Endovascular thrombolysis in deep cerebral venous thrombosis

We present two cases of acute thrombosis of the internal cerebral veins, vein of Galen, and straight sinus without sagittal sinus involvement. Both patients had hydrocephalus and severe edema of the basal ganglia and thalami, one with hemorrhagic infarction of the thalamus. Because both patients rapidly deteriorated to a comatose state, endovascular thrombolysis was performed with urokinase infusion of the deep venous structures. Thrombolysis was continued until a patent channel with brisk flow in the venous structures was achieved. Both patients survived with minimal neurologic deficits.     

Angiogenesis in brain tumors; pathobiological and clinical aspects

Angiogenesis is the outgrowth of new blood vessels from the preexistent vasculature. In 1971, Folkman hypothesized that solid tumors are dependent on angiogenesis for sustained growth and that anti-angiogenic treatment is a potential antineoplastic therapy. Because glioblastoma multiforma (GBM) frequently shows florid microvascular proliferation (MVP), this tumor has been considered since then as a suitable candidate for such treatment that attempts to eradicate or control a neoplasm by interfering with its blood supply. Indeed, in animal models the growth of glioma xenografts can be inhibited by targeting the angiogenic process. However, unlike many glioma xenografts, human infiltrating gliomas such as GBMs have a diffuse infiltrative growth pattern, and preexistent vessels may suffice to provide many tumor cells with much of their blood supply, particularly in the critical peripheral infiltrative margins. Thus, while attractive in concept, anti-angiogenic therapy of GBM must address the anatomic vascular realities of this neoplasm. Even if anti-angiogenic therapy ultimately has a role in infiltrative neoplasms, there are a host of other intracranial neoplasms whose discrete architecture might make them attractive candidates for anti-angiogenic therapy. This review summarizes the angiogenic process in GBM and suggests other types of tumors for which the efficacy of anti-angiogenic therapy might be studied.     

The hemodynamic effects of AT-112, an analog of ketanserin, in portal hypertensive rats

Proteins that are actively secreted by Mycobacterium tuberculosis generate immune responses in the infected host. This has prompted the characterization of protein components of mycobacterial culture filtrates to develop subunit vaccines and immunodiagnostic reagents. Fractionation of filtrates of M. tuberculosis cultures has yielded an abundant protein called MPT63, which has an apparent molecular mass of 18 kDa. We report the molecular cloning and nucleotide sequence of the mpt63 gene, purification of recombinant MPT63 antigen from Escherichia coli cells, and serological characterization of MPT63. Nucleotide sequence analysis of mpt63 identified an open reading frame encoding a protein of 159 amino acids (aa) consisting of a 29-aa secretion signal peptide and a 130-aa mature MPT63 protein. Recombinant MPT63 protein, purified from E. coli cells, and native MPT63, purified from M. tuberculosis culture filtrates, were indistinguishable in serological assays. Thus, the recombinant protein constitutes a valuable reagent for immunological studies. MPT63 evoked humoral immune responses in guinea pigs infected with virulent M. tuberculosis by the aerosol route. The mpt63 gene is found only in species of the M. tuberculosis complex, as shown by DNA hybridization experiments. Moreover, polyclonal antibody against MPT63 does not cross-react with proteins of a common environmental mycobacterial species, Mycobacterium avium. The absence of cross-reactive epitopes makes MPT63 an attractive candidate as an M. tuberculosis complex-specific diagnostic reagent. In particular, evaluation of MPT63 as an M. tuberculosis complex-specific reagent for diagnostic skin testing is under way.     

Postoperative epidural infusion of morphine and bupivacaine is safe on surgical wards. Organisation of the treatment, effects and side-effects in 2000 consecutive patients

BACKGROUND: There was an obvious need to improve the quality and safety of our postoperative pain treatment and to introduce an improved routine service on surgical wards. METHODS: It was decided to use postoperative epidural infusion of morphine 0.04 mg/ml and bupivacaine 2.5 mg/ml (0.25%) 4-8 ml/h as pain relief after major surgery. An education programme was run emphasising the benefits, side-effects and the importance of regular monitoring of pain intensity, vital functions (respiratory rate, blood pressure, heart rate), motor function of the legs and the need for additional drugs in order to detect side-effects as well as lack of adequate analgesic effect. A detailed observation sheet was used collecting information every 2 h throughout the epidural treatment period in order to secure monitoring and adjustment of the treatment. Close contact was maintained with the wards. RESULTS: We present a detailed analysis of our first 2000 postoperative patients, mainly after orthopaedic (46.1%), gastrointestinal (32.0%), urologic (8.7%) and vascular (8.5%) surgery. Duration of the treatment was less than 24 h in 41.4% and more than 48 h in 29.7%. Pain relief was adequate in most patients, best after vascular surgery in the lower extremities (mean VAS 0.15/10.0 (95% confidence interval 0.09-0.23)) and less after gastrointestinal (mean VAS 0.49/10 (0.43-0.54)) and thoracic surgery (mean VAS 0.59/10 (0.38-0.81)). The infusion was stopped due to respiratory depression in 3 patients (0.15%). Four (0.2%) had systolic blood pressure < 80 mmHg and had to be treated with vasopressors. A total of 56 (2.8%) patients were considered to be problem patients due to excessive sedation (0.4%), hypotension (0.7%), respiratory depression (1.6%) or lower extremity paralysis (0.05%). All patients had urinary catheter until 6 h after termination of the epidural treatment. One patient had the epidural catheter accidentally placed subarachnoidally and experienced severe respiratory depression. No permanent sequelae were recorded in the postoperative patients, but 2 traumatised patients developed epidural abscesses after 3 weeks of treatment, which resulted in lower extremity paralysis. Late response to the warning signs might have contributed to the irreversible paraplegia. CONCLUSION: Our experience with this postoperative epidural analgesia regime is favourable. It has been easy to administer and monitor. Pain relief was excellent, side-effects were few and picked up by the established routines followed by the ward staff except in the 2 trauma patients who developed epidural abscesses. The staff on the surgical wards were motivated for this kind of work. Education and strict surveillance routines are mandatory in order to secure prompt action when warning signs develops (e.g. lower limb paralysis).     

Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits: an in-vivo study

Photoablative laser trabecular surgery has been proposed as an outflow-enhancing treatment for open-angle glaucoma. The aim of the study was to investigate the time course of repair response following low-thermal Erbium: YAG laser trabecular ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM) was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns) laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter) quartz fiber tip, the left unoperated eye served as control. At time intervals of 30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2 resulted in visible dissection of the ligamenta pectinata and reproducible microperforations of the TM exposing scleral tissue accompanied by blood reflux from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22 +/- 8 microns. At two days post-operative, ablation craters were still blood- and fibrin-filled. The inner surface of the craters were covered with granulocytes. No cellular infiltration of the collateral thermal damage zone was observed. At 10 days post-operative, progressive fibroblastic proliferation was observed, resulting in dense scar tissue formation with anterior synechiae, proliferating capillaries and loss of intertrabecular spaces inside the range of former laser treatment at 60 days post-operative. Trabecular microperforations were closed 60 days after laser treatment in all rabbits. IOP in treated and contralateral eyes did not significantly change its level during whole period of observation. Low-thermal infrared laser energy with minimal thermal damage to collateral structures could not effectively prevent early scarring of trabecular surgery in rabbits.     

Citrobacter sedlakii meningitis and brain abscess in a premature infant

Citrobacter sedlakii was isolated from blood and cerebrospinal fluid cultures of a 5-day-old premature infant with sepsis, meningitis, and brain abscess. This newly described organism was difficult to identify due to discrepancies between the Vitek and API 20E identification systems. To our knowledge, this is the first report of the isolation of C. sedlakii from cerebrospinal fluid.     

Secretory IgA inhibits Pseudomonas aeruginosa binding to cornea and protects against keratitis

PURPOSE: To determine whether secretory IgA (SIgA) antibody inhibits Pseudomonas aeruginosa binding to cornea in vitro and if boosting SIgA antibody in tears using heat-killed P. aeruginosa as an immunizing antigen is protective in vivo in experimentally induced bacterial keratitis in the mouse. METHODS: SIgA, immunoglobulin-G, immunoglobulin-M, and an undiluted crude human milk preparation were tested in vitro for their ability to inhibit P. aeruginosa binding to the scarified corneas of adult (6 weeks to 6 months of age) mice by topical application of each before similar delivery of the bacterial inoculum. Scanning electron microscopy (scanning EM) was used to quantitate bacterial adherence. In vivo mice were immunized topically with heat-killed P. aeruginosa or sham immunized by application of a similar volume of phosphate-buffered saline (PBS). Tears were collected from both groups of mice and levels of immunoglobulins (Igs) measured by enzyme-linked immunosorbent assay (ELISA). After the second immunization, the same two groups were challenged ocularly with 5.0 x 10(7) colony forming units P. aeruginosa and the response to infection graded. RESULTS: In vitro, after a 30-minute preincubation with Igs, SIgA (250 micrograms/ml) significantly decreased P. aeruginosa binding to cornea in vitro when compared to the number of bacteria bound in PBS control specimens, and binding reduction was concentration dependent. In vivo, 15 days after a second ocular topical immunization, tear SIgA was elevated significantly and was specific for P. aeruginosa when measured by ELISA. In vivo, corneal disease response grades in the heat-killed antigen immunized mice also were significantly less severe when compared to sham-immunized mice. CONCLUSIONS: SIgA significantly inhibits binding of P. aeruginosa to the wounded mouse cornea in vitro, and inhibition is concentration dependent. In vivo, specific antipseudomonal SIgA in mouse tears can be elicited by topical ocular immunization with heat-killed P. aeruginosa, and a significant number of immunized animals with elevated levels of SIgA in their tears exhibited less severe ocular disease after bacterial challenge.