Microbubble detection following hyperbaric chamber dives using dual-frequency ultrasound.

Venous gas emboli (VGE) can be readily detected in the bloodstream using existing ultrasound methods. No method currently exists to detect decompression-induced microbubbles in tissue. We hypothesized that dual-frequency ultrasound (DFU) could detect these microbubbles. With DFU, microbubbles are driven with two frequencies: a lower "pump" (set to the resonant frequency of the desired bubble size) and a higher "image" frequency. A bubble of the resonant size emits the sum and difference of the two transmitted frequencies. For this study we used a pump frequency of 2.25 MHz and an image frequency of 5.0 MHz, which detects bubbles of roughly 1-10 µm in diameter in a water tank. Four anesthetized swine were pressurized at 4.5 ATA for 2 h and decompressed over 5 min, inducing moderate to very severe VGE scores. Four sites on the thigh of each swine were monitored with DFU before and after the dives. A single mock dive was also performed. The number of sites returning signals consistent with microbubbles increased dramatically after the chamber dive (P < 0.01), but did not change with the mock dive. The increase in DFU signal after the chamber dive was sustained and present at multiple sites in multiple swine. This research shows for the first time that decompression-induced tissue microbubbles can be detected using DFU and that DFU could be used to monitor decompression-induced microbubbles at multiple sites on the body. Additionally, DFU could be used to track the time course of microbubble formation and growth during decompression stress.

Dual-frequency ultrasound detection of stationary microbubbles in tissue.

Indirect evidence suggests that microbubbles that exist normally in tissue may play a key role in decompression sickness (DCS). Their sizes and locations are unknown. Dual-frequency ultrasound (DFU) exploits bubble resonance to detect bubbles over a wide size range and could potentially detect stationary tissue microbubbles. To test this capability, DFU was used to detect stationary microbubbles of known size (2-3 microm mean diameter) over a range of ultrasound pressures and microbubble concentrations. In gelatin phantoms doped with microbubbles and in ex vivo porcine tissue, signals indicative of bubbles were detected for microbubble concentrations of 5x10(5) per mL and greater. Signals were not returned from solid particle microspheres of similar size to the microbubbles or from saline controls. In the thigh of an anesthetized swine, signals were detected for concentrations of 5x10(7) per mL and greater. Because of its ability to detect bubbles over a wide range of sizes, this technique could potentially detect naturally-existing microbubbles in tissue and lead to (a) an improved understanding of the mechanics of bubble formation during decompression and (b) a new metric for evaluating DCS.

Mother-to-child transmission of HIV: developing integration of healthcare programmes with clinical, social and basic research studies. Report of the International Workshop held at Chobe Marina Lodge, Kasane, Botswana, 21-25 January 2003.

Considerable efforts are still needed in the public health sector, as well as in clinical, social and basic research, to improve programmes for HIV-1 MTCT (mother-to-child transmission) prevention and care. Advantage should be taken of the remarkable amount of expertise and resources that have accumulated over the past few years to accelerate the process of integration. Future initiatives should include integrating specialists and people with diverse backgrounds and targeting their scientific and programmatic ideas to address real-world problems in the area of MTCT of HIV-1.

An extensive maxillary pneumosinus dilatans.

Pneumosinus dilatans is a very rare lesion. An aggressive case of a maxillary pneumosinus dilatans is presented. CT and MRI showed that the lesion involved the orbit, cheek and nasal cavity. A reopening to the affected maxillary sinus as a FESS procedure was performed with success.

Efficacy of a therapeutic cocaine vaccine in rodent models.

Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.

Synthesis, pharmacological investigation and computational studies on a tricyclic ergoline analog with selective dopamine autoreceptor activity.

The novel aminobenzindolone 8 was prepared and evaluated as a potential antipsychotic agent. The target compound was synthesized in eight steps starting from the tetrahydrobenzindolone 9. The key step of the synthesis was an electrophilic amination of the aromatic ketone 11 followed by reductive degradation when the diethoxymethyl group was employed for protection of the lactam nitrogen and also for the benzylic position 2a. Dopamine and serotonin receptor binding studies revealed 8 to be a potent and selective ligand at the D-2 autoreceptor (ki = 4.0 nM). Further in vivo studies including the GBL-test and locomotor activity measurements indicated agonistic activity of 8 at the prejunctional binding sites. Comparison of ab initio based molecular electrostatic isopotential maps corroborates our hypothesis that the dopamine structure 6, containing an intramolecular hydrogen bond donating effect of the meta-HO-group, represents the conformation which is active at the dopamine D-2 autoreceptor.

Diagnosis of acute aortic occlusion by computer tomography.

We present a case of acute aortic occlusion, which was diagnosed immediately with CT. Since a prompt diagnosis is essential we recommend contrast enhanced CT as a quick procedure to confirm diagnosis and to exclude dissecting thoracic aneurysm and genuine abdominal aneurysm.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model.

PURPOSE: The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. METHODS AND MATERIALS: Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. RESULTS AND CONCLUSION: Dogs receiving IORT to the retroperitoneum through a 4 x 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses > or = 30 Gy. Radiation changes were present in the aorta and vena cava at doses > or = 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed a few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT.

Epithelioid hemangioendothelioma with multiple site involvement. Literature review and observations.

This report is a case of epithelioid hemangioendothelioma presenting as multiple lytic lesions of the ilium with radiographic findings of diffuse, bilateral lung involvement and biopsy-proven scalp involvement. Histologically, the tumor within bone and skin exhibited cords and nests of plump, epithelioid-appearing cells exhibiting rudimentary vascular differentiation within a myxohyaline stroma. Aggressive histologic features were not present. Immunohistochemical reactivity for Factor VIII-related antigen, Q-bend 10 (CD34), and cytokeratin were demonstrated. Ultrastructural studies revealed abundant intermediate cytoplasmic filaments, pinocytotic vacuoles, and Weibel-Palade bodies. The concurrent bone, skin, and lung involvement, low-grade histologic type, and female sex of the patient aroused speculation about the role of hormones in the development and possible treatment of the tumor, but estrogen and progesterone receptors were not detected. Despite intense combination chemotherapy, the patient died of widely metastatic disease. This report demonstrates the aggressive potential of histologically low-grade epithelioid hemangioendothelioma and the need for a thorough evaluation for metastases.

A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120.

Peptide-based vaccines that directly target T cell or B cell epitopes may have significant advantages over conventional vaccines. Further, synthetic chimeric peptides that combine strong T cell epitopes with poorly immunogenic, but immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful in eliciting antibody to such important regions. Here we characterize a human T cell epitope analyzed in 54 individuals immunized with a hepatitis B virus surface Ag vaccine. Primary cultures from a total of 59 immunized donors were assessed for their ability to respond to hepatitis B virus surface Ag and peptides, and five were non-responders (8.5%). T cell lines were established from the remaining 54 responders. Of the responders, it was found that the peptide representing amino acids 19 through 33 (19-33) elicited significant proliferation in lines derived from 50 donors. This "universal" T cell epitope, which was recognized in donors of many different HLA-DR and -DQ haplotypes, was then used to construct a chimeric peptide containing 19-33 and the third V region loop structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune response to the V3 loop peptide. The V3 loop is the region to which significant neutralizing antibody is directed. Thus, a strong immune response to a synthetic peptide that contains the strain-conserved V3 loop region could have significant therapeutic implications. The V3 loop/19-33 peptide was then used to prime mice, to determine whether V3 loop-specific antibody could be induced. The peptide elicited potent 19-33-specific proliferation in T cells isolated from draining lymph nodes, and in six of six mice anti-V3 loop antibody was elicited. Further, V3 loop/19-33-primed animals made significant levels of antibody that bound rgp120. These data suggest that, when a major T cell epitope is synthesized in tandem with the V3 loop, a significant immune response against the loop can be elicited. Thus, given the finding that neutralizing antibody may play a role in the control and/or prevention of HIV infection, an HIV vaccine composed of a T cell epitope-containing peptide may prove effective. In addition, this type of approach can be generalized to the design of peptide-based vaccines.

Blind zone determination of the femoral head.

An easily learned and applied method of accurately determining the blind zone of the femoral head is presented. This method is based on a geometric analysis of individual pins relative to the subchondral plate as apparent on mutually perpendicular roentgenograms. This method can be used with fluoroscopy or plain radiographs for intraoperative or postoperative evaluation.

[Diagnosis in neonatal hydronephrosis]. / Diagnostik ved neonatal hydronefrose.

Maternal ultrasonography makes it possible to detect hydronephrosis in the fetus. After birth, hydronephrosis should be confirmed by repeating the ultrasonic examination. Reflux may coexist with all causes of hydronephrosis, for which reason it is necessary to do a voiding cystourethrogram. It is also necessary to do a renography, partly to estimate the relative renal function of each kidney, and partly to estimate the drainage function. In most cases ultrasound, voiding cystourethrography and renography are able to reveal the cause of hydronephrosis. Only in case of doubt it is necessary to do an excretory urography, which is rendered difficult by excessive bowel gas and poor renal function in neonates.

A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors.

A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen. This antibody, ND4, is an IgG2a which does not cross-react with carcinoembryonic antigen (CEA), non-specific cross-reacting antigen, or blood group substances A, B, and H. Immunoprecipitation using lysates of cells grown in [35S]methionine or [3H]glucosamine and lysates of cells surface labeled with 125I showed binding to a cell surface glycoprotein with a molecular weight of approximately 160,000. Indirect immunofluorescence showed binding to the cell surface of 14 of 15 human colorectal carcinoma cell lines including six of six that do not secrete CEA. Two of seven human noncolorectal carcinoma lines and one of six nonhuman cell lines also bound antibody. Immunoperoxidase staining of formalin-fixed tissues showed prominent antibody binding with 19 of 33 (58%) human colorectal carcinomas, including five of six poorly differentiated tumors, five of 43 (12%) normal colonic mucosal biopsies, and one of 17 (6%) normal noncolonic tissues. One of 11 (9%) noncolonic tumors, a gastric adenocarcinoma, stained with ND4. Preliminary data obtained by a nonquantitative nitrocellulose dot-immunoassay have tentatively identified this glycoprotein in the serum of 15 of 37 (41%) patients with colorectal cancer. Three of the 15 patients had early stage disease and normal CEA levels (less than 2.5 ng/ml). Three patients had circulating antigen detectable preoperatively but not after tumor resection. Only one of 11 (9%) sera samples from normal subjects was positive. The characteristics of ND4 suggest that it may be of value in monitoring patients with colorectal carcinomas who do not have plasma CEA elevations. It may also be of value in the differential diagnosis of metastatic, poorly differentiated adenocarcinomas of unknown primary origin.

The antineoplastic effect of methylprednisolone pulse therapy in two patients with glucocorticoid receptor-positive glioblastoma multiforme.

Glucocorticoids in high concentrations inhibit in vitro the growth rate of glioblastoma multiforme. This presupposes the presence of glucocorticoid receptors in the cytoplasma. Glucocorticoid receptor positive patients with histological glioblastoma multiforme were postoperatively treated with high dose methylprednisolone pulse therapy during which CT-scanning initially demonstrated tumor regression. One patient's tumor size was unchanged after 24 weeks, whereas in the other patient, the tumor size after decreasing for 1 month began increasing again. The survival rate, at the present 15 and 10 months, without irradiation therapy and the decreasing glucocorticoid receptor concentrations at reoperations indicate an antineoplastic effect by continuous high-dose glucocorticoid pulse therapy.

Effect of pulley excision on flexor tendon biomechanics.

Flexor tendon function following excision of various portions of the fibro-osseous pulley system was measured biomechanically using a tensile testing machine. The biomechanical parameters measured were tendon excursion (the excursion of the tendon required to fully flex the digit) and work of flexion (the area under the force-excursion curve, representing all the forces that resist tendon flexion). In this experiment, work of flexion included the forces necessary to accomplish full digital flexion against a 15-g counter-weight, as well as the frictional forces that resist tendon gliding. The results indicate that the work of flexion was affected to a greater degree by pulley loss than was tendon excursion, suggesting that it is a more sensitive measurement of tendon function. A2 was found to be the single most important pulley for flexor tendon function, followed by A4. However, both A2 and A4 had to be present if near-normal hand function was to be achieved; sacrificing the A1 pulley was not associated with a significant loss of flexion. The "pulley effect" of the skin and soft tissue as a supplement to the fibro-osseous pulleys in reducing tendon bow-stringing was also noted. Although the parameters of tendon excursion and work of flexion were used in this study to determine the effect of pulley loss on tendon function, they can also be used to evaluate other flexor tendon studies, such as pulley reconstruction.