Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: report of four cases and literature review

Silent corticotroph adenomas (SCA) are rare pituitary tumors with histologic hallmarks of corticotroph differentiation, including ACTH immunoreactivity, but lacking clinical evidence of Cushing's syndrome. We report on four female patients, aged 19-66 years, each presenting with a nonfunctional macroadenoma. Leading symptoms were headache in two cases and visual field deficits in one. One patient was incidentally diagnosed while undergoing cranial MRI for an unrelated condition. Three patients had marked obesity; none of them presented constitutional signs of Cushing's syndrome. Serum cortisol levels were moderately elevated in the two patients systematically tested in this respect. Marginal to moderate hyperprolactinemia was present in two cases. Two patients also were shown to be deficient in either gonadotroph or thyrotroph axis, while a third had a combined insufficiency of both gonadotroph and thyrotroph axis. MRI scans revealed intratumoral hemorrhage and/or cystic change in three cases, as well as tumor-related occlusive hydrocephalus in one. The latter patient was biopsied only, while the remaining underwent gross total resection. Histologically, all four lesions were diagnosed as SCA subtype I displaying intense immunoreactivity for ACTH. In three tumors, scattered cells coexpressed PRL as well. In addition, Crooke's hyaline change was noted in a significant number of tumor cells and in residual non-neoplastic corticotrophs in one case each. With MIB-1 labeling indices of 1-3%, none of the tumors qualified as atypical adenoma. We conclude that SCAs are more likely to be discovered as expansile tumors, whose advanced local space-occupying character at surgery rather than an inherently aggressive growth potential may negatively influence the clinical outcome. Subtle morphologic evidence of corticotroph suppression in residual pituitary adjacent to tumor lends further support to literature data indicating minimal or intermittent functional activity in this tumor type.

[Retinal abnormalities in adult acute myeloid leukemia: semeiological features and prognostic correlations. Analysis of 178 cases]

INTRODUCTION: Adult patients with acute myeloid leukemia (AML) frequently present retinal abnormalities. We tried to find a relationship between fundus lesions and treatment responsiveness, prognosis, and several hematologic parameters. PATIENTS AND METHODS: We examined 178 adult patients with newly diagnosed AML. All patients were assigned to two groups regarding retinal parameters (1 or 2) and age (A or B). Group 1 included cases with retinal dysfunction classified as retinal abnormalities with impaired visual acuity; group 2 included cases with no or only minor retinal changes. Subgroup A included patients younger than 60 years (n=97), subgroup B patients older than 60 years (n=81). RESULTS: In this study, higher age and a lower Hb value were associated with retinal findings (group 1). Among the younger patients (subgroup A), 78% of those with complete remission had no retinal findings (group 2) compared to 18% of the nonresponders. In the elderly population (subgroup B), this ratio was 58% versus 19%. In the younger patients (subgroup A), the mean overall survival was 50 months if they had no retinal abnormalities (group 2) and 7 months in the case of retinal changes (group 1). In the older population (subgroup B), the ratio was 15 months versus 3 months, respectively. CONCLUSION: Retinal abnormalities in AML are generally associated with higher age, although they correlate with a shorter survival in both age groups. This association is stronger in younger patients.

Long-range correlations in rectal temperature fluctuations of healthy infants during maturation

BACKGROUND: Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (T(rec)) patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS: We measured T(rec) fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, alpha using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that T(rec) fluctuations exhibit fractal long-range correlations with a mean (SD) alpha of 1.51 (0.11), indicating that T(rec) is regulated in a highly correlated and hence deterministic manner. A significant increase in alpha with age from 1.42 (0.07) at 4 weeks to 1.58 (0.04) at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. alpha was not associated with mean room temperature or influenced by immunization CONCLUSIONS: This study shows that the quantification of long-range correlations using alpha derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time T(rec) pattern in young infants, reflective of maturation of the autonomic system. Detrended fluctuation analysis may prove useful for characterizing thermoregulation in premature and other infants at risk for life-threatening events.

Improving Management of Distributed Services Using Correlations and Predictions in SLA-Driven Cloud Computing Systems

Recent advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing environmental conditions and number of users, application performance might suffer, leading to Service Level Agreement (SLA) violations and inefficient use of hardware resources. We introduce a system for controlling the complexity of scaling applications composed of multiple services using mechanisms based on fulfillment of SLAs. We present how service monitoring information can be used in conjunction with service level objectives, predictions, and correlations between performance indicators for optimizing the allocation of services belonging to distributed applications. We validate our models using experiments and simulations involving a distributed enterprise information system. We show how discovering correlations between application performance indicators can be used as a basis for creating refined service level objectives, which can then be used for scaling the application and improving the overall application's performance under similar conditions.

Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease

The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.