Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.     

Monitoring nonresponsive patients who have celiac disease

Because of the wide variations in the clinical presentation of celiac disease and because treatment exists that is effective in most cases, screening of the general population for celiac disease has been considered. There is still no evidence that patients who have symptom-free celiac disease are at increased risk of small intestinal lymphoma or other complications. Prevention of osteoporosis seems to be the strongest indicator for widespread screening today [22].The major cause of failure to respond to a gluten-free diet is continuing ingestion of gluten, but other underlying diseases must be considered.Many different drugs (eg, anti-tumor necrosis factor [TNF]-alpha) have been used in patients who have RCD [23]. Steroid treatment has been reported to be effective even in patients who have underlying early EATL.Histologic recovery in patients who have celiac disease usually takes several months but can take up to 1 year, even if the patient remains on a strict gluten-free diet. Some patients report celiac-related symptoms for months after a single gluten intake.The definitions for RCD in literature vary. The authors consider the definition give by Daum and colleagues [24] suitable. They defined true RCD as villous atrophy with crypt hyperplasia and increased IELs persisting for more than 12 months in spite of a strict gluten-free diet.If a patient is not responding well to a gluten-free diet, three considerations are necessary: (1) the initial diagnosis of celiac disease must be reassessed;(2) the patient should be sent to a dietician to check for errors in diet or compliance problems, because problems with the gluten-free diet are the most important cause for persisting symptoms; (3) other reasons for persisting symptoms (eg, pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, protein-losing enteropathy,T-cell lymphoma, fructose intolerance, cavitating lymphadenopathy, and tropical sprue) should be considered.Other causes for villous atrophy are Crohn's disease, collagenous sprue, and autoimmune enteropathy.Abdulkarim and colleagues [25] examined 55 patients who had a diagnosis of nonresponsive celiac disease. He found that 6 did not have celiac disease, and25 still had some gluten ingestion.Tursi and colleagues [26] reported 15 patients who had celiac disease with persisting symptoms. Because histology improved in all patients after several months, RCD was excluded. Of the 15 patients, 10 had small intestinal bacterial overgrowth, 2 showed lactose malabsorption causing the described symptoms, 1 had mistakenly taken an antibiotic containing gluten, and 1 patient each had Giardia lamblia and Ascaris lumbricoides. Thus, other entities must be considered in patients who have celiac disease and ongoing symptoms.In a follow-up clinical trial, 158 patients who had celiac disease underwent follow-up small intestine biopsies within 2 years after starting a gluten-free diet.Eleven patients (7.0%) with persisting (partial) villous atrophy were considered to have RCD; 5 of them developed EATL [27].RCD type I is characterized by normal expression of T-cell antigens and polyclonal TCR gene rearrangement.RCD type II is characterized by an abnormal IEL phenotype with the expression of intracytoplasmic CD3e, surface CD103, and the lack of classic surface T-cell markers such as CD8, CD4, and TCR-alpha/beta. This clonal IEL population can be considered crypt IEL [24]. RCD II has a poor prognosis, which is a problem for therapy.Clonal TCR gene rearrangements and loss of T-cell antigens such as CD8 and TCR-beta in IELs may indicate the development of an EATL in patients who have RCD.The markers for an overt EATL are a positive stool blood test, increased lactate dehydrogenase, or beta2-microglobulin [24]. If an overt lymphoma is suspected, upper and lower endoscopy, an ear, nose, and throat work-up, CT scan, capsule endoscopy, and possibly double-balloon enteroscopy should be performed.Most reports of the difficulties in treating patients who have true RCE are casereports. Turner and colleagues [28] reported on an induction of remission by useof the anti-TNF-alpha antibody infliximab and maintenance with prednisoloneand azathioprine. Olaussen and colleagues [29] and Mandal and colleagues [30]tried a nonimmunogenic elemental diet.Gillet and colleagues [31] reported successful treatment of a patient who hadRCD using anti-TNF-alpha antibodies (infliximab) for induction and azathioprinefor maintenance.Maurino and colleagues [32] studied seven consecutive patients diagnosed ashaving refractory sprue and no response to oral or parenteral steroids. Aftertreatment with azathioprine (2 mg/kg/d) and oral prednisone (1 mg/kg/d), fivepatients had a complete clinical remission. Two patients who did not respond totreatment at any time died.Goerres and colleagues [33] described 18 patients who had RCD, 10 of whomhad type I RCD, and 8 of whom had type II RCD. Treatment consisted ofazathioprine combined with prednisone for 1 year. Consistent with reports byother investigators, the response rates in the two groups differed. Eight of the10 patients who had type I RCD had a histologic response. Seven of the eightpatients who had type II RCD died, and six of the eight developed a lymphoma.At present there is no effective treatment for type II RCD.Fig. 3 presents a proposed algorithm for monitoring patients who have ce-liac disease.     

Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin.

Anti-gliadin antibody was measured by radioimmunoassay in 30 Caucasians with gluten-sensitive enteropathy (GSE). 22 GSE patients maintained on a gluten-free diet for 1.5 to 20 yr (mean duration 76 mo) had elevated serum concentrations of IgG antigliadin antibody. Among GSE patients on a gluten-free diet, antigliadin antibody was seen only in those having the chromosome 14-encoded IgG immunoglobulin heavy chain allotype marker G2m(n). IgG antigliadin antibody was found in GSE patients with G2m(n) regardless of whether the HLA-B8 and/or -DR3 major histocompatibility complex antigens that occur frequently in GSE were present. No patient lacking G2m(n) had significant levels of antigliadin antibody. The association between antigliadin antibody and the immunoglobulin heavy chain allotype marker G2m(n) in GSE patients likely reflects the presence of Gmn-linked variable region genes or Gmn-linked genes that regulate variable region gene expression.     

Treatment of chronic hepatitis delta virus (HDV) infection with human lymphoblastoid alpha interferon

Ten patients with evidence of continuing HDV replication were treated with lymphoblastoid alpha-interferon and eight more were followed as a non-randomized control group. Four out of eight patients who completed one year of follow-up had cleared HDV-RNA from the serum whilst none of the control group did so. In these four responding cases there was a transient increase in transaminase levels during treatment and in two, this was followed by improvement. One patient also cleared HBV and seroconverted to anti-HBs (antibody to hepatitis B surface antigen--HBsAg). In one patient with sustained loss of HDV, recurrence of HDV infection was detected 18 months after completion of treatment. These data suggest that alpha-interferon can inhibit HDV replication in the short term but relapse after one to two years may occur. Inhibition of HDV-RNA is associated with improvement in the inflammatory liver disease and now larger studies are required to determine whether it influences survival.     

Severe spruelike enteropathy associated with olmesartan

ObjectiveTo report the response to discontinuation of olmesartan, an angiotensin II receptor antagonist commonly prescribed for treatment of hypertension, in patients with unexplained severe spruelike enteropathy.Patients and MethodsAll 22 patients included in this report were seen at Mayo Clinic in Rochester, Minnesota, between August 1, 2008, and August 1, 2011, for evaluation of unexplained chronic diarrhea and enteropathy while taking olmesartan. Celiac disease was ruled out in all cases. To be included in the study, the patients also had to have clinical improvement after suspension of olmesartan.ResultsThe 22 patients (13 women) had a median age of 69.5 years (range, 47-81 years). Most patients were taking 40 mg/d of olmesartan (range, 10-40 mg/d). The clinical presentation was of chronic diarrhea and weight loss (median, 18 kg; range, 2.5-57 kg), which required hospitalization in 14 patients (64%). Intestinal biopsies showed both villous atrophy and variable degrees of mucosal inflammation in 15 patients, and marked subepithelial collagen deposition (collagenous sprue) in 7. Tissue transglutaminase antibodies were not detected. A gluten-free diet was not helpful. Collagenous or lymphocytic gastritis was documented in 7 patients, and microscopic colitis was documented in 5 patients. Clinical response, with a mean weight gain of 12.2 kg, was demonstrated in all cases. Histologic recovery or improvement of the duodenum after discontinuation of olmesartan was confirmed in all 18 patients who underwent follow-up biopsies.ConclusionOlmesartan may be associated with a severe form of spruelike enteropathy. Clinical response and histologic recovery are expected after suspension of the drug.     

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study

BACKGROUND AND STUDY AIM: Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. PATIENTS AND METHODS: The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. RESULTS: At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. CONCLUSIONS: This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.     

The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term falls in antibodies to dust mite and pollen allergens in patients with asthma or hay fever

'Spontaneous' improvement in, or alteration of, allergic symptoms is a common occurrence, and the immunological basis is of interest in attempts to develop effective specific therapy. In the present study we measured levels of serum antibodies to Dermatophagoides pteronyssinus in patients diagnosed as having house-dust-allergic asthma up to 40 years previously. The results show a progressive fall in both IgG and IgE antibodies to antigen P1 and RAST binding to crude D. pteronyssinus extract. By contrast changes in total serum IgE were not marked. Within each of the groups of patients diagnosed 20, 30 and 40 years previously, 70% no longer suffered severe symptoms. However, the absence of detectable IgE antibody in serum was neither a necessary nor a sufficient condition for loss of symptoms. A group of patients who had spontaneously recovered from hay fever had significantly lower IgG and IgE antibody for the major grass pollen allergen Rye I and also lower total IgE than current hay fever sufferers. In neither hay fever nor asthma was there evidence to link spontaneous improvement in symptoms with an increase in IgG antibodies.     

Prevalence of Positive Serology for Acute Chlamydia pneumoniae Infection in Emergency Department Patients with Persistent Cough

Objective : To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough.
Methods : This was a case series consisting of a convenience sample of 65 patients ≥18 years of age who presented with a chief complaint of a cough lasting ≥2 weeks. Patients were treated in the ED of an urban university hospital. Patients with immunosuppression, lung disease, pneumonia, or a cough lasting ≥3 months were excluded. Acute and convalescent sera were assayed for antibody to C. pneumoniae . Subjects with C. pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of ≥16, or an IgG titer of≥512 were considered to have evidence of acute C. pneumoniae infection.
Results : Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C. pneumoniae infection. Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C. pneumoniae from those who did not have the disease. Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C. pneumoniae infection.
Conclusions : C. pneumoniae infection appears to be associated with a persistent cough in ED patients. Clinicians should consider this organism when evaluating these patients. It is unclear whether antibiotic therapy is indicated for these patients. If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.     

Coeliac disease detected by screening is not silent--simply unrecognized

Coeliac disease (CD) is associated with a wide spectrum of clinical presentation and may be overlooked as a diagnosis. There is some evidence that untreated CD is associated with a doubling of mortality, largely due to an increase in the incidence of malignancy and small intestinal lymphoma, which is decreased by a strict gluten-free diet. We studied the clinical features of screening-detected coeliacs compared to age- and sex-matched controls as a 3-year follow-up to a population screening survey, and followed-up subjects who had had CD-associated serology 11 years previously to determine whether they have CD or an increased mortality rate compared to the general population. Samples of the general population (MONICA 1991 and 1983) were screened for CD-associated serology and followed-up after 3 and 11 years, respectively, and assessed by a clinical questionnaire, screening blood tests and jejunal biopsy. Mortality rates for 'all deaths' and 'cancer deaths' were compared in subjects with positive serology in 1983 with reference to the general population. Thirteen coeliacs were diagnosed by villous atrophy following screening, compared to two patients with clinically detected CD, giving a prevalence of 1:122. Clinical features or laboratory parameters were not indicative of CD compared to controls. Subjects with positive serology followed up after 11 years did not have an excess mortality for either cancer deaths or all causes of death. Screening-detected CD is rarely silent and may be associated with significant symptoms and morbidity. In this limited study with small numbers, there does not appear to be an increased mortality from screening-detected CD, although the follow-up may be too short to detect any difference.     

The prevalence of growth hormone deficiency and celiac disease in short children

OBJECTIVES: To assess the occurrence of growth hormone deficiency (GHD) in patients with celiac disease (CD) referred for short stature. DESIGN: A retrospective, multi-center study. A total of 7066 children with short stature were referred to a number of centers for second-line evaluation over a 5-year period. All patients were screened for CD by antiendomysial antibodies (EMA) and antitissue transglutaminase IgA.Those with positive sera underwent intestinal biopsy. The EMA-negative patients and the EMA-positive ones who did not grow after 1 year of gluten-free diet underwent endocrinological investigation. RESULTS: Among the 7066 short children (age 2-14 years) evaluated, 650 (9.2%) had GHD and 44 (0.63%) had CD. An association of both CD and GHD was found in 16 short children (0.23%); these children did not grow after 1 year of gluten-free diet and therefore GH treatment was started. CONCLUSIONS: GH secretion should be evaluated in celiac patients showing no catch-up growth after an appropriate period on a gluten-free diet in spite of reversion to seronegativity for EMA.     

Disaccharidase Activity and Jejunal Morphology in Coeliac Disease

The disaccharidases of the small-intestinal mucosa are locatedin the microvilli of the epithelial absorptive cells and arereadily estimated in homogenates of jejunal biopsy specimens.When the jejunal mucosa is diffusely damaged, as in untreatedcoeliac disease, all the disaccharidase activity is markedlydepressed. The corollary is that the disaccharidases providean index of the degree of recovery when a disease such as coeliacdisease is given appropriate treatment. In the present study 45 patients with untreated coeliac diseasewere studied by jejunal biopsy, which plays a crucial role inthe diagnosis of the disease. All these patients had a jejunalmucosa which appeared ‘flat’ under the dissectingmicroscope and all showed the corresponding changes of severevillous atrophy and crypt hyperplasia on light microscopy. Allthe disaccharidases were greatly depressed when compared withthe findings in a group of healthy volunteers. In 10 of these patients, jejunal biopsy was repeated at leastonce after they had been placed on a gluten-free diet and were,to the best of our knowledge, adhering strictly to it. All showedevidence of morphological recovery, which was assessed by aquantitative histological method. As far as the disaccharidasesare concerned, the maltase and sucrase usually showed rapidrecovery and reached normal levels of activity within a fewmonths. The response of lactase was much more variable, sometimesshowing full recovery in a few months but sometimes remainingseverely depressed for years. The age of the patient was ofgreat importance in the rate of recovery of lactase activity,with patients aged less than 30 years usually showing full recoveryin the course of a few months whereas most of the older patientsshowed little or no recovery in this space of time. In one patient, an elderly woman who had shown an excellentclinical response to a gluten-free diet but in whom the jejunalmucosa remained morphologically abnormal and with severely depresseddisaccharidase activity, the effect of a two-month course ofcortico-steroids was studied. There was morphological improvementand enhanced disaccharidase activity, but reversion on cessationof the cortico-steroid treatment. Prolonged follow-up with repeatedjejunal biopsy showed a very slow morphological and enzymaticrecovery. In two of the patients who had made a perfect clinical, morphological,and enzymatic recovery on a gluten-free diet, the effect ofreintroducing ordinary bread into the diet has been studiedby serial biopsy. Both showed a rapid morphological deteriorationof the jejunal mucosa which was accompanied by severe depressionof disaccharidase activity. Neither experienced any symptomswhile this histological and biochemical disturbance was occurring.Subsequent return to a gluten-free diet was followed by evidenceof recovery. These observations demonstrate that, although a patient withcoeliac disease may be able to tolerate gluten from a symptomaticviewpoint, the gluten always damages the jejunal mucosa. Thecorollary is that patients with coeliac disease should remainpermanently on a gluten-free diet.     

Treatment of Chronic Hepatitis Delta Virus (HDV) Infection with Human Lymphoblastoid Alpha Interferon

Ten patients with evidence of continuing HDV replication weretreated with lymphoblastoid alpha-interferon and eight morewere followed as a non-randomized control group. Four out ofeight patients who completed one year of follow-up had clearedHIDV-RNA from the serum whilst none of the control group didso. In these four responding cases there was a transient Increasein transaminase levels during treatment and in two, this wasfollowed by improvement. One patient also cleared HBV and seroconvertedto anti-I-lBs (antibody to hepatitis B surface antigen - HBsAg).In one patient with sustained loss of HDV, recurrence of HDVinfection was detected 18 months after completion of treatment. These data suggest that alpha-interferon can inhibit HDV replicationin the short term but relapse after one to two years may occur.Inhibition of I-IDV-RNA is associated with improvement in theinflammatory liver disease and now larger studies are requiredto determine whether It influences survival.     

Focal segmental necrotizing glomerulonephritis in rheumatoid arthritis

We report ten patients with rheumatoid arthritis (RA) who developed a focal segmental necrotizing glomerulonephritis (FSNGN) and extracapillary proliferation typical of vasculitic glomerulonephritis. Five patients also had extrarenal vasculitis. Renal presentation was with renal impairment (n = 9) (median creatinine 726 mumol/l, range 230- 1592 mumol/l), microscopic haematuria (n = 8) and proteinuria (n = 10). Nine patients were seropositive for rheumatoid factor and nine had bone erosions. Serum from four of five patients tested by indirect immunofluorescence was positive for antineutrophil cytoplasmic antibody (ANCA) with perinuclear staining. Only three patients had penicillamine or gold therapy. Treatment was with prednisolone and cyclophosphamide (six patients, two of whom were also plasma-exchanged), prednisolone and azathioprine (two patients) and prednisolone alone (two patients). There was a marked improvement in renal function in eight patients. Two patients with dialysis-dependent renal failure recovered renal function, although in one patient this was transient and she required further dialysis 4 months later. Two other patients progressed to dialysis at 3 months and 1 year respectively. Four patients died, one remains dialysis-dependent, and four continue to have good renal function at 5 year follow-up (median creatinine 148.5 mumol/l, range 120-193 mumol/l). One patient was lost to follow-up at 5 years. FSNGN should be considered in all patients with RA and renal impairment, proteinuria and/or microscopic haematuria. This diagnosis appears to be more likely in patients with clinical extrarenal vasculitis, bone erosions or who are seropositive. In these cases, an urgent renal biopsy is indicated.      

To what degree is amelioration of angina following coronary revascularization associated with improvement in myocardial perfusion?

OBJECTIVE: To examine the association between changes in chest pain and changes in perfusion following revascularization as assessed by clinical evaluation and myocardial perfusion imaging (MPI) in patients with stable angina. DESIGN: In a prospective series of 380 patients (58.8 +/- 8.8 years) referred to angiography because of known or suspected stable angina, changes in chest discomfort and changes in perfusion after 2 years were assessed in 144 patients, who underwent revascularization, and 236, who did not. The decision to treat invasively was made without knowledge of the result of MPI. RESULTS: In revascularized patients, the presence of typical/atypical angina was reduced from 93% to 36% and the improvement was associated with improvement in perfusion. A small improvement in perfusion induced a high frequency of change from angina to no pain, whereas a further reduction caused little extra change. In non-revascularized patients the change in chest discomfort was not related to changes in perfusion, which were rarely present. CONCLUSION: Alleviation of chest discomfort 2 years after revascularization is associated with improvements in perfusion. This association appeared to be an all-or-nothing phenomenon. Non-revascularized patients also exhibited improvements in chest discomfort despite insignificant changes in perfusion.     

Epstein Barr virus-specific immune defects in patients with persistent symptoms following infectious mononucleosis

In a number of patients recovery from infectious mononucleosis (IM) following primary Epstein Barr virus (EBV) infection, is complicated by the persistence of symptoms for months or years. Normally recovery from infectious mononucleosis is associated with the development of EBV-specific antibodies and memory cytotoxic T-cells, which are present in the peripheral blood of all normal seropositive individuals. We studied four patients who had persistent symptoms for more than two years after infectious mononucleosis to determine if this abnormality was associated with a defect in EBV-specific or non-specific immune responses. All four patients had normal immunoglobulin concentrations, T- and B-cell numbers, T-cell proliferative responses and natural killer cell activity. However three of the four had reduced or absent antibodies to the EBV nuclear antigen (EBNA) although other EBV-specific antibody titres were normal. All four also had reduced EBV-specific cytotoxic T-cell activity as measured by the EBV regression assay. This defect was probably EBV-specific as alloreactive cytotoxic T-cell responses were normal. In addition, three of three patients tested had reduced in vitro antibody synthesis following pokeweed mitogen stimulation. These studies indicate that the syndrome of persistent symptoms following EBV mononucleosis may be associated with a defect in EBV-specific immunity, and thus suggest a possible immunological basis for the syndrome.     

Endoscopic and histological findings in the duodenum of adults with celiac disease before and after changing to a gluten-free diet: a 2-year prospective study

BACKGROUND AND STUDY AIMS: Published follow-up data on small-intestinal recovery in patients with celiac disease are scarce and contradictory. This is especially the case for adult patients, who often show incomplete histological recovery after starting a gluten-free diet (GFD). We conducted a 2-year prospective study to evaluate the effectiveness of a GFD in improving the endoscopic and histological duodenal findings in adults with celiac disease. PATIENTS AND METHODS: We studied 42 consecutive adults with newly diagnosed celiac disease (13 men, 29 women; mean age 32.7 years, range 15 - 72 years). All the patients underwent esophagogastroduodenoscopy and small-bowel biopsy. We devised our own grading system for the endoscopic appearance of the duodenum, which ranged from "normal" appearance to "mild", "moderate", or "severe" alterations. Small-bowel biopsies were obtained from the second part of the duodenum (and from the duodenal bulb when it had a micronodular appearance). The histopathological appearances were described according to modified Marsh criteria. RESULTS: A normal endoscopic appearance in the duodenum was found in 5/42 patients (11.9 %) at entry and in 32/42 patients (76.2 %) after 2 years on a GFD. Subdividing the patients according to age, patients aged from 15 years to 60 years showed significant improvement within 12 months ( P < 0.0001 for patients aged from 15 years to 45 years; P < 0.003 for patients in the 46 years to 60 years group), whereas the improvement in endoscopic findings in patients older than 60 years was not statistically significant, even 24 months after starting the GFD. "Normal" histology was reported in none of the patients at entry, but in 25 patients (59.5 %) after 24 months on a GFD, but this parameter did not show a significant improvement until the patients had been on the GFD for 12 months ( P < 0.0001). Only the younger patients (5 - 30 years) showed significant improvement of histology within 12 months ( P < 0.034); older patients (>30 years) showed histological improvement but this was not statistically significant, even after 24 months on a GFD. CONCLUSIONS: This study shows for the first time that endoscopic recovery is faster than histological recovery in adults with celiac disease who go on a GFD. Moreover, older patients showed incomplete endoscopic and histological recovery even 24 months after starting a GFD. We therefore advise, as a minimum recommendation, that follow-up biopsies should be taken 1 - 2 years after starting a GFD in adults with celiac disease.     

Clinical assessment and outcome in 70 patients with complaints of burning or sore mouth symptoms

OBJECTIVE: To review a series of patients with a burning or sore mouth for elucidation of associated conditions and treatment outcome. MATERIAL AND METHODS: We retrospectively studied 70 consecutive patients with a burning or sore mouth who were encountered at a tertiary-care center between 1979 and 1992. Clinical and laboratory findings were summarized, and follow-up data were analyzed. RESULTS: The study cohort of 56 women and 14 men had a mean age of 59 years. They had had a burning or sore mouth for a mean duration of 2.5 years. Multiple etiologic factors for the burning or sore mouth were present in 37% of the study subjects. The most frequently associated conditions were psychiatric disease (30%), xerostomia (24%), geographic tongue (24%), nutritional deficiencies (21%), and allergic contact stomatitis (13%). With a treatment course tailored to the suspected causal factor, 72% of the patients who had follow-up reported improvement. CONCLUSION: With a directed investigation, one or more causes could be identified in most patients who had a burning or sore mouth. Successful management of these symptoms was possible in a majority of the patients.     

Effect of endovascular treatment on headaches in patients with unruptured intracranial aneurysms

BACKGROUND: Patients with unruptured intracranial aneurysms often present with headaches. OBJECTIVE: To determine the effect of endovascular treatment on the character and frequency of headaches in patients with unruptured intracranial aneurysms. METHODS: We reviewed the medical records of all patients who underwent endovascular treatment for unruptured intracranial aneurysms within a 9.5-year period. These patients were mailed a standard questionnaire in which they were asked about the frequency and character of any headache experienced before or after (or both) endovascular treatment. They were also asked to grade improvement or worsening of headaches after the procedure as mild (activities of daily living were not affected), moderate (activities of daily living were affected), or significant (the change resulted in an ability to perform new activities of daily living or an inability to perform previous activities of daily living). RESULTS: Forty-seven patients with unruptured aneurysms who underwent Guglielmi detachable coil embolization responded to the questionnaire. Of these, 32 patients (mean age, 52.7 years [SD, 13.4]; 22 were women) had experienced headaches before the procedure. Nineteen patients (59%) reported improvement in severity of headaches after embolization. Improvement was graded as significant by 7 patients, moderate by 8, and mild by 4. Two patients (6%) reported worsening severity of headaches graded as moderate. Five of 15 patients without headaches before embolization reported onset of mild (n = 4) or severe (n = 1) headaches after treatment. CONCLUSION: Guglielmi detachable coil embolization of unruptured intracranial aneurysms was associated with reduction in severity of headaches in the majority of patients who had experienced preprocedural headaches.     

Use of cerebrospinal fluid flow rates measured by phase-contrast MR to predict outcome of ventriculoperitoneal shunting for idiopathic normal-pressure hydrocephalus

OBJECTIVE: To determine whether favorable clinical response and magnitude of improvement are associated with increased aqueductal cerebrospinal fluid (CSF) flow rates in patients who undergo ventriculoperitoneal shunting (VPS) for idiopathic normal-pressure hydrocephalus (NPH). PATIENTS AND METHODS: Between January 1995 and June 2000, 49 patients (14 men and 35 women; mean age, 72.9 years; range, 54-88 years) underwent magnetic resonance quantification of aqueductal CSF flow followed by VPS for presumed idiopathic NPH at the Mayo Clinic, Rochester, Minn. Logistic regression models for the odds of any improvement in score as a function of aqueductal CSF flow and separate models for any improvement in gait, incontinence, cognition, and total score were constructed. RESULTS: Forty-two patients (86%) had improvement in gait at postoperative follow-up (mean, 10 months). Of the 32 patients with incontinence, 27 (69%) improved. Of the 36 patients with cognitive impairment, 16 (44%) improved. In univariate and fully adjusted models, increased CSF flow through the aqueduct was not significantly associated with improvement or the magnitude of improvement in gait, cognition, or incontinence. Thirty-six patients underwent high-volume lumbar puncture preoperatively, of whom 5 (14%) had no response. The aqueductal CSF flow rates of these 5 patients were significantly higher than those of the patients who improved after lumbar puncture. Postoperative complications occurred in 15 patients. The aqueductal CSF flow rates in these 15 patients were not significantly different from those of patients who experienced no complications. CONCLUSION: Among patients who underwent VPS for the treatment of NPH, measurement of CSF flow through the cerebral aqueduct did not reliably predict which patients would improve after shunting or the magnitude of improvement.