Resuscitation with Recombinant Hemoglobin rHb2.0 in a Rodent Model of Hemorrhagic Shock

Background: Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity.

Methods: Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy.

Results: Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran.     

Atypical extraspinal musculoskeletal tuberculosis in immunocompetent patients: part II, tuberculous myositis, tuberculous bursitis, and tuberculous tenosynovites.

Tuberculosis involving the soft tissue from adjacent bone or joint is well recognized. However, primary tuberculous pyomyositis, tuberculous bursitis, and tuberculous tenosynovitis are rare entities constituting 1% of skeletal tuberculosis. Tuberculous tenosynovitis involves most commonly the tendon sheaths of the hand and wrist, and tuberculous bursitis occurs most commonly around the hip. The greater trochanteric bursa and the greater trochanter are the most frequent sites of tuberculous bursitis. Cases of primary tuberculous pyomyositis and tenosynovitis of the tendons of the ankle and foot are seldom reported in the radiology literature. All imaging modalities-plain radiography, bone scan, computed tomography, and magnetic resonance imaging (MRI)--provide information that is helpful in determining therapy. MRI in particular, with its multiplanar capabilities and superb contrast of soft tissue, can demonstrate the extent of the soft tissue mass and access the adjacent bones and joints. However, MRI has no diagnostic specificity in regard to tuberculosis, and in nonendemic areas, biopsy is strongly recommended. All patients in this review were permanent residents of North America or Western Europe and were immunocompetent. Examples of atypical presentations of the above entities are demonstrated.     

Overview of tacrolimus-based immunosuppression after heart or lung transplantation.

Transplantation has evolved into an accepted treatment for end-stage heart or lung disease. Acute rejection, complications related to immunosuppressive protocols, and the development of chronic rejection continue to challenge the long-term success of heart and lung transplantations. Wide acceptance of tacrolimus as an important immunosuppressant in renal and hepatic transplantations has led subsequently to its investigation as primary immunosuppression in heart and lung transplant recipients, either combined with azathioprine or with the newer agents mycophenolate mofetil or rapamycin. Studies have shown that tacrolimus is an effective therapeutic alternative to cyclosporine for primary immunosuppression in heart or lung transplantation and demonstrates equivalent if not improved prophylaxis of acute rejection, and more recently demonstrates a potential influence on chronic rejection, particularly in lung transplant recipients. Of importance, the enhanced immunosuppressive activity of tacrolimus is achieved without increased risk of infection or malignancy. Differences in tolerability profiles and side effects between tacrolimus and cyclosporine may be used in selecting the optimal immunotherapy after thoracic transplantation. In particular, the lesser propensity of tacrolimus to cause hypertension and hyperlipidemia potentially offers decreased cardiovascular risk for heart and lung transplant recipients.     

Up-to-date estimates of cancer patient survival even with common latency in cancer registration.

In an era of ongoing improvement in cancer patient survival, available long-term survival figures from cancer registries are often outdated and too pessimistic for two reasons: first, delay in availability of cancer registry data, typically in the order of a few years, and, second, application of cohort-based methods of survival analysis, which provide survival estimates for patients diagnosed many years ago. We developed a model-based period analysis approach aimed to overcome both problems. We provide extensive empirical evaluation of our approach by comparing its performance with that of previously available methods for monitoring of 5- and 10-year relative survival, with the use of data from the nationwide Finnish Cancer Registry of 490,279 patients ages >/=15 years and diagnosed with one of 20 common forms of cancer between 1953 and 1997. We show that, in most cases, the model-based approach predicts 5- and 10-year relative survival expectations of newly diagnosed patients quite closely and much better than any of the previously available methods, including standard period analysis. We conclude that the model-based approach may enable deriving up-to-date cancer survival rates even with the common latency in availability of cancer registry data.     

Karzinomassoziierte Retinopathie (CAR) bei Mammakarzinom und Karzinoid

Fragestellung: Die Karzinomassoziierte Retinopathie (CAR) stellt ein seltenes paraneoplastisches Syndrom dar, das bislang am h?ufigsten bei kleinzelligen Bronchialkarzinomen beschrieben wurde. Wir berichten über 3 Patientinnen mit CAR in Gegenwart eines Mammakarzinoms bzw. eines Karzinoids der Cervix uteri. Patienten und Methode: Es wurden biomikroskopische, perimetrische, angiographische und elektrophysiologische Befunde erhoben. Au?erdem erfolgte eine Testung der Immunreaktivit?t der Seren an humaner Retina. Ergebnisse: Die Befunde umfa?ten ringf?rmige Gesichtsfelddefekte mit statokinetischer Dissoziation und eine pathologische St?bchen- und Zapfenantwort im ERG. Bei 1 Patientin wurde immunhistochemisch eine Reaktion im Bereich der Photorezeptorinnensegmente, der ?u?eren K?rnerschicht sowie der ?u?eren plexiformen Schicht bei fehlendem Nachweis von Antik?rpern gegen Recoverin gefunden. Diskussion: Neben dem kleinzelligen Bronchialkarzinom k?nnen auch andere Prim?rtumoren mit einer CAR vergesellschaftet sein. Der Nachweis von retinalen Autoantik?rpern unterstützt die Annahme einer tumorinduzierten Immunantwort aufgrund der Expression identischer Epitope durch die Tumorzellen. Dabei kommen offensichtlich verschiedene retinale Proteine als Autoantigene in Betracht.      

The effect of comonomer composition, silane heating, and filler type on aqueous TEGDMA leachability in model resin composites

Experimental composites using either bisGMA/TEGDMA or UEDMA/ TEGDMA matrices, quartz or barium glass fillers, and 2 different filler silanization methods were evaluated regarding monomer leachability in distilled water. The leached amount was detected and quantified using gas chromatography. The results showed that twice as much TEGDMA is leached from a bisGMA/TEGDMA based composite than from an UEDMA/ TEGDMA based composite, when both contain 50 wt% TEGDMA. The hypothesis suggested that the higher degree of cure of UEDMA/TEGDMA based composites would be reflected in a lower monomer leaching value, and this hypothesis was supported by the findings. Whether such a correlation exists within groups of UEDMA/TEGDMA based matrices having different degrees of cure was not determined and needs to be investigated in future studies. Variables such as filler composition and silane treatment did not affect the leaching values of TEGDMA in water. That finding suggests that future studies should target differences in matrices, and that the need for considering effects of filler composition and silane treatment methods should not receive the same priority.