Typing of inflammatory lesions of the pituitary.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.

Evidence for a progenitor cell population in the human pituitary.

The ability to isolate and propagate adult stem/progenitor cells from the human brain opens novel avenues for cell replacement therapy. This will also apply to the pituitary gland, i.e., following tumor induced endocrine deficiency. Herein, we examine autopsy derived pituitaries to unravel a putative stem/progenitor cell population in humans. In tissue sections of the anterior lobe nestin immunoreactive cells co-expressing smooth muscle actin (SMA) were identified in the perivascular space, indicating a pericytic differentiation. Under clonal conditions, this particular cell population generated primary and secondary cell aggregates (spheres). Pituitary cell cultures maintained a stable cell cycle length with a doubling time of 10 days for over eight months. Forskolin treatment induced a prolactin-expressing phenotype in the majority of cell progenies as well as few betaIII-tubulin (Tuj1) expressing cells of putative neuronal lineage. The presence of sphere-forming, nestin-immunoreactive cells and their ability to generate differentiated cell lineages indicates the existence of a progenitor cell population persisting in the adult human pituitary. Further studies are needed to characterize this cell population in more detail and to clarify their potential to initiate neoplastic transformation for example in the cellular pathogenesis of pituitary adenoma.

No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo.

OBJECTIVE: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD) and Nelson's syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. MATERIALS AND METHODS: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days. RESULTS: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls. CONCLUSION: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.

Tetralogy of Fallot with diminutive pulmonary arteries: preoperative pulmonary valve dilation and transcatheter rehabilitation of pulmonary arteries.

OBJECTIVES: This study sought to determine the results of a novel transcatheter management approach in tetralogy of Fallot with diminutive pulmonary arteries. BACKGROUND: Tetralogy of Fallot with diminutive pulmonary arteries and severe pulmonary stenosis is rare and resembles tetralogy of Fallot with pulmonary atresia: There is a high incidence of aortopulmonary collateral channels, arborization abnormalities, stenoses and need for multiple operations. Because a combined catheter-surgery approach facilitates repair in these patients, such an approach may benefit those with diminutive pulmonary arteries and pulmonary stenosis. METHODS: Clinical, catheterization and surgical data were studied retrospectively for 10 such patients undergoing preoperative pulmonary valve balloon dilation, among other transcatheter interventions, from January 1989 to January 1995. RESULTS: Initially, the Nakata index ranged from 20 to 98 mm2/m2 (mean 67 +/- 28 mm2/m2). The pulmonary valve was first balloon dilated (mean balloon/annulus 1.5 +/- 0.3), and the mean initial valve annulus Z score (-4.0 +/- 1) increased to -33 +/- 1.1 (p < 0.01) Other interventions included branch pulmonary artery balloon dilation (7 patients, 23 vessels) and coil embolization of aortopulmonary collateral channels (8 patients, 31 collateral channels). At preoperative follow-up catheterization, the mean pulmonary annulus Z score was -3.1 +/- 0.7, and the Nakata index increased to 143 +/- 84 mm2/m2 (p < 0.03). All patients underwent complete surgical repair successfully. At a mean follow-up period of 2.6 +/- 2 years, right ventricular pressure was < 70% systemic in all patients and < 50% systemic in seven. CONCLUSIONS: In patients with tetralogy of Fallot, severe pulmonary stenosis and diminutive pulmonary arteries, initial pulmonary valve balloon dilation increases the annulus Z score and anterograde pulmonary blood flow and facilities simultaneous coiling of aortopulmonary collateral channels and access for branch pulmonary artery dilation, all of which results in pulmonary artery growth, simplifying surgical management.

Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria.

The results of transsphenoidal surgery as initial therapy for GH-secreting pituitary adenomas in 57 acromegalic patients were analyzed retrospectively. Patients with prior surgery or radiation therapy were excluded from the study. Three different criteria were used to define remission: glucose-suppressed (nadir) GH less than 1.0 microg/liter, a normal sex- and age-adjusted IGF-I level, and postoperative random GH levels of 2.5 microg/liter or less. Additionally, we analyzed the neuropathological data, including immunohistochemistry and ultrastructural categorization, and the surgical complications. The short-term remission rate (6-wk postoperative follow-up visit), as determined by a random GH measurement of 2.5 microg/liter or less, was 48.8%; the remission rate, as determined by nadir GH, was 51.4%. For 57 patients followed for 12 months or more after surgery (mean, 37.7 months), surgical remission was achieved in 70.2%, 66.7%, and 61.1%, respectively, for patients assessed by normal IGF-I, random GH, and nadir GH. One patient (1.1%) developed recurrence of active acromegaly 81 months after initially successful surgical therapy. Extrasellar growth of the tumor (P = 0.04) and dural invasion by the adenoma (P = 0.008) were significant univariate predictors of a poor outcome. Tumor size was significantly greater in patients with persistent or recurrent acromegaly (P = 0.02). Patients with tumors of the ultrastructural categories of mixed GH/PRL cell and mammosomatotroph adenomas had the lowest remission rates (50% and 42.9%, respectively). There were no perioperative deaths, and there was no serious morbidity. The permanent complication rate was 3.3% (1 permanent DI and 2 nasal septal perforations). Surgical management of acromegaly currently provides prompt, effective, and satisfactory initial treatment for the majority of patients. Using stringent criteria for remission, primary transsphenoidal surgery for GH-secreting pituitary adenomas is effective and often definitive therapy for acromegaly. These results provide a benchmark for the contemporary results of surgical management as assessed by modern outcome criteria.

Comparison of left ventricular outflow tract obstruction in interruption of the aortic arch and in coarctation of the aorta, with diagnostic, developmental, and surgical implications.

A morphometric comparison of the anatomic causes of left ventricular (LV) outflow obstruction in interruption of the aortic arch and in coarctation of the aorta with ventricular septal defect (VSD), based on 30 postmortem cases of each, revealed that posterior malalignment of the conal septum with a conoventricular VSD was significantly more prevalent with interruption (93%) than with coarctation (47%) (p <0.001). The ratio of the aortic valve diameter-to-the pulmonary valve diameter, which provided a quantitative index of the degree of posterior conal septal malalignment and of the consequent LV outflow tract obstruction at and immediately below the level of the aortic valve, was significantly smaller with interruption (

Transcatheter fenestration dilation and/or creation in postoperative Fontan patients.

There are very few therapeutic options for severely symptomatic Fontan patients after spontaneous complete or virtual fenestration closure. Its reopening in 14 such patients led to dramatic hemodynamic improvement in most. The clinical experience with transcatheter fenestration creation and/or dilation in symptomatic Fontan patients is reported demonstrating feasibility, safety, and a novel management option for these patients.

Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation.

OBJECTIVE: Low-velocity and nonlaminar flow patterns in the Fontan circulation, as well as abnormal liver function in some patients, may partly account for the coagulation abnormalities seen. We examined (1) coagulation factor abnormalities before and after the Fontan procedure and (2) regional coagulation factor abnormalities in the Fontan circulation. METHODS: Levels of factors V, VII, VIII, X, antithrombin III, prothrombin fragment F1+2, protein C, and protein S were measured in 2 groups of patients: In 14 patients undergoing the Fontan procedure, blood was analyzed before the operation and 5 days after the operation (group 1). The median age in this group was 3.2 years. In 10 patients who had undergone the Fontan procedure, cardiac catheterization was performed and samples were taken from the femoral vein, inferior vena cava, right atrium, and pulmonary artery (group 2). The median age in this group was 6.2 years and the median follow-up from the Fontan procedure was 4.1 years. RESULTS: In group 1 a significant increase was noted postoperatively in the concentration of factor VIII (P<.001), factor X (P<.001), and prothrombin fraction F1+2 (P <.001). A significant decrease in the levels of antithrombin III (P <.001), protein C (P<.004), and protein S (P<.02) was also found. The increase in factors VIII and X persisted at 4 years' follow-up in group 2 patients. In group 2, no significant regional differences were observed between the coagulation factors measured at different sites. CONCLUSIONS: There is an increased tendency toward coagulation after the Fontan procedure. A prothrombotic state is supported by thrombin generation associated with reduced antithrombin III concentration. This increase in coagulation may contribute to the early and late risks of thromboembolism observed after the Fontan procedure. We did not find any regional differences in coagulation abnormalities in patients late after the Fontan procedure. Therefore, the mechanisms and causes of the coagulation abnormalities remain unclear.

Twenty-five-year experience with rastelli repair for transposition of the great arteries.

OBJECTIVE: Our purpose was to describe the outcome of the Rastelli repair in D -transposition of the great arteries and to determine the risk factors associated with unfavorable events. METHODS: From March 1973 to April 1998, 101 patients with D -transposition of the great arteries and ventricular septal defect underwent a Rastelli type of repair. Median age and weight were 3.1 years (10th to 90th percentiles 0.3-9.9 years) and 12.8 kg (5.9-28.2). Pulmonary stenosis was present in 73 patients and pulmonary atresia in 18; 10 patients had no left ventricular outflow tract obstruction. RESULTS: There were 7 early deaths (7%) and no operative deaths in the last 7 years of the study. Risk factors for early death, by univariable analysis, included straddling tricuspid valve (P =.04) and longer aortic crossclamping times (P =.04). At a median follow-up of 8.5 years, there were 17 late deaths and 1 patient had undergone heart transplantation. Forty-four patients had reoperations for conduit stenosis, 11 for left ventricular outflow tract obstruction, and 28 had interventional catheterization to relieve conduit stenosis. Nine patients had late arrhythmias, and there were 5 sudden deaths. Overall freedom from death or transplantation (Kaplan-Meier) was 82%, 80%, 68%, and 52% at 5, 10, 15, and 20 years, respectively. Freedom from death or reintervention (catheterization or surgical treatment) was 53%, 24%, and 21% at 5, 10, and 15 years of follow-up, respectively. CONCLUSIONS: The Rastelli repair can be performed with low early mortality. However, substantial late morbidity and mortality are associated with conduit obstruction, left ventricular outflow tract obstruction, and arrhythmia.

Conversion of modified Fontan procedure to lateral atrial tunnel cavopulmonary anastomosis.

After modified Fontan procedures with atriopulmonary anastomoses or right atrium-right ventricle conduits, some patients have progressive exercise intolerance, effusions, arrhythmias, or protein-losing enteropathy. Theoretic advantages of a lateral atrial tunnel cavopulmonary anastomosis and published clinical results suggest that conversion of other Fontan procedures to the lateral atrial tunnel may afford clinical improvement for some patients. Eight patients (8 to 25 years old) with tricuspid atresia (n =4), double-inlet left ventricle (n = 3), and double-outlet right ventricle (n=1) underwent conversion to a lateral tunnel procedure between December 1990 and November 1994. An arbitrary clinical score was assigned before the lateral tunnel procedure and at follow-up. Before conversion, patients had decreased exercise tolerance (n = 8), arrhythmias (n = 6), effusions (n = 4), and protein-losing enteropathy (n = 8). At catheterization, all had a low cardiac index (1.9 +/- 0.7 L x min(-1) x M(-2), five had elevated pulmonary vascular resistance (>3 Wood units), and three had right pulmonary venous return obstruction by compression of an enlarged right atrium. Fenestrated lateral tunnel construction was undertaken 7.3 +/- 3.6 years after atriopulmonary anastomosis, with one early death related to low cardiac output. After the lateral tunnel procedure, two patients had no clinical improvement (no change in clinical score) but five patients had either marked or partial improvement. The right pulmonary vein compression present in three patients was resolved after conversion. The mean clinical scores improved from 4.5 +/- 1 to 3.0 +/- 2 (p < 0.04). In conclusion, conversion to a lateral tunnel procedure led to clinical improvement in five of eight patients at short-term follow-up and may be particularly indicated for patients with giant right atria or pulmonary vein compression who have symptoms. Pulmonary vein compression should be looked for in patients after modified Fontan procedures and can be relieved by conversion to the lateral tunnel procedure.

Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.

The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse.

Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank.

The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB). Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors. The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge. The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing. In contrast, language and visuospatial ability recovered to within the normal range. The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance. The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation. Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients.

Transcatheter intervention in the neonate with congenital heart disease.

Over the past 30 years, interventional cardiology has developed as a distinct subspecialty, playing a major role in the management of infants with CHD. In the neonatal period, a wide variety of transcatheter interventions are performed routinely, either as palliation or therapy, as adjunct to surgery, or in place of surgical intervention. Among these are creation or enlargement of ASDs to allow atrial mixing; balloon valvotomy to treat congenital valvar stenoses; balloon angioplasty or stenting of stenotic vessels (pulmonary arteries, coarctation of aorta, or systemic or pulmonary veins) or postoperative anastomoses; closure of [figure: see text] unwanted vessels (congenital fistulae or collaterals); and other miscellaneous interventions. A wide variety of patients are candidates for these procedures, including those with transposition of the great arteries or other defects with transposition physiology, left atrial outlet obstruction and hypertension, severe valvar pulmonary or aortic stenosis, hypoplastic stenotic pulmonary arteries with severe symptomatology, severe coarctation of aorta and high surgical risks, large aortopulmonary collaterals or other hemodynamically significant unwanted vessels, acute thrombosis of certain surgical anastomoses, and many more. In experienced hands, these procedures are highly successful and safe, with a low morbidity and mortality (less than 1%).

Alcohol, aggression and assertiveness in men: dosage and expectancy effects.

The effect of alcohol on aggression and assertiveness was examined in 54 men college students. A 2 (high vs low dosage expectancy) x 3 (0.0, 0.5 and 1.0 ml of 95% alcohol per kg of body weight) design was used. There was an increase in self-reported aggression at the moderate dosage but an increase only in profanity at the high dosage. The expectancy manipulation also produced an increase in self-reported aggression. Actual dosage and dosage expectancy did not influence assertiveness.

Brain injury online: accessing and using the Internet for consumers and healthcare professionals.

This article provides both consumers and healthcare professionals who share a common interest in brain injury with a basic overview of both how to access the Internet and how to use it effectively to gather and exchange online information. Recommendations regarding computer hardware requirements, connection options and popular software programs for web browsing, sending e-mail and searching topics are addressed. Some of the more interesting brain injury-related Internet sites and newsgroups are listed. Finally, specific technologic advancements that may facilitate computer use in a disabled population are discussed.

Return to work after brain injury: a self-directed approach.

For many, returning to work after a brain injury is an extremely difficult task. Many factors influence a person's decision whether or not to work. While some people with brain injury are excited to return to their old jobs, others are afraid of the physical, emotional, and financial consequences of returning to work, and some just do not want to work at all. The following manuscript provides a framework for persons with brain injury to address concerns regarding returning to work and alternatives to living productively. There are a number of ideas discussed within the framework of a self-guided therapeutic return to work program. Clinicians are encouraged to use the information provided to facilitate return to work discussions with their clients with brain injury and to adapt as necessary for use with persons with other neurological disabilities.

A multi-center investigation of neurobehavioral outcome after traumatic brain injury.

Outcome of 295 rehabilitation patients with mild, moderate, and severe brain injury was investigated prospectively at five regional medical centers using the Neurobehavioral Rating Scale. Mean factor scale scores were generally low. with the cognition mean highest and the excitement mean lowest. Regardless of scale, the most significant neurobehavioral difficulties were related to memory, insight, attention, alertness, fatigue, and blunted affect. Conversely, problems rated as least severe included hallucinations, guilt, excitement and lability of mood. Approximately 9% of the sample had at least a moderate problem with agitation, an item on the excitement scale. The general pattern of mean factor scale elevations was consistent with other studies. No relationship was found between injury severity and neurobehavioral characteristics. The relatively low incidence of neurobehavioral problems may reflect recovery and effective interdisciplinary management.

A longitudinal analysis of family needs following traumatic brain injury.

The present investigation assessed 38 family members' perceptions of unmet, partly met and met needs following the brain injury of a relative. Follow-up data was collected at two time intervals averaging 6 and 24 months post-injury. There was no significant difference between the proportion of needs rated as important or very important at time I or II. Highly ranked needs included requests for information, clear and honest explanations from professionals, reassurance, respite care, educational and social activities for the patient, emotional support, financial counseling, and advice about community resources. Relatives rated nearly half of the 40 needs as not met at either time. A significant difference was noted in the proportion of un met/partly met needs within each factor scale at time I and II. A larger number of Emotional Support and Involvement with Care needs were reported as not met at time II. Needs for Professional Support were more frequently reported as met at time II. For both time periods, Health information needs were generally perceived as met while needs relating to Instrumental Support were largely unmet. The findings are discussed in light of implications for treatment and long term adjustment to injury related changes.

Alcohol and drug use among young persons with traumatic brain injury.

The pre- and postinjury patterns of alcohol and illicit drug use of 87 persons with traumatic brain injury ages 16 to 20 were examined. Follow-up data were collected at two time intervals averaging 8 and 28 months postinjury. A comparison with large-sample studies revealed that patients had preinjury drinking patterns similar to those in the general population. A review of data provided evidence of a decline in alcohol use at initial follow-up; however, preinjury and second follow-up alcohol use patterns were similar. Analyses suggested that drinking quantity and frequency increased over time, perhaps eventually returning to postinjury levels. A review of the literature and the findings of the present investigation indicate that men and persons with a history of preinjury heavy drinking are at greatest risk for long-term alcohol abuse postinjury. Postinjury illicit drug use rates remained relatively low, falling below 10% at both follow-up intervals. Among persons taking prescribed medications, 17% reported moderate or heavy drinking at second follow-up.

Predictors of stress in adolescents: an exploratory study of pregnant and of parenting females.

PIP: A study of 152 adolescents enrolled in school-based programs for pregnant and parenting youth in Colorado in 1987-88 found no differences in overall stress levels between these two groups; however, salient predictors of stressful life events for pregnant teens were not the same as those for teen mothers. The mean age of study subjects was 16.5 years (range 14-19 years); most were living with a parent rather than the child's father. The dependent variable, level of stress, was measured through use of an abbreviated Life Events Questionnaire. Independent variables were assessed through administration of the Inventory of Social Supportive Behaviors, Rosenberg Self-Esteem Scale, and the Adolescent Coping Orientation for Problem Experiences scale. Of the 5 sources of stress measured (family, accidents, autonomy, deviance, relocation, and distress), only stress related to accidents differed significantly between pregnant and parenting adolescents. For pregnant adolescents, self-esteem was the only significant predictor of the overall level of stress; among parents, the only significant predictor was objective social support. Among adolescents, self-esteem was associated with more frequent use of social support and coping strategies. For parenting adolescents, self-esteem was correlated with the frequency of use of social support, satisfaction resulting from such use, and frequent use of coping strategies. Overall, the independent variables of social support, self-esteem, coping, and age were stronger predictors of stress in pregnant than in parenting adolescent females. This finding suggests that parenting teens may have successfully negotiated the multiple transitions involved in this new stage of the life-cycle. An important implication of this study is the need to design separate counseling components of school-based programs for pregnant versus parenting adolescents rather than to use a single curriculum.^ieng