Reversal of pretreatment hypotension and control of hemorrhage in trauma patients by a simple device

The injection of a suspension of Walker 256 carcinoma cells into the carotid artery of rats produced a model of hematogenously spread cerebral metastases. Most animals died from massive extracerebral tumors of the head and jaw; brain tumors were present in only one-quarter. External carotid artery ligation prior to tumor inoculation did not increase the incidence of fatal brain tumor. When cyclophosphamide, 15 mg/kg, was injected as a single dose on the fourteenth day after tumor inoculation, most of the extracerebral tumor disappeared. Fifty percent of the animals so treated were cured of tumor, but 90% of the remainder died of large intracerebral tumors. Severe cytopathic changes resulting from cyclophosphamide were present in extracerebral or choroid plexus tumors but were mild or nonexistent in intracerebral tumors. These selective effects of cyclophosphamide suggest that water-soluble agents are less effective against tumor in the brain than against extracerebral tumors despite the fact that metastatic tumor breaks down the blood-brain barrier.     

Hematuria and sickle cell disorders

To examine the relationship between gross hematuria and sickle cell disorders, all patients admitted to Grady Memorial Hospital with the diagnosis of a sickle cell disorder during a 14-month period were reviewed. Of 115 such patients, 65% had sickle cell disease and 35% had sickle cell trait. None of the former but seven of the latter group had gross hematuria. Mean age of the seven was 30 years. Comprehensive examinations and laboratory studies showed that all were free of concomitant disease. Physical findings, diagnostic modalities, and treatment were reviewed. Findings suggest that conservative therapy (bed rest, hydration, and diuresis) is usually effective.     

Anomalous double blood supply to the lung

We report an unusual case in which an apparently normal upper lobe of the right lung was supplied by major systemic arterial and pulmonary arterial vessels. The anomalous artery arose from the descending aorta. Following interruption of this vessel, the machinery-like murmur previously present disappeared.     

Preoperative irradiation therapy and radical hysterectomy: prognostic value of tumor regression after initial irradiation of squamous cell carcinoma of the cervix

OBJECTIVE: To investigate the role of tumor persistence in patients submitted to irradiation therapy and radical hysterectomy. DESIGN: A retrospective analysis of prognostic factors. LOCATION: Hospital A.C. Camargo, S?o Paulo, Brazil, a private non-profitmaking foundation and tertiary referral centre. PATIENTS: A total of 629 cases of invasive squamous cell carcinoma of the cervix were studied. Criteria for inclusion in the study were: confirmed histological diagnosis of squamous cell carcinoma and no previous treatment (except for preoperative radiotherapy carried out at the Hospital A.C. Camargo itself). At the end of the follow-up period, 410 patients (65%) had no evidence of disease and 219 (34.8%) had died because of the tumor. INTERVENTION: The patients were submitted to radical surgery and radiation therapy, separately or in combination between 1953 and 1982. MAIN OUTCOMES MEASURES: Multivariate analysis of the different variables was performed according to the Cox regression method. RESULTS: The variables of prognostic value were, in decreasing order of importance: the decade of patient admission (p = 0.0001), the modality of therapy employed (p = 0.0005), the presence of residual tumor in the surgical specimens (p = 0.0055) and the clinical stage of the disease (p = 0.0575). CONCLUSION: Radiation therapy controlled a considerable number of local tumors and pelvic lymph nodes but not all of them in every patient. There is a specific group of patients for whom radical surgery is necessary to achieve control of the disease.     

Dual flaA1 flaB1 mutant of Serpulina hyodysenteriae expressing periplasmic flagella is severely attenuated in a murine model of swine dysentery

The motility imparted by the periplasmic flagella (PF) of Serpulina hyodysenteriae is thought to play a pivotal role in the enteropathogenicity of this spirochete. The complex PF are composed of multiple class A and class B polypeptides. Isogenic strains containing specifically disrupted flaAl or flaB1 alleles remain capable of expressing PF, although such mutants display aberrant motility in vitro. To further examine the role that these proteins play in the maintenance of periplasmic flagellar structural integrity, motility, and fitness for intestinal colonization, we constructed a novel strain of S. hyodysenteriae which is deficient in both FlaA1 and FlaB1. To facilitate construction of this strain, a chloramphenicol gene cassette, with general application as a selectable marker in prokaryotes, was developed. The cloned flaAl and flaB1 genes were disrupted by replacement of internal fragments with chloramphenicol and kanamycin gene cassettes, respectively. The inactivated flagellar genes were introduced into S. hyodysenteriae, and allelic exchange at the targeted chromosomal flaA1 and flaB1 loci was verified by PCR analysis. Immunoblots or cell lysates with antiserum raised against purified FlaA or FlaB confirmed the absence of the corresponding sheath and core proteins in this dual flagellar mutant. These mutations selectively abolished the expression of the targeted genes without affecting the synthesis of other immunologically related FlaB proteins. The resulting flaA1 flaB1 mutant exhibited altered motility in vitro. Surprisingly, it was capable of assembling periplasmic flagella that were morphologically normal as evidenced by electron microscopy. The virulence of this strain was assessed in a murine model of swine dysentery by determining the incidence of cecal lesions and the persistence of S. hyodysenteriae in the gut. Mice challenged with the wild-type strain or a passage control strain showed a dose-related response to the challenge organism. The dual flagellar mutant was severely attenuated in murine challenge experiments, suggesting that the FlaA1 and FlaB1 proteins are dispensable for flagellar assembly but critical for normal flagellar function and colonization of mucosal surfaces of the gastrointestinal tract. This strain represents the first spirochete engineered to contain specifically defined mutations in more than one genetic locus.     

The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1

The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)