Suction sclerotherapy for the treatment of esophageal varices: a report of a preliminary feasibility study.

We report a new treatment modality for esophageal varices, suction sclerotherapy, which was designed to lift away mucosa and submucosa during treatment to prevent deep injection and resultant esophageal ulcerations. In order to compare the posttreatment complications of suction sclerotherapy against freehand sclerotherapy, we randomized 4 mongrel dogs to receive ten injections of 0.5-ml aliquots of absolute alcohol into the esophagus by either the suction or freehand sclerotherapy technique. The animals were humanely sacrificed after 48 h and examined. A total of five large, deep, confluent ulcers, free perforation, and lung abscess were seen in the animals randomized to freehand sclerotherapy. In contrast, a total of 14 shallow, discrete, erythematous lesions were found in the suction sclerotherapy group; none of these lesions extended deeper than the submucosa. We conclude that suction sclerotherapy produced local complications limited to the submucosa which were less severe as compared with freehand sclerotherapy.

Gentamicin distribution from a collagen carrier.

Local delivery of antibiotics by a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and subsequent surgical removal may not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (type I) in 66 adult White rabbits. Collagen impregnated with gentamicin (3 mg/kg) was implanted into the vastus lateralis, and data were collected from 15 minutes to 28 days after implantation. Local tissue biopsies were taken a minimum of 2 mm from the implantation site. The gentamicin was released into the local tissue and averaged more than 3,800 micrograms/ml during the initial 4 hours after implantation. Local levels fell to 6.90 +/- 5.22 micrograms/ml at 24 hours and subsequently were 2.70 +/- 1.75 micrograms/ml or more through day 28. Serum levels reached an average peak of 4.04 +/- 1.75 micrograms/ml at 5 hours after implantation, decreased after the initial 24 hours, and subsequently were less than 0.41 +/- 0.20 microgram/ml through day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local tissue concentrations above the minimum inhibitory concentration and serum concentrations below levels associated with systemic toxicity for 28 days after implantation.

A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but soon manifested marked medullary and extramedullary myeloid hyperplasia associated with cachexia, erosive arthritis, dermatitis, conjunctivitis, glomerular mesangial thickening, and high titers of anti-DNA and antinuclear antibodies. Myeloid progenitors from these mice showed no increase in sensitivity to growth factors. Treatment of young TTP-deficient mice with antibodies to tumor necrosis factor alpha (TNF alpha) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNF alpha synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNF alpha excess.

Prolonged total circulatory support using direct mechanical ventricular actuation.

Direct mechanical ventricular actuation (DMVA) is a unique, non blood contacting method for biventricular cardiac assist. Although DMVA has successfully provided cardiac assist for more than 7 days in humans, with long-term survival, its potential for long-term circulatory support has not been adequately investigated. DMVA has not been studied in the large ruminants commonly used to evaluate support devices. To develop a large animal experimental model of prolonged total circulatory support using DMVA, Suffolk sheep (n = 10) underwent sterile instrumentation for hemodynamic and chemistry monitoring. After baseline values were obtained, a left lateral thoracotomy and pericardotomy were performed. Upon electrical ventricular fibrillation (VF), DMVA was begun and the thoracotomy closed. Total circulatory support was continued until mean arterial pressure (MAP) persisted below 50% of the baseline value for more than 1 hr, with a goal of 7 days' support. Mean duration (plus or minus the standard deviation [SD]) of circulatory support was 65.9 +/- 56.8 hr (range, 10-168 hr). Pressors were not used during DMVA support. The subject supported for the maximal time (7 days) was defibrillated into sinus rhythm. No CK-MB fraction was greater than 1%, suggesting that DMVA, even with prolonged application during VF, does not result in myocardial injury. Blood urea nitrogen and creatinine levels indicate renal function was preserved. The model described represents the longest period any animal has been supported in VF using DMVA. This new model will be useful in determining what limitations, if any, exist to the prolonged use of DMVA for circulatory support.

Experimental murine cytomegalovirus infection in severe combined immunodeficient mice.

Severe combined immunodeficient (scid) and BALB/c mice were experimentally infected with murine cytomegalovirus (MCMV). Scid mice infected by the intraperitoneal route died or were moribund at dose-dependent times ranging from 12 to 13 days after inoculation for > or = 3.00 x 10(4) plaque forming units (pfu) of virus to 25 days for 1.17 x 10(2) pfu. Histologic lesions included severe adrenal necrosis at low doses and splenic necrosis at high doses. Multinucleate hepatocytes with multiple inclusion bodies were observed at all doses. In visceral organs, the inflammatory response consisted of cell necrosis and neutrophil infiltration. Scid mice infected with 1.00 x 10(3) pfu by the intranasal route were moribund by 24 or 25 days after inoculation. Viral titers in tissues examined from these mice increased in all organs examined until they became moribund. BALB/c mice infected intranasally had detectable virus titers in the adrenal glands, salivary glands, lungs, and spleen by 7 or 14 days after inoculation, but decreased thereafter. These mice remained clinically normal through the infection. In BALB/c mice, histologic lesions were present only in the salivary glands.

Blood gas and hematological changes in experimental peracute porcine pleuropneumonia.

The effect of experimental, peracute, porcine pleuropneumonia on arterial blood gases, acid base status, the leukogram, and gross and microscopic lung structure was studied in nine growing pigs (mean weight +/- SD 10.6 +/- 2.0 kg). Pigs were inoculated intranasally with a virulent serotype 5 isolate of Actinobacillus pleuropneumoniae, and all showed signs typical of the disease within four hours. Death occurred in all pigs from 4.5 to 32 hours postinoculation (mean 14 hours). Gross and microscopic changes were typical of porcine pleuropneumonia in all pigs. Changes in the leukogram included a rapid decline in total white cells, segmented neutrophils, lymphocytes, monocytes, and eosinophils. Pigs maintained alveolar ventilation throughout the study as arterial CO2 tension was unchanged; however, arterial O2 tension and pH decreased from (mean +/- SD) 95.2 +/- 5.7 torr and 7.463 +/- 0.018 at baseline to 62.1 +/- 12.3 torr and 7.388 +/- 0.045, respectively, within 90 minutes prior to death. The data showed that in this model of peracute porcine pleuropneumonia, progressive ventilatory failure was not a feature of the disease, and the blood gas values and acid base status were maintained within physiological ranges. The histopathological hematological and physiological findings were consistent with the hypothesis that peracute porcine pleuropneumonia resembles septic shock.

Effect of stage of lactation on transport of colloidal carbon or Staphylococcus aureus from the mammary gland lumen to lymph nodes in guinea pigs.

Guinea pig mammary glands which were either lactating, involuting or dry were infused with colloidal carbon or killed staphylococci. At different time intervals following infusion, animals were killed and the superficial inguinal lymph nodes examined for the presence of carbon. Sides which had nodes with visible carbon were designated 'positive'. The time intervals from infusion to positive for the three groups were compared using logistic regression. The times required for 50% of the sides to be positive were estimated to be approximately 4 h for lactating glands, 32 h for those in involution, and 13 min for dry glands. Histological differences in distribution of carbon in the mammary tissue suggest that differences in transit time may have been due to different mechanisms of transport through the glands in the three different physiological states. The distribution of bacteria was similar to that of the carbon in the corresponding tissues.

Use of polymer casts or metal particle infusion of ducts to study antigen uptake in the guinea pig mammary gland.

Microcorrosion casts were made of the duct system of guinea pig mammary glands by intramammary infusion of Mercox polyester resin following involution of the glands after the first lactation. The acinar configuration of the involuted gland was apparent on examination of the casts by scanning electron microscopy (SEM). Surface features, which were readily identified as those of imprints of ductal epithelium, were visible at higher magnifications. The morphology of these casts corresponded to the patterns observed by SEM of ethanol cryofractured specimens of mammary tissue. Cryofractured specimens of guinea pig mammary glands were also examined by SEM following intramammary infusion of tantalum. Tantalum particles were observed within the lumina of many ducts. Large phagocytic cells within the lumina were shown to contain tantalum by using back scatter imaging in conjunction with secondary imaging.