Pinhole imaging of <Superscript>131</Superscript>I-metaiodobenzylguanidine (<Superscript>131</Superscript>I-MIBG) in an animal model of neuroblastoma

Purpose To evaluate ¹³¹I-MIBG scintigraphic localization of xenotransplanted and spontaneously arising neuroblastomas in murine models of high-risk neuroblastoma.Methods Neuroblastoma xenografts were created by inoculation of human neuroblastoma cell suspensions into the subcutaneous flanks of athymic nude mice. In addition, spontaneous paraspinal neuroblastomas were detected by direct palpation in MYCN transgenic mice. After measured tumor volumes exceeded 200 mm³, each mouse received an intraperitoneal injection of 18 Ci/g ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG). Pinhole scintigraphy was performed to evaluate the MIBG biodistribution and to attempt to visualize the tumors. Each mouse was imaged on a gamma camera equipped with a 3-mm pinhole on one head and an HEGP collimator on the other.Results Images demonstrated absorption of radiolabeled MIBG and visualization of tumors. Analysis of the images allowed for quantification of relative MIBG uptake and for determination of linear and area measurements of the tumors.Conclusion High-energy pinhole imaging effectively demonstrates uptake of radiolabeled MIBG by human neuroblastoma tumors in murine laboratory models. This technique allows for in vivo assessment of tumor burden. In the future, we plan to use this method to evaluate sensitivity for detecting metastatic spread as well as investigating the therapeutic efficacy of high-dose ¹³¹I-MIBG in combination with radiosensitizing agents.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

IMMUNITY IN MUMPS : V. THE CORRELATION OF THE PRESENCE OF DERMAL HYPERSENSITIVITY AND RESISTANCE TO MUMPS

The results of skin tests read at 48 hours on several hundred adults and children in which heat-inactivated mumps virus was the antigen have been presented and discussed. They can be summarized as follows:— Of 89 persons tested before the onset of mumps, 89 per cent exhibited erythematous reactions 10 mm. or less in diameter and 95 per cent, reactions 15 mm. or less in diameter. Of 40 persons tested during the first 5 days of mumps, 95 per cent exhibited reactions 10 mm. or less and 98 per cent reactions 15 mm. or less. Of 480 exposed persons the attack rate of mumps was 46 per cent among 340 with reactions 10 mm. or less and 10 per cent among 240 with reactions greater than 10 mm. The attack rate was only 2 per cent among 161 with reactions exceeding 15 mm. The attack rates in 13 skin-tested groups which were exposed to mumps tended to be inversely proportional to the incidence of reactions exceeding 10 mm. The incidence of reactions exceeding 10 mm. was approximately twice as high among 529 adults (persons 18 years or older) as it was among 306 children (persons under 18 years). Of 179 adults giving positive histories of mumps, 82 per cent exhibited skin reactions exceeding 10 mm. In certain groups the correlation between history and positive skin test was as high as 0.9. Of 132 adults giving negative histories, 58 per cent exhibited skin reactions of this magnitude. The proportion of reactions exceeding 10 mm. in a small number of children giving positive histories was 75 per cent. The proportion of reactions less than 10 mm. was 15 per cent. Of 167 adults with positive complement fixation tests, 87 per cent exhibited skin reactions exceeding 10 mm. Of 111 adults with negative complement fixation tests, 52 per cent exhibited reactions exceeding 10 mm. Of 43 children with positive complement fixation tests, the skin test reactions exceeded 10 mm. in 70 per cent. The skin reactions exceeded 10 mm. in 29 per cent of 105 children with negative complement fixation tests. In 69 of 72 individuals in whom skin reactions exceeded 10 mm., complement-fixing antibody either appeared in the blood or increased in amount within about 2 weeks after the tests were done. Such antibody responses likewise were observed in 34 of 76 individuals in whom skin reactions were 10 mm. or less. The data summarized up to this point were obtained with virus derived from the infected parotid gland of monkeys. The results of simultaneous tests in 82 individuals employing materials prepared from infected monkey parotid gland and amniotic membrane of chick embryos infected with mumps virus indicated in general that the same individual responded in a similar manner to both antigens. In many instances, however, the membrane material produced weaker reactions. Occasionally an individual failed to react at all to one of these materials but did respond to the other.     

IMMUNITY IN MUMPS : IV. THE CORRELATION OF THE PRESENCE OF COMPLEMENT-FIXING ANTIBODY AND RESISTANCE TO MUMPS IN HUMAN BEINGS

Of 163 persons giving positive complement fixation tests who were exposed to mumps, 1 afterwards developed the disease; of 285 negative reactors similarly exposed, 56 afterwards came down with mumps. Of 78 individuals subjected to intimate exposure to mumps whose tests were originally negative and who failed to develop the disease, 41 per cent gave positive reactions when tested 1 month later. Seventy-seven per cent of complement fixation tests done on the sera of 565 normal adults who admitted a previous attack of mumps were positive. A similar correlation was recorded in tests on the sera of a small group of children with positive histories. Of 356 medical students admitting previous attacks, 80 per cent gave positive tests. Of 386 normal adults who denied previous attacks, 42 per cent gave positive tests; of 85 children giving negative histories, 38 per cent reacted positively. The results of complement fixation tests on the sera of 1665 normal adults (over 17 years) and 679 children (1 to 17 years) are recorded. It has been shown that 63 per cent of the adults and 57 per cent of the children had antibody in their blood which reacted with the virus of mumps. In groups in which exceptionally intense exposure was not known to have occurred in the past, the proportions of positive reactors were: adults, 61 per cent; children, 49 per cent. In contrast to these normal persons, the incidence of positive reactors among permanently institutionalized mental defectives was 38 per cent of 356 adults and 32 per cent of 475 children. In only 2 per cent of 320 normal adults and children did the titer of complement-fixing antibody reach 1–192. In no instance in which the endpoint was determined was a higher titer recorded. The results of complement fixation tests on the sera of mother and newborn infant were essentially the same in 5 instances.     

The cost-effectiveness of the RSI QuickScan intervention programme for computer workers: Results of an economic evaluation alongside a randomised controlled trial

Background  

The costs of arm, shoulder and neck symptoms are high. In order to decrease these costs employers implement interventions aimed at reducing these symptoms. One frequently used intervention is the RSI QuickScan intervention programme. It establishes a risk profile of the target population and subsequently advises interventions following a decision tree based on that risk profile. The purpose of this study was to perform an economic evaluation, from both the societal and companies' perspective, of the RSI QuickScan intervention programme for computer workers. In this study, effectiveness was defined at three levels: exposure to risk factors, prevalence of arm, shoulder and neck symptoms, and days of sick leave.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (Pi), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.2, 0.4, and 0.6 W). In both groups linear relationships were noted between power output and Pi/PCr; the slope of this relationship was used to compare PCr depletion patterns. At rest both groups had similar Pi/PCr ratios (normal subjects 0.12 +/- 0.06, those with heart failure 0.15 +/- 0.03) and pH (normal subjects 7.04 +/- 0.13, those with heart failure 7.10 +/- 0.11). In normal subjects exercise resulted in a progressive increase in Pi/PCr (slope = 1.17 +/- 0.20 Pi/PCr units/W), a reduction in pH only at 0.6 W (0.2 W: 7.03 +/- 0.10, 0.4 W: 7.01 +/- 0.10, 0.6 W: 6.88 +/- 16) and moderate fatigue (0.2 W: 0 +/- 0, 0.4 W: 1.3 +/- 0.5, 0.6 W: 1.9 +/- 0.6). In patients with heart failure exercise resulted in significantly greater fatigue at all workloads (0.2 W: 1.0 +/- 0.5, 0.4 W: 1.9 +/- 0.6, 0.6 W: 2.9 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)