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.

Accuracy of caring personnel in estimating water intake based on missing liquid in drinking vessels.

In this contribution a measurement regarding estimations of filling levels in drinking vessels is presented. Ensuring a sufficient hydration is an important task in nursing homes. Monitoring of fluid intake is normally achieved by visual examination of drinking vessels conducted by staff members. This contribution describes a measurement targeted at evaluating this method in order to analyze the requirements of technical aids. Data gained by conducting this measurement in a cooperating elderly people home is presented and analyzed. Key results are that residents drink on average 5 to 10 percent less than it is recorded and that estimations of especially partly filled vessels vary strongly. Both, the type of drinking vessel and the current filling level influence the accuracy and precision of the difference between estimation and actual missing liquid.

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas.

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plant Curcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl(2) treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.

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.

Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo.

Curcumin (diferuloylmethane) is the active ingredient of the spice plant Curcuma longa and has been shown to act anti-tumorigenic in different types of tumours. Therefore, we have studied its effect in pituitary tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 and somatotroph MtT/S rat pituitary cells as well as of corticotroph AtT20 mouse pituitary cells was inhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar. Fluorescence-activated cell sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reduction in cyclin D(1), cyclin-dependent kinase 4 and no change in p27(kip). FACS analysis with Annexin V-FITC/7-aminoactinomycin D staining demonstrated curcumin-induced early apoptosis after 3, 6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction of Bcl-2 and enhancement of cleaved caspase-3 further confirmed induction of apoptosis by curcumin. Growth of GH3 tumours in athymic nude mice was suppressed by curcumin in vivo. In endocrine pituitary tumour cell lines, GH, ACTH and prolactin production were inhibited by curcumin. Studies in 25 human pituitary adenoma cell cultures have confirmed the anti-tumorigenic and hormone-suppressive effects of curcumin. Altogether, the results described in this report suggest this natural compound as a good candidate for therapeutic use on pituitary tumours.

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.

Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients.

OBJECTIVE: Medical therapy with dopamine agonists (DA) is the primary treatment of choice in most patients with prolactinomas. 'Classical' surgical indications are intolerance or lack of efficiency of DA therapy. Focusing on a possible shift of recent indications, we retrospectively analyzed our results of surgical treatment in prolactinomas. PATIENTS AND METHODS: Between 1990 and 2005, we have operated on 212 consecutive patients with prolactinomas. Surgical indications were divided into 'classical' indications and 'modern' indications defined as cystic prolactinomas or patients with microprolactinomas who individually decided on a primary surgical treatment. RESULTS: Initial overall remission was accomplished in 53.2% including giant prolactinomas. However, in microadenomas, the remission rate was significantly higher with 91.3%. Overall remission at the latest follow-up was 42.7%, but 72.5% in intrasellar tumors, 80% in cystic prolactinomas, and 84.8% in microprolactinomas. The overall recurrence rate was 18.7%. Relapse of hyperprolactinemia in microprolactinomas was 7.1%. In our series, continually less patients were surgically treated for 'classical' indications. By contrast, the number of patients who individually decided on a primary surgical therapy has increased considerably. CONCLUSION: Remission rates after surgical treatment of prolactinomas remain excellent, particularly in microadenoma and intrasellar macroadenomas, whereas morbidity of transsphenoidal surgery is low in the hands of experienced pituitary surgeons. Our remission rates not only confirm the already interdisciplinarily accepted surgical indications, but also emphasize the value of primary transsphenoidal surgery as a discussion-worthy alternative to dopaminergic therapy in young patients with microprolactinomas or cystic tumors.

Alveolar rhabdomyosarcoma of the clivus with intrasellar expansion: Case report.

Rhabdomyosarcomas are common tumors of the head and neck region in children. However, a primarily intracranial localization of this tumor entity is rare. We report on a 3-year-old boy presenting with double vision due to left VI (th) nerve palsy. No other neurological deficits were recognized by clinical inspection. MRI scans visualized an enhancing mass lesion in the upper clivus compressing the cavernous sinus and the pituitary gland. Transsphenoidal biopsy was performed and histopathological examination as well as molecular diagnostics confirmed the diagnosis of an alveolar rhabdomyosarcoma (ARMS). Staging identified a metastatic lesion in the fourth thoracic vertebra resulting in the diagnosis of stage IV disease. Treatment modality included stereotactic radio- and chemotherapy.

Domains of a TBI minimal data set: community reintegration phase.

Efforts to establish a minimal data set for the period of community integration after traumatic brain injury (TBI) have been the focus of a working group of leading researchers, clinicians and advocates attending the Galveston Brain Injury Symposium in 2001 and 2002. The purpose of the data set is to increase the consistency and interpretability of TBI research and programme evaluation by providing a common set of measures to document key aspects of community integration. It is intended to be sensitive to intervention, comprehensive, reflect satisfaction and outcome and promote future treatment/therapy. In deciding on the components of a minimal data set, the tri-partite model of outcomes was adopted (initially employed in psychotherapy, adapted to TBI) which focuses on the needs of the individual, society and the health provider. Scales are recommended for the respective components of the model.

[Cemented total hip arthroplasty in Germany--an update]. / Zementierte Hüftendoprothetik in Deutschland -- ein Update.

AIM: The results of a national survey from 1998 had shown at the time that only around 10 % of orthopaedic surgeons in Germany had strictly implemented modern cementing techniques in total hip arthroplasty (THA). The same study was repeated 5 years later to evaluate the current situation and to determine whether modern cementing techniques have become more popular. METHODS: A detailed, slightly modified questionnaire regarding cement and bone preparation, cementing techniques on acetabulum and femur, and implant types was sent to 572 German orthopaedic and trauma hospitals, as well as to visiting surgeons with an interest in THA. In total, 293 questionnaires were available for evaluation and statistical analysis. RESULTS: Palacos bone cement remained the most widely used cement (> 90 %). The mixing times given varied significantly. Vacuum mixing systems had become more popular (67.9 %). In the femur 81.8 % of the surgeons attempted to preserve cancellous bone and 57.2 % used pulsatile lavage (jet-lavage). Retrograde cement application via a cement gun was done in 71.1 %. Cement restrictors were used in more than 95 %. Only two-thirds of the surgeons implemented sustained cement pressurisation and preferred a cement mantle thickness > 2mm (64 %). Only 16.9 % made multiple small acetabular keyholes and 48.6 % used jet-lavage. In 73.1 % no cement gun was used and in 68.3 % the cement was applied at high viscosity. Manual cement pressurisation was done in 58.1 %. The Muller straight stem device remained the most popular implant. For only 5 of the over 50 stem designs implanted have long-term results been published as yet. Only 10.6 % of surgeons/centres performed > 20 and almost 50 % implanted > 100 cemented THAs/year. CONCLUSION: The results of this survey demonstrated that, in comparison to 1998, the current state of cemented THA, in particular cementing technique has significantly improved. Future emphasis should be on continued surgeon education and training, as the operative, i. e., cementing techniques are of utmost importance for long-term success.

Functional outcomes and quality of life in patients with brain tumors: a preliminary report.

OBJECTIVES: To determine the relationship between functional outcome and quality of life (QOL) in patients with brain tumors receiving inpatient rehabilitation, and to assess the sensitivity of 4 assessment tools in measuring changes in that population. DESIGN: Prospective study using longitudinal data collected from consecutively admitted patients. SETTING: Acute inpatient rehabilitation unit. PARTICIPANTS: Ten patients with primary brain tumors admitted to an acute inpatient rehabilitation unit. INTERVENTIONS: Patients participated in an inpatient interdisciplinary rehabilitation program that used the following disciplines: occupational therapy, rehabilitation therapy, recreational therapy, speech therapy, physical therapy, rehabilitation nursing and case management. MAIN OUTCOME MEASURES: The FIM instrument, Disability Rating Scale (DRS), Karnofsky Performance Status Scale (KPS), Functional Assessment of Cancer Therapy-Brain (FACT-BR). RESULTS: Improvement in total functional outcome was indicated by all 3 functional measures (FIM: F = 46.84, p < .05; DRS: F = 19.25, p < .05; KPS: F = 10.11, p < .05). Significant improvements were found between admission and discharge scores for the FIM and DRS. The KPS revealed significant improvement between admission and 3-month follow-up scores. All admission and discharge functional scales (FIM, DRS, KPS) correlated significantly with each other. No significant change was noted in the FACT-BR between admission and discharge scores, but FACT-BR scores did improve at 1- and 3-months postdischarge relative to admission. The FIM, KPS, and DRS did not show significant correlation with the FACT-BR. Ninety percent of patients were initially discharged to a home environment. CONCLUSION: Although patients make functional gains during and after inpatient rehabilitation, gains in QOL are not significant until 1 month postdischarge. QOL does not appear to correlate well with functional outcomes. Further, the KPS is less sensitive than the FIM and DRS in detecting change in functional status.

Functional outcomes and quality of life in patients with brain tumours: a review of the literature.

OBJECTIVE: To review the literature with respect to functional outcomes and quality of life as it pertains to individuals with brain tumours. MAIN OUTCOMES: Most functional outcome papers have focused on acute inpatient rehabilitation. In general, patients with brain tumours have comparable rates of functional gains as other models of neurologic disability. Tumour type and concomitant treatment do not impact functional outcome. Functional independence may predict survivability in certain populations. Numerous instruments are used to measure the multiple facets of quality of life. Depression, anger and fatigue can impact both physical and psychological aspects of quality of life. The physical and functional aspects can vary depending on the tumour type. Treatment regimens can negatively impact quality of life. CONCLUSION: Brain tumour patients experience changes in function and quality of life during their disease course. Rehabilitation services may offer a unique opportunity to influence both functional outcome and more closely assess quality of life in these individuals.

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.

Healing response to the Clamshell device for closure of intracardiac defects in humans.

The healing response to intracardiac devices in humans is largely unknown. During regulatory trials using the Clamshell device in over 800 patients, attempts were made to perform histopathological evaluation of all explanted devices. We reviewed all those with complete histopathological examination (n = 12) from Fontan baffles (n = 4), ventricular septal defects (n = 2), and atrial septal defects (ASD; n = 6), explanted at 2.7 months to 3.6 years (median, 1.6 years), at autopsy (n = 1) or surgery (n = 11), performed for residual defects (n = 5), atrial masses (n = 3), or Fontan revision (n = 3). All but one were nearly (n = 3) or completely (n = 8) covered by pseudointima, composed of fibroelastic tissue, predominantly collagen, with focal foreign body reaction in contact with fabric, without acute inflammation or infection. Atrial masses of granulation tissue were present in three cases (ASD), opposite to protruding fractured arms. No associations were identified between coverage and closure status, position, arm fractures, or implant period. In conclusion, the healing response to transcatheter Clamshell implantation in humans is characterized by a relatively rapid development of a nonthrombotic pseudointima composed of fibroelastic tissue with minimal foreign body reaction. Cathet Cardiovasc Intervent 2001;54:101-111.

Dependency of cement mantle thickness on femoral stem design and centralizer.

Deficient cement mantles may be detrimental with regard to long-term outcome of cemented femoral stems. We performed a cadaver study on 48 left femora with 4 different stem designs (1 anatomic, 3 straight) to study the influence of stem design, centralizer, and femur type on cement mantle thickness. A radiographic and microradiograhic analysis was done. Overall, 88% of stems were aligned within 1 degrees of neutral in the frontal plane. In Gruen zones 1 through 7, we measured 24 thin cement mantles (<2 mm) in 19 specimens with no correlation to stem design or zone. In the sagittal plane, typical areas of thin cement mantles were identified in Gruen zones 8 and 9 (n = 39) and 12 (n = 21). The anatomic stem design carried the lowest risk (54%) of producing a thin cement mantle proximally in Gruen zones 8 and 9. The risk for straight stem designs was >90%. Straight stems without centralizer showed the highest risk of thin cement mantles in Gruen zone 12 (93%). Centralizers were efficient to prevent thin cement mantles in zone 12 but had no effect proximally. Lateral radiographs are essential to allow for adequate radiographic assessment of the cement mantle and stem alignment. There is a high risk of producing thin cement mantles in Gruen zones 8 and 9, in particular when straight stems are used. Posterior canal entry and low neck osteotomies are essential. Anatomic stems respect the anatomy, allow for more even cement mantles, minimize the risk of thin cement mantles without the use of centralizers, and may be considered in the femur with marked proximal bow.

Charges and lengths of stay for acute and inpatient rehabilitation treatment of traumatic brain injury 1990-1996.

This investigation evaluated yearly trends in charges and lengths of stay for patients with brain injury in acute care and rehabilitation settings over a 7 year period. Data was collected from 800 consecutive patients enrolled in four NIDRR Model Systems Traumatic Brain Injury programmes. Acute care daily charges showed almost routine increases, averaging nearly $550 per year. Conversely, lengths of stay generally showed a downward trend, with annual reductions averaging 2.25 days. Admission lengths of stay averaged 22-29 days between 1990-1994. Admissions averaged less than 20 days beginning in 1995, with the 1996 average of 16 days, nearly half that of the 1993 average. Between 1990-1996, average daily rehabilitation charges increased each year, with the rise averaging $83 or 7%. The rise in daily rehabilitation charges was offset by corresponding decreases in lengths of stay averaging 3.65 days or 8% annually. Increases in daily charges for brain injury rehabilitation care were roughly comparable to those for general medical care prices. However, the rate of change in acute care charges was substantially greater, with annual increases averaging 10% more than national medical care prices. The steady downward trend in lengths of stay raises serious concerns about the future availability of health care services to persons with brain injury.

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.

Long-term neuropsychological outcome after traumatic brain injury.

OBJECTIVE: To describe neuropsychological outcome 5 years after injury in persons with traumatic brain injury (TBI) who received inpatient medical rehabilitation. To determine the magnitude and pattern neuropsychological recovery from 1 year to 5 years after injury. DESIGN: Longitudinal cohort study with inclusion based on the availability of neuropsychological data at 1 year and 5 years after injury. SETTING: National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems of Care. PARTICIPANTS: One hundred eighty-two persons with complicated mild to severe traumatic brain injury. PRIMARY OUTCOME MEASURES: Digits Forward and Backward, Logical Memory I and II, Token Test, Controlled Oral Word Association Test, Symbol Digit Modalities Test, Trail Making Test, Rey Auditory Verbal Learning Test, Visual Form Discrimination, Block Design, Wisconsin Card Sorting Test, and Grooved Pegboard. RESULTS: Significant variability in outcome was found 5 years after TBI, ranging from no measurable impairment to severe impairment on neuropsychological tests. Improvement from 1 year after injury to 5 years was also variable. Using the Reliable Change Index, 22.2% improved, 15.2% declined, and 62.6% were unchanged on test measures. CONCLUSIONS: Neuropsychological recovery after TBI is not uniform across individuals and neuropsychological domains. For a subset of persons with moderate to severe TBI, neuropsychological recovery may continue several years after injury with substantial recovery. For other persons, measurable impairment remains 5 years after injury. Improvement was most apparent on measures of cognitive speed, visuoconstruction, and verbal memory.