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Biomedical subjects

P M Colombani

Publications and source records attributed to P M Colombani.

54 records · Page 3Linked to original sources
PubMed1987

Efficacy of emergency room thoracotomy in pediatric trauma.

With improved rapid transportation systems, an increasing number of children may arrive at the emergency room (ER) without detectable vital signs and may undergo vigorous resuscitation, including emergency room thoracotomy, aortic cross clamping, and open cardiac massage. Of 1,287 pediatric trauma admissions between 1980 and 1985, 101 deaths were recorded. Fifty (50%) of the deaths occurred in the ER. Thirty-three of the patients were pronounced dead with obvious irreversible injuries, while 17 (34%) with suspected thoracoabdominal injuries underwent ER thoracotomy during resuscitation. None of the 17 patients had detectable vital signs upon arrival to the ER. Fifteen patients had multisystem injuries associated with blunt trauma and two with isolated penetrating injuries. Despite maximal conventional resuscitation and ER thoracotomy, none of the 17 patients survived. In this group of pediatric blunt trauma victims who appear initially salvageable, and present in the ER with no detectable vital signs, ER resuscitative thoracotomy did not influence survival. ER thoracotomy in children, therefore, should be reserved for patients presenting with penetrating thoracic injuries or blunt injuries associated with detectable vital signs and deterioration despite maximal conventional therapy.

Adolescent↗
PubMed1987

The efficacy of computed tomography in evaluating abdominal injuries in children with major head trauma.

Physical examination may be unreliable in the evaluation of children with blunt abdominal trauma particularly in those with associated major head injuries. In the absence of obvious clinical signs or physical findings of intraabdominal injury, the usefulness of abdominal computed tomography in children is controversial. To test the efficacy of CT scans, a 12-month prospective study of computed tomography for the initial assessment of children with blunt abdominal trauma and major head injuries was carried out. Of 320 pediatric trauma admissions to our regional trauma center, 65 consecutive patients with Glasgow Coma Scores less than ten were managed with sequential head and abdominal computed tomography in the emergency room for (1) closed head injury and (2) suspected abdominal trauma. Fifteen patients (23%) were found to have significant intraabdominal injury. Only two required operative intervention. No patients died as a result of the abdominal injuries. In children with significant head trauma and suspected abdominal trauma, combined head and abdominal CT proved to be reliable.

Abdominal Injuries↗
PubMed1987

Calcium and calmodulin antagonists inhibit human malaria parasites (Plasmodium falciparum): implications for drug design.

The malaria parasite has an obligate calcium requirement for normal intracellular growth and invasion of host erythrocytes. Calmodulin (CaM) is a vital calcium-dependent protein present in eukaryotes. We found by radioimmunoassay that free parasites contain CaM. Schizont-infected erythrocytes had CaM levels of 23.3 +/- 2.7 ng per 10(6) cells compared to normals (11.2 +/- 1.5 ng per 10(6) cells). CaM levels were proportional to parasite maturity. Immunoelectron microscopy identified CaM diffusely within the cytoplasm of mature parasites and at the apical end of merozoites within the ductule of rhoptries, which may explain the calcium requirement for invasion. Cyclosporin A (CsA) was also found by electron microscopic autoradiography to concentrate in the food vacuole, as do chloroquine and mefloquine, and to distribute within the cytoplasm of mature parasites. The binding of dansylated CsA to schizont-infected erythrocytes was higher than to normal erythrocytes as analyzed by flow cytometry. Kinetic analysis revealed that binding was saturable for normal and infected erythrocytes and possibly free parasites. Competition for binding existed between dansylated CsA and native CsA as well as the CaM inhibitor W-7 and the classic antimalarial chloroquine. The in vitro growth of Plasmodium falciparum was sensitive to CaM antagonists, and in large part inhibition of the parasite was proportional to known anti-CaM potency. Antagonism existed between combinations of these drugs in multi-drug-resistant strains of P. falciparum, suggesting possible competition for the same binding site. In addition, the malaria parasite was also susceptible to calcium antagonists.

Animals↗
PubMed1986

Cyclosporine A, an in vitro calmodulin antagonist, induces nuclear lobulations in human T cell lymphocytes and monocytes.

Cyclosporine A is a noncytotoxic, natural, 11 amino acid cyclic peptide used clinically as an immunosuppressant to prevent organ rejection after transplantation. Cyclosporine A is an in vitro calmodulin antagonist. At the low concentrations required to inhibit calmodulin-dependent phosphodiesterase in vitro, cyclosporine A causes a dramatic alteration in the nuclear morphology of 23% of human peripheral blood mononuclear leukocytes in vitro without loss of viability. The shape of the nucleus changes from ovoid to a distinctive, radially splayed lobulated structure. The changes occur in a dose-dependent manner in 60 min at 37 degrees C. Specific monoclonal antibodies to human leukocytes identify the cells susceptible to nuclear lobulation by cyclosporine A as OKT4 antigen-positive T cell lymphocytes and monocytes. The lobulated nuclei are 2N as determined by flow cytometric measurement of ethidium bromide fluorescence of DNA. The cyclosporine A-induced lobulation of T cell nuclei requires both physiologic temperature and metabolic energy. Although structurally different than cyclosporine A, the calmodulin antagonists R24571 and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide] also produce T cell nuclear lobulations that are indistinguishable from the nuclear lobulations caused by cyclosporine A. These data indicate that nonmitotic structural elements that govern normal nuclear morphology in a subset of mononuclear leukocytes appear to require a calmodulin-mediated process. Cyclosporine A may be a useful noncytotoxic inhibitor of calmodulin-dependent systems that influence nuclear structure and function.

Antigens, Surface↗
PubMed1986

Cyclosporine and the immune response: basic aspects.

Cyclosporine (CsA) is a novel immunosuppressive agent currently used clinically, to prevent rejection of solid organ allografts and to prevent graft-vs.-host disease. Early studies in a variety of animal models exhibited transplantation tolerance after limited treatment with this unique agent. The apparent specific immunological unresponsiveness induced by CsA is thought to be maintained by antigen-specific suppressor T lymphocytes. Studies attempting to dissect the mechanism of action of this unique agent suggested that CsA selectively affected different T lymphocyte populations. Cyclosporine was very effective at inhibiting the production of interleukin-2 (IL-2), a soluble lymphokine known to amplify cytotoxic T cell responses and was also capable of preventing IL-2 receptor expression on the precursor cytotoxic T lymphocyte. In contrast, to the effect on T helper cells and on the precursor cytotoxic T lymphocyte, studies in vitro and in vivo demonstrated that CsA had a sparing effect on suppressor T cell induction. More recent studies have indicated that CsA allows for the amplification of suppressor T lymphocytes independent of interleukin-2 indicating that other cellular and/or soluble factors are important for potentiation of suppressor T lymphocyte activity. However, the molecular action of CsA at the cellular level still remains unresolved. Thus, CsA is not only a useful drug in clinical transplantation but it has become increasingly important as an immunologic probe allowing the dissection of complex cellular interactions involved in the immune response.

Animals↗
PubMed1985

Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes.

Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.

Binding, Competitive↗
PubMed1985

Life-threatening airway obstruction as a complication to the management of mediastinal masses in children.

Life-threatening airway obstruction from large mediastinal masses in children poses a difficult diagnostic and therapeutic dilemma, requiring the close coordination of a pediatric surgeon, anesthesiologist, radiologist, and oncologist. To focus on this problem, the anesthetic and surgical management of 50 consecutive children with mediastinal masses treated between 1978 and 1984 were reviewed. Thirty children presented with respiratory symptoms; nine had life-threatening respiratory compromise with dyspnea, orthopnea, and stridor. Thirteen of these symptomatic children had marked compression of the trachea and/or mainstem bronchi on radiographic studies. The tracheal cross-sectional area which was measured by computed tomography was decreased by 35% to 93% of the normal tracheal dimensions in these children. Nonresectable malignant neoplasms including lymphoma, Hodgkin's disease, rhabdomyosarcoma, and neuroblastoma were the eventual diagnoses in 10 of these patients. The other 3 patients were less than 4 years old and had benign lesions. General anesthesia was judged to be prohibitively risky in 5 of 13 patients. The diagnosis was established by node or needle biopsy under local anesthesia, and general anesthesia was deferred until the compromised airway was alleviated by radiation and chemotherapy. General anesthesia with endotracheal intubation was administered to 8 patients, 5 of whom developed total airway obstruction. Using a variety of maneuvers, ventilation was reestablished in all 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

One-year experience in a regional pediatric trauma center.

During 1982, 267 children with life-threatening injuries were admitted to the Maryland Regional Pediatric Trauma Center at the Johns Hopkins Hospital. Seventy-three percent of patients arrived directly from the injury scene by helicopter (46%), ambulance (50%), or other (4%). Mechanisms of injury included motor vehicle accidents (MVA; 55%), falls (27%), assaults (8%), and sports and other injuries (10%). In 75% of MVA the child was a pedestrian. Fifty-one percent of injuries were single organ system, 29% involved two systems, and 20% involved three or more systems. Remarkably, the mortality of 6.7% was not affected by the number of organ systems involved, but was directly related to the presence or absence of head injury. Fourteen of seventeen deaths resulted from head injury. Eighty percent of documented liver and spleen injuries were managed nonoperatively. This nonoperative plan of management simplified the optimal treatment of head injury. The high frequency of head injury has mandated a more aggressive approach to the management of brain trauma including intracranial monitoring to facilitate control of cerebral edema. Our data demonstrate that an excellent quality of life may be anticipated even in children with severe head injury.

Adolescent↗
PubMed1984

Early reconstruction of Poland's syndrome using autologous rib grafts combined with a latissimus muscle flap.

The complex chest wall deformity of Poland's Syndrome may require intervention in early childhood for missing ribs and paradoxical movement of the involved anterior chest with lung herniation. To stabilize the chest wall, we have used autologous rib grafts and prosthetic fabric to replace absent endothoracic fascia. While physiologically sound, this method does nothing for the cosmetic defect which consists of absence of the pectoralis minor and one half to two thirds of the pectoralis major muscles. Silastic implants are not satisfactory in childhood and have complications from recurrent trauma and mobility in young adults. We have had recent experience in three patients (ages 10, 14, and 16 years) with an original technique which results in chest wall stabilization and immediate cosmetic reconstruction without prostheses. The operation utilizes simultaneous rib grafts and a rotational latissimus muscle flap. The muscle not only produces a near-normal contour, but also maintains sensation and contractile function. We propose this technique as a method of choice for the correction of Poland's Syndrome and suggest that it may have wider application in children and teenagers who need soft tissue and muscle replacement of the chest wall for other reasons.

Adolescent↗
PubMed1982

Absorbable ligating clips.

Surgical clips have gained wide spread acceptance because of speed and utility in operative fields with difficult exposure. Certain disadvantages make metallic clips less than optimal for many operative situations. Such problems include difficulty in loading metallic clips into the applier, clips falling from the applier in the transfer from nurse to surgeon or while the surgeon is positioning the clip for application and clips coming off a vessel to which it was applied. The interference which metallic clips produce in computerized tomography and their permanency must be added as factors to be evaluated in comparison with absorbable clips.

Chemical Phenomena↗
PubMed1977

Perinatal aspects of omphalocele and gastroschisis.

Forty-one infants treated for abdominal wall defects were studied retrospectively. Using established anatomic criteria the infants were identified as having either an omphalocele or gastroschisis. They were compared for maternal and infant characteristics to determine if distinct perinatal characteristics exist between the two groups. Gastroschisis patients had lower mean maternal age, were more likely to be first born, and to be of lower birth weight. Major malformations apart from those associated with the gastrointestinal tract and the anterior abdominal wall occurred 12 times more often in omphalocele patients. Ventral defects warrant a careful anatomical and clinical differentiation, and in the case of omphalocele, a thorough search for other anomalies.

Abnormalities, Multiple↗
PubMedDate not supplied

Multipurpose central venous access in the immunocompromised pediatric patient.

During a 21-month period, 50 consecutive pediatric oncology patients undergoing bone marrow transplantation and/or cytoreductive chemotherapy had 61 silastic central venous catheters placed to facilitate their therapy. All catheters were used for medications, routine blood sampling, and transfusions, with 45% also used for hyperalimentation and 57% used for bone marrow transplantation. Catheters were utilized during both inpatient and outpatient therapy periods. Total catheter days numbered 8455, an average of 139 days per catheter. Forty-seven catheters (77%) were removed electively or were in place at time of patient death. Seven were removed for mechanical complications (1/1409 catheter days). Four additional episodes of presumed catheter sepsis were managed with antibiotics and did not require catheter removal (40% of septic episodes). One catheter is still in place after 585 days. Complication rates were not influenced by this multiple use protocol. With standardized catheter care and surveillance, multipurpose, long-term central venous access can be safely utilized in the immunosuppressed pediatric patient.

Adolescent↗