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Biomedical subjects

S T Ildstad

Publications and source records attributed to S T Ildstad.

At least 109 records · Page 6Linked to original sources
PubMed1991

Kinetics of early T-cell repopulation in fully xenogeneic chimeras (F344 rat----B10 mouse): evidence for rat T-cell maturation in a xenogeneic mouse thymus.

We recently reported the model of fully xenogeneic chimerism achieved by transplantation of rat bone marrow into mouse recipients (F344 rat----B10 mouse), resulting in stable long-term rat lymphoid chimerism. We have now extended this model to examine whether developing precursor rat T cells from rat bone marrow stem cells can undergo normal differentiation in mature lymphocytes under the influence of a xenogeneic mouse thymus. We examined thymic and splenic lymphoid cells from fully xenogeneic chimeras starting 1 week after bone marrow transplantation to characterize early T-cell repopulation and phenotype. Our data suggest that developing rat precursor T cells are able to undergo normal differentiation in the mouse thymus. The first precursor T cells appeared 2 weeks after reconstitution and by week 10 accounted for more than 90% of thymocytes present in the chimeras. In chimeras, developing rat T lymphocytes in the mouse thymus exhibited an immature pattern (Thy 1.1+, alpha beta-TCRdull, CD4+ plus CD8+) when analyzed by flow cytometry. This pattern was similar to a normal rat. In contrast, splenic T-lymphoid cells showed a mature rat phenotype (Thy 1.1-, alpha beta-TCRhi, CD4+ or CD8+), again similar to a normal rat. This development began 2 weeks after bone marrow transplantation, and both thymus and spleen from chimeras exhibited "normal" rat T-cell staining profiles by 10 weeks after reconstitution. Overall, these data indicate that developing rat T cells are capable of undergoing normal maturation in a xenogeneic mouse thymus of tolerant animals.

Animals↗
PubMed1990

Cardiac contusion in pediatric patients with blunt thoracic trauma.

To investigate the prevalence of myocardial contusion associated with blunt chest trauma in the pediatric age group, all patients admitted to our institution during a 6-month period with blunt thoracic trauma severe enough to produce a pulmonary contusion or rib fracture were prospectively evaluated. Cardiac evaluation was undertaken, including a multiple-gated acquisition (MUGA) cardiac scan, serial electrocardiograms (ECG), and serum creatine phosphokinase (CPK) and CPK isoenzymes. Seven patients, ranging in age from 2 1/2 to 18 years, with rib fractures or pulmonary contusion by chest roentgenograph were identified. One patient was injured as a passenger in a motor vehicle accident, five were struck by automobiles as pedestrians, and one sustained traumatic asphyxia when a car, supported by a jack, fell on his chest. All had at least one other major organ system injured. All patients had pulmonary contusions as determined by chest radiograph, and two had associated rib fractures. In 43% (three of seven) of patients, a significant cardiac contusion was identified, defined by abnormal right or left ventricular wall motion and a decreased ejection fraction on MUGA scan, and confirmed by an increase in cardiac enzymes and isoenzymes. However, in contrast with adults, no patients had ECG abnormalities. This limited series suggests that cardiac contusion may occur frequently in pediatric patients who have suffered from blunt thoracic trauma significant enough to result in pulmonary contusion. An MUGA scan provides a rapid, noninvasive assessment of cardiac damage in this setting. Further studies will be required to determine the clinical significance and long-term consequences of traumatic myocardial damage in the pediatric population.

Accidents, Traffic↗
PubMed1990

Percutaneous transperineal pouch localization in low imperforate anus: a new approach.

Patients who have an imperforate anus with associated infralevator, or low rectal pouch, are candidates for a perineal anoplasty. However, in the absence of a perineal fistula, intraoperative localization and isolation of the rectal pouch can be difficult. We have developed a technique to facilitate isolation and dissection of the rectal pouch for perineal anoplasty in patients with a low imperforate anus who do not have a perineal fistula present. Pouch localization is carried out preoperatively by fluoroscopic percutaneous transperineal placement of a Fogarty embolectomy catheter through the center of the anal wink. We have used this technique successfully in four consecutive patients who had a low imperforate anus, in the absence of a perineal fistula, with the pouches 1.0 to 1.5 cm from the perineum. Results have been excellent, and the dissection of the rectal pouch was facilitated greatly by the presence of the inflated Fogarty balloon.

Anal Canal↗
PubMed1990

High apical insertion of the right diaphragm in an infant with right-sided Bochdalek diaphragmatic hernia.

We report the case of a newborn full-term infant who presented to our service on the first day of life with a right-sided Bochdalek congenital diaphragmatic hernia associated with a high apical insertion of the right hemidiaphragm at the level of the second rib. This resulted in incarceration of the left lobe of the liver within the right hemithorax, but minimal pulmonary hypoplasia. A search of the literature failed to show a previous report of this variant of a duplication of the diaphragm in conjunction with a congenital diaphragmatic hernia. The approach taken for diaphragmatic reconstruction and closure of the defect is described.

Abnormalities, Multiple↗
PubMed1990

T-cell subsets in healthy teenagers: transition to the adult phenotype.

Little is known about the normal range and variability of T-cell subsets in older children. We analyzed peripheral blood mononuclear cell subsets in 112 healthy children, ages 12-19 years (mean +/- SD: 15.4 +/- 1.9 years), using monoclonal antibodies and flow cytometry. The study population included 28 blacks and 84 whites, with 59 boys and 53 girls. The mean +/- SD cell subset values were: CD3+ T cells, 74.0 +/- 7.8%; CD4+ helper-inducer T cells, 46.8 +/- 6.9%; CD8+ suppressor-cytotoxic T cells, 27.3 +/- 5.7%; CD4:CD8 helper:suppressor ratio, 1.81 +/- 0.57; CD16+ natural killer cells, 4.4 +/- 3.1%; CD19+ B cells, 10.0 +/- 5.3%; CD14+ monocytes, 20.0 +/- 6.5%; and HLA-DR cells, 15.4 +/- 4.8%. Overall, boys had a higher proportion of HLA-DR+ cells than girls, attributable to an increase in CD19+ B cells. Blacks tended to have a higher proportion of HLA-DR+ cells than whites, apparently due to an increase in activated T cells. Detailed analysis by age group revealed a striking transition in the pattern of CD4+ and CD8+ cell populations. The CD4:CD8 ratio, higher in boys than girls for ages 12-16, was reversed to the "adult" pattern in 17-19 year olds, with a higher CD4:CD8 ratio in girls. These data provide important baseline values for healthy children and stress the importance of establishing normative ranges for pediatric subjects separately from adults.

Adolescent↗
PubMed1990

The influence of donor age on graft survival in renal transplantation.

The current supply of kidneys from cadaver and living related donor sources is not sufficient to meet the demand. As a result, alternative sources of renal allografts are being explored, including very young donors and anencephalic newborns. However, data on the success of transplanting kidneys from very young donors are limited and conflicting. The purpose of this study was to determine whether the function and survival of renal grafts obtained from newborns and very young donors is different from that for grafts obtained from older donors. Thirty-six cadaveric donors under the age of 3 years, including seven anencephalic newborns, were evaluated. Allograft recipients ranged in age from 12 months to 57 years. The clinical outcome for these donor organs was compared with the graft survival for 136 kidneys transplanted from cadaver donors over age 3 years at our institution. There was a 65% 6-month and 64% 1-year graft survival in recipients of kidneys from donors greater than or equal to 3 years. Survival of grafts from donors under 12 months of age (n = 16) was significantly decreased compared with donors age 3 years and older, with a 31% 6-month (P less than .01) and 19% 12-month survival (P less than .001). Grafts obtained from anencephalic donors did not differ in survival or function from kidneys obtained from other donors less than 12 months of age. Survival for renal allografts from donors age 13 months to 3 years was also decreased relative to older donors: 55% at 6 months (P greater than .1) and 40% at 1 year (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras.

Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells.

Animals↗
PubMed1989

A multivariate analysis of determinants of survival for patients with squamous cell carcinoma of the head and neck.

The prognosis for patients with squamous cell carcinoma of the head and neck remains poor, despite refinements in conventional therapy and experimental protocols using alternative treatment modalities. Clinical characteristics reported to influence survival have included age and sex of the patient, the therapy used, location of the primary tumor, and stage at initial presentation. However, such variables are highly correlated, and previous reports have lacked sufficient statistical analysis to assess the independent influence of these competing variables on survival. To better define the principal determinants of survival, we used a Cox multivariate regression analysis of 542 patients with invasive squamous cell carcinoma of the head and neck treated exclusively at our institution from 1962 to 1976. All patients were followed for a minimum of 5 years after diagnosis, with 98% complete follow-up achieved. Stage at initial presentation was the single-most important factor influencing survival for all tumor locations (p less than 0.0001). Advanced age (p = 0.001) and location of the primary tumor in the tonsillar area (p = 0.01) were also independently associated with an inferior survival. The type of therapy used and sex of the patient did not significantly influence survival after controlling for stage. These data emphasize the need for early diagnosis and treatment of squamous cell carcinoma of the head and neck and underscore the limitations of current therapeutic approaches. Future investigations should incorporate multivariate statistical techniques whenever possible, and additional efforts must be directed at basic research into the biology and immunologic characteristics of these tumors in an attempt to identify innovative therapeutic modalities.

Adult↗
PubMed1988

Duplications of the alimentary tract. Clinical characteristics, preferred treatment, and associated malformations.

Duplications of the alimentary tract are unusual congenital anomalies that frequently present a diagnostic as well as therapeutic challenge to the surgeon. Because these lesions occur so infrequently, they are often not suspected until encountered intraoperatively. Due to the complicated anatomy and common blood supply shared between the duplication and associated native bowel, appropriate management requires a familiarity with the anatomy and clinical characteristics of this entity. To better define the range of patient characteristics, clinical presentation, and preferred therapy, 20 enteric duplications were reviewed in 17 patients treated at the Children's Hospital Medical Center from 1956 to 1986. Ages of patients ranged from 1 day to 11 years; 60% were less than 2 years of age at initial presentation. Seven duplications in six patients involved alimentary tract structures of foregut derivation (esophagus, stomach, and Parts I and II of duodenum), with a predominance of girls (4 of 6). Most of these patients (67%) presented with moderate to severe acute respiratory distress and a mass present on chest radiograph. In 67% of the patients, the correct diagnosis was established before operation. None required emergency operative intervention. By contrast, 13 duplications in 11 patients were of midgut or hindgut derivation (Parts III and IV of the duodenum, jejunum, ileum, and colon). In this group of patients, 62% of the duplications involved the cecum, 23% involved the ileum, and 16%, the jejunum. Seventy-eight per cent of the patients were boys. The most common symptoms were nausea and vomiting, and the most common sign was a palpable abdominal mass. Emergency operative intervention was required of eight of 11 patients with duplications involving the small bowel and colon. Three patients presented with an intussusception, four with signs and symptoms consistent with acute appendicitis, one with a small bowel obstruction, and two with gastrointestinal hemorrhage due to the presence of ectopic gastric mucosa within the duplication. It was found that two important points must be considered in regard to the management of enteric duplications: (1) the common blood supply shared between the duplication and native bowel must be carefully protected to avoid undue sacrifice of normal bowel, and (2) the presence of heterotopic gastric mucosa in 35% of patients negates internal drainage.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Multiple↗
PubMed1986

Alloresistance to engraftment of allogeneic donor bone marrow is mediated by an Lyt-2+ T cell in mixed allogeneic reconstitution (C57BL/10Sn + B10.D2/nSn----C57BL/10Sn).

In the mixed allogeneic reconstitution (B10 + B10.D2----B10) model, alloresistance to engraftment of allogeneic donor results if the syngeneic component of the mixed bone marrow inoculum is not depleted of Lyt-2+ cells before transplantation. Resultant experimental animals repopulate as fully syngeneic, reject B10.D2 skin allografts, and are reactive to B10.D2 lymphoid cells in vitro, as assessed by mixed lymphocyte culture proliferative and cellular cytotoxicity assays. In contrast, depletion of Lyt-2-reactive cells from the syngeneic component of the mixed bone marrow inoculum results in mixed lymphopoietic chimerism and specific in vivo transplantation tolerance to B10.D2 allogeneic donor skin grafts and in vitro unreactivity to B10.D2 lymphoid elements. Full reactivity to third party is evident both in vitro and in vivo in these animals. This model may be helpful in further study of the syngeneic host-type cell phenotypes responsible for alloresistance to bone marrow engraftment.

Animals↗
PubMed1986

Effect of selective T cell depletions in mixed xenogeneic reconstitution on specific hyporeactivity to transplantation across a species barrier.

We have recently reported the induction of long-term specific hyporeactivity to transplantation across a species barrier (rat----mouse) through reconstitution of irradiated recipients with a mixture of T-cell-depleted host-type C57BL/10Sn (B10) bone marrow plus T-cell-depleted F344 rat bone marrow (B10+F344----B10) (1). We report here the influence of selective T cell depletions of host-type and/or donor-type bone marrow on induction of such hyporeactivity. Mice that received mixed bone marrow inocula in which the syngeneic marrow had been T-cell-depleted, whether or not the xenogeneic donor marrow had been treated, showed specific prolongation of F344 donor-type skin grafts. In contrast, F344 rat skin grafts were promptly rejected by animals that had received mixed bone marrow inocula in which the syngeneic component had not been T-cell-depleted. Serologic reactivity against F344 lymphocyte cell surface antigens also differed among the four groups; animals that had received untreated syngeneic bone marrow demonstrated high levels of reactivity to F344 target cells, while animals reconstituted with mixed inocula in which the syngeneic component had been T-cell-depleted exhibited low levels, if any, of serologic reactivity against F344 splenocytes. This model for mixed xenogeneic reconstitution may be helpful to define the conditions required for induction of transplantation tolerance across a species barrier.

Animals↗
PubMed1986

Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10).

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow.

Animals↗
PubMed1986

Squamous cell carcinoma of the head and neck at the Massachusetts General Hospital: a comparison of biologic characteristics in men and women.

Little is known about the biologic behavior of squamous cell carcinoma of the head and neck in women. A few recent reports for selected sites have suggested that these tumors may be becoming more common in women. To evaluate potential differences between males and females with squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx and to assess whether the proportion of females with this disease is increasing, the authors have undertaken a retrospective review of 542 consecutive patients treated at our institution from 1962 through 1976. We report here the first detailed comparison of males and females with squamous cell carcinoma of the head and neck, with attention directed to stage at initial presentation, choice of therapy, response to therapy, age distribution, survival, and prevalence of second primary malignancies. It has been widely published that survival for women with squamous cell carcinoma of the head and neck is superior to that for men, and this has been attributed to a difference in the biologic characteristics of the disease between the two sexes. Although overall survival calculations in our series suggested a significantly better survival rate for women than for men, these rates were strongly influenced by the larger proportion of women (64%) who had stage I or II disease, compared with only 50% of men. When survival was compared stage by stage, there was no significant difference in survival between the two sexes. The proportion of females in the combined study population was 35%, increasing from 33% in the first 5 years of the study period to 40% in the last 5 years. Among patients born before 1920, 34% were female compared with 43% of patients born after 1920. Of the 13 patients less than 40 years of age at diagnosis, 62% were female. The rising proportion of women during the 15-year study period, particularly among young patients and those in more recent birth cohorts, strongly suggests that squamous cell carcinoma of the head and neck is increasing among women in this referral population. A review of the literature indicates that this trend began more than 40 years ago.

Adult↗