Citations

Abstract Background: Healthy older men have reduced testosterone (Te) production and frequent, small irregular LH pulses. Which is cause and which is effect are not known. Rationale: In model systems, frequent and irregular LH pulses reflect attenuated feedback inhibition by Te. Hypothesis: Factors associated with aging impair negative feedback by Te. Subjects and Setting: Healthy men at an academic medical center were studied. Methods: The study used quantification of the regularity of LH release patterns during blockade of gonadal steroidogenesis and graded transdermal Te addback in 18 healthy men aged 18–65 yr. Results: In the cohort as a whole, stepwise Te repletion repressed LH concentrations (P = 0.001) and enhanced the quantifiable orderliness of LH release patterns (P < 0.001). By regression analysis, age attenuated the capability of increasing Te concentrations to regularize LH secretion patterns (P = 0.019). However, after a fixed GnRH stimulus, the effect of Te on LH regularity was invariant of the age factor (P = 0.16), thus pointing to a hypothalamic locus of impaired Te feedback. Summary: Aging disrupts the capability of systemic Te concentrations to maintain orderly LH secretion under endogenous, but not exogenous, GnRH drive. Conclusions: Age or factors associated with increased age reduce negative feedback by any given total Te concentration on hypothalamopituitary GnRH-LH outflow, thus contributing to disorderly LH secretion.

Abstract Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease.

Background Congenital hyposensitivity to pain or hereditary sensory and autonomic neuropathy represents a variety of disorders characterized by decreased perception of nociception, loss of other modalities of sensation, and variable expression of autonomic dysfunction. Sensory loss, especially that of pain, is associated with self-mutilations that may require frequent operations. Little is known about the safety of anesthesia for these patients. Methods The authors performed a computerized search of the Mayo Clinic medical records database between January 1996 and November 2005 for patients with congenital hyposensitivity to pain and related disorders who underwent general anesthesia. Medical records were reviewed for demographics, anesthetic techniques and agents, use of opioids, and perioperative complications. In addition, the authors conducted a comprehensive review of the literature to summarize the current knowledge regarding anesthesia for patients with congenital hyposensitivity to pain, and compared it with the patients with hyposensitivity to pain identified at the Mayo Clinic. Results The authors identified seven patients with hereditary sensory and autonomic neuropathy II, IV, or V and undefined variants of congenital pain hyposensitivity who generated 17 anesthesia records: 12 for orthopedic operations, 3 for sural nerve biopsies, and 2 for ophthalmologic procedures. In all patients, standard doses of volatile agents were used during anesthesia. Small amounts of opioids were used during the course of eight operations. Most patients experienced mild hypothermia (lowest temperature 34.7 degrees C), and none experienced hyperthermia. All patients were hemodynamically stable during otherwise uneventful anesthesia. During recovery from anesthesia, opioids were given to only one patient, a single dose of 1 mg morphine. Even after major orthopedic operations, the patient did not require additional analgesia. Conclusions The patients with profound congenital hyposensitivity to pain underwent anesthesia without any adverse events. The authors found that despite reduced pain perception, the requirements for volatile anesthetics were within the expected range for population with normal pain perception, but they did not require opioids postoperatively. Intraoperative mild hypothermia was easily managed by adjustment of environmental temperature.

Summary Nine fresh frozen cadaveric shoulders were used to examine the changes in intraarticular pressure (IAP) of the shoulder joint and the position of the humeral head under various loads to determine the relationship between these parameters. All the soft tissues superficial to the rotator cuff were removed. The position of the humerus relative to the scapula was monitored using an electromagnetic tracking system before and after venting the capsule with 0, 0.5, and 1.0 kg of load applied to the humerus inferiorly in addition to the weight of the arm. Simultaneously, the IAP was monitored using a pressure transducer before venting the capsule. Venting had a significant effect on the position of the humeral head: the positions of the head after venting were significantly lowered in all loading conditions. The average IAP was −76 cm H 2 O without load, and the value decreased in a linear fashion with increased load; the correlations were significant in four of six shoulders without dislocation. The correlations were less significant between the pressure and the position, and there were no significant correlations between the load and the position. IAP, which is determined primarily by the load applied, is important to stabilize the shoulder inferiorly. Because IAP is intimately related to the external load and the response is specific to individuals, examination of IAP response to external load may be helpful in characterizing various instabilities of the shoulder.

Abstract Synovectomy is an effective procedure in many of the synovial proliferative diseases. It is the treatment of choice in pigmented villonodular synovitis and synovial chondromatosis. In addition, it may be a useful adjunct to treatment in carefully selected patients with rheumatoid arthritis and hemophilia. Synovectomy can now be accomplished effectively with arthroscopic techniques, and this has greatly diminished the previous morbidity and cost associated with open synovectomy. However, the indications for synovectomy remain the same, regardless of the technique.

Abstract The proper treatment of synovial proliferative disorders depends on an accurate diagnosis and a knowledge of the natural history of these afflictions. A simple classification of the major synovial disorders with a brief general description of each, highlighting the prominent clinical features, is helpful. A thorough history and physical examination should enable the clinician to categorize the nature of the synovial disorder. Further evaluation and consultation can then be directed within the appropriate category. Radiologic, laboratory, and microscopic studies aid in arriving at a definitive diagnosis. Once a diagnosis has been established, therapy or further evaluation can be instituted.