Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease.

BACKGROUND: Refractory sprue with malabsorption carries a risk of lymphoma. AIM: To examine whether a good clinical but poor histological response during a strict gluten-free diet predicts a poor outcome. METHODS: The study involved all coeliac patients who showed no histological recovery within 2 years on a strict gluten-free diet. Small intestinal biopsy and bone mineral density were investigated in 2001 and clinical features were followed up until 2005. The results were compared to those in 18 coeliac patients with a good histological recovery. RESULTS: Thirteen coeliac patients had persistent small intestinal villous atrophy despite maintaining gluten-free diet. All had demonstrated a good clinical response. Osteoporosis was found in 58% and 22% of the non-responders and responders, respectively (P = 0.04). In 2005, two of the non-responders had developed symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour, and one gastric adenocarcinoma was operated. None of the 18 controls had developed refractory sprue or malignancy. The frequency of histological non-responsive disease was 1.9%. CONCLUSIONS: Persistent villous atrophy in adult coeliac disease, even in the absence of symptoms, carries a risk of subsequent severe complications. The follow-up biopsy is important in detecting these individuals.

Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Nutritional status of newly diagnosed celiac disease patients before and after the institution of a celiac disease diet--association with the grade of mucosal villous atrophy.

No systematic studies have been carried out on the association of nutritional status with the severity of mucosal villous atrophy in newly diagnosed celiac disease patients. We examined the nutritional status of 40 adult patients with newly diagnosed celiac disease classified according to the grade of villous atrophy: partial, subtotal, and total. Nutritional status was determined by food records as well as by anthropometric and biochemical measurements. Anthropometric results did not differ among the three atrophy groups, but serum ferritin and erythrocyte folate were lower in patients with total villous atrophy than in the other groups. Most of the abnormal biochemical values were normalized during 1 y of a gluten-free diet; villous atrophy healed concomitantly. To conclude, patients with total mucosal villous atrophy at diagnosis had low erythrocyte folate and serum ferritin values, but no other major differences were found in nutritional status among celiac disease patients with different grades of villous atrophy.

Osteoporosis in adult patients with celiac disease.

We investigated the bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in adult celiac patients with varying disease states. In this cross-sectional study the data on the severity of celiac disease and BMD were collected from 77 celiac patients (28 newly diagnosed and 49 previously diagnosed celiac patients), and BMD results were compared with those of 157 control subjects matched for age, gender, and menopausal status. The celiac patients had significantly lower BMD than the control subjects at the lumbar spine (-6%) and femoral neck (-5%). The mean BMD did not differ significantly among celiac patients classified by severity of disease. Based on Z scores, 35% of the celiac patients and 17% of the control subjects had low BMDs for age at the lumbar spine (p = 0.005), whereas 31% of celiac patients and 16% of control subjects had Z scores of < or =-1 at the femoral neck (p = 0.01). Altogether, 26% of all celiac patients, but only 5% of control subjects, were classified as having osteoporosis (T score < or =-2.5 SD) at the lumbar spine (p = 0.03), whereas osteoporosis was rare at the femoral neck in both groups (3% vs. 1%, p = 1.00). Prevalence of osteopenia and osteoporosis was highest in newly diagnosed celiac patients and in patients with disease not in remission. A low 25-(OH)D vitamin concentration was a typical biochemical abnormality in our patients (64% of men and 71% of women). The main associated variables of low BMD were age (men), low serum vitamin D level, low body weight, and postmenopausal status (women). The present study suggests that celiac disease constitutes a risk factor for osteoporosis. This finding applies particularly to untreated and poorly treated patients.

Sucralfate as maintenance treatment for the prevention of duodenal ulcer recurrence.

Eighty-eight patients with endoscopically proven and healed duodenal or pyloric ulcer were randomly allocated into a double-blind, placebo-controlled, 12-month maintenance trial to determine whether sucralfate, 1 g twice daily, can be used to prevent a recurrence of ulceration. The patients were assessed endoscopically at three, six, and 12 months, or earlier if a symptomatic relapse occurred. Serum aluminum levels were also monitored. Sixteen patients were excluded from the study during the follow-up: nine of 41 in the sucralfate group, and seven of 47 in the placebo group. The groups did not differ with respect to age, sex, or smoking. The cumulative relapse rates in the sucralfate group were 28 percent after three months, 33 percent after six months, and 45 percent after 12 months, as compared with 49 percent (p less than 0.05), 64 percent (p less than 0.01), and 68 percent (p less than 0.05), respectively, in the placebo group. It is concluded that 1 g sucralfate twice daily is more effective than a placebo and is safe for the maintenance treatment of duodenal and pyloric ulcer disease.

Budesonide enema in active haemorrhagic proctitis--a controlled trial against hydrocortisone foam enema.

BACKGROUND: The aim was to compare budesonide enema, 2 mg/100 mL (Entocort) and hydrocortisone acetate foam enema, 125 mg (Colifoam) in patients with active haemorrhagic proctitis. METHODS: The trial was a controlled, randomized, investigator-blind study with two parallel groups. Endoscopy, histology and diary cards were used to assess the response to therapy. Safety was assessed by laboratory tests and adverse event recording. RESULTS: Seventy-two patients were included. Investigations were made before treatment and after 2 and 4 weeks. Both treatment groups showed statistically significant improvement in endoscopic scores but significant differences between the groups were not found. In the hydrocortisone group, plasma cortisol was significantly lowered after 4 weeks compared with budesonide. Bowel habits and quality of life variables did not differ between the treatments. The recorded adverse events were mild or moderate and may have been due to the proctitis. CONCLUSIONS: These results suggest that budesonide enema is as effective as hydrocortisone foam enema, but without the potential for side-effects associated with suppression of plasma cortisol.

Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma.

The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer.

Nuclear magnetic resonance spectroscopy of plasma to distinguish between malignant and benign diseases causing jaundice and cholestasis.

The sera of 51 patients with malignant (n = 25) and benign (n = 26) hepatopancreatobiliary disorders were analysed by 1H magnetic resonance spectroscopy (NMR) in order to distinguish between malignant and benign diseases causing jaundice and/or cholestasis. Macromolecular linewidths were determined both manually and automatically with a computed analysis, and both methylene (CH2) and methyl (CH3) resonances were evaluated. The mean linewidth of the CH3 peak was significantly narrower in the patients with malignant disease than in the patients with benign disease both in the manual and computed analyses, but no significant differences in the CH2 peak were detected. Diagnostic sensitivity and specificity of the CH3 peak determined in the computed analysis were 92% and 27% respectively. In the light of the current study, it seems obvious that because overlap between benign and malignant groups was too great, 1H NMR spectroscopy of plasma is not of practical value in distinguishing between benign and malignant causes of jaundice and/or cholestasis.

Occurrence of antibodies to teichoic acid in patients with diseases other than staphylococcal infection.

To determine the usefulness of the teichoic acid antibody (TAA) test in conditions where unspecific viral and bacterial antibodies are often encountered, we measured TAA by the gel-diffusion method in 475 patients without known staphylococcal disease; they included 213 patients with arthritis, 108 with liver diseases, 100 with gastro-intestinal disorders and 54 with acute pharyngitis. Positive controls were 104 patients with Staphylococcus aureus bacteraemia and 203 healthy adults were negative controls. Thirteen (6%) of the healthy adults had positive TAA titres (greater than or equal to 4), and the highest titre was 8 in two people (1%). Positive titres were found in 38% of patients with S. aureus bacteraemia and high titres (greater than or equal to 8) were seen in 24%. Among the patients with arthritis, positive TAA titres were found significantly more often than in healthy controls in patients with Yersinia arthritis (p less than 0.01) and systemic lupus erythematosus (SLE; p less than 0.02). In other patient groups, the percentage of positive TAA titres did not differ significantly from that in healthy adults. Eight (2%) of the 475 patients without known staphylococcal infection had TAA titres greater than or equal to 8 but these high titres were not associated with any particular disease group. Only two of these eight patients had slightly raised antibody to staphylococcal alpha-haemolysin. We conclude that the TAA test cannot be used as a reliable indicator of septic staphylococcal disease in patients with Yersinia arthritis or SLE, but that in general, TAA titres greater than or equal to 8 point strongly to S. aureus infection even in patients with autoimmune or liver diseases.

Effect of acetaldehyde and acetylsalicylic acid on HbA1c chromatography in the FPLC method with Mono S cation exchanger.

The effects of alcohol and aspirin on HbA1c chromatography in the Mono S method were studied in vitro and in vivo. A modified chromatography with enhanced resolution was used, making possible detailed examination of minor interfering peaks included in the routine HbA1c value. Incubation with acetylsalicylic acid increased a hemoglobin fraction separate from HbA1c. In vivo this fraction was elevated by 0.1% of the total hemoglobin during therapeutic aspirin ingestion for one month. In vitro acetaldehyde generated two labile hemoglobin fractions and slightly increased a minor stable fraction which was also elevated in vivo in both alcoholics and heavy drinkers. In relation to the HbA1c concentration, this stable fraction was equal in both alcoholic groups. We conclude that the in vivo effects of both aspirin and alcohol are negligible in routine HbA1c determination. Factors other than acetaldehyde might account for the unexpected HbA1c values in alcoholics.

Clinical evaluation of tissue polypeptide antigen (TPA) in the diagnosis of pancreatic carcinoma.

The serum values of tissue polypeptide antigen (TPA) were measured in a prospective series of 100 patients with jaundice, 54 patients with suspicion of chronic pancreatitis or a pancreatic tumour, and 19 patients with unjaundiced cholestasis to assess its value in diagnosing pancreatic cancer. There were altogether 25 patients with a cancer of the pancreas including 2 patients with a cancer of the papilla of Vater. The highest serum TPA values were noticed in patients with pancreatic cancer, but raised values were also seen in patients with malignant or benign liver diseases, and with cholangiocarcinoma. The sensitivity of TPA was 52% with a specificity of 85% and an efficiency of 80%. In comparison to CEA, CA 50 and CA 242, TPA showed lower sensitivity but higher specificity. When TPA was combined with the other markers, the specificity and efficiency improved clearly in all combinations, being highest in that of TPA and CA 242 (specificity 94.5%, efficiency 87.2%). The results suggest that the TPA test has a useful complementary role in the clinical use of the current serum tumour markers in the diagnosis of pancreatic cancer.

The value of combined use of serum tumour markers and nuclear magnetic spectroscopy of plasma in the detection of pancreatic cancer among patients with jaundice or cholestasis: results from a prospective study.

We studied a combined utilization of serum tumour markers and proton nuclear magnetic resonance 1H NMR spectroscopy of plasma in the detection of pancreatic cancer. Serum concentrations of carcinoembryonic antigen (CEA), carboanhydrate antigens CA 50 and CA 242, and 1H NMR spectra of plasma were determined in a series of 51 patients, of whom 25 had malignant and 26 benign hepatopancreatobiliary disorder. The measurements in 1H NMR spectra were performed both manually and by computed technique, and both methylene (CH2) and methyl (CH3) peaks were evaluated. In the patients with pancreatic cancer (n = 17, including two cases of cancer of the papilla of Vater), the mean serum values of all tumour markers were significantly (p = 0.001) higher than in the patients with benign disease. The diagnostic sensitivity of the tumour markers alone reached 82-100% with a specificity of 35-82%. In the 1H NMR spectra of sera, the mean linewidth of the CH3-peak both in the manual and computed measurement was significantly narrower in the patients with pancreatic cancer than in the benign disease group. Using the cut-off level of 33 Hz, the sensitivity and specificity of 1H NMR alone was in the manual measurement 53% and 76%, respectively, while in the computed measurement the corresponding figures were 94% and 20%. When the serum tumour markers and 1H NMR spectroscopy were evaluated as combinations, both in the manual and computed measurements the specificities and positive likelihood ratios were clearly better than those of the tumour markers alone, but efficiencies improved only slightly. The results suggest that the combined use of tumour marker tests and 1H NMR of plasma gives only slightly improved accuracy in the diagnosis of pancreatic cancer.

Multivariate analysis of six serum tumor markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and conventional laboratory tests in the diagnosis of hepatopancreatobiliary malignancy.

A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatobiliary disease was carried out to evaluate the value of six serum tumour markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and 16 conventional laboratory tests in the distinction between benign and malignant diseases. In univariate analysis, all tumour marker tests except TATI showed significantly (p < 0.001) higher serum values in the patients with malignant disease than in the patients with benign disease. Among the conventional laboratory tests serum bilirubin, alkaline phosphatase and leucine aminopeptidase showed significantly. (p < 0.001) higher values in the patients with malignant disease, whereas serum protein and amylase levels were significantly (p < 0.01) higher in the patients with benign disease. In a multivariate analysis, serum bilirubin (p < 0.001), antithrombin III (p < 0.01) and blood hemoglobin (p < 0.05) were the most significant independent predictors of hepatopancreatobiliary malignancy. To sum up the contributions of the best tests a diagnostic score (DS) was developed. The sensitivity of DS in detecting malignancy was 73% with a specificity of 82% and an efficiency of 79%. In conclusion, our results speak against the use of multiple tumour marker tests, and rather suggest the use of a relatively limited amount of conventional laboratory tests in the distinction between benign and malignant hepatopancreatobiliary disease.

A prospective study of the value of imaging, serum markers and their combination in the diagnosis of pancreatic carcinoma in symptomatic patients.

The diagnostic accuracy of ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and tumour markers CEA, CA 50 and CA 242 in pancreatic cancer (n = 26) was studied in 113 patients with jaundice, in 20 patients with unjaundiced cholestasis, and in 60 patients with the suspicion of chronic pancreatitis or a pancreatic tumour. The sensitivities of US, CT and ERCP were 61.9%, 95.2% and 82.3%, the specificities 93.9%, 92.9% and 94.1%, and the efficiencies 91.6%, 96.6% and 92.1%, respectively. The sensitivities of CEA, CA 50 and CA 242 were 92.3%, 96.1% and 61.5%, the specificities 59.2%, 58.0% and 95.2%, and the efficiencies 63.7%, 63.2% and 90.6% respectively. The combined use of the imaging methods and tumour markers was also analysed. When either the imaging method or the serum marker test was required to be positive, the sensitivities of the combinations were clearly better than those of US and CA 242 alone, but only slightly better than those of CT, ERCP or the tumour markers CEA and CA 50 alone. When both the imaging test and the marker test were required to be positive, the specificities of the combinations were clearly better than those of CEA and CA 50 alone, but they did not exceed the specificity of the imaging methods or CA 242 alone. We conclude that CT, ERCP and CEA and CA 50 are highly sensitive in the diagnosis of pancreatic cancer in symptomatic patients, while the sensitivity of US and CA 242 is lower. The specificity of the imaging methods and CA 242 is high, but that of CEA and CA 50 is low. Imaging methods and serum tumour markers could be more used in clinical practice in a complementary manner. In patients with jaundice and/or cholestasis or with a suspicion of pancreatic tumour or chronic pancreatitis, the combined use may yield higher sensitivity than US alone and higher specificity than CEA or CA 50 alone.

Clinical value of serum tumour markers CEA, CA 50 and CA 242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis; results from a prospective study.

A prospective study of 113 patients with jaundice and 20 patients with unjaundiced cholestasis was carried out to evaluate the value of serum tumour markers, carcinoembryonic antigen (CEA) and monoclonal antibodies CA 50 and CA 242, in the distinction between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 37) the serum values of all tumour markers were significantly higher than in the patients with benign disease (n = 96). The sensitivities of CEA, CA 50 and CA 242 in detecting malignancy were 70.2%, 94.5% and 56.7%, respectively, while the specificities were 57.2%, 33.3% and 77.0%, respectively. Serum alkaline phosphatase and bilirubin levels had a high positive correlation with CA 50, and CA 242 correlated positively with serum bilirubin levels. No correlation was seen between CEA and alkaline phosphatase or bilirubin levels. The CEA, CA 50 and CA 242 tests may be used as useful complements to other investigative methods in the distinction between benign and malignant causes of jaundice and/or cholestasis. In particular, the rather high specificity of the CA 242 test for malignant diseases seems promising.

Prevalence of gastric metaplasia in the duodenal bulb is low in Helicobacter pylori positive non-ulcer dyspepsia patients.

BACKGROUND: Gastric metaplasia in duodenum is a common phenomena in duodenal ulcer patients. However, the role of gastric metaplasia in patients with non-ulcer dyspepsia is not clear. It is not known either whether Helicobacter pylori infected non-ulcer patients who are CagA-seropositive have gastric metaplasia in duodenum more often than CagA-negative patients. AIMS: To compare prevalence of gastric metaplasia in duodenum in non-ulcer dyspepsia patients according to Helicobacter pylori status. PATIENTS AND METHODS: A series of 400 unselected dyspeptic patients in primary care were investigated. Patients with no endoscopic evidence of organic disease (n=236) were enrolled in the study. Duodenal bulb and gastric biopsies were collected, as well as blood samples for Helicobacter pylori determination. RESULTS: There were no differences between CagA-seropositive and -seronegative Helicobacter pylori infected patients as far as concerns gastric metaplasia in duodenal bulb (20% vs 25%). Helicobacter pylori negative non-ulcer patients more often had gastric metaplastic changes (46%, p<0.0001) in duodenum. CONCLUSION: Helicobacter pylori infection has no major role in development of gastric metaplasia in duodenal bulb in non-ulcer dyspeptic patients. Furthermore, it does not result in positive CagA-serology, an increased risk for gastric metaplasia compared with CagA-seronegative cases.

Elevated blood acetaldehyde in alcoholics with accelerated ethanol elimination.

Alcoholics and controls given ethanol (1.2 g/kg body weight) were analyzed for blood and breath acetaldehyde using the more sensitive and reliable semicarbazide method. The acetaldehyde levels in controls were almost undetectable (less than 2 microM), but were found to be elevated (10--10 microM) in 6 of 8 alcoholics. Breath acetaldehyde and blood acetaldehyde co-fluctuated during the experiments. Fructose infusion transiently increased blood acetaldehyde, but only in 4 of the alcoholics. The apparent discrepancy between our finding and the simultaneously reported low acetaldehyde level in alcoholics (Eriksson and Peachy, this volume) may be explained by the different status of the alcoholics tested. Our alcoholics were tested on the day after hospital admission and eliminated ethanol 5% faster than controls. It is suggested that elevated blood acetaldehyde occurs regularly after interrupted drinking in heavy alcohol abusers with fast ethanol elimination, possibly combined with reduced liver aldehyde dehydrogenase activity, but that the phenomenon may rapidly disappear upon abstinence and hospital treatment, which reduces disturbances in hepatic functions and the ethanol elimination rate.

Diagnostic accuracy of ultrasound, computed tomography and endoscopic retrograde cholangiopancreatography in the detection of pancreatic cancer in patients with jaundice or cholestasis.

A prospective study of jaundiced and/or cholestatic patients (N = 220) was carried out to evaluate the diagnostic accuracy of ultrasound (US), computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) in the detection of pancreatic cancer. Thirty-one patients had the final diagnosis of pancreatic cancer and two patients had a cancer of the papilla of Vater. The sensitivities of US, CT and ERCP were 60%, 97%, 89% and specificities were 92%, 92%, 94%, respectively. The differences in sensitivity between US and other methods were statistically significant (US vs. CT p less than 0.01, US vs. ERCP p less than 0.05). In US studies, most false negative results were caused by unsatisfying visualization. On the basis of this study, we recommend CT as a diagnostic test of pancreatic cancer, if pancreatic cancer is suspected as a cause of jaundice and/or cholestasis.

A prospective study on the value of ultrasound, computed tomography and endoscopic retrograde cholangiopancreatography in the diagnosis of unjaundiced cholestasis.

The purpose of this study was to investigate the diagnostic accuracy of ultrasound (US), computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) in the distinction between extrahepatic and intrahepatic causes of unjaundiced cholestasis. Moreover, attention was paid to the ability of these methods to distinguish between benign and malignant causes of obstruction. The inclusion criteria of laboratory values suggesting cholestasis were serum alkaline phosphatase 350 U/l and gammaglutamyl transpeptidase 100 U/l or liver-specific alkaline phosphatase elevated. The diagnostic value of the imaging methods was tested in 33 patients. The most common cause of unjaundiced obstruction was choledochal stone disease. The diagnostic sensitivities of US, CT and ERCP for the detection of extrahepatic cholestasis were 53%, 53% and 79%, respectively. In patients on whom all three imaging studies were done (n = 20), the difference between US and ERCP was statistically significant (p > 0.05). The specificities of US, CT and ERCP were 100%, 86% and 90%, respectively. CT was better than US in defining the benign nature of obstruction, but ERCP was superior in this respect. In malignant obstructions CT was comparable to ERCP. In conclusion, ERCP seems to be considerably sensitive for the detection of extrahepatic obstruction in cases of unjaundiced cholestasis, whereas US and CT are rather insensitive. The specificity of all these imaging methods is high. The results are in favour of CT as the best noninvasive investigation method, and also indicate the important role of ERCP. However, in many cases all three imaging methods are needed, and a flexible and complementary use of them is recommended.

Breath acetaldehyde: evidence of acetaldehyde production by oropharynx microflora and by lung microsomes.

After alcohol ingestion, acetaldehyde is found in expired air and is thought to originate from blood. However, we found that the ratio of acetaldehyde to ethanol was higher in dead space than in alveolar (end-expiratory) air. This observation suggested production of acetaldehyde in the airways. To study this, we washed the mouth of normal subjects with 10 ml of either saline or 5 mM ethanol. Washings with ethanol produced 5.1 +/- 1.3 nmol/ml of acetaldehyde per minute (vs none with saline). Saline mouth washings incubated with ethanol produced acetaldehyde. This reaction could be prevented by boiling or by microfiltration of the washings suggesting that it was due to microbial enzymes of the oropharynx. We also studied the possibility of pulmonary production of acetaldehyde. Rat lung slices produced 1.32 +/- 0.19 mnol of acetaldehyde/g lung (wet weight)/minute; microsomal production of acetaldehyde was also detected and this was enhanced by chronic ethanol feeding.