Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout

OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination. RESULTS: Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy.     

A two‐stage approach to the treatment of hyperuricemia in gout: The “dirty dish” hypothesis

Objective

It is commonly accepted that the target serum urate level in patients receiving urate‐lowering therapy for dissolution of urate crystals in hyperuricemia of gout is <6 mg/dl, and that patients with gout should continue urate‐lowering therapy for the rest of their lives. This study was undertaken to reevaluate whether this stringent therapeutic target to dissolve crystals must be maintained lifelong to prevent new crystal formation.

Methods

In a prospective cohort of 211 patients with gout, urate‐lowering therapy was withdrawn after 5 years if no tophus was present at baseline, or 5 years after resolution of the last tophus. Data on recurrence of gout and on serum urate levels and other potentially associated variables were analyzed.

Results

Multivariate regression analysis of time to crystal‐proven recurrence of gout showed that serum urate levels during urate‐lowering treatment and after its withdrawal were independently related to gout recurrence. None of the patients who had average serum urate levels of <7 mg/dl after urate‐lowering therapy withdrawal developed a crystal‐proven recurrence of gout. Post hoc analysis showed that weight loss and use of drugs that lower serum urate, such as losartan or fenofibrate, were associated with serum urate levels of <7 mg/dl during followup after urate‐lowering therapy withdrawal; use of diuretics was associated with failure to achieve serum urate levels of <7 mg/dl during followup.

Conclusion

Our data support the hypothesis that after appropriate long‐term treatment of hyperuricemia in gout with urate crystal dissolution being the therapeutic target, lifelong treatment can be targeted to achieve serum urate levels just below the threshold for saturation to avoid new crystal formation, similar to cleaning a dirty dish: more is required to get it clean than to keep it clean.

     

Diuretic use,increased serum urate levels,and risk of incident gout in a population‐based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study

Objective

To quantify the role of diuretic use in gout development in an adult population with hypertension.

Methods

The Atherosclerosis Risk in Communities study, a prospective population‐based cohort from 4 US communities, consisted of 4 visits over a 9‐year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self‐reported onset of gout after baseline. Using a time‐dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time‐varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level.

Results

There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P < 0.001).

Conclusion

Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

     

Tophaceous hip gouty arthritis revealing asymptomatic axial gout

Background

Hip and axial involvement is uncommon during gout and may raise diagnostic challenges. We describe a rare case of tophaceous hip gout which lead to the diagnosis of asymptomatic axial tophaceous gout at a single rheumatology center.

Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007–2008

Objective

To estimate the prevalence of gout and hyperuricemia based on the latest nationally representative sample of US men and women (National Health and Nutrition Examination Survey [NHANES] 2007–2008).

Methods

Using data from 5,707 participants in NHANES 2007–2008, we estimated the prevalence of gout and hyperuricemia. During home interviews for NHANES 2007–2008, all participants were asked about a history of health professional– or physician‐diagnosed gout. Our primary definition of hyperuricemia was a serum urate level of >7.0 mg/dl for men and >5.7 mg/dl for women. We explored potential secular trends in these estimates and their possible explanations by comparing them with estimates based on 18,825 participants in NHANES‐III (1988–1994).

Results

The prevalence of gout among US adults in 2007–2008 was 3.9% (8.3 million individuals). The prevalence among men was 5.9% (6.1 million), and the prevalence among women was 2.0% (2.2 million). The mean serum urate levels were 6.14 mg/dl among men and 4.87 mg/dl among women, corresponding to hyperuricemia prevalences of 21.2% and 21.6%, respectively. These estimates were higher than those in NHANES‐III, with differences of 1.2% in the prevalence of gout (95% confidence interval [95% CI] 0.6, 1.9), 0.15 mg/dl in the serum urate level (95% CI 0.07, 0.24), and 3.2% in the prevalence of hyperuricemia (95% CI 1.2, 5.2). These differences were substantially attenuated after adjusting for body mass index and/or hypertension.

Conclusion

These findings from nationally representative samples of US adults suggest that the prevalence of both gout and hyperuricemia remains substantial and may have increased over the past 2 decades, which is likely related to increasing frequencies of adiposity and hypertension.

     

Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day,multicenter, phase II,randomized, double‐blind,placebo‐controlled,dose‐response clinical trial examining safety and efficacy in patients with gout

Objective

Gout affects ∼1–2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (≥8.0 mg/dl).

Methods

We conducted a phase II, randomized, double‐blind, placebo‐controlled trial in 153 patients (ages 23–80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.

Results

Greater proportions of febuxostat‐treated patients than placebo‐treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40‐mg, 44% in the 80‐mg, and 59% in the 120‐mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40‐mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8–13%). Incidences of treatment‐related adverse events were similar in the febuxostat and placebo groups.

Conclusion

Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.

     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Central role of complement membrane attack complex in monosodium urate crystal–induced neutrophilic rabbit knee synovitis

Objective

Monosodium urate monohydrate (MSU) crystals promote gouty inflammation that is critically mediated by neutrophil recruitment and activation. Interleukin‐8 (IL‐8) and closely related chemokines are major neutrophil chemotaxins in experimental gout. But MSU crystals also activate the classical and alternative pathways of complement, and MSU crystals directly cleave C5 on the crystal surface. Unlike IL‐8, the roles in acute gout of individual complement‐derived peptides and of the terminal C5b–9 complement components that comprise the membrane attack complex (MAC) are unclear. Hence, we studied rabbits deficient in the MAC component C6 to determine if MAC mediated urate crystal–induced arthritis.

Methods

We injected C6‐deficient and C6‐sufficient rabbit knee joints with 10 mg of pyrogen‐free urate crystals and analyzed IL‐8 levels, leukocyte influx, and joint inflammation 24 hours later.

Results

There was a significant decrease (>60%) in swelling in MSU crystal–injected knees of C6‐deficient animals as compared with C6‐sufficient animals (P < 0.05). An attenuated rise in MSU crystal–induced joint effusion levels of IL‐8 also was observed, which was concordant with diminished numbers of neutrophils (P < 0.05) but not monocytes in MSU crystal–induced knee synovial fluid from C6‐deficient animals. Synovial tissue analysis confirmed mononuclear leukocyte infiltration in response to MSU crystal injection in all animals, but substantial neutrophil infiltration only in C6‐sufficient animals.

Conclusion

MAC activation appears to play a major role in intraarticular IL‐8 generation and in neutrophil recruitment in experimental acute gouty arthritis of the rabbit knee. C6 and MAC activation may represent novel therapeutic targets for suppression of neutrophil‐mediated joint inflammation in gout.

     

Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment

Valdemarsson S, Lindblom P, Bergenfelz A (Departments of Internal medicine and surgery, Lund University Hospital, Lund Sweden). Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 1998; 244 : 241–49.

Objectives

Untreated primary hyperarathyroidism (pHPT) is accompanied by an excessive morbidity in circulatory disorders, associated with blood pressure and diabetes. The aim of the present study was to further penetrate the impact of pHPT on glucose, urate, lipid and lipoprotein concentrations, known to be interrelated metabolic cardiovascular risk factors.

Design

Longitudinal study of patients with pHPT before and 1 year after surgical treatment.

Setting

Departments of Internal Medicine and Surgery, Lund University Hospital.

Subjects

One hundred and seventeen consecutive patients with pHPT referred to surgical treatment. At presentation, 11 patients had previously diagnosed diabetes mellitus.

Intervention

All patients were successfully operated for pHPT.

Main outcome measures

Fasting blood glucose and serum concentrations of cholesterol, triglyceride and urate were determined before and 1 year after surgery. The concentration of LDL- and HDL-cholesterol was separately analyzed in 21 cases. These data as well as the systolic and diastolic blood pressure were related to intact PTH and ionized calcium at presentation. Glomerular filtation was separately measured pre-operatively and related to the urate values.

Results

While the mean value for glucose remained unchanged among 11 patients with previously diagnosed diabetes at presentation, a significant decrease of glucose from 5.03 ± 0.13 to 4.71 ± 0.08 mmol/L (P < 0.05) was found among patients without known diabetes. Out of these patients, eight had diabetic glucose values at presentation, decreasing from 8.35 ± 0.54 to 5.10 ± 0.35 mmol/L (P < 0.05), and 12 had glucose values indicating impaired glucose tolerance, decreasing from 5.94 ± 0.06 to 5.10 ± 0.38 mmol/L (P < 0.05) after surgery. Total cholesterol and trigylceride concentrations were not changed. However, male patients had significantly lower triglyceride levels at follow-up, 1.16 ± 0.09 mmol/L compared to 1.57 ± 0.14 mmol/L before surgery (P < 0.05). Significantly lower triglyceride values were also found among patients with glucose values indicating impaired glucose tolerance at presentation. The LDL/HDL cholesterol ratio remained normal. The serum level of urate decreased in both male and female patients after surgery, and was positively correlated to the PTH and ionized calcium values and inversely correlated to renal function before treatment. There was no significant correlation between calcium or PTH and the other metabolic variables studied.

     

Development of the American College of Rheumatology Electronic Clinical Quality Measures for Gout

Objective

Electronic clinical quality measures (eCQMs) are increasingly used by health registries and third parties to evaluate and improve the quality of health care. To complete these eCQMs, data are extracted from electronic health records (EHRs). The treatment of gout has been an area identified with gaps in quality of care. On behalf of the American College of Rheumatology (ACR), we sought to develop and test eCQMs to evaluate gout care.

Methods

Drawing from the 2012 ACR gout guidelines, a working group developed candidate gout process measures that were evaluated by an interdisciplinary panel of health care stakeholders, the ACR Quality Measures Subcommittee (QMS), and ultimately the ACR Board of Directors for formal validity testing. For each of the selected gout eCQMs, 3 clinical sites using different EHR systems tested the scientific feasibility and validity of the measures. Measures appropriate for accountability were presented for national endorsement.

Results

Of the 10 proposed eCQMs, 4 were endorsed by the ACR QMS, 3 were incorporated into the ACR's Rheumatology Informatics System for Effectiveness (RISE) Registry, and 2 were endorsed by the National Quality Forum. The 3 eCQMs incorporated into RISE (evaluating indications for urate‐lowering therapy [ULT]), monitoring serum urate, and treat‐to‐target outcome) demonstrated high validity and reliability. Proportions of patients passing these 3 eCQMs in RISE and at the 3 clinical testing sites ranged between 32% and 58%, indicating significant room for improvement in care.

Conclusion

Three eCQMs have been validated and implemented into RISE. Two of these measures (evaluating indications for ULT and monitoring serum urate) are available for use in federal quality reporting programs. Performance on these measures suggests there is significant room for improvement in the management of gout.

     

Epidemiology of gout in women: Fifty‐two–year followup of a prospective cohort

Objective

Despite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men.

Methods

Using prospective data from the Framingham Heart Study, we examined over a 52‐year period (1950–2002) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men.

Results

We documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person‐years according to serum uric acid levels of <5.0, 5.0–5.9, 6.0–6.9, 7.0–7.9, and ≥8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction = 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index ≥30 kg/m²), alcohol intake (≥7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women.

Conclusion

These prospective data with long‐term followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women.

     

Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air‐pouch model of acute gouty arthritis

Objective

To examine the role of chemokines, S100A8, and S100A9 in neutrophil accumulation induced by the causative agent of gout, monosodium urate monohydrate (MSU) crystals.

Methods

MSU crystal–induced neutrophil migration was studied in the murine air‐pouch model. Release of chemokines, S100A8, S100A9, and S100A8/A9 in response to MSU crystals was quantified by enzyme‐linked immunosorbent assays. Recruited cells were counted following acetic blue staining, and the subpopulations were characterized by Wright‐Giemsa staining of cytospins.

Results

MSU crystals induced the accumulation of neutrophils following injection in the air pouch, which correlated with the release of the chemokines CXCL1, CXCL2, CCL2, and CCL3. However, none of these was found to play an important role in neutrophil migration induced by MSU crystals by passive immunization with antibodies directed against each chemokine. S100A8, S100A9, and S100A8/A9 were also found at high levels in the pouch exudates following injection of MSU crystals. In addition, injection of S100A8, S100A9, or S100A8/A9 led to the accumulation of neutrophils in the murine air pouch, demonstrating their proinflammatory activities in vivo. Passive immunization with anti‐S100A8 and anti‐S100A9 led to a total inhibition of the accumulation of neutrophils. Finally, S100A8/A9 was found at high concentrations in the synovial fluid of patients with gout.

Conclusion

S100A8 and S100A8/A9 are essential to neutrophil migration induced by MSU crystals. These results suggest that they might be involved in the pathogenesis of gout.

     

Serum pulmonary and activation‐regulated chemokine/CCL18 levels in patients with systemic sclerosis: A sensitive indicator of active pulmonary fibrosis

Objective

To clarify the clinical significance of serum levels of pulmonary and activation‐regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL‐6 antigen or surfactant protein D (SP‐D) levels.

Methods

Serum PARC levels were determined by enzyme‐linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF.

Results

PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF.

Conclusion

Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL‐6 or SP‐D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.

     

Engagement of fatty acids with toll‐like receptor 2 drives interleukin‐1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal–induced gouty arthritis

Objective

The concept that intraarticular crystals of uric acid by themselves trigger episodes of painful gouty arthritis is inconsistent with the clinical reality. Patients with large deposits of monosodium urate monohydrate (MSU) crystals (tophi) do not necessarily experience gouty attacks. In fact, it is the excessive consumption of food or alcohol that elicits the inflammation of the acute gout attack. The aim of this study was to identify the precise mechanism that initiates flares of gouty arthritis.

Methods

Human peripheral blood mononuclear cells (PBMCs) and murine macrophages were stimulated in vitro with MSU, free fatty acids (FFAs), or both in combination. Thereafter, production of interleukin‐1β (IL‐1β) and activation of caspase 1 were determined. Gouty arthritis was induced in mice with deficiencies in the genes for caspase 1, ASC, NALP3, or IL‐1β, and the lack of inflammasome activity during joint swelling or other joint pathologic features was investigated in these mice.

Results

MSU crystals had no biologic effects on PBMCs from healthy subjects, whereas the FFA C18:0 in the presence of MSU crystals induced the release of large amounts of IL‐1β following engagement of Toll‐like receptor 2 (TLR‐2). Interaction of FFAs, but not alcohol, with TLR‐2 synergized with MSU crystals to induce an inflammatory reaction. An important event of MSU/FFA‐induced acute joint inflammation is the activation of the inflammasome. MSU/FFA‐induced release of IL‐1β was dependent on activation of caspase 1 and ASC, but surprisingly, not NALP3.

Conclusion

The synergistic effect between FFAs and MSU crystals leads to ASC/caspase 1–driven IL‐1β release. This mechanism could explain how constitutionally derived metabolic events initiate attacks of gout via the induction of IL‐1β–mediated joint inflammation.

     

Serum levels of matrix metalloproteinase 3 and macrophage colony‐stimulating factor 1 correlate with disease activity in ankylosing spondylitis

Objective

To assess the usefulness of measuring serum matrix metalloproteinase 3 (MMP‐3) and macrophage colony‐stimulating factor (M‐CSF) in patients with ankylosing spondylitis (AS).

Methods

Serum levels of MMP‐3 and M‐CSF were measured in AS patients who did and did not receive infliximab treatment. These were compared with those of 28 healthy subjects.

Results

In the group of AS patients not treated with biologics, both M‐CSF and MMP‐3 correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) values, but not with each other. Logistic regression analysis showed that MMP‐3 values were high in those with severely active disease. Infusions of infliximab in AS patients led to a significant decrease in the values of the BASDAI as well as the serum MMP‐3, but no change in the serum M‐CSF values.

Conclusion

MMP‐3 and M‐CSF are potentially useful markers of AS disease activity.

     

Anti–tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection

Objective

To examine the safety of using anti–tumor necrosis factor (TNF) therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C virus (HCV) infection.

Methods

The charts of 5 patients known to have RA requiring anti‐TNF therapy as well as established HCV infection were reviewed retrospectively for laboratory data of hepatic parenchymal inflammation and viral proliferation while taking these agents.

Results

In a mean ± SD followup period of 41 months (± 28.2 months), no patient displayed evidence of sustained elevation of serum aminotransferases during therapy with anti‐TNF. Additionally, 1 patient was observed to have a decreased HCV viral load after extended treatment with only anti‐TNF (no therapy for HCV).

Conclusion

Anti‐TNF therapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection. Therefore, this approach should be further evaluated prospectively for longterm safety.

     

Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery

Lindgren A, Lindstedt G, Kilander AF (Borås Central Hospital and Sahlgrenska University Hospital, Göteborg, Sweden). Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery. J Intern Med 1998; 244 : 341–349.

Objectives

Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency.

Design

Clinical study of consecutive patients.

Setting

The catchment area of Sahlgrenska University Hospital, Göteborg.

Subjects

A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery.

Interventions

Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin.

Main outcome measures

Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin.

Results

About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests.

Conclusions

Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.

     

Low circulating leptin levels in protein-energy malnourished chronically ill elderly patients

Cederholm T, Arner P, Palmblad J (Karolinska Institute at the Centre for Inflammation & Hematology Research, and Huddinge University Hospital, Huddinge, Sweden). Low circulating leptin levels in protein-energy malnourished chronically ill elderly patients. J Intern Med 1997; 242 : 377–82.

Objective

To evaluate serum leptin, a fat cell-derived protein, levels in relation to the malnutrition often observed in chronic disease.

Design

A comparison of circulating leptin concentrations in malnourished chronically ill elderly and in age-matched controls.

Setting

A university-affiliated teaching hospital in Stockholm, Sweden.

Subjects

Nineteen protein–energy malnourished elderly patients (74 ± 1 years) with various chronic nonmalignant diseases and 18 healthy controls (72 ± 1 years).

Main outcome measures

Serum leptin levels measured by radioimmunoassay technique, nutritional status as expressed by body mass index (kg m^?2), triceps skin fold, arm muscle circumference and serum albumin, and serum orosomucoid concentrations indicating inflammatory status.

Results

Patients and controls displayed body mass indexes of 17.4 ± 0.7 and 25.0 ± 1.1 (P < 0.001), respectively. Triceps skin fold (TSF) measurements revealed a pronounced fat depletion in the patients, being 8.5 ± 0.9 and 22.3 ± 1.5 mm (P < 0.001) in female and 6.1 ± 0.7 and 10.8 ± 0.8 mm (P < 0.001) in male patients and controls, respectively. Patient serum leptin concentrations were less than half of the corresponding concentrations in the controls, 4.3 ± 1.1 and 9.3 ± 1.3 ng mL^?1 (P < 0.01), respectively. The highest leptin concentrations were registered in female controls, 12.1 ± 1.6 ng mL^?1. The serum leptin levels in the controls correlated with TSF (r= 0.74; P < 0.001). No such correlation was found in the patients.

Conclusions

Serum leptin levels were low and did not seem to be directly associated with fat and muscle depletion in elderly patients with chronic illness, whereas they appeared to be positively correlated to body fat in healthy elderly.