent tuberculous infection progresses rapidly to clinically significant disease and the likelihood that latent tuberculous infection will reactivate is enormously increased. The accelerating and amplifying influence of HIV infection is contributing to the increasing incidence of disease caused by multidrug-resistant strains of Mycobacterium tuberculosis. Neither clinical features nor radiographic abnormalities reliably distinguish the majority of patients with HIV-associated tuberculosis from those without HIV infection. Some persons with HIV infection, however, present with atypical manifestations of tuberculosis and these patients may be difficult to diagnose. Six months of daily or thrice weekly chemotherapy with the usual regimen of 4 then 2 antituberculosis drugs cures most patients, but many die during or after treatment of other AIDS-related complications.     

Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (<1%). In off-line image analysis, variance components due to subjects and segments, inter-analyst variance, and residual fluctuation were 88%, < 1% and 11%, respectively. Intra-analyst variance was negligible (<1%). The major source of B-mode ultrasound IMT measurement variability finds its origin in subjects and their arterial walls. Although sonographers proved a lesser source of variability, in comparative studies they should enter a study well trained and should be randomly assigned to subjects. Follow-up examinations should preferably be done by the same sonographer. Off-line image analysis contributed little to IMT measurement variability.     

Factitious orbital emphysema: an unusual presentation of Munchausen''s syndrome

The role of radical cystectomy as the standard treatment of localised infiltrating bladder malignancy is challenged by the development radiotherapy and chemotherapy combinations. The published studies are difficult to compare because of large differences in the patients selection criteria and in the assessment of local involvement (only clinical in combined treatment, based on pathology and therefore unquestionable in surgical series). The advantages of radical surgery are its precedence and a well-established technique, simplified follow-up procedures and seemingly higher survival rates acquired after 3 years. Conversely, the combination of radiotherapy and chemotherapy allows bladder preservation in about 40% of the patients (at 5 years), but only in 23% without bladder relapses. A complete initial endoscopic resection is the best and only prognostic factor of these results which nevertheless needs a very carefully and endless follows. The comparison of the quality of life achieved by both treatment modalities remains insufficiently documented.     

Levels and correlates of maternal nutritional status in urban Bangladesh

OBJECTIVE: To determine the levels and correlates of maternal nutritional status. DESIGN: Cross-sectional maternal weight, height, and mid-upper arm circumference (MUAC) data were correlated with sociodemographic data. SETTING: Slums of Dhaka, Bangladesh. SUBJECTS: Weight, height and MUAC were collected from a representative sample of 2417 nonpregnant mothers. Socioeconomic data such as age, education, religion and household economic status was collected from 2048 mothers; data on reproductive experiences such as number of pregnancies and number of children born alive now dead was available from 1314 mothers; and both sets of data from 1185 mothers. METHODS: Using weight, height, MUAC and body mass index (BMI) data, the levels of maternal nutritional status were estimated. Bivariate and multivariate relationships of maternal nutritional status with socioeconomic and reproductive experiences variables were examined. RESULTS: Mothers' mean weight, height, MUAC and BMI were 41.8 kg, 148.8 cm, 232.5 mm, and 18.8 respectively. In multivariate regression analyses, mothers' weight, BMI and MUAC were significantly positively correlated with mothers' years of schooling (P < 0.05) and household economic status (P < 0.01). Mothers' height was significantly positively correlated with years of schooling (P < 0.05), but not with household economic status. Maternal height and weight were significantly negatively correlated with number of child deaths (P < 0.05). CONCLUSIONS: The findings suggest a possible inter-generational effect; thus, improvement of the nutritional status of girls of this generation would improve child survival in the next generation. This, however, will require complex and long-term planning. As an interim measure, shorter mothers should be targeted for appropriate antenatal and obstetric services.     

Effects of auditory stimuli on intracranial pressure and cerebral perfusion pressure in traumatic brain injury

In the kidney, ischaemia-reperfusion results in both hypoxic and oxidant cellular injury which is most marked in the tubules of cortex and outer medulla. These contrasting conditions may have opposite effects on the expression of enzymes that reduce or repair oxidant damage. To investigate this, the activities of CuZn and Mn superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured after 4 h and 3, 6, and 10 days of reperfusion following sham surgery or 45- or 90-min left renal artery occlusion. The right kidney served as internal control. Sham surgery had no effect on Mn SOD or GPx, but caused small (p < 0.05) reductions in CuZn SOD and GST activities. Forty-five minutes of ischaemia had no net effect on Mn SOD, increased GPx activity (maximum at 6 days, p < 0.01), and reduced CuZn SOD (nadir 3 days, p < 0.02) and GST (nadir 6 days, p < 0.02) activities. Ninety minutes of ischaemia again had no net effect on Mn SOD, prevented the induction of GPx, and further suppressed the activities of CuZn SOD and GST. The activity of the non-anti-oxidant enzyme lactate dehydrogenase was equal in left and right kidneys after 45 min of ischaemia, but different (p < 0.01) 10 days following 90-min injury, due to a combination of reduced activity in the ischaemic kidney and an increase of activity in the internal control. The immediate effect of ischaemia-reperfusion injury on the kidney is to reduce the activity of intracellular anti-oxidant enzymes in proportion to the severity of the ischaemic insult. Recovery or net induction of enzyme activity paralleled tubular regeneration. Protection resulting in acquired resistance to a second ischaemic event is unlikely to be due to induction of anti-oxidant enzymes if it occurs within 6 days.     

Ki-1 large cell anaplastic lymphoma--a clinicopathological study

Ki-1 large cell anaplastic lymphoma is a recently described variant of malignant lymphoma. A retrospective study of 10 cases of Ki-1 lymphoma was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi to document its clinical and morphological features. The morphological features were evaluated by a study of paraffin embedded sections stained with haematoxylin and eosin stains. Immunohistochemical stains for BER-H2 and leucocyte common antigen (LCA) were performed in all cases. The age of the patients ranged from 2 to 60 years and male to female ratio was 2.3:1. Cervical lymphadenopathy was the most common presentation. Histologically, there was a complete effacement of the lymph node architecture in 8 cases. The Reed-Sternberg like cells were seen in 2 and histiocyte like cells in 7 cases. Immunohistochemically all cases were positive for BER-H2. It is suggested that the possibility of Ki-1 lymphoma should be considered in all cases of lymphoma with pleomorphic morphology.     

The synthesis and thymidylate synthase inhibitory activity of L-gamma-L-linked dipeptide and L-gamma-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.     

Protective effects of a recombinant N-terminal fragment of bactericidal/permeability increasing protein on endotoxic shock in conscious rabbits

Endotoxin (lipopolysaccharide, LPS) can induce shock, multiple organ failure, and death. A recombinant N-terminal fragment of bactericidal/permeability increasing protein, rBPI23, binds with high affinity to gram-negative bacterial LPS and neutralizes its biological activity. We sought to determine the effect of rBPI23 on LPS-induced respiratory dysfunction and cardiovascular depression in conscious rabbits. Rabbits were injected with Escherichia coli O113 LPS (6 micrograms/kg) and treated with rBPI23 (2 mg/kg), vehicle, or control protein after recovery from surgery performed to implant catheters for hemodynamic assessments and intravenous injections. LPS challenge caused respiratory dysfunction including tachypnea, significant decreases in arterial O2 tension (PO2), arterial oxygen content, and an increase in alveolar-arterial O2 gradient (A-aDO2). LPS administration also resulted in profound and prolonged decreases in mean arterial blood pressure and cardiac index. Treatment with rBPI23 prevented LPS-induced respiratory dysfunction and significantly ameliorated the cardiovascular depression. 5 of 16 LPS-challenged animals died of respiratory failure and acidosis, whereas none died in the rBPI23 treated group (p = .11). The results demonstrate that rBPI23 protects animals against LPS-induced cardiopulmonary depression in endotoxic shock.