Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Buprenorphine versus tramadol as perineural adjuvants for postoperative analgesia in patients undergoing arthroscopic rotator cuff repair under middle interscalene block: a retrospective study.

BACKGROUND: The aim of this retrospective study was to compare buprenorphine and tramadol, in order to assess their different efficacy in prolonging postoperative analgesia and their associated side effects when used as perineural adjuvants with a local anesthetic. METHODS: The clinical records of 161 consecutive ASA 1-2 adult patients scheduled for arthroscopic rotator cuff repair and fulfilling the inclusion/exclusion criteria were reviewed retrospectively. The anaesthesia was performed using the middle interscalene block (MIB). The 161 patients were divided into three groups (A, B, T) according to their utilization of buprenorphine (B), tramadol (T) or neither of the latter (A) as perineural adjuvants: group A (54 patients) - levobupivacaine 0.75%, 0.4 mL/kg; group B (56 patients) - levobupivacaine 0.75%, 0.4 mL/kg + 0.15 mg buprenorphine; group T (51 patients) - levobupivacaine 0.75%, 0.4 mL/kg + 100 mg tramadol. RESULTS: The results showed that the group treated with buprenorphine benefited from a longer post-operative analgesia than that treated with local anesthetic alone (P<0.0001). Otherwise, a less evident not statistically significant (P=0.4825) difference turned out between the group treated with the anesthetic alone and the group treated with tramadol as adjuvant. No difference turned out to be between the local anesthetic alone treatment and the tramadol-local anesthetic one (P=0.4825; HR=0.863, 95% CI 0.574-1.299); on the contrary, a significant difference was demonstrated between the buprenophine-local anesthetic group and the local anesthetic alone one (P<0.0001; HR=0.330, 95% CI 0.216-0.530) CONCLUSION: Both buprenorphine and tramadol are effective as perineural adjuvants used in order to prolong the postoperative analgesia, buprenorphine proving more efficacious for this purpose than tramadol.

Coeliac disease: a histological follow-up study.

AIMS: To assess the histological response to a gluten-free diet (GFD) in a series of coeliac patients in clinical remission, of different ages and with varying degrees of mucosal damage at diagnosis. METHODS AND RESULTS: Biopsy samples from 249 coeliac patients (F 165, M 84) were analysed basally and after clinical and biochemical remission following a GFD. All patients showed an improvement in mucosal findings after starting a GFD, but complete histological normalization was observed in 74.1% of paediatric cases (diagnosed before 14 years of age) and in only 17.5% of adults. Statistical analysis showed that sex, the clinical picture at diagnosis and the length of time between biopsy at the time of diagnosis and on a GFD were not related to histological normalization. In contrast, the age at diagnosis was statistically significantly related to it (P < 0.0001). In addition, the presence/absence of Helicobacter pylori was independent of the normalization of the duodenal mucosa. CONCLUSIONS: In clinical practice the criteria for diagnosis of coeliac disease are sufficiently standardized, whereas for follow-up they are less well defined. We suggest that in order to compare the results from different studies, it should be stated whether remission after treatment is based on clinical or histological criteria or both.

Natural history of hepatitis C virus infection in adult renal graft recipients.

AIM: To study the natural history of hepatitis C virus infection in renal transplantation, 464 HbsAg negative patients were prospectively studied from 1989. METHODS: AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA tests. RESULTS: Two hundred nine patients were antiHCV positive (C+). HCVRNA was confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+ had undergone longer periods of dialysis (P = .0001), were more transfused (P = .01), and included more retransplants (P = .002). Immunosuppression was azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients. Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing cholestatic hepatitis in 2 patients. Histologic progression of liver disease was confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C-) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%, neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75% in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001) and C+ (P = .019) correlated with a worse patient survival. If patients were stratified according to age (<40 vs > or =40), younger C+ patients had a lower survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60% in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72% in C-) (P = .13). CONCLUSION: The presence of C+ significantly reduced both patient and graft survival in the long-term with liver failure being the second most frequent cause of death.

Effect of oral or transdermal hormone replacement therapy on homocysteine levels: a randomized clinical trial.

OBJECTIVE: Aim of this randomized trial was evaluate the effect on homocysteine plasma levels of two different hormone replacement therapy (HRT) formulations in a group of late postmenopausal women. METHODS: Eligible for this study were women: in postmenopause since 5 years or more (confirmed from FSH level > or = 40 mIU/l); with body mass index (BMI) < or = 35; without endocrine, hepatic or renal diseases; not current users of vitamin B or folic acid supplements; not users of any lipid-lowering drugs and sex steroids in the 6 months before trial entry. Group A: oral estradiol valerate 2 mg per day per oral normegestrol acetate 2.5 mg per day (n = 98) for 12 months; Group B: a weekly patch releasing estradiol (50 microg per day) per oral normegestrol acetate 2.5 mg per day (n = 101) for 12 months. RESULTS: The mean values of the homocysteine levels in the group A and B at baseline, 3, 6 and 12 months were 7.9 and 9.1, 8.7 and 8.9, 9.3 and 10.2, 9.6 and 10.2, respectively, the differences between the two treatments were not statistically significant (time by treatment interaction, P = 0.32). Otherwise, the changes of homocysteine level at the four visits was statistically significant (P = 0.0001) in both groups. In particular, in the oral treatment group homocysteine levels increased from baseline of 10.5% at 3 months, of 17.2% after 6 months of therapy and of 21.9% at the end of the study; in the transdermal group, after a little decrease at 3 months (1.5%), the increases were of 12.1 and 12.9%, respectively. CONCLUSIONS: This study does not show any different effect of oral and transdermal treatment with estradiol plus normegestrol acetate on homocysteine levels. Further it does not support previous suggestion of a lowering effect of HRT on plasma homocysteine.

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly.

OBJECTIVE: Ghrelin, a gut-brain peptide involved in the control of energy homeostasis, affects antero-pituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. DESIGN AND METHODS: The effect of ghrelin (3.3 microg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. RESULTS: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6+/-0.6 to 52.9+/-7.8 and from 9.7+/-0.8 to 24.2+/-4.8 microg/l (means+/-S.E.M.), respectively) and acromegalic subjects (from 11.2+/-4.9 to 91.6+/-21.0 and from 42.9+/-26.1 to 113.8+/-79.0 microg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (-80+/-21 vs -17+/-4 pmol/l, P<0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1+/-5.0 to 92.2+/-39.0 pmol/l) and the SS response (from 11.9+/-3.0 to 19.7+/-4.0 ng/l) were quite variable. CONCLUSIONS: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.

Non-transferrin-bound iron in alcohol abusers.

BACKGROUND: Non-transferrin-bound iron, a low-molecular-weight iron complex capable of initiating free radical formation and lipid peroxidation, has been detected in the serum of animals experimentally fed with alcohol, but no data have been reported in alcohol abusers. The purpose of this study was to evaluate whether non-transferrin-bound iron is present in chronic alcohol abusers with liver involvement and whether alcohol plays any part in its appearance. METHODS: We measured non-transferrin-bound iron in a cohort of chronic alcohol abusers with and without liver cirrhosis at presentation, when 43 were active abusers and 33 were abstainers, and in a smaller group during a follow-up period. RESULTS: At presentation, non-transferrin-bound iron was detectable in 83.7% of active abusers but only in 21.2% of abstainers, and within the group of abusers, patients with cirrhosis had significantly higher non-transferrin-bound iron than patients without. Non-transferrin-bound iron was present not only in patients with transferrin saturation >45% but also in those with transferrin saturation < or =45%. Multiple regression analyses revealed that only alcohol intake and total bilirubin were associated independently with non-transferrin-bound iron values. Longitudinal study confirmed the data of the cross-sectional study. CONCLUSIONS: Non-transferrin-bound iron could have a role in initiating or promoting alcohol-induced liver damage.

Kidney transplantation in patients with IgA mesangial glomerulonephritis.

BACKGROUND: Strategies for treating IgA glomerulonephritis (IgAGN) are controversial, particularly with regards to the long-term results of kidney transplantation, including the risk of recurrence of IgAGN post-transplant and the impact of this recurrence on graft survival. METHODS: The outcomes of 106 adults transplanted because of a biopsy-proven IgAGN and of 212 patients without IgAGN transplanted during the same period were analyzed. To evaluate the risk of recurrence, patients with hematuria, proteinuria, or an increase in plasma creatinine were submitted to allograft biopsy. Factors influencing recurrence and the impact of recurrence on graft survival were analyzed. RESULTS: The ten-year patient (0.93 vs. 0.92) and graft survival (0.75 vs. 0.82) probabilities were not significantly different between IgAGN patients and controls. Only plasma creatinine and proteinuria at six months were associated with an increased relative risk (RR) of graft failure (RR 2.79 and 5.94, respectively). Histological recurrence of IgA glomerulonephritis was diagnosed in 37 patients. Younger age (RR 2.63), increased plasma creatinine (RR 2.39), and proteinuria (RR 6.02) at six months were associated with the risk of recurrence. If proteinuria and plasma creatinine at six months were considered in the Cox model, IgA recurrence per se was not associated with an increased risk of graft failure (P = 0.181). The main causes of graft failure were glomerulonephritis in patients with recurrence of IgAGN and chronic rejection in patients without recurrence. CONCLUSIONS: The ten-year graft survival rate was similar in patients with IgAGN or other renal diseases. At least 35% IgAGN patients had biopsy-proven recurrence, and younger patients were more prone to the risk of recurrence. Recurrence did not affect the ten-year graft survival.

Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases.

BACKGROUND: The reported prevalence of gallstone disease (GD), defined as current gallstones or previous cholecystectomy for gallstones, in patients with Crohn disease ranges from 13% to 34%. The aim of this study was to characterize the still undefined risk factors of this complication. METHODS: A total of 330 consecutive patients with Crohn disease (189 males and 141 females aged 17-82 years, mean +/- SD age, 41 +/- 14 years) underwent liver ultrasonography. RESULTS: A diagnosis of GD was made in 78 patients (24%), 54 with current gallstones and 24 who had undergone previous cholecystectomy. Its frequency was comparable in males and females (23% vs 25%), but was significantly associated with age (P =.001), being 13%, 36%, and 51% in patients aged 44 years and younger, 45 to 59 years, and 60 years and older, respectively (P =.001). Its prevalence significantly differed according to the site of the disease at diagnosis (P =.02) and was unrelated to disease duration. Gallstone disease was more frequent in patients who had undergone surgery (34% vs 14%; P =.001) and was significantly associated with the number (P =.001) and site of bowel resections (P =.001), increasing from 28% in the patients who had undergone 1 resection to 53% in those having had 2 or more resections (P =.005) and being significantly higher in patients with a resection involving the ileocecal region. Multivariate analysis showed that age; site of disease at diagnosis; and the presence, number, and site of bowel resections were significantly related to GD. CONCLUSIONS: In patients with Crohn disease, the frequency of GD is significantly higher than that reported in the general population with comparable characteristics (z = 5.04, P<.001). Age; site of disease at diagnosis; and the history, number, and site of bowel resections are independently associated with GD.

Serological markers for coeliac disease: is it time to change?

BACKGROUND: Anti-gliadin and anti-endomysium antibodies are useful markers in the screening and follow-up of coeliac disease. The recent finding that tissue transglutaminase is the main auto-antigen of anti-endomysium has led to the discovery of anti-tissue transglutaminase antibodies. AIM: To compare, in a prospective study, the diagnostic accuracy of anti-tissue transglutaminase, anti-gliadin and anti-endomysium antibodies in a large series of adult patients. METHODS: The study involved 80 consecutive subjects undergoing upper gastrointestinal tract endoscopy for suspected coeliac disease (subsequently confirmed in 40 cases), 195 coeliac patients on a gluten-free diet, and 70 patients with different gastrointestinal disor ders and normal duodenal histology. Anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies levels were measured using commercial kits. RESULTS: The diagnostic sensitivity and specificity of anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were, respectively, 95% and 89.1%, 100% and 97.3%, and 100% and 98.2%: the agreement between the markers was substantial or almost perfect. In terms of follow-up, the positivity of the markers varied according to the strict adherence to, and duration of the gluten-free diet; the agreement between antiendomysium and anti-tissue transglutaminase antibodies was almost perfect. CONCLUSIONS: Anti-endomysium and anti-tissue transglutaminase antibodies are both highly efficient for routine laboratory screening: the choice of one or the other will depend on the available facilities. However, neither can replace intestinal biopsy for general population screening because, in this case, their respective positive predictive values are only 15.7% and 21.8%. During follow-up, anti-gliadin retain their value as an early predictor of gluten ingestion.

Clinical relevance of microvessel density in laryngeal squamous cell carcinomas.

The clinical implications of microvessel density (MVD) in head and neck tumors have not been fully elucidated. We investigated the clinicopathologic correlates and prognostic relevance of MVD in a series of 122 consecutive patients with surgically treated laryngeal squamous cell carcinoma followed-up for a mean of 79 months. MVD was evaluated after CD34 immunostaining in 3 250x microscopic fields representative of the "hot spot" area, and expressed as the mean value of the vessel counts per millimeter squared. The overall median value of the intratumoral vessel count was 69.5/mm(2). In the 20 cases we analyzed, MVD increased significantly from normal to dysplastic mucosa and infiltrating carcinoma (p = 0.0001). Nineteen carcinomas (15.6%) had MVD values that were equal to or lower than the highest MVD value (52.7/mm(2)) observed in normal mucosa samples (in which the median MVD count was 34.5/mm(2), range 16.6-52.7/mm(2), mean 35.1 +/- 11.5/mm(2)) and were therefore considered poorly vascularized. Periodic acid-Schiff (PAS) staining revealed intratumoral PAS-positive connective tissue septa in 13 cases (10.7%). The patients with poorly vascularized tumors showed a tendency toward a better prognosis, but the anatomical site, tumor extension and clinical stage were the only variables significantly associated with disease-free and overall survival.

Obstructing colonic cancer: failure and survival patterns over a ten-year follow-up after one-stage curative surgery.

BACKGROUND: Large-bowel cancers that present as obstructing lesions have a poor prognosis. However, little is known of the reasons for the dismal survival and of failure patterns after potentially curative treatment. METHOD: An observational study and multivariate analysis were conducted to identify determinants of survival and to compare recurrence patterns between obstructing and nonobstructing tumors after primary resection and anastomosis as curative treatment. RESULTS: Over a period of ten years (1980-1989), 528 patients with colonic cancer were treated at one institution. The cancer was obstructing in 179 cases and nonobstructing in 349. One-stage primary resection and anastomosis as curative treatment were performed in 107 obstructed and 256 nonobstructed patients. Three hundred thirty-six potentially cured survivors (94 in the former group and 242 in the latter) were followed for a median of 55 months. During follow-up, local recurrence occurred in 37 patients (12 obstructed (12.8 percent) and 25 nonobstructed (10.4 percent), P = 0.44) and metastatic disease in 68 (25 obstructed (27.6 percent) and 43 nonobstructed (17.8 percent), P = 0.029). Multivariate analysis of survival showed that age over 70 years, Dukes stage, histologic grade, and recurrence were the only prognostic factors. No statistically significant determinant turned out for local recurrence, whereas at multivariate analysis for metastatic and overall relapse, Dukes stage, positive nodes, and obstruction remained independent prognostic factors. CONCLUSIONS: After one-stage emergency curative treatment, patients presenting with obstructing tumors of the colon have a smaller survival probability than that of patients with nonobstructing lesions. Local recurrence pattern is similar between groups. Conversely, obstruction, along with pathologic stage and positive nodes, carries a significantly higher risk of metastatic tumor recurrence and death.

Increased frequency dependence of specific airway resistance in patients with laryngeal hemiplegia.

The aim of this study was to investigate whether patients with laryngeal hemiplegia (LH) show a frequency-dependent increase in specific airway resistance (sRaw), measured by body plethysmography. In addition to the flow-volume loop, usually considered in the functional evaluation of upper airway obstructions, variations in sRaw at respiratory frequencies of 30+/-5 (=0.5 Hz), 60+/-5 (=1 Hz) and 90+5 breaths x min(-1) (=1.5 Hz) in 21 never-smoking patients (LH group, mean age+/-SD 55+/-12.09 yrs; 17 females) whose unilateral vocal-cord paralysis was documented by laryngoscopy and who had no signs or symptoms of other respiratory diseases studied. They were compared to 21 healthy control subjects (C group: 50.1+/-15.44 yrs; 10 females). The sRaw values at 30+/-5 breaths min(-1) were similar in the two groups (5.54+/-1.88 versus 5.68+/-1.06 cmH2O x s(-1); p=NS), but at increasing frequencies (30+/-5, 60+/-5 and 90+/-5 breaths min(-1)), they progressively and significantly increased in the LH patients (from 5.54+/-1.88 to 6.63+/-1.96 and 8.05+/-2.6 mH2O x s(-1); p<0.0005), and not significantly in controls (5.68+/-1.06, 5.85+/-0.95 and 5.9+/-1.12 cmH2O x s(-1); p=NS). Linear discriminant analysis using AsRaw (sRaw at 1.5 Hz-sRaw at 0.5 Hz) and forced inspiratory flow at 50% of the vital capacity made it possible to correctly classify all of the controls and 19 of the 21 patients. In conclusion, the multiple, rapid and noninvasive plethysmographical testing of frequency-dependent increase in specific airway resistance with the flow-volume loop, allows the sufficiently satisfactory discrimination of laryngeal hemiplegia patients from controls.

Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation.

OBJECTIVES: To assess the incidence of shoulder-hand syndrome (SHS) in neurosurgical patients (head injuries, intracranial ruptured aneurysms and intracranial meningiomas), treated with barbiturates. SHS is a chronic condition characterized by intense tenderness and functional impairment affecting one hand, the shoulder or both. Barbiturates have been identified as cause of SHS, although there is controversial evidence on the incidence of this disorder in patients started on long-term Phenobarbital (PB) therapy. METHODS: One hundred and twenty-six neurosurgical patients, treated with barbiturates, and a control group of 108 patients, treated with carbamazepine or phenytoin, were enrolled. Both groups were followed up for at least 24 to 36 months. RESULTS: Thirty-five PB-treated patients (27.6%) experienced SHS. In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction. None of the patients in the control group developed SHS. CONCLUSIONS: The occurrence of SHS in the study group was much more common than that reported previously. This higher incidence should depend upon the coexistence of separate risk factors such as age over 50 years, surgery and intracranial pathology. Early diagnosis and rapid withdrawl of treatment are important for symptomatic relief and full functional recovery.

Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes.

BACKGROUND: The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control. RESULTS: Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059). CONCLUSIONS: Our study indicates that the expression of cyclin D1 correlates with the presence of occult cervical metastases in head and neck carcinoma patients, thus suggesting that its immunohistochemical evaluation in biopsy samples may be used as an additional tool for identifying patients to be treated with elective neck dissection.

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had

Chronic unexplained hypertransaminasemia may be caused by occult celiac disease.

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained hypertransaminasemia.

Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron.

Carbohydrate-deficient transferrin (CDT), a microheterogeneous form of serum transferrin (Tf), has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported. We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH). In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 +/- 16.5 U/L vs. 33.3 +/- 11.7 U/L; P <.01), with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6 +/- 2. 2 U/L vs. 15.7 +/- 3.3 U/L; P <.0001), whereas, patients with iron deficiency anemia had significantly higher levels than controls (28. 1 +/- 5.8 U/L vs. 15.7 +/- 3.3 U/L; P <.0001). In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7 +/- 6.6 U/L vs. 21.7 +/- 5.2 U/L; P =.0007), while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 +/- 2.0 U/L vs. 14.7 +/- 4.0 U/L; P =.001). Alcohol abusers had a significant relationship between liver iron concentration (LIC) and the reciprocal of CDT (r =.65; P <.0001), while in nonabusers, there was a significant correlation between Tf and CDT (r =.72; P <.0001). In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.