DbpA, but not OspA, is expressed by Borrelia burgdorferi during spirochetemia and is a target for protective antibodies

DbpA is a target for antibodies that protect mice against infection by cultured Borrelia burgdorferi. Infected mice exhibit early and sustained humoral responses to DbpA and DbpB, suggesting that these proteins are expressed in vivo. Many antigens expressed in mammals by B. burgdorferi are repressed in vitro at lower growth temperatures, and we have now extended these observations to include DbpA and DbpB. To confirm that the protective antigen DbpA is expressed in vivo and to address the question of its accessibility to antibodies during infection, we examined B. burgdorferi in blood samples from mice following cutaneous inoculation. B. burgdorferi was visualized by dark-field microscopy in plasma samples from spirochetemic mice, and an indirect immunofluorescence assay showed that these spirochetes were DbpA positive and OspA negative. We developed an ex vivo borreliacidal assay to show that hyperimmune antiserum against DbpA, but not OspA, killed these plasma-derived spirochetes, demonstrating that DbpA is accessible to antibodies during this phase of infection. Blood transferred from spirochetemic donor mice readily established B. burgdorferi infection in naive recipient mice or mice hyperimmunized with OspA, while mice hyperimmunized with DbpA showed significant protection against challenge with host-adapted spirochetes. Antiserum from persistently infected mice had borreliacidal activity against both cultured and plasma-derived spirochetes, and adsorption of this serum with DbpA substantially depleted this killing activity. Our observations show that immunization with DbpA blocks B. burgdorferi dissemination from the site of cutaneous inoculation and suggest that DbpA antibodies may contribute to control of persistent infection.     

Portal hemodynamics after large-volume paracentesis in patients with liver cirrhosis and tense ascites

Large-volume paracentesis with a plasma expander has been extensively evaluated and shown to be an effective and safe therapy. While hepatic and systemic hemodynamics have been studied extensively, there is little information on portal hemodynamics by duplex Doppler. Portal vein diameter, portal flow velocity, and portal blood flow were measured with duplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There were no significant changes in the portal vein diameter (9.88+/-2.62 mm vs 10.09+/-2.73 mm), portal flow velocity (10.65+/-2.60 vs 10.01+/-2.58 cm/sec), and portal blood flow (488+/-288.9 vs 502+/-73.38 ml/min), before and 24 hr after large-volume paracentesis. Thus, significant changes in portal hemodynamics do not occur after large-volume paracentesis.     

Intratumoral infusion of fluid: estimation of hydraulic conductivity and implications for the delivery of therapeutic agents

We have developed a new technique to measure in vivo tumour tissue fluid transport parameters (hydraulic conductivity and compliance) that influence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to produce a radially symmetrical fluid source in the centre of human tumours in immunodeficient mice. At constant flow, the pressure gradient generated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured as a function of the radial position with micropipettes connected to a servo-null system. To evaluate whether the fluid infused was reabsorbed by blood vessels, infusions were also performed after circulatory arrest. In the colon adenocarcinoma LS174T with a spherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 microl min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm2 mmHg(-1) s. Compliance estimates were 35 microl mmHg(-1) in vivo, and 100 microl mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26T, hydraulic conductivity and compliance were not calculated because of the asymmetric distribution of the fluid infused. The technique will be helpful in identifying strategies to improve the intratumoral and systemic delivery of gene targeting vectors and other therapeutic agents.     

Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer

PURPOSE: To optimize the dose of fractionated brachytherapy for palliation of advanced esophageal cancer. METHODS AND MATERIALS: One hundred and seventy-two patients with advanced esophageal cancer were randomized to receive 12 Gy/2 fractions (group A); 16 Gy/2 fractions (group B), and 18 Gy/3 fractions (group C) by high dose rate intraluminal brachytherapy (HDRILBT). Treatment was given weekly and dose prescribed at 1 cm from the source axis. Patients were followed up monthly and assessed for dysphagia relief and development of complications. RESULTS: Twenty-two patients died before completing treatment due to advanced disease and poor general condition. The overall survival was 19.4% at the end of 12 months for the whole group (A--9.8%, B--22.46%, C--35.32%; p > 0.05). The dysphagia-free survival was 28.9% at 12 months for the whole group (A--10.8%, B--25.43%, C--38.95%; p > 0.05). Forty-three patients developed fibrotic strictures needing dilatation (A--5 of 35, B--15 of 60, C--23 of 55; p = 0.032). Twenty-seven patients had persistent luminal disease (A--11, B--6, C--10), 15 of which progressed to fistulae (A--7, B--2, C--6; p = 0.032). There was no effect of age, sex, race, histology, performance status, previous dilation, presenting dysphagia score, presenting weight, grade, tumor length, and stage on overall survival, dysphagia-free, and complication-free survival (p > 0.05). On a multivariate analysis, brachytherapy dose (p = 0.002) and tumor length (p = 0.0209) were found to have a significant effect on overall survival; brachytherapy dose was the only factor that had an impact on local tumor control (p = 0.0005), while tumor length was the only factor that had an effect on dysphagia-free survival (p = 0.0475). When compared to other forms of palliation currently available (bypass surgery, laser, chemotherapy, intubation, external radiotherapy), fractionated brachytherapy gave the best results with a median survival of 6.2 months. CONCLUSIONS: Fractionated brachytherapy is the best modality for palliation of advanced esophageal cancer. It offers the best palliation to patient when compared to all other modalities currently available. The optimal brachytherapy dose ranges between 16 Gy in two fractions and 18 Gy in three fractions given a week apart.     

MR demonstration of a giant cavernous carotid aneurysm with occlusion of the contralateral intracranial carotid artery: an unusual complication of cavernous sinus thrombosis

We present an unusual combination of vascular complications of cavernous sinus thrombosis in a 7-year-old girl. MRI and MR angiography showed occlusion of the intracranial portion of the left internal carotid artery and a contralateral giant cavernous carotid aneurysm. This combination of vascular findings may influence the management in such cases.     

A new substrate for the rapid evaluation of enteric microbial overgrowth

The possibility of a new approach to diagnosis of intestinal bacterial overgrowth has been evaluated in laboratory animals. The diagnostic test involves oral administration of an enzyme-labile substrate consisting of para-aminobenzoic acid (PABA) conjugated to a bile acid. In the presence of enteric bacteria, PABA is split from the bile acid and is rapidly absorbed and excreted in the urine. The amount of PABA recovered during the 6 hr following the administered dose of the conjugate may be used as an index of bacterial overgrowth in the upper-gastrointestinal tract. The procedure has been shown to be a reliable index of this condition in laboratory animal models.     

Effects of erythromycin on membrane-bound chloroplast ribosomes from wild-type Chlamydomonas reinhardi and erythromycin-resistant mutants

The properties of peripheral cutaneous units in the hairy skin of cat's forelimb were studied by single-fiber recordings with tungsten microelectrodes. The response properties and receptive field (RFs) of total 193 units in superficial branch of radial nerve (SRN) were studied. The SRN sample included the following five major types of mechanoreceptive units; two types of low-threshold units (type I and II, slowly adapting), two types of hair units (G and D, rapidly adapting) and field units (F, responding principally to slow skin movement). Afferent conduction velocities of these units ranged from 9.0 to 56.0 m/sec. D hair fibers conducted much slower than other types of afferents and their conduction velocities were between 9.0 and 23.3 m/sec. Most of the smaller RFs of G, D and F units were found in the paw and digits. The disto-proximal increase of the mean size of RFs was marked in D hair units. The distributions of the RFs of simultaneously recorded paired units, which were supposed to be adjacent fibers, were examined. Among 23 paired units, more than half of them were homonymous combinations of unit types and there were no marked prevalence of particular types in heteronymous combinations. The RFs of paired units were close to each other, but showed little overlaps and some were separated by up to several cm over the skin surface. Some functional properties of cutaneous afferents from the forelimb were discussed.     

Observations on the transmissibility of lentogenic strains of Newcastle disease virus: significance of variables

Virus strain and age of chicken influenced the transmissibility of lentogenic strains of Newcastle disease virus (NDV). The ability of LaSota, B1, V4, CT, F, and Ulster strains to spread from cages of oronasally inoculated chickens to adjacent cages of susceptible chickens was assessed by virus isolation, serology, and immunity to challenge with virulent NDV. Although all inoculated chickens were immune to challenge, the immunity of contact chickens ranged from 100% for LaSota and CT strains to 0% for Ulster strain. The transmissibility of B1 and V4 strains for chickens 1, 4, 8, and 16 weeks old was assessed by within-cage contact infection, exposure to contaminated food and water containers, and exposure to air from infected chickens. Serology and immunity to challenge with virulent virus were used as criteria. Differences in transmissibility were observed for the strain of virus used, route of exposure, and age of chickens. Care must be used in interpreting the significance of strain differences until the effect of variables can be minimized by further improvements in design of the test procedure.