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S Sundaresan

Publications and source records attributed to S Sundaresan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs.

BACKGROUND: Heat shock proteins are expressed during several forms of stress and inflammation. This study was done to determine whether the expression of heat shock protein HDJ-2 (heat shock protein 40), heat shock protein 60, and heat shock protein 70 are increased during rejection in human pulmonary allografts. METHODS: Thirty-five transbronchial biopsy specimens were obtained from adult lung transplant recipients. Histologic analysis and assessment of heat shock protein HDJ-2, heat shock protein 60, and heat shock protein 70 mRNA expression was performed. Total RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with oligonucleotide primers specific for the heat shock proteins. The identity of the amplified message was verified by Southern blot and slot blot analysis. RESULTS: The expression of heat shock protein HDJ-2 was significantly higher in samples from lung transplant recipients undergoing rejection when compared with recipients without rejection or infection. Heat shock protein 70 expression was also increased in rejection. Expression of heat shock protein 60 did not show any increase in recipients with no evidence of rejection and infection or transplant recipients with rejection or infection. Serial analysis of heat shock protein HDJ-2 and heat shock protein 70 obtained in biopsy specimens during and after rejection showed a decrease of heat shock protein HDJ-2 and heat shock protein 70 expression after resolution of lung rejection. CONCLUSION: Our data demonstrate that the expression of heat shock protein HDJ-2 and heat shock protein 70 increases during lung rejection. However, only heat shock protein HDJ-2 was able to differentiate between rejection and infection. Measurement of heat shock protein HDJ-2 in transbronchial biopsy specimens may assist in the differential diagnosis between rejection and infection in lung transplant recipients.

Carrier Proteins↗
PubMed1998

The impact of cytolytic therapy on bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and death after lung transplantation. Therapy has focused on augmented immunosuppression with a variety of agents. Although transient responses are often achieved, sustained remission has been unusual. The outcome of cytolytic therapy for BOS at our center has been analyzed and is reported. METHODS: Between July 1988 and July 1994, 233 patients underwent lung transplantation at Barnes-Jewish Hospital. Among 207 recipients (88.8%) who survived more than 3 months, 81 recipients (39%) had development of BOS; 48 of these patients underwent 64 courses of treatment with a cytolytic agent (antilymphocyte globulin, antithymocyte globulin, or OKT3 monoclonal antibody). The cases of BOS were retrospectively analyzed to determine the impact of cytolytic therapy. RESULTS: The 4-year survival rate was significantly greater in recipients without BOS than in those with BOS (82.8% vs 46.0%; p < .05). Various clinical factors, including diagnosis, forced expiratory volume in 1 second at onset of BOS, presence or absence of pathologically proven bronchiolitis obliterans, type of transplant operation, cytomegalovirus serologic status, and cytomegalovirus pneumonia, were examined, but no significant predictor of survival after the development of BOS was discerned. The mean decrement in forced expiratory volume in 1 second was significantly reduced by cytolytic therapy (-23.5% +/- 2.3% in the 3 months before therapy vs -9.9% +/- 3.5% in the 3 months after the therapy; p < .002). Nevertheless, the stage of BOS progressed over time in spite of therapy in most cases, and only 4 recipients (4.9%) with BOS remained in a lower BOS stage 2 years after treatment. CONCLUSIONS: Recipients with BOS had a significantly lower survival rate than recipients without BOS. No predictor of survival after the onset of BOS was identified. Although cytolytic therapy decreased the rate of decline in pulmonary function in the 3 months after treatment, the stage of BOS ultimately progressed in most patients.

Antilymphocyte Serum↗
PubMed1997

Retrieval by other procurement teams provides favorable lung transplantation outcome.

BACKGROUND: During the last 4 years, we have increasingly used lungs retrieved by other procurement teams. We therefore investigated whether the use of those lungs affected the outcome of lung transplantation. METHODS: We analyzed the results of 159 consecutive lung transplantations performed at our institution between July 1, 1992, and December 31, 1995. The transplants were divided into three groups: distant donor lungs retrieved by our team (DB group, n = 68); distant donor lungs retrieved by other teams (DX group, n = 46); and local donor lungs retrieved by our team (LB group, n = 44). One transplantation with a local donor lung retrieved by another team was excluded from the analysis. RESULTS: No significant differences were noted between the three groups in alveolar-arterial oxygen gradient immediately after transplantation (DB group, 359 +/- 18 mm Hg; DX group, 329 +/- 23 mm Hg; LB group, 327 +/- 20 mm Hg) and at 24 hours; days on ventilator; days in the intensive care unit; length of hospital stay; 30-day mortality; and actuarial 1-year survival (DB group, 81%; DX group, 87%; LB group, 89%). CONCLUSIONS: The use of donor lungs retrieved by other teams achieves an equivalently satisfactory outcome after lung transplantation as lungs retrieved by our team.

Adult↗
PubMed1997

Pulmonary embolectomy after single-lung transplantation.

Single-lung transplantation for pulmonary hypertension results in a significant ventilation/perfusion mismatch with dramatic shift of blood flow, but not ventilation, to the replacement organ. This raises concern that the patient may be precariously dependent on the function of the transplanted lung. We report the successful management of a massive central pulmonary embolus to the transplanted lung in a 43-year-old woman 4 years after single-lung transplantation for primary pulmonary hypertension.

Adult↗
PubMed1997

Quantitative autoradiographic analysis of ionotropic glutamate receptor subtypes in human temporal lobe epilepsy: up-regulation in reorganized epileptogenic hippocampus.

Medically intractable temporal lobe epilepsy is a common disease typically associated with hippocampal damage (sclerosis) and synaptic remodelling. These changes could include increased glutamate receptor expression, enhancing excitability and the potential for neuronal injury. We directly assessed this hypothesis using quantitative in vitro receptor autoradiography to determine the densities of glutamate-, NMDA-, quisqualate/alpha-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA)- and kainic acid-preferring binding sites in surgically removed hippocampi from patients with mesial temporal lobe epilepsy (sclerosis; MTLE) and patients with mass-associated temporal lobe epilepsy (no sclerosis; MaTLE), compared with autopsy material. Neuronal cell counts and in situ total protein densities were also obtained. In general, MaTLE and autopsy binding densities were indistinguishable. In contrast, some regions of MTLE hippocampi exhibited decreased receptor densities, with a corresponding loss of protein. In the hilus and CA1, however, ligand binding densities did not differ from the comparison groups in spite of markedly reduced protein content, consistent with increased glutamate receptor density. Kainate-preferring sites were distributed differently from the other glutamate subtypes and were uniformly decreased throughout the MTLE hippocampus, except for a unique expression within the outer dentate molecular layer. Along with increased NMDA and AMPA receptor densities in the hilus and CA1, this distinctive population of kainate receptors establishes that increased glutamate receptor expression is a feature of the remodelled MTLE hippocampus. These observations suggest that enhanced sensitivity to glutamate may be an important element in the pathophysiology of temporal lobe epilepsy.

Adult↗
PubMed1997

Expression of ryanodine receptors in the pituitary gland: evidence for a role in gonadotropin-releasing hormone signaling.

GnRH elicits secretion of LH and FSH from gonadotropes by activating an array of intracellular signals including the generation of inositol triphosphate and the release of intracellular calcium. Given the important role of calcium in the secretory responses to GnRH, we examined the expression and function of the ryanodine receptors, which are known to modulate calcium release from intracellular stores. Using RT-PCR analysis, we found that ryanodine receptor (RyR) types 2 and 3, but not type 1, are expressed in rat pituitaries. Pulses of GnRH were administered to perifused primary rat pituitary cells in the presence or absence of a ryanodine receptor antagonist, ruthenium red, to assess effects on GnRH-mediated LH secretion. Treatment with ruthenium red resulted in a 40% decrease in the spike phase of GnRH-induced LH release and a 35% reduction in the plateau phase. Ruthenium red also inhibited GnRH-mediated transcription of a transfected alpha-LUC reporter plasmid. RyR messenger RNA (mRNA) expression varied during the rat estrous cycle with maximal levels following increases of progesterone. The effects of gonadal steroids on pituitary RyR mRNA levels were examined directly in ovariectomized rats that were treated with estrogen (E), or estrogen and progesterone (P). In this paradigm, E decreased, whereas E + P increased RyR3 mRNA levels. These results indicate that RyR is expressed and hormonally regulated in the rat pituitary and suggest that it might play a role in mediating GnRH-induced gonadotropin synthesis and secretion.

Animals↗
PubMed1997

Increased concentration of soluble human leukocyte antigen class I levels in the bronchoalveolar lavage of human pulmonary allografts.

BACKGROUND: Human leukocyte antigen (HLA) class I antigens, are glycoproteins expressed on the cell surface and are also secreted (sHLA) into the surrounding fluids. This study investigates whether pulmonary allograft rejection is associated with an increased amount of sHLA class I in the bronchoalveolar lavage (BAL) fluid. METHODS: Enzyme-linked immunosorbant assays were used to measure sHLA class I levels in BAL samples from 66 lung transplant recipients. RESULTS: Analysis of pulmonary allograft recipients revealed that the mean concentration of sHLA class I was significantly higher in samples from recipients with acute rejection than in recipients with no evidence of rejection. Seventy-two percent of the patients with rejection had sHLA levels above the normal range for patients with infection or rejection. Conversely, sHLA levels were within normal limits in 94% of the control population. Time kinetic analysis revealed that in subjects with rejection, sHLA class I levels peaked in the first 2 weeks after transplantation and decreased thereafter. Increased levels of sHLA were found in patients with acute rejection but not in those with chronic rejection. Fifty-nine percent (n = 10) of the patients with infection had sHLA levels within the normal (no infection or rejection) range. The remaining 41% (n = 7) with infection had sHLA above the normal range. Fifty-seven percent (n = 4) of the latter group had cytomegalovirus infection. These results were confirmed in a prospective study carried out by analyzing paired samples obtained during and after rejection. Eight of the nine patients had high BAL sHLA class I during acute rejection, and low BAL sHLA class I levels after resolution of the acute rejection. CONCLUSION: Our data demonstrate that measurement of sHLA class I levels in BAL samples is a sensitive indicator of acute rejection.

Acute Disease↗
PubMed1997

Assessment of iodine deficiency in selected blocks of east and west Champaran districts of Bihar.

OBJECTIVE: A survey conducted in 1964 reported a goitre prevalence of 40.3% in East and West Champaran districts of Bihar. No recent survey has been documented on the prevalence of iodine deficiency in these districts. The present study was therefore undertaken (i) to assess the prevalence of IDD in these districts, and (ii) to estimate the iodine content of salt consumed by population. METHODOLOGY: In each district, one block was selected. In each block more than 630 children in the age group of 6-12 years were included in the study and were clinically examined. Urine samples were collected from 261 children and were analyzed using standard laboratory procedures. A total of 456 salt samples were collected from children and 35 from traders from the two districts and analyzed using the standard iodometric titration method. RESULTS: The total goiter prevalence was 11.6%. The percentage of children with < 2, 2.0-4.9, 5.0-9.9 and > or = 10 mcg/dl of urinary iodine excretion level were 12.3, 13.4, 23.4 and 51.0, respectively. The median urinary iodine excretion of the children was 10.0 mcg/dl. None of the families were consuming salt with a nil iodine content and about 29.3%, were consuming salt with less than 15 ppm of iodine. Of the 35 salt samples collected from traders, all had iodine and about 17% had less than 15 ppm of iodine. CONCLUSION: The study stresses the need for strengthening the existing system of monitoring of quality of salt being provided in the East and West Champaran districts by Government of Bihar.

Child↗
PubMed1996

Stimulation of mitogen-activated protein kinase by gonadotropin-releasing hormone: evidence for the involvement of protein kinase C.

GnRH regulates gonadotropin biosynthesis and secretion. Multiple intracellular signaling pathways are activated by GnRH, including phosphoinositol turnover, release of intracellular calcium and influx of extracellular calcium, and activation of protein kinase C (PKC), among others. In this study, we investigated whether GnRH stimulates mitogen-activated protein kinase (MAPKs), and whether this pathway plays a role in the transcriptional activation of the gonadotropin alpha-gene. In alpha T3-1 gonadotrope cells, treatment with GnRH caused 4- to 5-fold induction of MAPK activity. Stimulation of MAPK activity was detected within 5 min of GnRH treatment and persisted for 60 min. MAPK activation by GnRH was also seen in primary cultures of rat pituitary cells. Treatment with phorbol 12-myristate 13-acetate (TPA) caused 4- to 5-fold induction of MAPK activity in alpha T3-1 cells. Pretreatment with TPA, however, decreased both GnRH- and TPA-induced MAPK activation, suggesting that PKC is involved in GnRH-mediated activation of MAPK. Western blot analyses of PKC isoforms alpha and epsilon confirmed that they were depleted by chronic treatment with TPA, whereas MAPK protein levels were unaffected. Because transcriptional stimulation of the glycoprotein hormone alpha-gene by GnRH is also inhibited by PKC depletion, additional experiments were performed to explore a potential role for MAPK in alpha-gene expression. Cotransfection of a dominant negative inhibitors of MAPK isoforms (ERK1 and ERK2) suppressed basal expression of the alpha-promoter by 60%, but had less effect on the extent of GnRH stimulation in alpha T3-1 cells. These experiments indicate that GnRH stimulates MAPK activity, probably through a pathway involving PKC. Although PKC depletion inhibits both MAPK- and GnRH-stimulated alpha-gene transcription, pathways other than MAPK are also likely to be involved in mediating the transcriptional effects of GnRH.

Animals↗
PubMed1996

Sexually dimorphic transcriptional responses to gonadotropin-releasing hormone require chronic in vivo exposure to estradiol.

GnRH regulates secretion of the gonadotropins, LH and FSH, in a sexually dimorphic manner. In the present study, we examined GnRH regulation of the gonadotropin alpha-subunit promoter to assess whether sex-dependent hormonal effects are manifest at the transcriptional level. Primary cultures of male or female rat pituitary cells were transfected with a reporter gene containing the alpha-promoter linked to luciferase (-420 alpha-LUC) and then subjected to treatment with GnRH for 24 h. Basal alpha-LUC expression was 4.2-fold greater in pituitary cells from males than in those from females. alpha-LUC activity was stimulated 5.3-fold by GnRH in males, whereas GnRH induced a 148-fold increase in alpha-promoter activity in females. The GnRH responsiveness of the transfected alpha-promoter did not vary in pituitary cells isolated at different stages of the female reproductive cycle, suggesting that acute changes in the hormonal milieu are not sufficient to alter transcriptional responses to GnRH. In males, orchidectomy minimally influenced alpha-LUC activity, indicating that testosterone does not exert a suppressive effect on GnRH responsiveness. In ovariectomized females, basal expression of alpha-LUC increased 3.7-fold, and GnRH stimulation was reduced from 165- to 11-fold, suggesting that an ovarian factor suppresses basal activity and enhances GnRH stimulation. Treatment of ovariectomized females with estrogen suppressed basal activity and restored GnRH stimulation of alpha-LUC, but the estrogen effects required long term treatment (10 days). Addition of progesterone to estrogen or treatment with the progesterone antagonist, RU486, had little effect on GnRH responsiveness. We conclude that estrogen exerts dual effects to suppress basal expression and to dramatically enhance GnRH responsiveness of the alpha-promoter. This model reveals potent actions of estrogen at the level of transcription and should provide new insights into the mechanisms that control estrogen priming of gonadotrope cells.

Animals↗
PubMed1996

Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation.

Current experimental research on subarachnoid hemorrhage (SAH) has been limited by the lack of a small-animal model that physiologically resembles SAH and consistently demonstrates acute and delayed cellular injury. Recently, a model for inducing SAH by endovascular perforation of the internal carotid artery has been developed in the rat. This model physiologically resembles SAH. However, little histological data detailing cellular injury after SAH are available in this or other models. Using immunocytochemistry, the authors investigated the induction of the 70-kD heat shock protein, HSP70, a sensitive marker for cellular stress or injury in the brain, 1 and 5 days following endovascular SAH. The authors also used the conventional histological techniques of cresyl violet and hematoxylin and eosin staining to investigate cellular damage 1 and 5 days after the endovascular SAH. One day following the SAH, HSP70 was induced in all six animals examined in multiple anatomical regions, including the basal forebrain, thalamus, neocortex, striatum, and hippocampus. This HSP70 induction was observed in multiple vascular distributions bilaterally. Immunostaining with HSP70 occurred primarily in neurons but also was observed in glia and endothelium. Five days after the SAH, a similar but more intense pattern of HSP70 immunostaining was observed in all eight animals examined. Specifically, HSP70 immunoreactivity was observed in at least one region of the hippocampus more often at 5 days (six of eight animals) than at 1 day (one of six animals, p < 0.05, one-tailed Fisher's exact test). No HSP70 immunostaining was observed in control animals at 1 day or at 5 days. Conventional histology demonstrated foci of ischemic neuronal damage and cellular necrosis; however, HSP70 immunocytochemistry detailed cellular injury far better than conventional histology in all animals tested at both 1 day and 5 days. Our results demonstrate that HSP70 is induced in multiple regions and cell types 1 day and 5 days following endovascular SAH. Because ischemia is a known inducer of stress genes, the authors propose that acute and delayed ischemia are the processes responsible for the induction of HSP70 that was observed at 1 day and 5 days, respectively. Investigation of HSP70 induction following endovascular SAH may also serve as the basis for a new, inexpensive animal model to assess potential therapeutic interventions.

Animals↗
PubMed1995

Single lung transplantation for pulmonary hypertension. Single institution experience in 34 patients.

BACKGROUND: The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival. METHODS AND RESULTS: Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed. CONCLUSIONS: Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.

Actuarial Analysis↗
PubMed1995

Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy.

The distribution of the VIP receptor in the human hippocampus was studied by receptor autoradiography using [3-iodotyrosyl-125I]Vasoactive Intestinal Peptide (VIP) as a ligand, and the relationship of receptor distribution to the distribution of the peptide (visualized by immunocytochemistry) was examined in hippocampi surgically removed from patients with medically intractable temporal lobe epilepsy (TLE) and hippocampi obtained at autopsy from neurologically normal subjects. In the autopsy hippocampi and hippocampi from TLE patients with extrahippocampal temporal lobe lesions [125I]VIP binding was highest in the dentate molecular layer, with lower levels in the fields of Ammon's Horn (CA fields) and the subiculum. In hippocampi from patients with no temporal lobe lesions but considerable hippocampal neuronal loss there were significant elevations in the levels of ligand binding in all CA fields and the subiculum. Ligand binding densities in all CA fields of the patient hippocampi were strongly negatively correlated with neuronal numbers. Immunocytochemical localization of VIP shows no obvious change in the distribution patters of VIP immunoreactivity in the patient groups. This is the first demonstration of VIP and its receptor distribution in the human hippocampus. It is suggested that the elevated levels of receptor binding in the hippocampal seizure focus may indicate a mechanism for greater excitability of neurons and/or for their survivability in the face of the increased excitation and potential for injury in a seizure focus.

Adolescent↗
PubMed1995

Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality in lung transplantation. This study was designed to accurately determine the prevalence of this syndrome of chronic lung allograft dysfunction (which is presumed to be due to chronic rejection). METHODS: A retrospective analysis was done of 212 consecutive lung transplantations performed at Barnes Hospital between July 1988 and March 1994 to characterize the prevalence and course of BOS. One hundred eighty-seven transplant recipients survived at least 3 months after transplantation, putting them at risk for BOS. Recipients free of BOS (group I) were distinguished from those with BOS (group II) based on the presence of declining spirometry (forced expiratory volume in 1 second persistently less than 80% of previous baseline) or histologic obliterative bronchiolitis in group II. RESULTS: There were 110 transplantations in group I (59%) and 77 in group II (41%). At follow-up, BOS was detected using the following criteria: declining forced expiratory volume in 1 second alone, 40 of 77 (52%); positive histologic results alone, 7 of 77 (9.1%); and both, 30 of 77 (38.9%). Declining spirometry was the most common initial sign of BOS onset (57 of 77, 74%). There were no differences between groups with respect to age, sex, indication for transplantation, or type of transplantation performed. The mortality rate was significantly higher with BOS (group II, 22 of 77 [28.6%] versus group I, 8 of 110 [7.3%]; p = 0.001) and was not related to either the type of transplantation performed or the indication for transplantation. Follow-up of group II (mean 35.1 months; range, 7.1 to 63.7 months) showed a delay until BOS onset (16.1 +/- 1.2 months); when BOS was fatal, death ensued within 11.5 +/- 2.4 months of its onset. Comparison of the first and last quartiles of recipients in this series (QTR1 versus QTR4, 53 patients in each) demonstrated a higher prevalence of BOS in QTR1 (24 with BOS of 43 at risk [55.8%] versus QTR4, 5 with BOS of 52 at risk [9.6%]; p < 0.001) and a worse BOS functional score in QTR1 (2.2 +/- 0.2 versus QTR4, 0.8 +/- 0.2; p = 0.007). CONCLUSIONS: (1) Bronchiolitis obliterans syndrome is truly a clinical syndrome, not simply a pathologic entity; (2) BOS displays considerable latency in onset and progression; (3) lung transplant recipients must therefore be followed up for a sufficient interval to determine the actual prevalence and mortality rate of BOS; and (4) the prevalence and mortality rates of BOS are higher than previously appreciated, exceeding 50% and 40%, respectively.

Adult↗
PubMed1995

Improved airway healing after lung transplantation. An analysis of 348 bronchial anastomoses.

We evaluated various clinical factors to identify predictors of airway complication after lung transplantation. Two hundred twenty-nine consecutive single (n = 110) and bilateral (n = 119) lung transplants were done between September 1988 and August 1994. These 348 bronchial anastomoses were retrospectively analyzed. Airway complication that necessitated clinical intervention affected 33 anastomoses (9.5%) in 29 patients (12.8%). Satisfactory healing was achieved in 22 of these patients by conservative therapy such as one or a combination of dilation, stent, and laser. There were five deaths (2.2%) attributable to airway complications. One patient had an early postoperative death unrelated to airway complication and one patient has a recalcitrant bronchus intermedius stricture. Complication occurred more often in single-lung than in bilateral lung transplants (16/110, 14.4%, versus 17/238, 7.1%; p < 0.05). The use of a mattress suture (21/153, 13.7%) was associated with more frequent complications than was simple interrupted suture (8/122, 6.6%) or figure-of-eight suture (4/73, 5.5%) (p < 0.05). For patients in whom airway complications subsequently developed, the duration of postoperative mechanical ventilation was greater than that for those in whom an airway complication did not develop. The prevalence of airway complications as our program evolved was evaluated by separating the 229 transplants into three groups: phase I, the first 77 transplants; phase II, the next 76 transplants; and phase III, the most recent 76 transplants. The airway complication rate per anastomosis was significantly lower in phase III (5/126, 4.0%) than in phase I (12/110, 10.9%; p < 0.05) and phase II (16/112, 14.3%; p < 0.01). The majority of airway complications are successfully treated and rarely fatal. The recent reduction in prevalence of airway complications is likely a result of better maintenance immunosuppression and rejection surveillance.

Adult↗
PubMed1995

Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs.

Lung transplantation is limited by a shortage of suitable donors. To address this shortage, we have begun using donor lungs that do not meet all of our previous rigorous donor criteria. Of 133 consecutive lung transplants done between June 1991 and March 1994, 89 donors were considered ideal because they satisfied all of the following accepted donor criteria (group I): age younger than 55 years, smoking less than 20 pack-years, arterial oxygen tension greater than 300 mm Hg (using inspired oxygen fraction of 1.0 and positive end-expiratory pressure 5 cm H2O), and chest radiograph negative for infiltrate or trauma (contusion or pneumothorax). Thirty-seven donors failed to satisfy one of these criteria and seven donors failed to satisfy two of them, yielding 51 criteria denoting marginal status in the 44 donors in the marginal group (group II) as follows: age older than 55 years, 2; smoking history 20 or more pack-years, 9; unsatisfactory chest radiograph, 34; and arterial oxygen tension less than 300 mm Hg, 6. Sixty-three single lung transplants were done (group I, 44 versus group II, 19) compared with 70 bilateral sequential transplants (group I, 45 versus group II, 25). In 24 cases in group II, at least one of the lungs actually being implanted contained contusion or infiltrate. Evaluation of recipients from the two groups showed no significant difference in median duration of postoperative mechanical ventilation (3 days in both group I and group II) nor in alveolar-arterial oxygen gradient immediately after transplantation (group I, 304 +/- 14 mm Hg versus group II, 275 +/- 22 mm Hg; p = 0.266) or at 24 hours (group I, 125 +/- 12 mm Hg versus group II, 122 +/- 18 mm Hg; p = 0.933) (all values represent mean plus or minus the standard error). However, cardiopulmonary bypass was required to facilitate second graft insertion in bilateral sequential transplants more often in the marginal group (5 of 25, 20%) than in group I (6 of 45, 13%). There were three deaths within 30 days in group I (operative mortality, 3.4%) and none in group II. Currently, 74 (83.2%) of 89 remain alive in group I compared with 38 (86.4%) of 44 in group II. On the basis of these data, we conclude that successful outcome of lung transplantation can be achieved with the use of marginal donor lungs.

Age Factors↗
PubMed1995

Regional distributions of hippocampal Na+,K(+)-ATPase, cytochrome oxidase, and total protein in temporal lobe epilepsy.

Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.

Autoradiography↗