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Biomedical subjects

L Graca

Publications and source records attributed to L Graca.

7 recordsLinked to original sources

Regulatory T cells in transplantation tolerance.

Our ability to harness tolerance mechanisms will have a major impact in organ transplantation if it becomes possible to minimize drug maintenance, or even wean off immunosuppressive drugs. An improved understanding of the biology of regulatory T cells will make it possible to replace current induction regimens with those favouring the vaccination and selection of T cells that prevent graft rejection. Once tolerance is established, the continuous supply of graft antigens should sustain T cell mediated regulation as the dominant mechanism preventing graft rejection.

Animals↗

Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance.

Nondepleting anti-CD154 (CD40 ligand) mAbs have proven effective in inducing transplantation tolerance in rodents and primates. In the induction phase, anti-CD154 Ab therapy is known to enhance apoptosis of Ag reactive T cells. However, this may not be the sole explanation for tolerance, as we show in this study that tolerance is maintained through a dominant regulatory mechanism which, like tolerance induced with CD4 Abs, manifests as infectious tolerance. Therefore, tolerance induced with anti-CD154 Abs involves not only the deletion of potentially aggressive T cells, but also a contagious spread of tolerance to new cohorts of graft-reactive T cells as they arise.

Adoptive Transfer↗

Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans.

Changes in cerebral blood volume (CBV) after head injury may be an important determinant of intracranial pressure (ICP). To determine the normal response of CBV to hypoxemia, hypercapnia, and hypocapnia, eight normal subjects (5 males and 3 females; ages 25 to 43) were studied under these conditions. Cerebral blood volume was measured using an external collimated gamma detector to determine 99m-Tc-labeled red blood cell (RBC) activity in the intracranial vascular pool, and cerebral blood flow (CBF) was determined by internal carotid artery duplex scanning. Hypocapnia (Paco2 = 26.0 +/- 1.7 mm Hg, mean +/- SE) was achieved by hyperventilation, hypercapnia (Paco2 = 47.8 +/- 1.5 mm Hg) was achieved by inhalation of 6% CO2, and hypoxemia (Pao2 = 38.1 +/- 1.1 mm Hg, O2 saturation = 76.7 +/- 2.0%) was achieved by inhalation of 10% O2. Changes in CBF and CBV were determined by comparing the values in each condition to the immediately preceding period of normoxia and normocapnia. For conditions of hypocapnia, hypercapnia, and hypoxemia, the percentage of change in CBV was: -7.2 +/- 0.01, 12.8 +/- 0.01, and 5.2 +/- 0.03, respectively. The simultaneous percentage of change in CBF for the same conditions was -30.7 +/- 4.0, 29.5 +/- 9.2, and 18.4 +/- 6.9, respectively. For all conditions, changes in CBF were greater than changes in CBV; however, this was most pronounced during hypocapnia induced by hyperventilation. Because the change in CBV reflects the potential change in ICP in response to treatment, therapeutic hyperventilation may impair CBF to a greater degree than it reduces ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of hyperventilation, mannitol, and ventriculostomy drainage on cerebral blood flow after head injury.

Therapies to lower intracranial pressure (ICP) after traumatic brain injury (TBI) include hyperventilation (HV), intravenous mannitol (IM), and cerebrospinal fluid drainage from a ventriculostomy (DV). To determine the effects of these therapies on cerebral blood flow (CBF), fiberoptic oximetry was used to measure jugular venous O2 saturation (SjvO2) as an index of the CBF to cerebral metabolic rate for O2 (CMRO2) ratio after IM (25 g IV for more than 5 min), DV (3 min), or HV (increase respiratory rate by 4) therapy for elevated ICP. Assuming CMRO2 is constant, changes in SjvO2 reflect changes in CBF. Continuous measurements of SjvO2, ICP, blood pressure, arterial O2 saturation, and end-tidal CO2 were obtained in 22 patients with a Glasgow Coma Scale score of 5.3 +/- 0.4 (mean +/- SD) in the first 5 days after TBI. Therapy was initiated a total of 196 times when ICP was > 15 mm Hg for > 5 minutes, and measurements made at 20 minutes after treatment were compared with those made just before. After DV, ICP fell in 90% of the observations by 8.6 +/- 0.7 mm Hg (mean +/- SEM, n = 119); after IM, ICP fell in 90% of the observations by 7.4 +/- 0.7 mm Hg (n = 43); and after HV, ICP fell in 88% of the observations by 6.3 +/- 1.2 mm Hg (n = 14). In patients where ICP fell, SjvO2 increased by 2.49 +/- 0.7% saturation (from 68.0 +/- 1.3%) with IM, but only by 0.39 +/- 0.4% saturation (from 67.2 +/- 0.9%) with DV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A pediatric trauma center without a pediatric surgeon: a four-year outcome analysis.

Approximately 25% of all injury victims are in the pediatric age group, and one in four injured children will require a pediatric trauma center. According to the American College of Surgeons as well as many state guidelines, a level I pediatric trauma team should be directed by a pediatric surgeon. In 1986, the pediatric surgeon left our pediatric trauma center, but the center remained open under a cooperative effort by the adult trauma surgeons and pediatric intensivists. We have retrospectively reviewed the charts of all pediatric trauma patients (age less than or equal to 15 years) for the subsequent 4 years to determine the outcome of treatment without a pediatric surgeon. During this period, we treated 303 pediatric patients with multiple or serious single-system injuries. The mean age was 6.9 +/- 0.3 (SEM) years and 66% were boys. Falls were the cause of injury in 31% of the patients, with pedestrian/bicycle, motor vehicle crashes, and penetrating injuries resulting in 26%, 19%, and 3% of the injuries, respectively. The mean ISS was 15.6 +/- 0.8, and 73% of the patients had at least one AIS greater than or equal to 3. Surgical procedures were required in 48% of the patients. There were 27 deaths in this group, most commonly related to head injury (89%). The mean Pediatric Trauma Score of the patients who died was 1.6 +/- 0.8 and no patient with a Pediatric Trauma Score greater than 7 died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Benefits of intra-abdominal pack placement for the management of nonmechanical hemorrhage.

Massive nonmechanical bleeding following severe liver injury is a difficult problem. Placement of intra-abdominal packs tamponades this nonmechanical bleeding and allows time for correction of various metabolic disturbances (ie, hypothermia, hypotension, acidosis, and coagulopathy). The purpose of this retrospective study was to evaluate the severity of these metabolic disturbances at the time of pack placement and the sequential improvement. It was found that most life-threatening disturbances that developed during the initial operative procedure could be corrected within 18 hours after pack placement and aggressive resuscitation. We concluded that the onset of nonmechanical bleeding and a coagulopathy marks a grave prognosis for the patient, and consideration should be given at this time for pack placement. Patients can then be aggressively resuscitated and returned to the operating room within 24 hours for pack removal if stability is achieved.

Acidosis↗