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1.
Obes Rev ; 16(3): 234-47, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25588316

ABSTRACT

Body weight is determined via both metabolic and hedonic mechanisms. Metabolic regulation of body weight centres around the 'body weight set point', which is programmed by energy balance circuitry in the hypothalamus and other specific brain regions. The metabolic body weight set point has a genetic basis, but exposure to an obesogenic environment may elicit allostatic responses and upward drift of the set point, leading to a higher maintained body weight. However, an elevated steady-state body weight may also be achieved without an alteration of the metabolic set point, via sustained hedonic over-eating, which is governed by the reward system of the brain and can override homeostatic metabolic signals. While hedonic signals are potent influences in determining food intake, metabolic regulation involves the active control of both food intake and energy expenditure. When overweight is due to elevation of the metabolic set point ('metabolic obesity'), energy expenditure theoretically falls onto the standard energy-mass regression line. In contrast, when a steady-state weight is above the metabolic set point due to hedonic over-eating ('hedonic obesity'), a persistent compensatory increase in energy expenditure per unit metabolic mass may be demonstrable. Recognition of the two types of obesity may lead to more effective treatment and prevention of obesity.


Subject(s)
Body Weight , Hypothalamus/metabolism , Neural Pathways/metabolism , Obesity/metabolism , Appetite Regulation/physiology , Body Weight/physiology , Eating/physiology , Energy Metabolism/physiology , Homeostasis/physiology , Humans , Hypothalamus/physiopathology , Obesity/classification , Obesity/physiopathology , Reward
2.
Minerva Endocrinol ; 39(4): 261-73, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25078028

ABSTRACT

Hyperglycemia is common in critical illness and leads to increased morbidity and mortality. Controversy exists whether tight glycemic control via intensive insulin therapy can safely and effectively improve outcomes. In this review article, we will sort through the pertinent evidence base to identify salient, yet emergent, paradigms to guide management. To this end, we will discuss underlying biologic mechanisms relevant to hyperglycemia and insulinization in critical illness, summarize results of major randomized controlled clinical trials for glycemic control in the intensive care unit (ICU), and fill in the gaps with necessary information. We will conclude with specific messages, not only reflecting our own clinical experiences, but amenable to implementation in different ICU settings.


Subject(s)
Blood Glucose/analysis , Critical Care/methods , Critical Illness , Disease Management , Hyperglycemia/drug therapy , Hypoglycemia/prevention & control , Adaptation, Physiological , Clinical Protocols , Critical Care/economics , Diabetes Complications/blood , Diabetes Complications/physiopathology , Dyslipidemias/drug therapy , Dyslipidemias/etiology , Humans , Hyperglycemia/economics , Hyperglycemia/etiology , Hyperglycemia/physiopathology , Hyperglycemia/prevention & control , Hypoglycemia/etiology , Insulin/adverse effects , Insulin/pharmacology , Insulin/therapeutic use , Intensive Care Units , Medicare/economics , Multicenter Studies as Topic , Nutritional Support , Oxidative Stress/drug effects , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Stress, Physiological/physiology , United States
3.
Curr Med Chem ; 21(9): 1146-51, 2014.
Article in English | MEDLINE | ID: mdl-24304280

ABSTRACT

Reprogramming technologies have been developed to revert somatic differentiated cells into pluripotent stem cells that can be differentiated into different lineages potentially useful in stem cell therapy. Reprogramming methods have been progressively refined to increase their efficiency, to obtain a cell population suitable for differentiation, and to eliminate viral plasmid which could be responsible for many unwanted side-effects when used in personalized medicine. All these methods are aimed to introduce into the cell genes or mRNAs encoding a set of four transcription factors (OCT- 4, SOX-2, KLF-4 and c-MYC) or a set of three lincRNAs (large intragenic non-coding RNAs) acting downstream of the reprogramming transcription factors OCT-4, SOX-2 and NANOG. Translational clinical applications in human pathologies and in developmental, repair and cancer biology have been numerous. Cancer cells can be, at least in principle, reprogrammed into a normal phenotype. This is a recently raised issue, rapidly advancing in many human tumors, especially endocrine-related cancers, such as breast, prostate and ovarian ca. The present review aims to describe basic phenomena observed in reprogramming tumor cells and solid tumors and to discuss their meaning in human hormone-related cancers. We will also discuss the fact that some of the targeted transcription factors are "normally" activated in a number of physiological processes, such as morphogenesis, hypoxia and wound healing, suggesting an in vivo role of reprogramming for development and homeostasis. Finally, we will review concerns and warnings raised for in vivo reprogramming of human tumors and for the use of induced pluripotent stem cells (iPSCs) in human therapy.


Subject(s)
Cellular Reprogramming , Endocrine System , Neoplasms/metabolism , Animals , Cell Differentiation , Humans , Neoplasms/pathology , Neoplastic Stem Cells/metabolism
4.
Aliment Pharmacol Ther ; 30(10): 1078-86, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19735230

ABSTRACT

BACKGROUND: Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. AIM: To assess the effectiveness of a corticosteroid withdrawal method. METHODS: Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29-75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. RESULTS: Median durations for disease and corticosteroid dependency were 21 (range 3-45) and 14 (range 2-45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5-73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). CONCLUSIONS: Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Dexamethasone/therapeutic use , Inflammatory Bowel Diseases/complications , Substance Withdrawal Syndrome/drug therapy , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Female , Humans , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged , Retrospective Studies , Substance-Related Disorders , Time Factors , Treatment Outcome
5.
Biomed Pharmacother ; 60(8): 393-5, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16905290

ABSTRACT

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved performance and implementation of guidelines.


Subject(s)
Guideline Adherence , Practice Guidelines as Topic , Thyroid Nodule/diagnosis , Biopsy, Fine-Needle/statistics & numerical data , Cost-Benefit Analysis , Humans , Radionuclide Imaging , Thyroid Gland/diagnostic imaging , Thyroid Gland/pathology , Thyroid Nodule/pathology , Thyrotropin/blood , Ultrasonography
6.
Biomed Pharmacother ; 60(8): 396-404, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16904860

ABSTRACT

The preoperative evaluation of thyroid nodules currently relies on a clinical assessment of risk factors and an algorithm based on imprecise tests. With serum TSH, thyroid ultrasound and fine-needle aspiration (FNA) with or without ultrasound guide, accounting for the routine initial evaluation, indeterminate aspirates remain the major obstacle for confidently advising patients whether to have surgery or not. Recent clinical guidelines have attempted to settle various controversies but many inherent errors of clinical testing result in delayed diagnosis and unnecessary surgery. A better solution may ultimately involve the use of molecular markers of thyroid carcinogenesis but further research is still needed regarding the basic biology of thyroid cancer.


Subject(s)
Practice Guidelines as Topic , Preoperative Care/methods , Thyroid Nodule/diagnosis , Biopsy, Fine-Needle , Humans , Molecular Diagnostic Techniques , Risk Factors , Thyroid Gland/diagnostic imaging , Thyroid Gland/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Nodule/pathology , Thyrotropin/blood , Ultrasonography
7.
Arch Otolaryngol Head Neck Surg ; 127(7): 821-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11448357

ABSTRACT

OBJECTIVE: To examine the role of intraoperative rapid parathyroid hormone (PTH) monitoring in the surgical management of hyperparathyroidism. DESIGN: Thirty-eight-month retrospective review. SETTING: Tertiary care academic medical center. PATIENTS: One hundred consecutive patients undergoing surgery for primary hyperparathyroidism. INTERVENTION: All patients underwent preoperative technetium Tc 99m sestamibi scan localization and intraoperative blood PTH monitoring by means of a rapid (12-minute) immunochemiluminometric assay. MAIN OUTCOME MEASURES: The influence of intraoperative PTH levels on extent of surgical dissection and achievement of postoperative normocalcemia. RESULTS: Intraoperative PTH levels dropped an average of 64%, 75%, and 83% at 5, 10, and 20 minutes, respectively, after excision of all hyperfunctioning parathyroid tissue. A PTH decrease of 46% or more at 10 minutes and 59% or more at 20 minutes after excision of hyperfunctioning tissue was predictive of postoperative normocalcemia. In 79 patients (79%), the sestamibi scan provided accurate preoperative localization; all but 1 of these patients were treated successfully, most often with a limited, gland-specific dissection. In 24 patients with inaccurate, negative, or misleading preoperative sestamibi scans, 23 (96%) were treated successfully with the use of the intraoperative PTH assay. CONCLUSIONS: The rapid intraoperative PTH assay accurately predicts postoperative success in patients with primary hyperparathyroidism. The rapid PTH assay allows for greater confidence in performing limited dissections in well-localized uniglandular disease. In cases of inaccurate preoperative localization, the rapid PTH assay directly affects surgical decision making and provides greater confidence in determining when surgical success has been achieved.


Subject(s)
Hyperparathyroidism/surgery , Monitoring, Intraoperative , Parathyroid Hormone/blood , Parathyroidectomy , Adult , Aged , Aged, 80 and over , Calcium/blood , Female , Humans , Hyperparathyroidism/blood , Hyperparathyroidism/diagnostic imaging , Male , Middle Aged , Postoperative Complications/blood , Predictive Value of Tests , Radionuclide Imaging , Recurrence , Reoperation , Retrospective Studies , Technetium Tc 99m Sestamibi , Treatment Outcome
8.
Otolaryngol Head Neck Surg ; 124(5): 531-6, 2001 May.
Article in English | MEDLINE | ID: mdl-11337658

ABSTRACT

OBJECTIVE: To assess the diagnostic accuracy of fine-needle aspiration (FNA) and frozen section (FS) in nodular thyroid disease. SETTING: Tertiary care academic medical center. STUDY DESIGN: Retrospective review of 139 consecutive patients undergoing surgery for nodular thyroid disease. FNA and FS sensitivity, specificity, and accuracy were calculated with respect to permanent section histology. RESULTS: Among 63 patients with an FNA interpreted as either benign (n = 38) or malignant (n = 25), FNA was accurate (sensitivity 89%, specificity 97%, accuracy 94%). FS identified only one case of carcinoma missed by FNA. Among 76 patients with a "suspicious" FNA, FS was reasonably accurate (sensitivity 67%, specificity 100%, accuracy 89%), but was deferred in 50% of cases. CONCLUSION: Given high FNA accuracy, more selective use of FS is suggested. SIGNIFICANCE: The study results will assist with intra-institutional patient counseling and intraoperative decision-making with respect to FNA and FS results in patients with nodular thyroid disease.


Subject(s)
Frozen Sections , Thyroid Neoplasms/pathology , Thyroid Nodule/pathology , Adenoma/pathology , Adenoma/surgery , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Carcinoma, Papillary, Follicular/pathology , Carcinoma, Papillary, Follicular/surgery , Female , Humans , Intraoperative Period , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Thyroid Neoplasms/surgery , Thyroid Nodule/surgery , Thyroidectomy
9.
Clin Nucl Med ; 26(5): 412-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11317021

ABSTRACT

PURPOSE: The authors have often observed on Tl-201 and Tc-99m sestamibi (MIBI) scans in patients with thyroid cancer a small focus of increased uptake in the right midparasternal region (focus A) or sometimes in the lower mid chest at the level of the lower sternum (focus B) just inferomedial to focus A. The objective of this study was to assess the frequency of this finding on Tl-201 MIBI studies, to assess the incidence of true pathologic lesions corresponding to these foci, and to identify their nature. MATERIALS AND METHODS: One hundred ten whole body Tl-201 studies using 4 mCi (148 MBq) and 84 MIBI studies using 20 mCi (740 MBq: first-pass, planar, and SPECT images) were reviewed. The appearance of either focus A or focus B on three orthogonal SPECT images was correlated with an atlas of cross-sectional anatomy and computed tomography. If focus A was seen on the immediate static image (obtained at the end of the first-pass acquisition without moving the patient), this image was coregistered with a selected image from the first-pass study showing the superior vena cava and also with another selected image showing the ascending aorta. RESULTS: Focus A was seen in 40% of Tl-201 scans and in 49% of MIBI scans, whereas focus B was seen in 20% of Tl-201 scans and 39% of MIBI scans. On correlation of the SPECT images with a cross-sectional anatomy atlas, focus A and focus B invariably corresponded to the superior portion of the right auricle and basal superoanterior right ventricular wall, respectively. These myocardial regions are prominent and sometimes appear as discrete foci because they are considerably thicker than other parts of the right atrial and right ventricular muscle, respectively, and because they are seen partly end-on in the anterior projection. CONCLUSIONS: The superior portion of the right auricle and basal superoanterior right ventricular myocardium often appear as isolated foci on whole-body Tl-201 and MIBl scans. Neither focus should be interpreted as a metastatic lesion in patients with possible cancer or as an ectopic parathyroid adenoma in patients with hyperparathyroid disease.


Subject(s)
Heart Atria/diagnostic imaging , Heart Ventricles/diagnostic imaging , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Thallium Radioisotopes , Thyroid Neoplasms/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Thyroid Neoplasms/pathology , Whole-Body Counting
10.
J Spinal Cord Med ; 24(4): 235-40, 2001.
Article in English | MEDLINE | ID: mdl-11944781

ABSTRACT

OBJECTIVE: To determine the biochemical effects of combined calcitriol-pamidronate therapy on bone hyperresorption in patients with spinal cord injury (SCI). METHODS: This was a retrospective study of 21 SCI inpatients (4 women and 17 men, mean age 34 years) treated for bone hyperresorption. Initial treatment was 0.5 microg oral calcitriol once daily and 1,250 mg CaCO3 twice a day (1000 mg elemental calcium/day). On days 4 through 6 following the initial treatment, patients received 30 mg pamidronate intravenously once daily (total of 3 doses). Urinary N-telopeptide (NTx) and calcium excretion rates, and serum parathyroid hormone (PTH), 25-hydroxyvitamin D (25-D), 1,25-dihydroxyvitamin D (1,25-D), calcium, and phosphorus levels were measured within 2 weeks prior to and 2 weeks following pamidronate therapy. RESULTS: Patients demonstrated increased urinary NTx and calcium excretion, indicative of bone hyperresorption, and suppressed PTH and 1,25-D levels as early as 9 days post-SCI. Combined calcitriol-pamidronate therapy decreased urinary NTx and calcium excretion by 71% (P < .001) and 73% (P < .001), respectively. This therapy also increased serum levels of PTH (P <.05) and 1,25-D (P < .005). Post-pamidronate hypocalcemia or hypophosphatemia was observed in 44% (P < .01) or 53% (P < .01), respectively. CONCLUSION: Combined calcitriol-pamidronate therapy significantly inhibited bone hyperresorption in SCI patients.


Subject(s)
Bone Remodeling/drug effects , Bone Resorption/drug therapy , Calcitriol/administration & dosage , Diphosphonates/administration & dosage , Spinal Cord Injuries/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Bone Resorption/urine , Calcitriol/adverse effects , Calcium/urine , Calcium Carbonate/administration & dosage , Calcium Carbonate/adverse effects , Collagen/urine , Collagen Type I , Diphosphonates/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Pamidronate , Peptides/urine , Spinal Cord Injuries/urine
12.
Chest ; 118(3): 761-6, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10988200

ABSTRACT

STUDY OBJECTIVE: The chronically critically ill (CCI) are a subgroup of critically ill patients who have survived an acute critical illness but remain profoundly debilitated and ventilator dependent. We have previously shown that CCI patients have a very high prevalence of bone hyperresorption. The objective of this present study was to determine the biochemical response of bone hyperresorption in CCI patients to treatment with either calcitriol alone or calcitriol and pamidronate. DESIGN: Retrospective survey. SETTING: Respiratory care step-down unit (RCU) at a tertiary-care teaching hospital. PATIENTS: Fifty-five ventilator-dependent CCI patients transferred from ICUs within the same institution who had elevated urine N-telopeptide (NTx) levels at RCU admission, who were treated with either calcitriol alone (n = 44) or calcitriol and pamidronate (n = 11), and who had urine NTx levels remeasured following treatment. INTERVENTION: None. MEASUREMENTS AND RESULTS: Patients treated with calcitriol alone had a significant reduction in serum parathyroid hormone (PTH; 93+/-145 pg/mL vs 40+/-28 pg/mL; p = 0.02) but not in urinary NTx (187+/-146 nmol bone collagen equivalents [BCE]/mmol creatinine [Cr] vs. 178+/-123 nmol BCE/mmol Cr, p = 0.59). In contrast, patients treated with both calcitriol and pamidronate had a significant decrease in urine NTx at follow-up (329+/-238 to 100+/-85 nmol BCE/mmol Cr; p<0.01) but not in serum PTH (36+/-29 to 53+/-51 pg/mL; p = 0.44). CONCLUSION: The bone hyperresorption of CCI patients is PTH independent and biochemically responds to treatment with calcitriol and pamidronate but not calcitriol alone.


Subject(s)
Calcitriol/therapeutic use , Calcium/blood , Collagen/urine , Diphosphonates/therapeutic use , Osteoporosis/metabolism , Parathyroid Hormone/blood , Peptides/urine , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , Biomarkers/blood , Biomarkers/urine , Calcium Channel Agonists/therapeutic use , Chronic Disease , Collagen Type I , Creatinine/urine , Critical Illness/rehabilitation , Female , Humans , Male , Middle Aged , Osteoporosis/drug therapy , Osteoporosis/etiology , Pamidronate , Respiratory Care Units , Retrospective Studies , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/etiology , Vitamin D Deficiency/metabolism
13.
Crit Care Med ; 27(11): 2418-21, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10579258

ABSTRACT

OBJECTIVE: To determine the prevalence of hypotestosteronemia in chronically critically ill (CCI) men. DESIGN: Prevalence survey. SETTING: Step-down respiratory care unit (RCU) at a tertiary care teaching hospital. PATIENTS: Thirty ventilator-dependent CCI men transferred from intensive care units (ICUs) within the same institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total testosterone and bioavailable testosterone (bioT) concentrations were measured within 48 hrs of RCU admission. Patients were hospitalized a median of 40 days (range, 9-185 days) before RCU admission, with a median ICU length of stay of 25 days (range, 9-177 days). At RCU admission, total testosterone concentrations averaged 104+/-96 ng/dL, with average bioT concentrations of 19+/-20 ng/dL (16+/-9% of total testosterone). Twenty-nine of the 30 patients (96%) had bioT concentrations well below the lower limit of normal for their age range. bioT concentrations, expressed as a percentage of the normal mean for each patient's age range, were positively correlated with the number of days that the patient was in the ICU before transfer to the RCU (n = 30, r2 = .17, p = .025). However, if the single patient who remained in the ICU for 177 days was excluded, this correlation disappeared (n = 29, r2 = .07, p = .09). No other relationship was found between bioT concentrations and any other variable, including type of patient, ICU length of stay, reason for either initial admission to the ICU or prolonged mechanical ventilation, type of nutritional support, or use of dopamine. CONCLUSIONS: CCI men have a very high prevalence of hypotestosteronemia, which may impede their recuperation and rehabilitation. Further studies are needed to determine whether additional pharmacologic treatment with testosterone can improve the recovery of these patients.


Subject(s)
Hypogonadism/blood , Testosterone/deficiency , Adult , Aged , Biomarkers/blood , Chronic Disease , Critical Illness/therapy , Follow-Up Studies , Humans , Hypogonadism/epidemiology , Hypogonadism/etiology , Intensive Care Units , Length of Stay , Male , Middle Aged , Prevalence , Respiration, Artificial , Testosterone/blood
14.
Chest ; 114(4): 1122-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9792587

ABSTRACT

STUDY OBJECTIVE: Chronically critically ill (CCI) patients are primarily elderly people who have survived a life-threatening episode of sepsis but remain profoundly debilitated and ventilator dependent. The objective of this study was to determine the prevalence of bone hyperresorption and parathyroid hormone (PTH)-vitamin D axis abnormalities in these patients. DESIGN: Prevalence survey. SETTING: Respiratory care step-down unit (RCU) at a tertiary care teaching hospital. PATIENTS: Forty-nine ventilator-dependent CCI patients transferred from ICUs within the same institution. INTERVENTION: None. MEASUREMENTS AND RESULTS: N-telopeptide (NTx) levels in 24-h urine collections and serum intact PTH, 25-vitamin D, and 1,25-vitamin D levels were measured within 48 h of RCU admission. Patients were hospitalized a median of 30 days before RCU admission. Four patients (9%) had normal NTx and PTH levels. Forty-five patients (92%) had elevated urine NTx levels consistent with bone hyperresorption. Nineteen patients (42% of total patients) had elevated PTH levels consistent with predominant vitamin D deficiency, 4 patients (9%) had suppressed PTH levels consistent with predominant hyperresorption from immobilization, and 22 patients (49%) had normal PTH levels consistent with an overlap of both vitamin D deficiency and immobilization. There were no differences in vitamin D metabolites among these groups. CONCLUSIONS: CCI patients have a high prevalence of bone hyperresorption in which PTH levels may clarify the cause. Further studies will determine the efficacy and cost-effectiveness of routine NTx and PTH screening in these patients and the role of vitamin D and antiresorptive therapies.


Subject(s)
Bone Resorption/epidemiology , Critical Illness , 25-Hydroxyvitamin D 2/blood , 25-Hydroxyvitamin D 2/deficiency , Adult , Aged , Aged, 80 and over , Bed Rest/adverse effects , Biomarkers/blood , Biomarkers/urine , Bone Resorption/etiology , Bone Resorption/metabolism , Calcitriol/blood , Calcitriol/deficiency , Chronic Disease , Collagen/urine , Collagen Type I , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Parathyroid Hormone/blood , Peptides/urine , Prevalence , Prospective Studies , Respiratory Care Units , Vitamin D Deficiency/complications , Vitamin D Deficiency/metabolism
15.
J Endocrinol Invest ; 20(8): 462-70, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9364249

ABSTRACT

The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I-healthy volunteers; II-sick/normal FTI; and III-sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.


Subject(s)
Critical Illness , Hypothalamo-Hypophyseal System/physiopathology , Thyroxine/deficiency , Adult , Aged , Aged, 80 and over , Critical Care , Female , Humans , Male , Middle Aged , Pituitary Function Tests , Pituitary Hormones/blood , Prospective Studies , Thyroid Hormones/blood , Thyroxine/blood
16.
Arch Phys Med Rehabil ; 78(7): 692-6, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9228870

ABSTRACT

OBJECTIVE: To demonstrate that after spinal cord injury (SCI) suppression of the parathyroid-vitamin D axis is associated with the degree of neurologic impairment and not the level of injury. DESIGN: A retrospective analysis of clinical and biochemical data obtained from hospital records of patients with SCI compared to a control group of patients with traumatic brain injury (TBI). SETTING: The inpatient rehabilitation unit of a tertiary care hospital. SUBJECTS: The medical records of 82 consecutive admissions to the rehabilitation unit with a diagnosis of SCI or TBI were reviewed. Patients with SCI were classified by the American Spinal Injury Association (ASIA) impairment scale and then grouped based on the completeness and level of injury. MAIN OUTCOME MEASURE: Comparisons of serum parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25-D) were planned. Multiple comparisons were performed for total and ionized serum calcium levels, serum phosphorus levels, and 24-hour urinary calcium excretion rates to reflect changes in mineral homeostasis. Multiple comparisons were also performed for serum albumin, prolactin, thyroid function tests, and AM cortisol levels, as well as 24-hour urinary urea nitrogen and cortisol excretion rates to reflect metabolic responses to stress. RESULTS: Patients with SCI had significant suppression in PTH (p < .000009) and 1,25-D (p < .02) levels with elevated phosphorus (p < 0.03) and prolactin (p < .03) levels compared to patients with TBI. Also, more patients with SCI were hypoalbuminemic (p < .003) than patients with TBI. Patients with complete SCI (ASIA A) had more suppressed PTH (p < .03) and higher urinary urea nitrogen (p < .05) levels than SCI patients with incomplete injuries (ASIA B-D). Patients with complete, but not incomplete, SCI had lower albumin levels than patients with TBI (p < .05). These differences were not found between patients with tetraplegic and paraplegic SCI. ASIA motor scores did not correlate with any of the measured parameters but when used as a covariate did abolish differences in PTH and 1,25-D among the study groups by ANOVA. CONCLUSION: In patients with SCI, the degree of neurologic impairment, and not the level of injury, is associated with PTH suppression and markers of metabolic stress.


Subject(s)
Calcitriol/blood , Parathyroid Hormone/blood , Severity of Illness Index , Spinal Cord Injuries/blood , Spinal Cord Injuries/classification , Vitamin D/analogs & derivatives , Activities of Daily Living , Adult , Analysis of Variance , Brain Injuries/blood , Calcium/blood , Cross-Sectional Studies , Female , Humans , Male , Motor Skills , Retrospective Studies , Vitamin D/blood
17.
Thyroid ; 7(1): 63-6, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9086573

ABSTRACT

We present the unusual case of a 29-year-old man diagnosed in 1975 with papillary carcinoma of the thyroid metastatic to regional lymph nodes. The patient underwent surgical resection, postoperative iodine-131 (131I) radioablation and levothyroxine suppression. He was subsequently lost to follow-up. In 1991, he presented with extensive metastatic disease that was not demonstrable on whole-body 131I imaging, but was seen on computerized tomography and whole-body thallium chloride scanning. The patient was treated with cisplatin (Platinol) and doxorubicin (Adriamycin). Repeat 131I imaging after three cycles of chemotherapy showed significant 131I uptake in previously non-iodine-concentrating lesions. The patient was subsequently treated with 200 mCi 131I. We postulate this patient's non-iodine-concentrating thyroid cancer may have become functional by either a differentiating effect of chemotherapy on the tumor cells, or perhaps a selective cytotoxicity against nonfunctional, less differentiated papillary thyroid cancer cells, or both. This would allow more functional differentiated cells to overgrow and become the predominant cell type in the lesions. Chemotherapy may be beneficial in patients with advanced non-iodine-concentrating differentiated thyroid carcinoma by inducing radioiodine uptake and allowing subsequent radioiodine therapy. The possible mechanisms of induction of iodine uptake by chemotherapy are discussed.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Papillary/diagnostic imaging , Iodine/metabolism , Thyroid Neoplasms/diagnostic imaging , Adult , Antibiotics, Antineoplastic/therapeutic use , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/pathology , Cisplatin/therapeutic use , Doxorubicin/therapeutic use , Humans , Male , Radionuclide Imaging , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Thyroidectomy , Whole-Body Counting
18.
J Surg Res ; 65(2): 101-8, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8903454

ABSTRACT

We used a porcine endotoxemic model of acute lung injury to compare extravascular lung water (EVLW) measured by right transthoracic bioimpedance to postmortem gravimetric EVLW measurements. Adult pigs were randomized into control (N = 5) or endotoxin groups [150 microgram/kg Escherichia coli lipopolysaccharide B for 1 hr followed by 3 hr of resuscitation for a thermodilution cardiac output less than 90% of baseline using either isotonic saline (N = 5) or isooncotic albumin (N = 5)]. Right lung resistance was measured using a novel electrode array and a highly sensitive analyzer and was used to calculate right lung resistivity. At the end of the experiment, animals in the endotoxin-albumin group had higher gravimetric EVLWs than those in the endotoxin-saline or control groups (P < 0.05). Right lung resistivity corrected for body weight significantly correlated with gravimetric EVLW (r2 = 0.49; SEE = 0.96; P = 0.0038). Using multiple regression analysis, a predictive equation for EVLW based on right lung resistivity, body weight, and mean pulmonary artery pressure was generated (r2 = 0.81; SEE = 0.60; P < 0.0001). These results demonstrate that right lung resistivity measurements can provide a noninvasive estimate of EVLW. In addition, crystalloid may be preferable to colloid for fluid resuscitation in noncardiogenic pulmonary edema.


Subject(s)
Electric Impedance , Extravascular Lung Water/metabolism , Lung Diseases/metabolism , Lung/metabolism , Pulmonary Edema/metabolism , Animals , Body Composition/physiology , Electrophysiology/instrumentation , Female , Hematocrit , Hemodynamics/physiology , Lung/pathology , Organ Size , Oxygen/blood , Pulmonary Circulation , Pulmonary Edema/chemically induced , Regression Analysis , Resuscitation
19.
J Nucl Med ; 37(9): 1487-91, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8790199

ABSTRACT

UNLABELLED: The purpose of this study was to determine the concordance and discordance between diagnostic 131I and 201TI whole-body scintigraphy in patients with differentiated carcinoma of the thyroid. METHODS: Following thyroidectomy for differentiated thyroid carcinoma, 50 patients underwent whole-body 131I and 201TI scanning (60 pairs of scans in total). Fifteen pairs of studies were obtained before ablative therapy, 30 pairs after ablative therapy and 15 pairs after 131I therapy for metastatic disease. Serum thyroglobulin levels were concurrently determined by radioimmunoassay. RESULTS: Thirty-six 131I whole-body scans (in 34 patients) showed residual uptake in the neck, but only six (17%) of the corresponding whole-body thallium studies had detectable uptake in the neck. Fourteen 131I scans (in nine patients) identified multiple metastatic lesions, whereas the thallium scans were interpreted as either negative, nonspecific or showing fewer lesions. In four study pairs, the thallium scans showed solitary lesions that were not detected by the corresponding radioiodine scans. In 16 scans, the thallium studies gave false-positive results. CONCLUSION: Iodine-131 scintigraphy for differentiated thyroid carcinoma is more sensitive and more specific than 201TI scintigraphy for detection of distant metastases and residual activity in the neck following thyroidectomy.


Subject(s)
Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Papillary/diagnostic imaging , Iodine Radioisotopes , Thallium Radioisotopes , Thyroid Neoplasms/diagnostic imaging , Adenocarcinoma, Follicular/secondary , Adenocarcinoma, Papillary/secondary , False Positive Reactions , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm, Residual , Radionuclide Imaging , Sensitivity and Specificity , Thyroid Neoplasms/pathology , Thyroidectomy , Time Factors
20.
J Nucl Med ; 37(9): 1532-5, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8790212

ABSTRACT

A 67-yr-old woman who underwent total thyroidectomy 32 yr ago developed accelerated hyperthyroidism after injection of iodinated contrast media to evaluate a left hemipelvis mass. The patient was managed with propylthiouracil, beta-blockers and digoxin. Whole-body 201TI and 131I scans demonstrated a functioning metastasis in the left hemipelvis where biopsy revealed a well differentiated follicular thyroid carcinoma. Palliative external beam radiotherapy was administered. The patient then received radioiodine treatment with granulocyte colony-stimulating factor to minimize bone marrow toxicity. Clinically significant thyrotoxicosis occurring in metastatic thyroid carcinoma is rare and results from abnormal ectopic thyroidal tissue iodine metabolism. Iodide-containing medications and contrast media should be avoided in patients with functioning thyroid metastases to prevent abrupt increases in circulating thyroid hormone levels.


Subject(s)
Adenocarcinoma, Follicular/secondary , Contrast Media/adverse effects , Pelvic Neoplasms/secondary , Thyroid Neoplasms/pathology , Thyrotoxicosis/chemically induced , Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Follicular/therapy , Aged , Choristoma/complications , Female , Humans , Iodine/adverse effects , Iodine Radioisotopes , Pelvic Neoplasms/diagnostic imaging , Pelvic Neoplasms/therapy , Radionuclide Imaging , Thallium Radioisotopes , Thyroid Gland , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/therapy , Thyroidectomy
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