The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Perioperative antibiotic, steroid, and nonsteroidal anti-inflammatory agents in cataract intraocular lens surgery

Ophthalmologists continue to choose topical antibiotics and corticosteroids more frequently than injectable agents for their current cataract surgical techniques. The preoperative use of povidone-iodine 5% and the postoperative use of impregnated soft contact lenses have helped augment our therapeutic armamentarium. NSAIDs play an important role in decreasing postoperative convalescence with fewer side effects. The intracameral administration of heparin and antibiotic solutions is discussed.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Do workers exposed to intermittent aircraft noise suffer from occupational deafness? A study in Alexandria airport

The study aimed at assessment of noise levels in Alexandria airport and measurement of hearing acuity--among other health parameters of the working personnel. By performing 65 sound pressure level measurements, a questionnaire and air conduction audiometry, significant hearing defects could be revealed. Deficiencies affected hearing levels at all frequencies but especially higher frequencies in workers exposed to noise of aircrafts and other airport activities at the exterior of the airport building. The importance of pre-employment and periodic ear and audiometric examinations is thus expressed.     

Comparative study between different diagnostic techniques in huge splenomegaly cases in El-Minia Province

Fifty four patients presenting by huge splenomegaly were admitted to Tropical Medicine Department, El-Minia University Hospital. Tissue biopsy revealed pure bilharziasis due to S. hematobium in 10 (19%) cases, liver cirrhosis in 23 (42%), mixed schistosomiasis and cirrhosis in 8 (15%), hepatoma in 3 (6%), lymphoma in 6 (11%) and hematological diseases in the form of chronic myeloid leukemia in 2 (3.5%) and thalassemia major in 2 (3.5%) cases. The sensitivity and specificity of abdominal ultrasonography was 100% and 97% in cases of schistosomiasis, 100% and 100% in cases of hepatoma, 87% and 100% in cases of liver cirrhosis, 33% and 100% in cases of lymphoma respectively. There was a positive significant correlation between endoscopic variceal grading, portal vein diameter, splenic vein diameter, size of the spleen and the grading of the portal tract thickenings. The pathological and ultrasonographic diagnosis was the same in 38 (70%) cases. Splenogram was characteristic but not diagnostic in cases of schistosomiasis and liver cirrhosis. It was diagnostic and similar to peripheral blood picture in the 2 cases of chronic myeloid leukemia and was normal in cases of thalassemia major. Splenic aspiration was able to diagnose all cases of lymphomas. It can be considered as a useful adjunct to the usual diagnostic procedures, both in staging and follow up, especially in cases presenting only by splenomegaly.     

A prospective, randomized study of cardiopulmonary bypass temperature and blood transfusion

BACKGROUND: We hypothesized that normothermic cardiopulmonary bypass (CPB) would be associated with decreased blood loss and allogeneic transfusion requirements relative to hypothermic CPB. METHODS: After obtaining institutional review board approval and informed patient consent, we conducted a prospective, randomized study of 79 patients undergoing CPB for a primary cardiac operation at normothermic (37 degrees C) (n = 44) or hypothermic temperature (25 degrees C) (n = 35). Blood loss and transfusion requirements in the operating room and for the first 24 hours in the intensive care unit were determined. A paired t test and rank sum tests were used. A p value of less than 0.05 was considered significant. RESULTS: The normothermic and hypothermic CPB groups did not differ in demographic variables, CPB or cross-clamp duration, heparin sodium or protamine sulfate dose, prothrombin time, or thromboelastogram results. There were no differences between the two CPB groups in blood loss or transfusion requirements. CONCLUSIONS: We found that when there was no difference in duration of CPB, normothermic and hypothermic CPB groups demonstrated similar blood loss and transfusion requirements even though other studies have shown hypothermia induces platelet dysfunction and alters the activity of the coagulation cascade.     

Variable waveforms in downbeat nystagmus imply short-term gain changes

A patient with downbeat nystagmus subsequent to ankylosing spondylitis was studied. His nystagmus was found to exhibit both increasing- and decreasing-velocity exponential slow phases as well as the linear form more often reported. Alternation between waveforms sometimes occurred on a beat-to-beat or even intrabeat basis. Possible explanations for all three waveforms are presented in terms of short-term gain changes in cerebellar compensation for leaky brainstem neural integrators. A computer model was developed and its results are discussed.     

Acute poisoning caused by the herbicide dichlorprop (preparation SYS 67 PROP)

We report on the acute poisoning of a 5-year-old boy by the herbicide "dichlorprop". This preparation is described as an effective means of plant protection. The effects of the intoxication were established by changes observed in almost all of the child's organs. The predominant effect was haemolytic anemia. All the pathological parameters regressed as a result of symptomatic therapy. General conclusions are drawn about intoxication, especially by means of plant protection agents.