A clinical nude mouse metastatic model for highly malignant human pancreatic cancer

Pancreatic cancer is a highly aggressive and treatment-refractory cancer. A clinically-relevant animal model is necessary to develop therapy for metastatic pancreatic cancer. In this study we evaluated the efficacy of mitomycin C (MMC) and 5-FU against the human pancreatic adenocarcinoma cell line PAN-12 in an orthotopic human metastatic pancreatic cancer nude mice model. The model is constructed by surgical orthotopic implantation (SOI) of histologically intact tumor tissue in the tail portion of the pancreas near the spleen. PAN-12 grew very aggressively in the control group of nude mice with extensive local invasion and distant metastasis to various organs with a propensity for the lung but to other organs as well, including the liver, kidney and regional and distant lymph nodes. In a striking effect none of the mice in the MMC-treated group developed tumor. Although mice in the 5-FU treated group survived statistically significantly longer than those in the untreated control, the overall incidence of metastasis in these mice was equivalent to those in the control. However no liver or kidney metastases were found in the 5-FU treated animals perhaps accounting in part for their longer survival. This "clinical" nude mouse model of highly metastatic pancreatic cancer can now be used to discover new effective agents for this disease.     

Frequency dependence of specific airway resistance in a commercialized plethysmograph

Specific airway resistance (sRaw) measured by body plethysmography has been shown to decrease markedly with decreasing breathing frequency when the inspired air is not conditioned to body temperature, atmospheric pressure and saturation with water vapour (BTPS). The phenomenon has been attributed to noninstantaneous gas warming and wetting in the airways. The aim of this investigation was to assess whether the phenomenon was also present in a commercialized plethysmograph featuring an "electronic BTPS correction". Airway resistance (Raw) and sRaw were measured in 15 healthy subjects at six breathing frequencies ranging 0.25-3 Hz, using a constant volume plethysmograph in which a correction for non-BTPS gas conditions was applied by electronically flattening the box pressure-airway flow loop (Jaeger Masterscreen Body, version 4.0). The temperature and water vapour saturations in the box averaged 26.5 +/- 1.3 degrees C and 59 +/- 6%, respectively. Raw and sRaw exhibited a clear positive frequency dependence in all but one subject. From 0.25 to 3 Hz Raw increased from (mean+/-SD) 0.62 +/- 0.55 to 1.71 +/- 0.76 hPa x s x L-1 (p<0.001), and sRaw from 2.34 +/- 1.90 to 7.55 +/- 3.08 hPa x s (p<0.001). The data are consistent with a simple model, in which gas conditioning in the airways and external dead space occurred with a time constant of 0.39 s. We conclude that the electronic BTPS correction of the instrument was inadequate, probably because it is assumed that gas conditioning in the airways is instantaneous. We recommend that, with similar instruments, airway resistance be measured using as high a panting frequency as feasible.     

Influence of external factors in resistance of Corynebacterium urealyticum to antimicrobial agents

Corynebacterium urealyticum is usually resistant to multiple antibiotics. We analyzed whether previous hospitalization and/or the use of antibiotics was a factor associated with the appearance of resistance to different antibiotics in C. urealyticum. Our findings suggest that resistant strains of C. urealyticum are likely to be acquired directly from the hospital environment and that the use of antibiotics in the hospital setting could favor the appearance of multiresistant strains.     

An assessment of test criteria for evaluating the performance and integrity of sterilizing filters

Measurements of serum calcitonin (iCT) were performed in 300 relatives of 43 Norwegian patients with medullary thyroid carcinoma (MCT). Prior to the screening, familial occurrence of the disease was known in only one of the families. Persistant hypercalcitoninemia (serum levels greater than 0.50 ng/ml) was demonstrated in 2 healthy persons from this family and in 3 first degree relatives of 2 patients with apparently sporadic disease. Additional 7 relatives of 5 other "sporadic" cases showed elevation of serum iCT on one occasion, while later controls revealed normal values. Twenty persons had high normal serum levels (0.35 ng/ml less than or equal to iCT less than 0.50 ng/ml). The significance of transitory hypercalcitoninemia and high normal values are at the present unknown, but these persons will have further tests. Stimulation tests for iCT secretion were found to be of limited value in distinguishing between normal and pathological serum iCT. All individuals found to have chronic hypercalcitoninemia belonged to families in which the probands showed one or several of the following "high risk" factors: A positive history of thyroid disease, early age of onset, bilateral presence of the thyroid tumour, association with other endocrine or peripheral neurogenic tumours, and marphanoid habitus. The iCT screening was however negative in the relatives of the two probands revealing 4 and 5 of these factors. Since neither the family history nor the presence or absence of "high risk" factors distinguished between sporadic and familial cases, it is concluded that serum iCT measurements should be carried out in primary relatives of all patients with MCT.     

The early detection of colorectal cancer

A review of the American Cancer Society's statistics for colorectal cancer indicates that there has been little improvements in the survival rate for this disease in the past 25 years. Although there have been advances in surgical techniques, radiation therapy, and chemotherapy, the key to improved survival rates is earlier diagnosis. A significant percentage of patients continues to present with regional or distal metastasis at the time of their initial diagnosis. Both proctosigmoidoscopy and guaiac impregnated filter slide paper methods have been productive in diagnosing this disease at an earlier stage. The "Hemoccult" test, however, is inexpensive, can be used on a routine basis, is easier for patients to perform themselves, and is aesthetically pleasing. It represents a significant cost savings compared to proctosigmoidoscopy and should be advocated for routine use in all patients over 40 years of age. Although there continues to be a role for local and regional mass screening programs, significant improvements in colorectal survival rates cannot be expected until routine application of this type of screening is practiced.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.