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Biomedical subjects

Robert G Carroll

Publications and source records attributed to Robert G Carroll.

8 recordsLinked to original sources

The Pre-Optic Anterior Hypothalamus (POAH) partially mediates the hypothermic response to hemorrhage in rats.

Two sets of experiments were performed to characterize the role of the Pre-Optic Area of the Anterior Hypothalamus (POAH) in the decrease in set point and hypothermia that follows severe hemorrhage. In the first set, lidocaine or artificial cerebrospinal fluid (ACSF) was microinjected into the POAH of rats at the time of hemorrhage. Lidocaine microinjection attenuated the hemorrhagic hypothermia by approximately 50%. The mean drop in core temperature (Tc) following hemorrhage was 1.5 degrees C with ACSF microinjection (N = 6), 0.70 degrees C (N = 6) with lidocaine, and 1.77 degrees C (N = 6) after sham microinjection. This partial attenuation of the hemorrhagic hypothermic response indicates that an intact POAH is necessary for at least some of the hypothermia following hemorrhage. In the second experimental set, hypothalamic tissue temperature (Thyp) was modulated in an attempt to alter the hemorrhagic hypothermic response. Bilateral closed-ended cannulas were inserted into the POAH. One cannula consisted of a water-perfused thermode to change local tissue temperature. The other housed a thermocouple to measure local temperature. The effectiveness of the thermode was first confirmed in conscious rats, evidenced by an inverse deflection in Tc upon Thyp modulation. Then, the POAH region was either heated, cooled, or sham perfused following hemorrhage. The mean drop in Tc following hemorrhage was 2.16 degrees C (N = 5) with hypothalamic heating, 1.35 degrees C (N = 5) with cooling, and 1.44 degrees C (N = 5) following the sham perfusion control. Heating of the POAH significantly exacerbated the hemorrhagic hypothermic response. These data further suggest that the POAH is at least partially responsible for mediating hemorrhagic hypothermia.

Adaptation, Physiological↗

Sustained oxygenation without ventilation in paralyzed pigs with high-flow tracheal oxygen.

OBJECTIVES: It is generally assumed that ventilation is necessary for oxygenation. This study tested if paralyzed animals without respirations can maintain arterial oxygenation when administered high-flow oxygen delivered by a catheter in the trachea. METHODS DESIGN: Prospective observational study. SETTING: University research laboratory. PARTICIPANTS: 3 anesthetized/paralyzed swine weighing 29.5 +/- 4.2 kg. INTERVENTIONS/OBSERVATIONS: Pigs were intubated, anesthetized with intravenous tiletamine and a pentobarbital drip. A femoral arterial line was placed to record arterial blood gases and vital signs every 5 minutes. Respiratory paralysis was obtained with vecuronium 150 microg/kg and repeated at any sign of movement. A catheter was placed in the trachea to deliver oxygen at 15 L/min. Outflow gas from the endotracheal tube was analyzed for O2 and CO2. O2 was discontinued at 75 minutes. The institutional animal care and use committee approved the protocol. RESULTS: All pigs survived to 75 minutes. PaO2 was more than 100 mm Hg throughout the study period. Mean PaCO2 was 37.4 +/- 2.8 mm Hg at baseline, 146 +/- 59 at 30 minutes, then rose above 200 mm Hg in all pigs by 45 minutes. Mean arterial pH fell from 7.47 +/- 0.04 at onset to 6.75 +/- 0.06 at 75 minutes. When oxygen was terminated at 75 minutes, PaO2 fell to 16.5 +/- 7.6 mm Hg within 5 minutes, and all pigs were sacrificed within 10 minutes. For outflow gas, O2 was more than 98% and expired CO2 less than 1% throughout the study period. CONCLUSIONS: Paralyzed, unventilated pigs receiving high-flow oxygen via a tracheal catheter remained alive after 75 minutes, although a profound respiratory acidosis developed.

Animals↗

Thermoregulatory set point decreases after hemorrhage in rats.

Hemorrhage in rats causes a drop in body core temperature that is proportional to the hemorrhage volume. We tested the hypothesis that the hemorrhagic hypothermia is due to a downward shift in the thermoregulatory set point. If so, rats subjected to hemorrhage would prefer a cooler ambient temperature to enhance heat loss during the posthemorrhage period. Male Sprague-Dawley rats were fitted with carotid arterial catheters and biotelemetry temperature probes. Two days later, rats were placed in a temperature gradient chamber that allowed the rat to move between ambient temperatures of 15 degrees C to 40 degrees C. Rat location within the gradient was recorded as the selected ambient temperature. After 48 h, a 24 mL/kg hemorrhage was induced via the carotid cannula followed by a 24-h recovery period in the gradient. Body core and selected ambient temperatures significantly decreased after hemorrhage. Within 50 min, selected ambient temperature decreased by 11 degrees C, and returned to normal 100 min after hemorrhage. Within 80 min after hemorrhage, core temperature decreased by 2.3 degrees C, and returned to normal by 8 h after hemorrhage. Expanded analysis of the first hour after hemorrhage showed that reduction in selected ambient temperature preceded the drop in body core temperature. Importantly, the decrease in selected ambient temperature persisted even during the peak decrease in body core temperature. These results indicate that a decrease in thermoregulatory set point contributes to the drop in body core temperature after hemorrhage.

Animals↗

Dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer: largest safe dose using a risk-adapted approach.

UNLABELLED: This study is a retrospective analysis of 124 differentiated thyroid cancer patients who underwent dosimetric evaluation using MIRD methodology over a period of 15 y. The objectives of the study were to demonstrate the clinical use of dosimetry-guided radioactive iodine ([RAI] (131)I) treatment and the safe and effective application of a 3-Gy bone marrow (BM) dose in patients with differentiated thyroid cancer. METHODS: Tumor and BM dose estimates were obtained. The administered activity that would deliver a maximum safe dose to the organ at risk (red BM or lungs) was determined as well as the resulting doses to the metastases. The clinical benefit of an individual RAI treatment was predicted on the basis of the dose estimates and the expected therapeutic response. Each patient's response to treatment was assessed clinically and by monitoring the hematologic profile. RESULTS: One hundred twenty-four patients underwent 187 dosimetric evaluations. One hundred four RAI treatments were performed. A complete response at metastatic deposits was attained with absorbed doses of >100 Gy. No permanent BM suppression was observed in patients who received absorbed doses of <3 Gy to BM. The maximum administered dose was 38.5 GBq (1,040 mCi) with the BM dose limitation. CONCLUSION: Dosimetry-guided RAI treatment allows administration of the maximum possible RAI dose to achieve the maximum therapeutic benefit. Estimation of tumor dose rates helps to determine the curative versus the palliative intent of the therapy.

Adolescent↗

Outpatient radioimmunotherapy with Bexxar. Closed, clean air reservoir minimizes personnel radiation exposure.

BACKGROUND: Radioimmunotherapy (RIT) with Bexxar (tositumomab and iodine-131 tositumomab; Coulter Pharmaceutical, South San Francisco, CA) has been shown to be effective in the treatment of low-grade and transformed low-grade non-Hodgkin lymphoma (NHL). METHODS: Patient-specific dosimetry with 5 mCi of iodine-131 tositumomab preceded by 450 mg of tositumomab was utilized to calculate the radionuclide dose needed to deliver 75 cGy whole-body radiation (65 cGy for platelet counts of 100,000-149,000/mm(3)). To safely infuse the approximately 95 mCi (range, 52-211mCi) of iodine-131 needed for this treatment, a shielded, closed system was developed to minimize radiation exposure for personnel administering the treatment infusions and to eliminate possible release of aerosolized iodine-131. RESULTS: Twenty-five patients who could be evaluated were infused with a single course of iodine-131 tositumomab therapy and achieved a 76% total response rate at 3 months (32% complete response [CR], 44% partial response [PR]); 59% total response at 6 months (40% CR, 18% PR); and 38% total response at 12 months (31% CR, 6% PR). Administration of RIT using our unique, totally closed system significantly reduced personnel exposure and potential for radioactive spills. The sum of all individuals who administered and monitored the infusions was < 120 mRem whole body exposure over 22 months, well within the ALARA (as low as reasonably achievable) Level I guideline limits. No radioiodide was detectable in the thyroid of any staff member. CONCLUSIONS: In NHL patients who had experienced failure with conventional therapy, RIT with iodine-131 tositumomab therapy was safe and effective. Response rates obtained were equivalent to those obtained at the university medical centers where the Phase I-III clinical trials were performed.

Adult↗