Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake.

Calcium malabsorption, hypocalcemia and skeletal demineralization are well-recognized features of untreated celiac disease. This study investigates calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a gluten-free diet. Twenty-four adult females with treated celiac disease and twenty age- and sex-matched control subjects were studied. Mean body mass index (MBI), energy intake, serum calcium, and serum 25(OH)D concentrations in treated celiacs did not differ from controls. However, while both dietary calcium and protein intake were significantly higher in celiacs (P<0.012), fractional calcium absorption was lower (mean percentage+/-SD; treated 39.8+/-12 versus controls 52.3+/-10, P<0.001). Thus, after adjusting for calcium intake, the estimated amount of calcium absorbed daily was similar in both groups. Whole body, spine and trochanter BMD were significantly lower in treated celiac patients compared with controls (P<0.05). There were significant inverse correlations between: serum parathyroid hormone (PTH) and femoral neck or total body BMD (P<0.01), PTH and duration of gluten-free diet (P=0.05), and fractional calcium absorption and alkaline phosphatase (P=0.022). Increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac patients, but may not normalize the BMD. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac patients.

Efferent loop small intestinal vitamin D receptor concentration and bone mineral density after Billroth II (Polya) gastrectomy in humans.

Animal studies have demonstrated that the highest concentration of vitamin D receptors (and greatest capacity for active calcium absorption) occurs in the proximal duodenum. By passing the duodenum following Polya/Billroth II gastrectomy could result in the development of a metabolic bone disease and low bone mineral density (BMD). We thus compared the vitamin D receptor (VDR) concentration in mucosal biopsies taken at endoscopy from two functionally corresponding areas of the small intestine: the jejunum (or efferent loop) in 21 patients with a history of Polya/Billroth II gastrectomy and the second part of the duodenum in age/sex-matched control subjects. We also measured the BMD by dual energy X-ray absorptiometry. The mean VDR concentration was not significantly different between the two groups (patients vs controls, fmol/mg protein, mean +/- SE: 34.99 +/- 2.57 vs 34.67 +/- 3.71; P = 0.22), even when subgrouped as males (36.22 +/- 3.16 vs 31.2 +/- 4.24; P = 0.351) or females (31.93 +/- 4.7 vs 43 +/- 6.76; P = 0.193). In Polya/Billroth II gastrectomy patients, the VDR concentration in the efferent loop declined with age (r = -0.78, P = 0.02). In the same group, BMD, as compared with matched controls, was significantly reduced at the lumbar spine (Z-score: patients vs controls: -1.138 vs 0.099, P = 0.01), but not at the femoral neck (Z-score: -0.69 vs 0.7, P = 0.084). There was no correlation between VDR and time since operation or BMD. These results suggest that following Polya/Billroth II gastrectomy, the functional capacity of the jejunal efferent loop in reference to VDR concentration is similar to that of the second part of the duodenum in normal subjects. Therefore, the reduced BMD in our patients, also a common finding in other studies, may not be secondary to the reduced capacity of the VDR system that facilitates the active calcium transport pathway in the proximal small intestine.

Gallstone ileus: a new role for abdominal computed tomography.

This case report illustrates the difficulties in making the clinical diagnosis of gallstone ileus. In addition to an unusual clinical picture, the changes normally expected on abdominal X-ray in gallstone ileus were subtle and missed in our patient. The diagnosis was made using abdominal computerised tomography (CT). We recommend the early use of abdominal CT scanning in the investigation of clinical bowel obstruction, especially in the elderly, where gallstone ileus is a more common condition.

Cholesterol nucleation time measurement in nasobiliary or nasoduodenal bile. Comparison with surgical bile.

The usual technique of collecting gallbladder bile at laparotomy is not suitable for sequential studies of cholesterol nucleation time (NT) in patients receiving therapy to prevent or dissolve cholesterol gallstones. Our aim was to study the feasibility of measuring NT in bile obtained by nasobiliary or nasoduodenal intubation. We studied a total of 10 cholesterol gallstone patients; in 8 bile was collected by nasobiliary drainage, in 7 it was collected by nasoduodenal intubation, and in 3 it was collected at laparotomy the next day. Three patients developed abdominal pain and increased serum amylase after endoscopic retrograde cannulation. All three biles obtained at operation nucleated quickly (NT, 1-4 days), whereas duodenal biles were all beyond the expected range (NT, > 21 days). Chymotrypsin activity, as a marker of pancreatic juice contamination, was detected in five of eight nasobiliary biles and in all seven duodenal biles but in none of the surgical biles. Free fatty acids (reflecting lipolysis) were significantly higher in duodenal than in surgical biles, with nasobiliary bile showing intermediate values. Nasobiliary bile showed either a rapid (median NT, 3 days) or a slow (median NT, 22 days) NT, depending on whether chymotrypsin activity was absent or present (p < 0.05). We conclude that duodenal bile is never suitable for NT determination because of contamination by pancreatic enzymes, and that nasobiliary bile, if not contaminated by pancreatic enzymes, may be suitable for NT determination but that its collection via a nasobiliary tube after cholecystokinin injection carries a risk of pancreatitis.

Cardiopulmonary responses to continuous positive airway pressure in acute asthma.

The effects of nasal continuous positive airway pressure (CPAP) on expiratory flow, arterial blood gas tensions, cardiovascular status, and dyspnea were studied in 21 patients with acute asthma. Therapy consisted of the following CPAP sequence: 30 minutes at 5 cm H2O, 20 minutes at 0 cm H2O, 30 minutes at 7.5 cm H2O, and 20 minutes at 0 cm H2O. Six control patients were fitted with a CPAP mask but given no positive-pressure therapy. Significant reductions in respiratory rate occurred from a baseline of 22.0 +/- 1.0 to 19.8 +/- 3.8 breaths/min at CPAP 5 cm H2O and to 19.4 +/- 4.3 breaths/min at CPAP 7.5 cm H2O (P < .05). No significant change occurred in forced expiratory volume in 1 second (FEV1), heart rate, mean arterial blood pressure, or arterial blood gas tension with either level of CPAP. Dyspnea, as assessed by a breathlessness score, improved during CPAP therapy (P < .05). These levels of CPAP were tolerated without deleterious side effects. In comparison, the control group showed no change in heart rate, respiratory rate, or breathlessness score during the study period. These data show that application of CPAP in acute asthma reduces respiratory rate and dyspnea with no untoward effects on gas exchange, expiratory airflow, or hemodynamics.

Blunted seasonal variation in serum 25-hydroxy vitamin D and increased risk of osteomalacia in vegetarian London Asians.

Serum 25-hydroxy vitamin D levels were measured in 297 adult Asians and 68 white subjects at different times of year and seasonal variation compared between subjects grouped according to ethnic origin, religion and dietary habit. A sub-group of Asians with symptoms and biochemical changes suggestive of osteomalacia underwent bone biopsy, and static bone histomorphometry was performed. Histological osteomalacia was detected in 15 Asians and borderline changes in 13. The majority of these cases were among vegetarian Hindus. Significant seasonal variation in 25-hydroxy vitamin D was observed in all groups, but with lower peak and trough levels among Asians, and especially the Hindus and vegetarian Asians. Summer rises in 25-hydroxy vitamin D levels were blunted among Hindus and vegetarian Asians, compared to whites, Muslims and non-vegetarian Asians. Vegetarian Asians had significantly lower serum calcium and higher PTH levels than non-vegetarians, but multivariate analysis indicated that this was an effect of osteomalacia, not vegetarianism. We conclude that solar exposure has a significant effect on vitamin D status in Asians resident in London. Non-vegetarian Asians have similar rise and peak levels to whites, but those taking a vegetarian diet (in particular, Hindus) have an impaired seasonal rise in 25-hydroxy vitamin D levels, and are at particular risk of metabolic bone disease. This effect did not appear to be mediated through secondary hyperparathyroidism consequent on a vegetarian diet.

Clinical and histological spectrum of osteomalacia among Asians in south London.

In a prospective study of 175 adult Asian patients attending a medical out-patient clinic we found a spectrum of metabolic bone disease. Twenty-four patients (13.5 per cent) had definite osteomalacia, of whom 11 (6 per cent) had severe clinical osteomalacia on the basis of associated symptoms and radiological signs. Fifteen (8.5 per cent) had borderline osteomalacia, while the remaining 136 (78 per cent) had normal bone biopsy, or were presumed to be normal. This histological spectrum was paralleled by the increasing prevalence of musculoskeletal symptoms (thigh pain, change in gait and difficulty rising from seated position) attributable to osteomalacia. Multivariate analysis showed that the major determinant of osteomalacia in Asians in South London was vegetarian diet. Increasing severity of bone disease was associated with increasingly strict vegetarian practice, which accounted for the excess risk of females, Hindus, and Asians originating from East Africa. Covering skin when outdoors also contributed to the female excess risk, and suggested a role for reduced solar exposure. Clinically significant osteomalacia is underdiagnosed in the Asian population, but evidence of dietary adaptation suggests this problem may diminish with time.

Risk of tuberculosis in immigrant Asians: culturally acquired immunodeficiency?

Study of the 620 Asian immigrants with tuberculosis notified in the Wandsworth area of south London between 1973 and 1988 showed a bimodal pattern of tuberculosis notifications: in 1977 there was a peak among Asians from East Africa, and in 1981 a peak among those from the Indian subcontinent. There was a mean lag time of five years between clinical presentation and immigration. Logit analysis showed that, although overall more men had tuberculosis than women, glandular tuberculosis was more common among women of all groups, and pulmonary tuberculosis was more common among Hindu women than Hindu men. Both subgroups of Asians had a substantially higher incidence of tuberculosis than white people, particularly at extrapulmonary sites. Hindus were also at a significantly greater risk of tuberculosis at all sites than Muslims (Hindu:Muslim risk ratio 5.5 for women and 3.7 for men). The increased susceptibility to tuberculosis of Hindus, particularly Hindu women, may be related to a culturally acquired immunodeficiency caused by vegetarianism and associated vitamin deficiency.

Noncardiogenic pulmonary edema following laser therapy of a tracheal neoplasm.

Nd-YAG laser phototherapy has been demonstrated to be effective for the treatment of airways obstruction caused by tracheal tumors. Pulmonary edema has been reported as a complication following acute relief of an upper airway obstruction. We describe a case where laser photoresection of an endotracheal malignancy resulted in acute pulmonary edema. It is important to recognize this potential cause of respiratory deterioration following successful phototherapy to obstructing lesions of the upper airways.

Duodenal pseudotumour: a silent impacted common bile duct calculus.

We report the case of a man with mild dyspeptic symptoms referred for barium meal, who was initially thought to have a duodenal tumour. Subsequent investigation showed this to be a pseudotumour caused by impaction of a gallstone in the distal common bile duct, and endoscopic sphincterotomy effected a cure. This readily treatable condition should be remembered when filling defects are demonstrated in the duodenal loop.

A non-parametric grading system for intestinal metaplasia: correlations with gastric tissue enzymes.

A novel method for grading intestinal metaplasia, with general applicability, is described. Highly significant agreement was found by kappa analysis both for intra-observer (k = 0.90) and for inter-observer (k = 0.85) variation, confirming the reproducibility of the method. The ranks derived by this method were correlated with gastric tissue levels of the enzymes beta-glucuronidase, lactic dehydrogenase (LDH), and %m-LDH. A significant (P less than 0.05) positive correlation was found between intestinal metaplasia and %m-LDH, but there was no correlation between intestinal metaplasia and beta-glucuronidase or LDH.

Chronic cavitary Pneumocystis carinii pneumonia in a patient with AIDS.

A 39-year-old man with AIDS presented with cough, chest pain, dyspnea on exertion, fever, and a cavitary lesion in the upper lobe of the left lung. The cavity increased in size over the next five months with disease involvement limited to the left upper lobe. Pneumocystis carinii infection was then diagnosed. Symptoms and cavity resolved with trimethoprim/sulfamethoxazole therapy.

Rapid noninvasive diagnosis of Pneumocystis carinii from induced liquefied sputum.

Pneumocystis carinii organisms cluster in alveolar casts. A method for concentrating alveolar casts in sputum specimens might improve the diagnostic usefulness of sputum studies in possible cases of pulmonary infection with Pneumocystis carinii. The use of sputum induction to detect Pneumocystis carinii was studied in 40 consecutive patients with known or suspected human immunodeficiency virus infection having bronchoscopy for evaluation of pulmonary disease. Sputum produced by deep coughing induced by 3% saline via a jet nebulizer was liquefied with dithiothreitol, and cells were sedimented and stained. Liquefaction of mucus allowed concentration of alveolar casts where P. carinii cysts were readily identified. A total of 28 patients were found to have P. carinii, which was detected in concentrated sputum in 21 of 38 patients, unconcentrated sputum in 10 of 38 patients, and by bronchoscopy in 25 of 37 patients. Sensitivity of concentrated sputum compared with bronchoscopy was 78% (95% CI, 58 to 90), with a negative predictive value of 71% (95% CI, 47 to 87). Values for unconcentrated sputum were 43% (95% CI, 25 to 63) and 48% (95% CI, 30 to 67), respectively. Liquefaction of adequately induced sputum facilitates processing and interpretation and increases yield for P. carinii, eliminating the need for invasive procedures in most patients.

Gastric enzymes as a screening test for gastric cancer.

Levels of lactic dehydrogenase and beta-glucuronidase were measured in gastric wash samples obtained from 445 patients over 40 years old attending a routine diagnostic endoscopy clinic. An index was derived from the two levels and used as a test for the presence of gastric cancer. Of the 24 patients with an endoscopic diagnosis of gastric cancer, 21 (91.3%) proved positive on this test, including all four cases of early gastric cancer, which were found at repeat endoscopy. The specificity of the test for gastric cancer was 81.3%. Among those patients with false positive results who had endoscopic biopsy were four out of the five cases of severe dysplasia, and four out of the 13 cases of type 2B intestinal metaplasia. Atrophic gastritis alone or with intestinal metaplasia was found in 95.9% of the false positives who were biopsied.

Beta-glucuronidase, LDH and LDH isoenzyme levels and screening for gastric cancer.

Lactic dehydrogenase (LDH) and beta-glucuronidase (bGLU) levels are elevated in the gastric juice of patients with gastric cancer, and these enzymes have been used as a screening test for gastric cancer. False positives are common, however, and we have measured enzyme levels, including LDH isoenzyme fraction, in tissue homogenates from resected stomach specimens and compared these with histological features. Increases in bGLU were found in carcinoma and chronic gastritis, an increase in LDH was found in carcinoma, whilst mLDH fraction was increased in chronic gastritis, carcinoma and intestinal metaplasia, particularly the sulphomucin variant. These findings indicate the basis for the screening test, and also the reason for the false positives. An elevated mLDH fraction may be a useful marker of a group at increased risk of developing gastric cancer, and worthy of long-term follow-up.

Effect of N-acetylcysteine on the ciliary beat frequency of human bronchial explants.

The effect of N-acetylcysteine on human bronchial cilia was evaluated by measuring the changes in ciliary beat frequency (CBF) on human bronchial explants exposed to 1%, 2%, 3%, 4%, and 5% concentrations of N-acetylcysteine solution in nutrient medium. There was a progressive reduction in CBF at increasing concentration, indicating an inhibitory effect on human ciliary activity in vitro (P less than 0.05).

Ciliary beat frequency of human respiratory tract by different sampling techniques.

The intrinsic ciliary beat frequency of human respiratory epithelium collected by 3 different biopsy techniques was examined. Ciliated epithelium was obtained by nasal brush, endobronchial brush, and endobronchial forceps biopsies from 15 patients during bronchoscopy, and ciliary beat frequency was determined in vitro at 37 degrees C using a photoelectric technique. The overall mean beat frequencies of nasal brush biopsy, endobronchial brush biopsy, and endobronchial forceps biopsy specimens were 14.3, 14.4, and 14.6 hertz, respectively. There were no significant differences (p greater than 0.05) in the overall means. Although for a given patient ciliary beat frequency was not significantly different between specimens obtained by the 3 different biopsy techniques, the pooled mean beat frequency varied from one subject to another (p less than 0.01).