Tumor imaging using technetium-99m bound to pH-sensitive peptides.

Solid tumors often display metabolic abnormalities that consistently produce low pH in the extracellular space of poorly perfused tissue. These acidic regions may provide a mechanism for drug targeting. Peptides have been designed in such a manner that they exist in an anionic hydrophilic form at the pH of normal tissues, but then undergo a sharp transition to a non-ionic lipophilic form at reduced pH. Peptides were labeled with fluorescein or technetium-99m (99mTc) and evaluated in vitro and in two murine models of cancer. Our studies suggest that PAP-1, an 18 amino acid pH activated peptide with a pH of transition between hydrophilic and lipophilic forms (pT) of 6.4, will deliver fluorescein and 99mTc to tumors. Activation of PAP-1 by low pH and penetration into the plasma membrane of cells and tumors were confirmed using flow cytometry, fluorescence microscopy, and gamma scintigraphy. These results support our central hypothesis that PAP-1 may enable the selective delivery of macromolecules to tumors. This technology has potential for exploiting a common property of tumors to achieve highly specific medical intervention.

Mandibular fracture repair in a harbor seal.

A 30-year-old captive female harbor seal (Phoca vitulina) bit down upon a metal ring within a hoop-net normally used to assist in securing the seal for routine physical examination. Radiographic examination performed under general anesthesia revealed a unilateral closed fracture of the rostral left mandible between the first and second premolar teeth. The rostral fragment was displaced ventrally and slight laxity of the mandibular symphysis was noted. The fracture was repaired surgically using an oral dental acrylic splint incorporating circumferential mandibular cerclage wire. The mandibular symphysis was stabilized using interdental wire between the right and left canine teeth. The fixation device was removed following evaluation of radiographs that showed signs of bony union 12-months postoperatively.

Use of laryngeal mask airway compared to endotracheal tube with positive-pressure ventilation in anesthetized swine.

OBJECTIVE: To compare the ease of placement and ventilatory parameters of a laryngeal mask airway (LMA) with an endotracheal tube (ETT) in anesthetized swine during positive-pressure ventilation (PPV). STUDY DESIGN: Prospective, randomized, experimental trial. ANIMALS: Nine young domestic swine, weighing between 40 and 49 kg (mean 45.1 kg), being used for a separate terminal surgical study. METHODS: The pigs were immobilized with tiletamine/zolazepam, 2.7-3.6 mg kg(-1), intramuscularly, followed by isoflurane in oxygen delivered by facemask. The lungs were mechanically ventilated through an ETT or an LMA, in random order, during the anesthetic period. Positive-pressure ventilation was adjusted to maintain end-tidal CO2 (Pe'CO2) between 35 and 45 mmHg, with peak inspiratory pressure (P(insp)) of 15-23 cmH2O. Buprenorphine, 0.3 mg intramuscularly, was given to each pig after instrumentation. Isoflurane vaporizer settings were adjusted to maintain a surgical plane of anesthesia. Respiratory rate (RR), tidal volume (V(T)), minute volume (V(E)), and Pe'CO2 were measured and recorded at 5-minute intervals. After the collection of 1 hour of data, the alternate airway was placed. Swine were given at least 30 minutes to stabilize and another hour of data were recorded. At the time of airway placement, the ease of placement was assessed based on time and the number of personnel required. Data were analyzed using paired Student's t-test or Wilcoxon signed rank test where appropriate. RESULTS: Laryngeal mask airways were significantly easier to place than ETT. Values for V(T) and V(E) were not significantly different between treatments. Peak inspiratory pressures were higher in ETT-ventilated swine. CONCLUSIONS AND CLINICAL RELEVANCE: An LMA may be used as an alternative to an ETT in mechanically-ventilated anesthetized swine. Use of an LMA may reduce time and personnel required for placement of an airway.

Chitosan dressing provides hemostasis in swine femoral arterial injury model.

OBJECTIVE: Chitosan dressings have been shown to be effective in improving survival of severe parenchymal injuries in an animal model and in treating prehospital combat casualties. Our goal was to test the efficacy of chitosan acetate dressings in providing durable hemostasis in a high-flow arterial wound model. METHODS: A proximal arterial injury was created with 2.7-mm vascular punches in both femoral arteries of fourteen anesthetized swine. By using a crossover design, 48-ply gauze (48PG) or a chitosan dressing (HC) was applied with pressure to the injury for 3 minutes and then released. If hemostasis was not maintained for 30 minutes, a second identical attempt was made by using the same dressing type. If hemostasis was still not achieved, the dressing was considered an acute failure and the alternate dressing type was applied. If failure of hemostasis occurred between 30 and 240 minutes after application, the dressing was considered a chronic failure and the artery was ligated. RESULTS: All 25/25 (100%) of the HC tests and 3/14 (21%) of the 48PG maintained hemostasis for 30 minutes. At 240 minutes, 21/25 (84%) of the HC tests and 1/14 (7%) of the 48PG maintained hemostasis. Statistical analysis by Fischer's exact test shows a significant (p < 0.001) difference in hemostatic efficacy between the 48PG and HC groups in this model, both at 30 minutes and at 240 minutes. CONCLUSION: Chitosan acetate hemorrhage control dressings provided superior hemostasis to 48 ply gauze in high inguinal femoral arterial injuries. Chitosan-based dressings may provide prehospital treatment options for hemostasis in patients with severe hemorrhagic arterial injuries.

Concentrated albumin as a biological glue for hemorrhage control on hepatic resection with argon beam coagulation.

Topically applied concentrated albumin with argon beam coagulation (ABCA) has been shown to be more effective at achieving hemostasis than using argon beam coagulation alone (ABC) in a liver injury model. This study investigated the host response to the concentrated albumin after argon beam coagulation. Complete hemostasis was achieved using ABCA (N = 10) or ABC (N = 10) on a nonanatomic liver resection in a heparinized porcine model. The repairs were evaluated grossly and microscopically at postoperative periods of 30 and 90 days. We found no evidence of biliary leakage, rebleeding, or intraabdominal infection. Blood analysis indicated liver chemistry indices were within normal range after ABC and ABCA treatments. The histopathology showed that the postoperative healing response was similar in both groups: a moderate chronic inflammatory response as part of an on-going normal healing process. All repairs were encapsulated by fibrous tissue. There was no difference in the postsurgical adhesion scores for the ABCA (mean 3.4) and ABC (mean 3.8). It was concluded that use of the concentrated albumin as biological glue in conjunction with argon beam coagulation is a safe and efficient procedure for controlling hepatic hemorrhage in surgery. Further studies are warranted to investigate the clinical significance of this technique.

Tibial plateau leveling osteotomy in a llama with a ruptured cranial cruciate ligament.

A 3-year-old 155-kg (342-lb) castrated male llama was examined because of left hind limb lameness of acute onset. A diagnosis of cranial cruciate ligament and medial collateral ligament rupture was made, and tibial plateau leveling osteotomy was recommended. The tibial plateau leveling osteotomy procedure was performed as described for dogs, except that 2 orthopedic plates were used to stabilize the osteotomy because of the size of the llama. The medial collateral ligament was sutured and reinforced with 2 strands of size-2 polypropylene placed in a figure-8 fashion between cancellous bone screws in the femur and tibia. Four days after surgery, failure of the medial collateral ligament repair was evident. Approximately 3.5 years after surgery, the llama was reexamined. The owners reported that the llama had full use of its left hind limb, and only mild lameness (grade 1 of 5) was evident. Results suggest that tibial plateau leveling osteotomy may be applicable in camelids with rupture of the cranial cruciate ligament. However, additional study is needed before tibial plateau leveling osteotomy can be routinely recommended. In particular, additional information is needed on the tibial plateau slope in healthy camelids, the role of the fibula in tibial plateau leveling osteotomy procedures, and the prevalence of cranial cruciate ligament rupture in camelids.