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Biomedical subjects

M Rull

Publications and source records attributed to M Rull.

At least 19 recordsLinked to original sources

The effect of bariatric surgery on adipocytokines, renal parameters and other cardiovascular risk factors in severe and very severe obesity: 1-year follow-up.

AIMS: To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs). METHODS: A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery. CONTROLS: 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded. RESULTS: Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity. CONCLUSION: Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.

Adiponectin↗

HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos.

The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.

Adult↗

Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch.

OBJECTIVE: To examine the effects of three commonly used intra-articular depot corticosteroid preparations tested in a rat air pouch model and their effect against monosodium urate (MSU) crystal-induced inflammation. Rheumatologists use intra-articular corticosteroid preparations to relieve pain and inflammation of acute monoarthritis without really knowing their effects on the synovial fluid and membrane or the differences between distinct preparations. This work compares the effect of three commonly used corticosteroid preparations in vivo, showing that they behave differently. METHODS: A subcutaneous air pouch was formed in male Sprague-Dawley rats. A first group of 6-day-old air pouches were injected with 10 ml of 6 mg/ml normal saline solution, 6 mg/ml betamethasone containing both depot betamethasone acetate and soluble betamethasone phosphate (Celestone) in 9 ml of normal saline solution, 20 mg/ml of prednisolone tebutate (Hydeltra) in 9 ml of normal saline solution or 20 mg/ml of triamcinolone hexacetonide (Aristospan) in 9 ml of normal saline solution. A second group (group 2) of air pouches were injected with 15 mg of synthetic MSU crystals and 24 h later they were reinjected with 1 ml of the same three corticosteroid suspensions. For each condition four rats were killed at 6, 24, 48 h and 7 days. Pouch fluid and tissue were analysed. RESULTS: In the first 6 h after normal saline solution or corticosteroid injection into the air pouch there were mildly increased leucocyte counts in the air pouch fluid. Betamethasone-injected pouches showed no cells in the fluid after 6 h and no crystals after 24 h, triamcinolone-injected pouches still showed rare cells at 7 days. Both triamcinolone and prednisolone crystals persisted in higher numbers and lasted longer in the fluid than did betamethasone (P<0.05). In group 2 MSU crystal phagocytosis in the fluid was decreased in the betamethasone- (P<0.01), prednisolone- (P<0.003) and triamcinolone- (P<0.006) injected pouches when compared with the MSU crystal-injected pouches alone. Pouches injected with MSU crystals alone showed the most intense tissue inflammation at all times. After MSU, betamethasone-injected pouches had a rapid but mild decrease in the number of lining cells and inflammation. In contrast, triamcinolone- and prednisolone-injected pouches showed a very thin tissue with few or no vessels and almost no inflammation at 7 days. The pouches injected with MSU crystals and any of the corticoid preparations had three times more tophus-like structures and persistent crystals identified than the ones injected with MSU crystals alone. CONCLUSION: Each of the corticosteroid preparations by themselves produced very mild transient inflammation. The betamethasone preparation with a soluble steroid component had a quicker but milder anti-inflammatory effect on MSU crystal-induced inflammation. In contrast to the doses used, prednisolone tebutate and triamcinolone hexacetonide preparations dramatically suppressed urate crystal-induced inflammation at 7 days, but both produced atrophy and necrosis of the membrane, yielding a very thin membrane with almost no vessels. When used for MSU crystal-induced inflammation these corticosteroid preparations suppressed some aspects of inflammation but may actually promote the persistence of MSU crystals and the formation of tophi.

Animals↗

Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?

OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. METHODS: A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. RESULTS: There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. CONCLUSION: A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.

Allopurinol↗

Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: an approach to its validity.

BACKGROUND: Sentinel node biopsy (SNB) has been proposed as an alternative to axillary lymph-node dissection (ALND) in breast cancer. Before implementing SNB in our practice, we wished to test its validity by comparing it to the standard ALND, both in our hands and with other reported series. PATIENTS AND METHODS: One hundred thirty-two patients were included prospectively. SNB and immediate ALND were performed. For SNB, a technetium-colloid was used to produce preoperative lymphoscintigraphy and intraoperative gamma-probe search for the SN. Serial sectioning and immunostains were used on the SN. A comprehensive review of the literature was done in order to run a meta-analysis of diagnostic tests using a summary receiver operating characteristic curve (SROC) to calculate the pooled parameters of sensitivity and associated 95% confidence interval (95% CI), including our own data. RESULTS: Our technical success rate was 96%. Local sensitivity was 96%, with a 95% CI from 85%-99%. Seven patients were upstaged by the SNB. A literature search identified 18 studies published from 1996-1999. Estimates of sensitivity ranged from 83%-100%. The pooled data meta-analysis gave a global sensitivity of 91%, with a 95% CI from 89%-93%. The area under the global SROC curve was 0.9967. CONCLUSIONS: The minimally invasive SNB was shown to be a practical alternative to ALND. We propose to use local as well as global sensitivity and associated 95% CI to test the validity of SNB in the clinical setting. Due to limitations of ALND as the golden standard, SNB can in fact be considered a more accurate method for nodal staging.

Adult↗

[Selective biopsy of the sentinel ganglion in patients with breast cancer. Initial results].

BACKGROUND: Sentinel-node biopsy is meant to excise the first-echelon node from a primary tumor, which is the one that most probably harbors early metastases. PATIENTS AND METHODS: We report our results in 35 patients with breast cancer, using a radiotracer by peri-tumoral injection, pre-surgical scintigraphy and intraoperative mapping with a gamma probe. RESULTS: The technical success rate was 97%, negative predictive value 95.2%, accuracy 97%, and added value to staging 40%. CONCLUSION: Compared with the conventional lymph-node staging procedure for breast cancer, sentinel-node biopsy with pre-surgical scintigraphy seems a good practical choice.

Adult↗

Protease inhibitor-containing regimens compared with nucleoside analogues alone in the suppression of persistent HIV-1 replication in lymphoid tissue.

OBJECTIVE: Lymphoid tissue provides a reservoir where HIV can persist. However, therapies incorporating a protease inhibitor can target this reservoir. This study was designed to investigate the relative long-term effects on lymph-node viral load and cellular architecture of regimens containing multiple nucleosides alone or in combination with protease inhibitors. METHODS: Axillary lymph-node biopsies from 12 patients with undetectable viraemia (viral load < 20 copies/ml: mean CD4 cells 525 x 10(6)/l) for a mean period of 25 months (range, 10-52 months) were investigated for the presence of HIV by in situ hybridization and coculture. Four patients were receiving multiple nucleoside analogues alone or in one case with a suboptimally dosed protease inhibitor (group I). Protease inhibitor was added to the regimen of seven patients at least 6 months prior to lymph-node biopsy (group II). Standard flow cytometry and virological data were obtained from peripheral blood every 3 months. RESULTS: By in situ hybridization, more productively infected CD4+ T cells were found in the lymph nodes of group I patients treated with nucleoside analogues alone. Very low numbers of productively infected lymph node cells were detected in the protease inhibitor-treated group II. No trapping of virions on the follicular dendritic cell (FDC) network was detectable in protease inhibitor-treated patients. In contrast, large deposits of FDC-bound virions were observed in three out of five patients from group I. Virus cultures from lymph node cells were positive in these three group I patients compared with only one out of seven patients from group II. Sequencing reverse transcriptase and protease genes from these isolates revealed typical mutations conferring resistance to the previously administered nucleoside analogue. A more preserved lymph node architecture and less signs of immunopathological change were also observed in protease inhibitor-treated patients. CONCLUSIONS: Undetectable plasma viraemia using the ultrasensitive PCR assay for prolonged periods of time does not always reflect complete HIV-1 suppression within the lymphoid compartment. Our results suggest that protease inhibitor-containing regimens target HIV reservoirs in lymphoid tissue more effectively and preserve or restore lymph node architecture.

Anti-HIV Agents↗

[Hypotension refractory to ephedrine after sympathetic blockade in a patient on long-term therapy with tricyclic antidepressants].

A 61-year-old woman in chronic treatment with 25 mg of amitriptyline underwent ovarian cancer resection under combined general and epidural lumbar anesthesia. After administration of local anesthetic she presented signs of severe arterial hypotension that was refractory to high doses of ephedrine and administration of dopamine alpha-adrenergic substances. Control was achieved with 200 micrograms of noradrenaline. We review the anesthetic implications of chronic use of tricyclic antidepressives as they affect choice of vasopressin for treating hypotensive events during anesthesia.

Adrenergic Uptake Inhibitors↗

[Fastrach intubation in patients with cervical disease].

The Fastrach laryngeal mask for intubation is a new device designed for blind orotracheal intubation in patients with criteria predictive of difficult airway control. The new device looks like the conventional laryngeal mask but offers a series of design changes that allow orotracheal intubation to be accomplished without visualization of the glottis. The rigid metal tube is bent and incorporates a metal handle; the two fixed bars that prevent the epiglottis from falling and blocking the opening have been replaced by a moveable bar that rises with the passage of the endotracheal tube and the exit of the V-shaped metal tube guides the endotracheal tube that was specially designed for this use. We describe three patients with cervical disease, one with advanced ankylosing spondylitis, one with traumatic luxation of the C6-C7 articulation and one diagnosed of two cervical disk hernias. All their tracheas were intubated without difficulty through the Fastrach mask with the patients' heads in neutral position. Although fiberoptic bronchoscopy is the method of choice in patients with cervical problems, the non-availability of the technique and the need for training in its use make the Fastrach mask an alternative worth considering for such patients.

Aged↗

Band erosion in patients who have undergone vertical banded gastroplasty: incidence and technical solutions.

OBJECTIVES: To study the incidence of band erosion in patients who have undergone vertical banded gastroplasty and to describe the reparative techniques used. DESIGN: A retrospective review case series. SETTING: A university hospital-based tertiary referral center. PATIENTS: Two hundred fifty consecutive morbidly obese patients who underwent vertical banded gastroplasty between 1987 and 1995. MAIN OUTCOME MEASURES: The development of band erosion into the stomach, reparative surgical techniques, and long-term weight loss control. RESULTS: Band erosion developed in 7 (2.8%) of the patients. Two patients had symptoms 1 month after undergoing forced endoscopy. Six patients required reoperation. The operative findings included 2 cases of "external" band erosion through the lesser curvature into the stomach and 4 cases of "internal" band erosion through the circular staple line. The surgical techniques used for repair depended on the radiological and endoscopic data and on the operative findings; the techniques included conversion into a gastric bypass, band replacement after the creation of a new stoma, and gastroplasty plus distal gastric bypass. There were no complications, and adequate long-term weight loss was achieved in all but 1 of the patients who underwent reoperation. CONCLUSION: Band erosion may be corrected using appropriate surgical techniques to allow for adequate long-term weight loss in patients who have undergone vertical banded gastroplasty.

Adult↗

Increased leptin production in vivo and insulin cleavage by the omental adipose tissue of morbidly obese patients.

OBJECTIVE: The aim of this investigation was to assess the insulin cleavage capacity in obese humans. Increased insulin degradation by visceral adipose tissue has previously been demonstrated in obese rats and could be interpreted as a physiological response to hyperinsulinaemia. The recent characterization of leptin receptors in pancreatic beta cells, liver and muscle suggests that leptin may influence insulin function and metabolism. Our study focuses on the possible relationship between leptin secretion and adipose tissue insulin-degrading capacity. DESIGN AND PATIENTS: Insulin and leptin were measured in arterial blood and in the epiploic vein of morbidly obese (n = 7) and non-obese patients (n = 7) who were undergoing abdominal surgery. Arteriovenous insulin difference (AV insulin) was considered an in vivo marker of insulin degradation by the omental fat tissue. Statistical comparison between venous and arterial leptin was used to assess endogenous leptin production. MEASUREMENTS: Insulin was measured using an oligoclonal IRMA and leptin levels were determined by using a specific radioimmunoassay. RESULTS: Morbidly obese patients were hyperinsulinaemic compared to non-obese patients according to arterial insulin levels (P = 0.049) but not to venous levels. Insulin cleavage capacity, nil in the control group, was clearly significant in the morbidly obese patients (P = 0.001). In the morbidly obese group, leptin levels in venous epiploic samples were significantly higher (P = 0.028) than in the arterial samples, confirming in situ the synthesis of leptin by human white adipose tissue. We also observed a correlation between insulin arterial levels and venous leptin concentrations (P = 0.009) which supports the chronic leptinogenic effect of insulin suggested in previous works. Finally, our results show that venous leptin levels are correlated with the extent of insulin cleavage by omental tissue (P = 0.033). CONCLUSIONS: Morbidly obese patients have a higher white adipose tissue insulin cleavage capacity, which could partially diminish hyperinsulinaemia-derived adverse effects. High leptin production, a consequence of high insulin levels, may act as a signal to the insulin-degrading tissues in order to lower insulinaemia.

Adipose Tissue↗

Growth hormone-binding protein directly depends on serum leptin levels in adults with different nutritional status.

The aim of this work was to assess the relationship between GH-binding protein (GHBP) and leptin. Both peptides are nutritionally regulated, but the recent implication of a role for leptin in the GH axis requires further study. To avoid the sexual dimorphism in leptin values, we performed leptin standardization according to gender (SD score-leptin). The relationship between SD score-leptin and GHBP was studied in 128 adults with different nutritional status [8 groups according to body mass index (BMI)], ranging from severely underweight anorexia nervosa to highly morbid obesity. Both GHBP and SD score-leptin significantly increased according to BMI within the range from 18-27 kg/m2, whereas no significant differences were found among underweight groups (BMI, < 18 kg/m2) or among obesity grades (BMI, > 27 kg/m2). We found a strong correlation between GHBP and SD score-leptin (r = 0.8; P < 0.0001). Multiple regression analysis revealed SD score-leptin to be a significant determinant of GHBP, accounting for 64% of the variation, whereas BMI did not contribute further to explaining changes in GHBP. This suggests a physiological pathway involving both GHBP (the soluble fraction of GH receptor) and leptin. Thus, we might speculate that leptin could be the signal that induces the related nutritional changes observed in GHBP/GH receptor expression.

Adolescent↗

Calcium crystal-associated diseases and miscellaneous crystals.

Calcium crystal-associated diseases are still a challenge in clinical and basic science. Advances in understanding crystal formation and dissolution and crystal participation in inflammation are reported here. Studies on different methods of identification are reviewed, emphasizing the need for accurate and reproducible ways to study and diagnose calcium crystal-associated diseases. Reports of uncommon presentations are also described, including a controlled study on calcification of the ligamenta flava of the spine and a study involving 19 years of clinical follow-up of families with hydroxyapatite chondrocalcinosis with spondyloepiphyseal dysplasia. Studies on miscellaneous crystals are few. Two recent reviews are described on cholesterol crystal embolization syndrome and cryocrystalglobulinemia.

Apatites↗