Coordination of hypothalamic and pituitary T3 production regulates TSH expression

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.     

severe disease complicated by osteoporosis

In this illustrative case, rheumatoid disease changed an active, self-supporting woman into a disabled, dependent and depressed person. When disease activity is continuous, early efforts to prevent severe deformity take on great urgency. It is also important to alleviate the psychosocial impact of the disease, which may well be more than even a highly motivated patient can handle alone.     

Statin-Associated Polymyositis Following Omeprazole Treatment

Statins are an extensively used class of drugs, and myopathy is an uncommon, but well-described side effect of statin therapy. Inflammatory myopathies, including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy, are even more rare, but debilitating, side effects of statin therapy that are characterized by the persistence of symptoms even after discontinuation of the drug. It is important to differentiate statin-associated inflammatory myopathies from other self-limited myopathies, as the disease often requires multiple immunosuppressive therapies. Drug interactions increase the risk of statin-associated toxic myopathy, but no risk factors for statin-associated inflammatory myopathies have been established. Here we describe the case of a man, age 59 years, who had been treated with a combination of atorvastatin and gemfibrozil for approximately 5 years and developed polymyositis after treatment with omeprazole for 7 months. Symptoms did not resolve after discontinuation of the atorvastatin, gemfibrozil, and omeprazole. The patient was treated with prednisone and methotrexate followed by intravenous immunoglobulin, which resulted in normalization of creatinine kinase levels and resolution of symptoms after 14 weeks. It is unclear if polymyositis was triggered by interaction of the statin with omeprazole and/or gemfibrozil, or if it developed secondary to long-term use of atorvastatin only.     

Anterior cruciate ligament reconstruction affects proprioception in the cat's knee

To study the cat's knee after anterior cruciate ligament reconstruction, we compared its neural and muscular activity with that in the normal and the unstable knee. We recorded the electric activity in the articular nerves (posterior -PAN and medial -MAN) and periarticular muscles (quadriceps and hamstring) while performing passive flexion, extension, external and internal rotation, and also anterior translation of the tibia at 30° and 90° of flexion. The same series of maneuvers was performed in the same knees after surgical section of the anterior cruciate ligament and then after anterior cruciate reconstruction. The electric activity recorded in the reconstructed knee was compared to that in the same knee before surgery and in the same unstable knee after anterior cruciate section. We observed that the reconstructed knee, compared to the injured knee, showed a decrease in articular nerves and quadriceps activity while it regained stability. This decrease converged to the recordings in the normal knee. However, differences in MAN, PAN and hamstring activity were still present in the reconstructed knee. This suggests that, although anterior cruciate reconstruction seems beneficial for restoring articular nerve and periarticular muscle activities to a certain degree, proprioception in the reconstructed knee does not match that in the normal knee.     

Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research

Oriol R, Candelier J‐J, Taniguchi S, Balanzino L, Peters L, Niekrasz M, Hammer C, Cooper DKC. Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research. Xenotransplantation 1999; 6: 79‐89. ©Munksgaard, Copenhagen.
Abstract: we investigated the main glycotopes expressed on the tissues of 44 animal species, including primates, nonprimate mammals, marsupials, birds, and a reptile. Paraffin‐embedded tissue sections of kidney, heart, liver, pancreas, lung, brain and intestine of 24 domestic animal species were stained with seven fluorescent‐labeled lectins. Testis sections of 20 African wild animal species were tested with the same lectins. Overall, three main immunofluorescence patterns were found in the vascular compartment. First, humans and Old World monkeys express genetically polymorphic ABH antigens and do not express αGal. Second, New World monkeys, other mammals, and marsupials do not express ABH antigens, but have large amounts of a genetically monomorphic αGal. Third, birds and reptiles do not express either ABH or αGal, but have monomorphic βGal, probably different from the lactosamine precursor of ABH and αGal. Epithelial cells producing exocrine secretions also expressed carbohydrate epitopes. The fluorescence patterns of the cells of the exocrine compartment are similar, but not identical, to those expressed in the vascular compartment. All the animals tested have some ABH and βGal in exocrine tissues, but New World monkeys and lower mammals are the only ones expressing αGal in exocrine tissues.     

Extended pericranial flap and bone graft reconstruction in anterior skull base surgery.

OBJECTIVES: The objectives of this study was to establish a rationale for repairing large anterior skull base defects with an extended pericranial flap and split calvarial bone graft; to define large anterior skull base defects as those spanning the anterior cranial measuring at least 3.0 x 4.0 cm; and to describe the surgical technique and compare it with alternative strategies.Study design Thirty-four patients underwent anterior craniofacial resection of anterior skull-based tumors of varying histology with reconstruction using an extended pericranial flap and split calvarial bone graft. RESULTS: The survival of the pericranial flap and bone graft was maintained in 33 of 34 patients. There was 1 episode of postoperative cerebrospinal fluid leak, 1 episode of osteomyelitis of the bone graft and an epidural abscess, and 1 episode of asymptomatic pneumocephalus. CONCLUSION: Split calvarial bone graft with an extended pericranial flap is an effective technique for reconstructing large anterior skull base defects.     

Renal Disease in Colombia

Chronic renal disease represents a problem of public health in Colombia. Its prevalence has increased in last decade, with a prevalence of 44.7 patients per million (ppm) in 1993 to 294.6 ppm in 2004, considering that only 56.2% of the population has access to the health. This increase complies with the implementation of Law 100 of 1993, offering greater coverage of health services to the Colombian population. The cost of these pathologies is equivalent to the 2.49% of the budget for health of the nation. The three most common causes of renal failure are diabetes mellitus (DM; 30%), arterial hypertension (30%), and glomerulonephritis (7.85%). In incident patients, the DM accounts for 32.9%. The rate of global mortality is 15.8%, 17.4% in hemodialysis and 15.1% in peritoneal dialysis. In 2004, 467 renal transplants were made, 381 of decease donor with an incidence of 10.3 ppm.

The excessive cost of these pathologies can cause the nation's health care system to collapse if preventative steps are not taken. In December of 2004, the Colombian Association of Nephrology with the participation of the Latin American Society of Nephrology and Arterial Hypertension wrote the “Declaration of Bogotá,” committing the state's scientific societies and promotional health companies to develop a model of attention for renal health that, in addition to implementing national registries, continues to manage renal disease.     

Mental and Physical Health Consequences of the September 11, 2001 (9/11) Attacks in Primary Care: A Longitudinal Study

The magnitude of the September 11, 2001 (9/11) attacks was without precedent in the United States, but long‐term longitudinal research on its health consequences for primary care patients is limited. We assessed the prevalence and exposure‐related determinants of mental disorders, functioning, general medical conditions, and service utilization, 1 and 4 years after the 9/11 attacks, in an urban primary care cohort (N = 444) in Manhattan. Although the prevalence of posttraumatic stress disorder (PTSD) and levels of functional impairment declined over time, a substantial increase in suicidal ideation and missed work was observed. Most medical outcomes and service utilization indicators demonstrated a short‐term increase after the 9/11 attacks (mean change of +20.3%), followed by a minor decrease in the subsequent year (mean change of ?3.2%). Loss of a close person was associated with the highest risk for poor mental health and functional status over time. These findings highlight the importance of longitudinal assessments of mental, functional, and medical outcomes in urban populations exposed to mass trauma and terrorism.     

Perceived Social Support in Spanish Cancer Outpatients with Psychiatric Disorder

This study examines differences in perceived social support during oncology treatment of cancer patients, whilst taking into account the presence of psychiatric disorder. Of particular interest were cancer patients who received psychopharmacology treatment compared with those who did not. A total of 760 cancer outpatients were recruited from one hospital in Spain. Multivariate analysis of variance with the general linear model procedure was used. The Medical Outcomes Study Social Support Survey was used to assess social support perceived. The Diagnostic Interview Schedule using DSM‐III‐R criteria was utilized for the diagnosis of psychiatric disorders. There were significant differences between the patients diagnosed with a psychiatric disorder and those not diagnosed with psychiatric disorders in terms of perceived Emotional/Informational Support (F = 19.11, p < 0.01), Affectionate Support (F = 12.30, p < 0.01) and the Overall Support Index (F = 16.73, p < 0.01). In patients requiring psychopharmacology treatment, significant differences were presented with Structural Support (F = 4.32, p < 0.05), Emotional/Informational Support perceived (F = 7.87, p < 0.01), Instrumental Support (F = 4.17, p < 0.05) and Overall Support Index (F = 7.84, p < 0.01). Psychopharmacology treatment helped to increase the perception of social support received by the patient. Healthcare professionals could provide support that would normalize cancer patients' distress, taking into account the importance of perceived social support for the psychological well‐being of patients. Copyright © 2013 John Wiley & Sons, Ltd.     

Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer

Background

Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease.

Objective

To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management.

Design, setting, and participants

From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D’Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP).

Outcome measurements and statistical analysis

Complications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed.

Results and limitations

This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61–73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5–8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43 g (IQR: 33–55). The median International Prostate Symptom Score was 6 (IQR: 3–10), and the median International Index of Erectile Function score was 20 (IQR: 15–23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2–5.1, 1.1–4.7, and 1–4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications.

Conclusions

FT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications.