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Biomedical subjects

L Flores

Publications and source records attributed to L Flores.

At least 19 recordsLinked to original sources

Gastroesophageal reflux: prevalence of psychopathological disorders and quality of life implications.

There is evidence in the literature that psychosocial aspects affect the symptoms and results of surgery for gastroesophageal reflux. The purpose of this study was to estimate the prevalence of psychopathological disorders measured using the General Health Questionnaire (GHQ-28) in a sample of patients with gastroesophageal reflux, and to assess the influence of such disorders on their quality of life. A prospective study was conducted in 74 consecutive patients before gastroesophageal reflux surgery; patients answered the GHQ-28, the health questionnaire SF-36, and the Gastrointestinal Quality of Life Index (GIQLI). The convergent validity of the GHQ-28 questionnaire as compared to the other two questionnaires and preoperative quality of life was tested. A pathological result of the GHQ-28 questionnaire was found in 38.3% of patients. A correlation was seen between the results of the GHQ-28 questionnaire and all categories of the SF-36 and GIQLI questionnaires. Patients with pathological results in the GHQ-28 questionnaire had poorer results in all dimensions of the SF-36 and GIQLI quality of life questionnaires as compared to patients with a normal result in the GHQ-28 questionnaire. In conclusion, 38.3% of patients with gastroesophageal reflux showed psychopathological disorders when administered the GHQ-28 questionnaire. These patients also had poorer results in quality of life studies.

Adult↗

The effects of smoking and its cessation on 8-epi-PGF2alpha and transforming growth factor-beta 1 in Type 1 diabetes mellitus.

BACKGROUND: Oxidative stress and transforming growth factor-beta 1 (TGF-beta1) are associated with diabetic complications, and smoking is a risk factor. AIMS: This study aimed (i) to compare urinary 8-epi-PGF2alpha and plasma and urinary TGF-beta1 levels obtained in heavy smokers with Type 1 diabetes with those observed in age-matched non-smoker patients with Type 1 diabetes and controls, and (ii) to investigate the effects of smoking cessation (SC) on the above-mentioned parameters in patients with Type 1 diabetes. METHODS AND RESULTS: Compared with control subjects (n = 12), non-smoker diabetic patients (n = 12) presented higher values of urinary 8-epi-PGF2alpha (74.2 +/- 29.6 vs. 29.6 +/- 11.1 pg/mg urinary creatinine, P = 0.01), plasma TGF-beta1 (7.7 +/- 4.7 vs. 3.6 +/- 1.7 ng/ml, P = 0.001) and urinary TGF-beta1 (15.3 +/- 6.3 vs. 8.1 +/- 4.4 ng/mg urinary creatinine, P = 0.02). Compared with non-smoker diabetic patients, smoker diabetic patients (n = 16) showed higher levels of urinary 8-epi-PGF2alpha (107.8 +/- 40.2 vs. 74.2 +/- 29.6 pg/mg urinary creatinine, P = 0.0001), plasma TGF-beta1 (12.6 +/- 4.9 vs. 7.7 +/- 4.7 ng/ml, P = 0.001) and urinary TGF-beta1 (27.5 +/- 16.0 vs. 15.3 +/- 6.3 ng/mg urinary creatinine, P = 0.01). Smoker patients were included in a smoking cessation programme. In the 10 patients that gave up smoking there was a reduction of urinary 8-epi-PGF2alpha (basal: 110.47 +/- 47.0 vs. week 12: 73.2 +/- 25.6; P < 0.001), plasma TGF-beta1 (basal: 11.2 +/- 5.9 vs. week 12: 4.89 +/- 2.25; P < 0.01) and urinary TGF-beta1 (basal: 18.12 +/- 9.27 vs. week 12: 10.32 +/- 2.0; P < 0.01) levels. CONCLUSIONS: In patients with Type 1 diabetes, smoking increased oxidative stress, evaluated by lipid peroxidation, and TGF-beta1 production. Smoking cessation decreased these parameters, providing additional support to encourage diabetic patients to give up smoking.

Adult↗

Transforming growth factor beta at clinical onset of Type 1 diabetes mellitus. A pilot study.

AIMS: The aims of the study were to determine whether transforming growth factor beta1 TGF-beta1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose. SUBJECTS AND METHODS: Fourteen patients (mean age 24.3 +/- 4.9 years) admitted to hospital for onset of Type 1 diabetes were studied. On the first day of hospitalization, before insulin therapy, and at 1, 4 and 16 weeks, fasting blood glucose, HbA(1c), lipid profile and TGF-beta1 levels and TGF-beta1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group. RESULTS: Plasma and urinary TGF-beta1 levels were significantly lower in controls (4.7 (1.6-6.8) ng/ml P < 0.001; 5.7 (1.5-8.5) ng/mg urinary creatinine, P < 0.01) than in patients with Type 1 diabetes mellitus [10.5 (1.8-24.9) ng/ml; 10.1 (4.2-29.8) ng/mg urinary creatinine]. On study completion, HbA(1c) fell from 11.6 +/- 2.0 to 5.4 +/- 0.6% (P < 0.001). Improved metabolic control was not associated with changes in plasma (9.4 (2.6-19.5)/5.9 (1.6-21.5)/7.0 (2.3-30.2)/10.5 (1.8-24.9) ng/ml at baseline, 1, 4 and 16 weeks, respectively) or urinary (12.0 (4.7-29.5)/10.9 (1.5-20.5)/8.7 (4.3-16.9)/10.1 (4.2-29.8) ng/mg urinary creatinine) TGF-beta1 levels. A statistically significant correlation was observed between plasma TGF-beta1 and insulin dosage (U/kg/day) (r = 0.52, P = 0.037). CONCLUSIONS: The increased TGF-beta1 production observed herein was not modulated by glycaemic reduction and could be a response to immuno-inflammatory activation present at the onset of Type 1 diabetes.

Adult↗

Islet neogenesis: an apparent key component of long-term pancreas adaptation to increased insulin demand.

This study aimed to determine the relative importance of different functional and morphological pancreatic changes induced by the chronic administration of a sucrose-rich diet (SRD) to maintain normal glucose homeostasis. Male Wistar rats were fed either sucrose (SRD) or starch (CD) for 6 and 12 months. At both periods, serum glucose and triacylglycerol levels were significantly higher (P<0.05; paired and unpaired Student's t-test) in SRD rats. Serum insulin levels were significantly lower in SRD only at 12 months. At 6 months, the insulin secretion dose-response curve in SRD rats showed a shift to the left that was no longer observed at 12 months, when SRD islets decreased their response to 16 mM glucose. At 6 months, SRD rats showed a significant increase in beta-cell volume density (Vvi) and islet cell replication rate, together with a decrease in beta-cell apoptotic rate. Changes were not detected in the percentage of PDX-1- and islet neogenesis associated protein (INGAP)-positive cells. Conversely, at 12 months, there was a significant decrease in beta-cell Vvi and in the percentage of PDX-1-positive cells; the islet cell replication rate was not modified, and the number of apoptotic beta-cells increased significantly. No signs of increased neogenesis or INGAP-positive cells were recorded at any period in SRD rats. Our results show that SRD rats are unable to develop functional and morphological pancreatic reactive changes sufficient to maintain normal glucose and triacylglycerol levels for a long period. Such failure could be ascribed to their inability to increase the rate of neogenesis and of INGAP production.

Adaptation, Physiological↗

Fractal scattering of microwaves from soils.

Using a combination of laboratory experiments and computer simulation we show that microwaves reflected from and transmitted through soil have a fractal dimension correlated to that of the soil's hierarchic permittivity network. The mathematical model relating the ground-penetrating radar record to the mass fractal dimension of soil structure is also developed. The fractal signature of the scattered microwaves correlates well with some physical and mechanical properties of soils.

Journal Article↗

Immediate vs. delayed imipenem treatment in cancer patients with profound neutropenia induced by high-dose chemotherapy: results of a randomized study.

A study was carried out to compare the use of prophylactic imipenem administered at the onset of profound neutropenia (immediate) with therapeutic imipenem administered at the onset of neutropenic fever (delayed) in cancer patients treated with high-dose chemotherapy. A total of 65 patients who were scheduled to receive two cycles of high-dose cyclophosphamide, etoposide, cisplatin (CEP) chemotherapy were randomized to receive imipenem either at presentation of neutropenia (immediate imipenem arm, prophylactic arm) or at commencement of neutropenic fever (delayed imipenem arm, therapeutic arm). Treatment was crossed over when the second CEP chemotherapy cycle was received. Of the 65 patients, 41 received the two planned cycles and 24 received only the first. Compared with the delayed imipenem arm, the immediate imipenem arm was associated with lower fever incidence (86.3% vs. 100%, p=0.0142) and Gram-negative bacteria infection [4/51 (7.8%) vs. 14/55 (25.5%), OR=0.24, p =0.031]. There were fewer episodes of pneumonia (2% vs. 12.7%), septic shock (0% vs. 3.6%) and deaths from infection (0% vs. 3.6%), but these differences did not reach statistical significance. With regard to delayed imipenem, for every seven patients with immediate imipenem, one episode of febrile neutropenia was avoided; for every six patients administered immediate imipenem, one case of Gram-negative infection was avoided; and for every nine patients administered immediate imipenem, one episode of pneumonia was avoided. There were no differences in the incidence of Gram-positive infections nor in the length of hospitalization between the two treatment arms. In conclusion, compared to its conventional delayed use, immediate imipenem significantly reduces the frequency of febrile neutropenia and Gram-negative infections in patients with high-dose chemotherapy.

Adolescent↗

The correlation between 99mTc-MIBI uptake and MIB-1 as a nuclear proliferation marker in glioma--a comparative study with 201Tl.

Technetium-99m methoxy-isobutylisonitrile (MIBI), like thallium-201 (201Tl), is a highly efficient agent for the diagnosis and monitoring of glioma tumors. Although 201Tl uptake is known to be partly associated with proliferative activity, little is known about the correlation between MIBI uptake and proliferation activity in gliomas. The current study was performed to assess the correlation between MIBI uptake and proliferative activities in gliomas, estimated by the monoclonal antibody to Ki-67 antigen (MIB-1) staining method. By comparing the results with those of 201Tl, we determined which tracer would be suitable for estimating proliferative activities. Twenty-four presurgical glioma patients (six with low-grade gliomas, five with anaplastic astrocytomas, and 13 with glioblastomas) were given MIBI and 201Tl SPECT. Early (10 min after injection) and delayed images (3 h after injection) were obtained for both MIBI and 201Tl scintigraphy. SPECT parameters, early ratio (ER), delayed ratio (DR), and retention index (RI) were obtained in both radiopharmaceuticals. All patients underwent subsequent surgical excision, and the specimens were immunostained for MIB-1. The proliferative activity was measured as a percentage positive nuclear area for MIB-1 (MI; MIB-1 index). To evaluate the relationship between the proliferative activity and SPECT parameters, we performed a correlation analysis. MI correlated with the MIBI uptake ratio (r = 0.75 for ER, and r = 0.7 for DR). Both DR and RI of 201Tl also correlated with MI, but weakly (r = 0.6 for DR, and. r = 0.59 for RI). There was no significant correlation between the MIB-1 index and the other parameters. MIBI-uptake parameters demonstrated a stronger positive correlation with the MIB-1 index than that of 201Tl. With the use of MIBI SPECT, we can estimate the proliferative activity of glioma noninvasively.

Adolescent↗

Analysis of nonpenetrating clips versus sutures for arterial venous graft anastomosis.

The use of nonpenetrating clips (NPC) for vascular anastomosis is quickly becoming accepted. Studies attest to decreased anastomotic time, comparable patency rates, and decreased blood loss. Few human studies on the use of NPC have been done to date. The purpose of this study was to evaluate primary patency rates, operative time, and complications associated with NPC compared to those with standard sutures for arterial venous graft (AVG). We retrospectively reviewed the clinical course of 82 patients with a mean age of 45 years (range, 22 to 87) from February 1996 to July 1999. All patients underwent upper extremity AVG construction. The procedures were performed at a single institution, by a single, well-experienced surgeon who has extensive experience with NPC. Primary patency rates, operative time, and complications were analyzed. Overall thrombotic incidence of AVG when NPC were used (27/48, 56%) was similar to that of sutures (17/34, 50%). Thrombotic incidence within the first year was similar as well (23/48, 48% and 13/34, 38%). The mean time to primary thrombosis was similar in both groups (6.9 and 6.8 months). The operative time required to construct an AVG with NPC (83 min) was significantly less than that with sutures (96 min) (p = 0.015). There was no significant difference in incidence of graft infection or pseudoaneurysm formation. NPC for AVG reduced operative time and resulted in primary patency and complication rates similar to those associated with use of sutures. The mean time to primary thrombosis was similar for both groups. Our findings suggest an intimal hyperplastic response of a similar nature resulting in thrombosis of both NPC and sutured AVGs.

Adult↗

Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects.

This study evaluated the discriminant validity of subjects differentially scaling the sensory and affective dimensions of pain. It sought to determine (1) whether subjects can differentially scale sensory and affective aspects of phasic laboratory pain in the absence of task demand bias that fosters apparent differential scaling; (2) whether psychophysiologic responses to painful stimuli can predict pain report (PR); and (3) whether such responses contribute more to affective than to sensory judgments. Fifty-six men and 44 women repeatedly experienced varied painful electrical fingertip stimuli at low, medium, and high intensities. On half of the trial blocks, subjects made sensory judgments; on the remainder they made affective judgments. Response measures included PR, pupil dilation, heart rate, respiration rate, skin conductance response (SCR), and late near field evoked potentials. Subjects did not rate the stimuli differently when making sensory versus affective judgments. The psychophysiologic variables, principally the SCR, accounted for 44% of the variance in the PR. Psychophysiologic response patterns did not differentiate affective and sensory judgment conditions. Noteworthy sources of individual differences included baseline PR levels and the linear effects of SCR on PR.

Journal Article↗

Effect of losartan on TGF-beta1 and urinary albumin excretion in patients with type 2 diabetes mellitus and microalbuminuria.

BACKGROUND: The aim of the present study was to determine the effect of losartan on transforming growth factor-beta1 (TGF-beta1) plasma levels and urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus, mild hypertension and microalbuminuria. METHODS: Fourteen patients (eight males, aged 55+/-6 years) with type 2 diabetes mellitus, mild arterial hypertension and microalbuminuria, participating in an open, uncontrolled, pilot study were included. Patients were treated for 8 weeks with losartan. TGF-beta1 plasma levels, UAE and 24-h blood pressure monitoring were determined at baseline and at 4 and 8 weeks. RESULTS: At 4 and 8 weeks of treatment, a reduction was observed in TGF-beta1 plasma levels (5.5+/-4.5 vs 2.0+/-0.6 and 2.6+/-1.0 ng/ml, P<0.005), UAE (96+/-65 vs 59+/-59 and 64+/-47 microg/min, P<0.01), 24-h systolic blood pressure (136+/-9 vs 129+/-9 and 130+/-10 mmHg, P<0.01) and 24-h diastolic blood pressure (77+/-9 vs 74+/-8 and 74+/-7 mmHg, P<0.03). Stratifying the patients by baseline TGF-beta1, seven had TGF-beta1 plasma values higher than normal controls. At 4 and 8 weeks, they showed a marked reduction in TGF-beta1 values (9.0+/-3.9 to 2.1+/-0.7 and 2.5+/-0.7 ng/ml, P<0.01) and UAE (106+/-83 to 49+/-42 and 38+/-26 microg/min, P<0.05), with good correlation between the percentage reduction of both parameters (r=0.83, P<0.01). The remaining seven patients, with normal baseline TGF-beta1 plasma levels, showed no change in TGF-beta1 plasma levels and UAE after treatment. CONCLUSION: Treatment with losartan decreases TGF-beta1 plasma values and UAE in type 2 diabetes mellitus patients with high baseline TGF-beta1 levels, suggesting that TGF-beta1 may be a marker to detect patients who may particularly benefit from renin-angiotensin system blockade.

Albuminuria↗

Cyclospora cayetanensis in three populations at risk in Guatemala.

In 1996 and 1997, outbreaks of Cyclospora cayetanensis in North America were linked to Guatemalan raspberries. From April 1999 to April 2000, we undertook a survey for C. cayetanensis in raspberry farm workers, malnourished children, and human immunodeficiency virus and AIDS patients in Guatemala. Stool samples were analyzed using ethylacetate-formalin concentration, wet preparation, modified acid-fast staining method, and epifluorescence. Oocysts were found in 1.5% of the subjects, none of whom were raspberry farm workers.

AIDS-Related Opportunistic Infections↗

Metallothionein isoform 1 and 2 gene expression in the human prostate: downregulation of MT-1X in advanced prostate cancer.

BACKGROUND: Studies have shown an association of metallothionein (MT) overexpression with tumor type and grade. However, a family of genes underlies the expression of these proteins. The goals of this study were to define the expression of MT genes and protein in normal human prostate and to provide evidence that the expression of the MT isoforms is altered in prostate cancer. METHODS: Immunohistochemistry was used to localize MT protein, reverse transcription-polymerase chain reaction (RT-PCR) to determine the MT isoform-specific mRNAs, and immunoblot analysis to determine MT protein levels. RESULTS: The localization of MT in the prostate was further defined using the E9 antibody. Using normal prostate tissue dissected from glands removed for prostate cancer, it was demonstrated that MT protein expression in the normal prostate is supported by mRNA from the MT-1A, MT-1E, MT-1X, and MT-2A genes. No expression of the MT-1X gene was demonstrated in cases of advanced prostate cancer. The expression of MT-1 and MT-2 isoform-specific mRNA varied among three commonly utilized prostate cancer cell lines. CONCLUSIONS: MT protein in the normal human prostate is supported by transcription of mRNA from the MT-1A, MT-1E, MT-1X, and MT-2A genes. Expression of MT-1X mRNA is downregulated in advanced prostate cancer. Variable expression of MT mRNA in prostate cell lines provides evidence that MT gene expression may be altered among individual prostate cancers.

Cell Line↗

White coat hypertension in type 1 diabetic patients without nephropathy.

The aim of our study was to determine the prevalence of white coat hypertension (WCH) in type 1 diabetic patients. Therefore, ambulatory blood pressure monitoring (ABPM) and 24-h urinary albumin excretion (UAE) were determined in 47 patients with type 1 diabetes mellitus (27 with new diagnosis of hypertension by office blood pressure (BP) measurement and 20 with normotension). WCH was diagnosed in 20 patients (74%). Patients with WCH presented higher values of systolic and diastolic BP and UAE than normotensive patients. The results indicate that in type 1 diabetes mellitus WCH is very frequent. Thus, WCH may represent a potential risk for the development of diabetic complications, mainly diabetic nephropathy.

Adult↗

Functional characterization of transcriptional regulatory elements in the upstream region of the yeast GLK1 gene.

The glucokinase gene GLK1 of the yeast Saccharomyces cerevisiae is transcriptionally regulated in response to the carbon source of the growth medium. Northern-blot analysis shows that the GLK1 gene is expressed at a basal level in the presence of glucose, de-repressed more than 6-fold under conditions of sugar limitation and more than 25-fold under conditions of ethanol induction. lacZ fusions of the GLK1 gene promoter were constructed and a deletion analysis was performed in order to identify the cis-acting regulatory elements of the promoter that controls GLK1 gene expression. First, the expression seemed to be mediated mainly by one GCR1 and three stress-responsive element (STRE) activating elements. Secondly, an ethanol repression autoregulation (ERA)/twelve-fold TA repeat (TAB) repressor element was identified within the promoter region of the GLK1 gene. A specific and differential protein binding to the STRE was observed with extracts from de-repressed and repressed cells. No differential binding to the GCR1 or ERA/TAB elements was observed with extracts from de-repressed and repressed cells, but, in both cases, the binding was competed for by an excess of the unlabelled GLK1(GCR1) and GLK1(ERA) sequence. The transcription factors Msn2 and Msn4, which bind to the GLK1 upstream region through the STRE, contribute to inductive activation. The transcription factor Gcr1, which binds through the GCR1 element, contributes to constitutive activation. In order to achieve the severe glucose repression of GLK1, constitutive repressor factors acting through the ERA/TAB element must counteract constitutive activation generated by Gcr1 binding to the GCR1 element. Full expression of the GLK1 gene is produced by inductive activation of three STRE when Msn2 and Msn4 proteins are translocated to the nucleus by covalent modification. The combinatorial effect of the entire region leads to the regulated transcription of GLK1, i.e., silent in media with glucose and other preferred carbon sources, such as fructose or mannose, and increased levels of expression upon glucose depletion.

Base Sequence↗

The usefulness of Tc-99m MIBI for evaluating brain tumors: comparative study with Tl-201 and relation with P-glycoprotein

PURPOSE: This study was undertaken to determine the usefulness of Tc-99m methoxyisobutylisonitrile (MIBI) in brain tumors compared with TI-201 imaging. The authors evaluated the correlation between MIBI uptake and the presence of P-glycoprotein, and also the relation between MIBI uptake in response to combined radiotherapy and chemotherapy in glioblastoma. MATERIALS AND METHODS: Thirty-four brain tumors composed of 15 glioblastoma multiforme (GBM), 5 anaplastic astrocytomas, 5 low-grade astrocytomas, and 9 metastases were evaluated. Early and delayed images were obtained for MIBI and Tl-201 scintigraphy. P-glycoprotein status in all GBM, 2 anaplastic astrocytomas, 2 low-grade astrocytomas, and 2 metastases were evaluated immunohistochemically. Patients with GBM were divided into an effective and a noneffective group according to the change in tumor size. MIBI uptake indices were compared for these two groups. RESULTS: Both radiopharmaceuticals accumulated in all GBM and anaplastic astrocytomas. In low-grade astrocytomas, only one case showed tracer uptake. In metastasis, two cases showed high uptake on early images and marked washout on delayed images. Uptake ratio values (early uptake ratio and delayed uptake ratio) in all tumors were significantly higher in MIBI than in Tl-201. Immunohistochemical studies showed that the metastases were positive for P-glycoprotein but the GBM were not. In low-grade astrocytomas, a few cells were positively stained. In relation to the therapeutic outcome of GBM, both the early and delayed uptake ratios of MIBI were significantly greater in the noneffective group. CONCLUSIONS: Although diagnostic ability was comparable in MIBI and Tl-201, the imaging quality was better in MIBI. Both radiopharmaceuticals are useful in differentiating low-grade glioma from high-grade glioma. MIBI delayed imaging could also reflect the presence of P-glycoprotein. Intense MIBI uptake was also predictive of a poor clinical outcome in GBM.

Journal Article↗

The role of IGF binding protein-3 as a parameter of activity in acromegalic patients.

OBJECTIVE: The production of insulin-like growth factor binding protein-3 (IGFBP-3), the main IGF-I binding protein, is regulated by GH, and its serum levels are increased in acromegaly. We investigated its potential value as a parameter of acromegaly activity or remission in comparison with IGF-I, taking GH suppression below 2 microg/l after glucose load as the normal standard. METHODS: Data from 40 acromegalic patients (12 males and 28 females, aged 28 to 79 years) were obtained retrospectively from stored samples. From these, 145 pairs of IGF-I/IGFBP-3 values were collected; in 67 of them, simultaneous measurement of GH after glucose loading allowed their classification as active or inactive acromegaly. Relationships between IGF-I, IGFBP-3 and GH after glucose load were assessed, as well as differences between IGF-I and IGFBP-3 levels in active and inactive acromegaly. RESULTS: Significant positive correlation between IGF-I and IGFBP-3 in 145 samples was observed (r=0.49, P<0. 0001). As for the 67 samples in which activity or remission could be defined in terms of GH after glucose load, 50 were active and 17 inactive. Both IGF-I and IGFBP-3 significantly correlated with minimum GH (r=0.53, P<0.0001 and r=0.41, P<0.001 respectively). For both parameters, significant differences of means between active and inactive cases were observed (623+/-296 vs 300+/-108 ng/ml, P<0.0001 for IGF-I, and 4.1+/-1.3 vs 3.2+/-0.9 microg/ml, P<0.006 for IGFBP-3). Yet, when comparing in individual cases their classification as active or inactive with the finding of normal or increased IGF-I and IGFBP-3, among active cases 16% appeared as normal according to IGF-I, and 50% appeared as normal in terms of IGFBP-3. Among inactive cases, 23.5% appeared as active according to IGF-I, while 17.5% appeared as active in terms of IGFBP-3. CONCLUSION: Even though IGFBP-3 reflects GH secretion, it offers no advantage over IGF-I in the assessment of acromegaly, and it may underestimate disease activity in acromegalic patients.

Acromegaly↗