13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: Report from the childrens cancer study group

The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m², 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma. © 1992 Wiley-Liss, Inc.     

Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?

Recently it has been suggested that the Australian snake antivenoms made by CSL Ltd. are in fact not truly monovalent and may contain antibodies to other snake venoms because the horses are injected with multiple snake venoms. It is unclear to what extent various monovalent antivenoms can neutralise the effect of other venoms, whether this is due to a mixture of antibodies or true cross-reactivity, and whether this has any clinical significance. We aimed to study the immunological and functional properties of brown snake (Pseudonaja spp.) antivenom (BSAV) and tiger snake (Notechis spp.) antivenom (TSAV) against their respective venoms using enzyme immunoassays (EIA) and in vitro clotting studies. There was significant overlap between the two antivenoms with both TSAV and BSAV being detected by EIA on brown snake venom (BSV)-coated and tiger snake venom (TSV)-coated wells, respectively. In a competition EIA, increasing amounts of immunoaffinity-purified hen anti-brown antibodies (IgYp) mixed with TSAV reduced TSAV measured on TSV-coated wells. Both BSAV and TSAV prevented the clotting activity of both venoms. IgYp also prevented the clotting activity of TSV, suggesting true cross-reactivity. The cross-reactivity of TSAV and BSAV with BSV and TSV, respectively, was likely due to each being a mixture of anti-brown and anti-tiger antibodies, but there was partial cross-reactivity demonstrated by the effect of IgYp. Single-polyvalent antivenom for brown snake and tiger snake may be feasible in the future.     

Virtual real-time digital processing of hemodynamic data

At present, the majority of cardiac catheterization laboratories acquire and store hemo-dynamic data in analog form. To examine the possibility of performing complex analysis of digital data during the catheterization procedure, we examined whether virtual realtime digital (fast Fourier) analysis improves the accuracy of clinical data. We compared digital filtering of fluid manometry during right heart catheterization with 10-Hz and 250-Hz analog filters. Using the simultaneously acquired micromanometry as the “gold standard,” we found that analog filtering is associated with a greater error and time delay than digital filtering. This study demonstrates that digital hemodynamic data analysis performed during cardiac catheterization can improve the quality of data obtained during right heart catheterization, with the results available within seconds. More extensive use of computers in the cardiac catheterization laboratory may be useful for both clinical and research purposes. © 1992 Wiley-Liss, Inc.     

Investigation of focal hepatic lesions: Is tomographic red blood cell imaging useful?

Noninvasive diagnosis of cavernous hemangioma of the liver is an important step in the investigation of patients with focal hepatic lesions since biopsy may result in life-threatening hemorrhage. To determine the diagnostic accuracy of 99m-technetium red blood cell (^99mTc-RBC) imaging with tomography, 50 patients with various types of focal liver lesions were studied. Thirty-two patients had 45 hemangiomas and 7 other benign lesions while 18 patients had either primary (n=8) or secondary (n=10) hepatic malignancies. Tomographic imaging identified 12 more hemangiomas than planar imaging, improving sensitivity from 53% to 80%, and was found most useful for detection of smaller lesions (mean size, 2.1 cm). Specificity for hemangiomas was 100% with all lesions greater than 1.9 cm showing the characteristic scintigraphic pattern of blood-pooling on delayed images. There was excellent agreement between 2 independent observers concerning interpretation of tomographic images (89% for the hemangioma group and 100% for other patients). Therefore^99mTc-RBC scintigraphy with tomography is an accurate diagnostic technique in the investigation of cavernous hemangiomas. Its major value resides in its ability to distinguish hemangiomas from other types of hepatic pathology.

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Resumen El diagnóstico no invasivo del hemangioma cavernoso del hígado es un paso de importancia en el proceso de investigación de pacientes con lesiones hepáticas focales, puesto que la biopsia puede resultar en hemorragia de consecuencias potencialmente fatales. Con el objeto de determinar la certeza diagnóstica de la tomografía con glóbulos rojos marcados con tecnecio 99m, se estudiaron 50 pacientes con varios tipos de lesiones hepáticas focales. Treinta y dos pacientes presentaron 45 hemangiomas y 7 lesiones benignas, en tanto que 18 pacientes presentaron neoplasias malignas primarias (n=8) o secundarias (n=10). Las imágenes tomográficas obtenidas por este método lograron identificar 12 hemangiomas más, en comparación con imágenes convencionales, aumentando la sensibilidad de 53% a 80%, y demostró ser de máxima utilidad para la detección de las lesiones más peque¯nas (tamaño promedio, 2.1 cm). La especificidad para los hemangiomas fue 100%, con todas las lesiones mayores de 1.9 cm exhibiendo el patrón centelleográfico característico de estancamiento sanguíneo en las imágenes tardías. Se encontró excelente correlación entre 2 observadores independientes en la interpretación de las imágenes tomográficas (89% para el grupo de pacientes con hemangiomas y 100% para el resto de los pacientes). En consecuencia, la escintigrafía con glóbulos rojos marcados con^99mTc aparece como una técnica certera en el diagnóstico de los hemangiomas cavernosos. Su mayor valor reside en su habilidad para diferenciar los hemangiomas de otra clase de patología.

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Résumé Le diagnostic non invasif d'hémangiome caverneux du foie est une étape importante dans l'investigation des patients ayant des lésions hépatiques focales, puisque la biopsie risque de se résoudre par une hémorrhagie menaçant le pronostic vital. Pour définir la précision diagnostique de la tomoscintigraphie après marquage des hématies au technetium 99m (^99mTc), on a étudié 50 patients ayant des types différents de lésions focales du foie. Trente-deux patients avaient 45 hémangiomes et 7 lésions bénignes tandis que 18 patients avaient des tumeurs hépatiques malignes soit primaires (n=8) soit secondaires (n=10). L'imagerie tomographique a identifié 12 hémangiomes de plus que l'imagerie planaire, améliorant la sensibilité de 53% à 80% et s'est avérée très utile pour détecter les lésions plus petites (taille moyenne, 2.1 cm). La spécificité pour les hémangiomes était de 100% pour toutes les lésions dépassant 1.9 cm montrant les caractères scintigraphiques typiques d'accumulation de sang sur les images retardées. Il y a eu concordance totale entre 2 observateurs indépendents sur l'interprétation des images tomographiques (89% pour le groupe des hémangiomes et 100% pour les autres patients). Voilà pourquoi la scintigraphie^99mTc avec tomographie est une technique de diagnostic précis dans l'investigation des hémangiomes caverneux. Sa valeur essentielle est sa capacité de distinguer les hémangiomes des autres types de pathologie hépatique.

     

Psychiatric morbidity in policemen and the effect of brief psychotherapeutic intervention — a pilot study

The level of psychiatric morbidity and perceived sources of stress among police officers were investigated using the General Health Questionnaire (GHQ) and a stress situation questionnaire, which were sent to 171 officers. Half of the responders were invited to attend group counselling sessions weekly for 12 weeks. Outcome measures studied were a second GHQ completed at the end of the treatment period and the amounts of sick leave taken in the 12-week period before, during and after the treatment period. The results were that 61 people returned the first GHQ of whom 59 were male and of whom 14 were classed as ‘cases’. Of the 31 assigned to the treatment group, 22 attended at least one session. Responses to the stress situation questionnaire and the content of counselling sessions tended to confirm the impression that internal aspects of the organization were viewed as prime sources of stress and dissatisfaction. There were no significant changes in GHQ score within or between groups, nor were there significant differences in the amount of sick leave taken. Nevertheless the sessions appeared to be valued and we conclude that this sort of intervention is at least feasible. We recommend that similar studies measure psychiatric morbidity during treatment and at follow-up, rather than immediately after finishing, when reactions to this termination are prominent.     

Immunology: High fecundity rates following in- vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin

This study was undertaken to explore whether intervention withheparin and aspirin (H/A) in selected patients undergoing in-vitrofertilization (TVF) and embryo transfer could improve fecundityrates. Specifically, it explored the possibility that womendiagnosed with organic pelvic disease who demonstrated antiphospholipidantibodies (APA) could benefit from H/A administration in asimilar manner to that used in patients with recurrent pregnancyloss. We used an enzyme–linked immunosorbent assay forsix different phospholipids to identify patients who expressedAPA before they underwent IVF/embryo transfer. This study wasconfined to the first IVF/embryo transfer cycle that followedassessment of APA status and accordingly, the number of IVF/embryotransfer cycles corresponds with the number of patients treated.APA seropositive patients were treated with aspirin, 81 mg orallyq.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 ofcontrolled ovarian stimulation. The endpoint for success wasa live birth or an ultrasound confirming fetal cardiac activity(a viable pregnancy). The prevalence of APA in patients diagnosedwith organic pelvic disease (53%) was much higher than in thosewithout female pathology (14%). The administration of H/A toAPA seropositive patients significantly (P < 0.05) improvedthe viable pregnancy rate (49%) compared to the untreated APAseropositive group (16%). The viable pregnancy rate for APAseropositive women treated with H/A was also significantly (P< 0.001) higher than for untreated APA seronegative patients(27%). We conclude that all women undergoing IVF/embryo transfershould be tested for APA prior to initiating ovarian stimulation,and those with APA seropositivity should be treated with H/A.     

db/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.