A.E. Perrin

Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption.

BACKGROUND The standard treatment for cobalamin (vitamin B(12)) deficiency involves regular intramuscular cobalamin injection. It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption. SUBJECTS AND METHODS We prospectively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months. Complete blood counts and serum cobalamin, homocysteine, and folate levels were determined at baseline and after 3 months of treatment. Patients were reexamined after 6 months. RESULTS After 3 months of treatment, all patients had increased hemoglobin levels (mean increase, 1.9 g/dL; 95% confidence interval: 0.9 to 3.9 g/dL;P <0.01 compared with baseline) and decreased erythrocyte cell volume (mean decrease, 7.8 fL; 95% confidence interval: 0.9 to 16.5 fL;P<0.001). However, 2 patients had only minor, if any, responses. Serum cobalamin levels were increased in all 8 patients in whom it was measured. CONCLUSION Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption.

The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients.

BACKGROUND: To date, only case reports or small studies have documented the syndrome of food-cobalamin malabsorption in specific populations of patients or situations. In this paper, we present the data from 80 unselected patients with cobalamin deficiency related to food-cobalamin malabsorption. METHODS: We studied 80 patients with well-established food-cobalamin malabsorption who were extracted from an observational cohort study (1995-2000) of 127 consecutive patients with cobalamin deficiency and who were followed in a department of internal medicine. RESULTS: The median age of patients was 66 years and the female to male ratio was 1.2. The mean hemoglobin level was 113+/-27 g/l (range 32-159 g/l) and the mean erythrocyte cell volume was 95.4+/-12.3 fl (range 55-140 fl). Mean serum vitamin B12 and homocysteine levels were 153+/-74 pg/ml (range 35-200 pg/ml) and 20.6+/-15.7 μmol/l (range 8-97 μmol/l), respectively. The main clinical findings noted were peripheral neuropathy (46.2%), stroke (12.5%), confusion or dementia (10%), asthenia (18.7%), leg edema (11.2%), and digestive disorders (7.5%). The commonest associated conditions were atrophic gastritis (39%) with evidence of Helicobacter pylori infection (12.2%) and alcohol abuse (13.7%). Three patients had Sjögrens syndrome and one had systemic sclerosis. Ten percent of all patients were on long-term metformin (10%) and 7.5% on acid-suppressive drugs. Correction of the serum vitamin B12 levels and hematological abnormalities was achieved equally well in all patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSION: This study suggests that food-cobalamin malabsorption may be the leading cause of vitamin B12 deficiency in adults. As other studies have also reported, the condition is often associated with neuro-psychiatric findings and with several other conditions. Oral and parenteral cobalamin appear to be equally effective in correcting serum B12 levels and hematological abnormalities and, in many cases, they also relieve symptoms.

Physical activity-related energy expenditure with the RT3 and TriTrac accelerometers in overweight adults

Objective: The objective was to evaluate two accelerometers, the RT3 and the TriTrac‐R3D for their ability to produce estimates of physical activity‐related energy expenditure (PAEE) in overweight/obese adults.

Anémies par carence en vitamine B12 chez le sujet âgé de plus de 75 ans : nouveaux concepts. À propos de 20 observations*

PURPOSE New hypotheses have recently been developed on vitamin B12 deficiency and the frequently observed occurrence in the elderly subject of food cobalamin malabsorption, i.e., the non-dissociation of B12 and its carrier protein (ND B12), and the possibility of rectifying this imbalance by oral crystalline B12 supplementation. The aim of this study was therefore to confirm these hypotheses in a series of patients aged over 75 years with anemia due to B12 deficiency. METHODS A retrospective study was carried out over a 5-year period on patients aged over 75 years presenting with megaloblastic anemia (hemoglobin [Hb] < 12 g/dL) and vitamin B12/cobalamin deficiency (B12 < 160 pg/mL). RESULTS Twenty cases were analyzed. The average age of the patient population was 82.5 +/- 6 years, and the F/M sex ratio was 1:2. Mean Hb levels were 7.9 +/- 2.4 g/dL, mean serum B12 levels were 83 +/- 24 pg/mL, and mean homocysteinemic levels were 35 +/- 27 mumol/L. The diagnosis was as follows: food cobalamin malabsorption/ND B12 (n = 10), Biermers disease/pernicious anemia (n = 5), malabsorption due to pancreatic insufficiency (n = 1), and low dietary B12 levels (n = 1). Disorders associated with ND B12 were: atrophic gastritis and Helicobacter pylori infection (n = 6), antacid or biguanide intake (n = 3), alcohol abuse (n = 2), or idiopathic syndrome (n = 2). In the patients who were followed up (n = 10), i.m. (n = 5) or oral (n = 5) administration of crystalline B12 resulted in the correction of hematological abnormalities. CONCLUSION In the elderly subject, food cobalamin/ND B12 malabsorption appears to be the main cause of B12 deficiency, and is frequently associated with atrophic gastritis. In these cases, administration of oral crystalline B12 may be an efficient means of treating this disorder.

Actigraphic assessment of the circadian rest–activity rhythm in elderly patients hospitalized in an acute care unit

Abstract Hospitalization for acute illness is a major risk factor of rest–activity rhythm disturbance among elderly subjects. The rest–activity rhythm is disturbed by the acute illness, aging and hospital environment. The purpose of this study is to assess the rest–activity rhythm and light exposure (using a wrist worn actigraph) of 10 patients (mean age 81 years, seven females) admitted on an acute care unit, suffering from cardiac, respiratory or renal acute disease. A non‐parametric method was used to analyze activity data. With an improvement of the underlying diseases, the mean relative amplitude of rhythm increased from 0.31 ± 0.19 for the first 5‐day period after admission to 0.54 ± 0.21 for the second period before discharge (P < 0.05). The amount of time at night spent above a lighting threshold of 50 lux decreased from 31.4 to 12.3 min between the two periods. The rhythm of elderly subjects hospitalized in the acute care unit is severely altered during the initial period and is progressively resynchronized following clinical improvement. Under the acute underlying disease and/or aging, environmental conditions (light, noise) should be considered to maintain regular rest–activity rhythm.

Sympathovagal response to orthostatism in overt and in subclinical hyperthyroidism

Heart rate variability (HRV) is a measure of the physiological variation of R-R intervals, reflecting the sympathovagal balance. In both overt and subclinical hyperthyroidism, a relative increase in sympathetic activity has been demonstrated, mainly due to a decrease in vagal activity. The modifications of HRV during orthostatism in normal subjects resemble those seen in hyperthyroidism. We have studied the response of 19 patients with overt hyperthyroidism and 12 with subclinical hyperthyroidism during orthostatism using HRV and compared the results to those of 32 healthy controls. In the three groups, the R-R intervals decreased in the same proportion after orthostatism. The low frequency power (LF)/[LF + high frequency power (HF)] ratio, which reflects the sympathetic tone, also increased in the same proportion in the three groups. However, the mechanisms of the modulation of the sympathovagal balance during orthostatism were different among the three groups. In controls, the relative increase of sympathetic tone after orthostatism was due principally to a decrease in vagal tone (reflected by decreased power in the HF band), while in overt hyperthyroidism, where the power in the HF band was already minimal in the lying position, there was a clear increase in the LF band power during orthostatism. The results were intermediate in the subclinical hyperthyroidism group, reflecting a continuum of effects of the thyroid hormone excess on the autonomic nervous system. Our study shows that despite an apparent normal cardiovascular adaptation to orthostatism in hyperthyroidism, the modulation of the autonomic nervous system is profoundly modified.

Évolution et pronostic à long terme des syndromes inflammatoires biologiques persistants inexpliqués

Purpose. – Unexplained inflammatory syndrome is a frequent and worrying condition in Internal Medicine. However, the long-term clinical outcome of these patients cannot be inferred from the literature. The aim of this study is to describe the long-term follow-up and the prognosis of a group of patients hospitalised for an inflammatory syndrome and discharged without causal diagnosis. Methods. – This retrospective study was carried out on 46 patients, 15 men and 31 women, aged 21 to 90 years, hospitalised between 1992 and 1999. Data concerning the hospital stay were obtained from the patients’ medical record. Follow-up was performed by consulting the treating physician. Results. – The prognosis of these patients is fairly good. In one third of the cases, the inflammatory syndrome resolved spontaneously (n = 13). In the second third, a definite diagnosis was established after discharge (n = 14) and consisted mainly of chronic inflammatory diseases (n = 9), cured with a specific treatment. In the remaining third (n = 12), the inflammatory syndrome persisted, in clinically asymptomatic patients. Conclusion. – These results suggest that the persistence of an inflammatory syndrome is not a poor prognostic factor. Thus we propose for patients discharged with an undiagnosed persistent inflammatory syndrome despite thorough investigations, a simple clinical and biological follow-up instead of repeated etiological investigations.

Métastases musculaires révélatrices d'un adénocarcinome

The authors report the case of a 67-year old man, with no particular medical history, presenting a large swelling of the left thigh. Investigations conclude to metastases located in muscles of the left thigh and of the pelvis, secondary to an adenocarcinoma of presumed pancreatic origin. With reference to this case, features of muscular metastases are reviewed. Muscular metastases seldom occur during the course of a cancer and are exceptionally the first manifestation of a neoplastic process. They are usually described as a painful mass, but symptoms can be misleading and delay diagnosis. Images obtained by ultrasonography, tomodensitometry and magnetic resonance imaging are not specific and histological examination is necessary to confirm the diagnosis.

Short-Term Oral Cobalamin Therapy for Food-Related Cobalamin Malabsorption

TO THE EDITOR: Oral cobalamin (vitamin B12) therapy may be effective for treating patients with cobalamin deficiency, especially those with food–cobalamin malabsorption (FCM).1 We have established that 3 months of oral cobalamin therapy is beneficial.2 To date, however, the duration of treatment has not been determined.3 We report preliminary results of an open-label, non–placebo-controlled study on 30 patients with established cobalamin deficiency (serum vitamin B12 <200 pg/mL ± homocysteine >13 μmol/L) related to FCM4 who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Methods. All patients were white (mean age 72 ± 13 y); 20 were women. Clinical findings included alteration of cognitive function (impaired concentration, memory loss, disorientation) (n = 9), sensitive peripheral neuropathy (n = 7), and ischemic stroke (n = 2). The mean pretreatment vitamin B12 and total homocysteine levels were 135 ± 32 pg/dL (range 82–192) and 20.2 ± 4.6 μmol/L (range 14–35), respectively (Table 1). All patients met the criteria for cobalamin deficiency related to FCM. No serum antibodies to intrinsic factor were detected. Schilling’s test results were normal in 10 of 10 patients who were tested (mean ± SD 57Co/58Co ratio 0.95 ± 0.1). Two patients also had mild deficiency due to low vitamin B12 intake. All the patients were treated with oral crystalline cyanocobalamin for ≥1 month. Oral cobalamin 250–1000 μg/d was administered. Compliance with therapy was good and no adverse events were reported. Results. Response to treatment is indicated in Table 1. During the first month of treatment, 87% of the patients achieved normal serum cobalamin levels; all had increased serum cobalamin levels (mean 167 pg/dL; p < 0.001 compared with baseline), evidence of medullar regeneration, and corrected initial macrocytosis. Anemia was corrected in 54%. All patients had increased hemoglobin levels (mean 0.6 g/dL), reticulocyte count (mean 35 × 103/mm3), and decreased erythrocyte cell volume (mean 3 fL) (all p < 0.05). Discussion. These findings suggest that patients with cobalamin deficiency related to FCM promptly benefit from oral crystalline cyanocobalamin. In fact, during the first month of therapy, most patients had significant improvement in serum cobalamin levels as well as in blood cell counts. These results are consistent with those observed in larger studies that used long-term (3–6 mo) or higher doses (>2000 μg/d) parenteral cyanocobalamin.2,3,5 We observed a dose–response effect of oral cyanocobalamin treatment. Limitations of our study include the small population and lack of a control group. However, because of the apparent effectiveness of oral therapy and its possible benefits compared with intramuscular treatment (e.g., better compliance, lower cost), further studies with larger sample sizes that use different cyanocobalamin doses and duration are warranted.

An economic comparison of ill-defined diagnostic problems in internal medicine and uncomplicated normal vaginal delivery

Reaching a diagnosis is an important part of the medical hospitalizations and 52 hospitalizations in conventional activity in the field of internal medicine. The diagnosis of units). The mean duration of stay was 19611 days. All of diseases that are generally considered to be difficult often these patients were discharged without a final diagnosis has a significant financial impact due to the duration of being reached, despite thorough and often costly invesstay and the cost of the various diagnostic procedures. tigations. The long-term prognosis was fairly good. In In France, the evaluation of medical activity in hospitals one-third of cases, the inflammatory syndrome resolved is based on data recorded in the Program Medicalizing spontaneously. In a second third of cases, a definite Information System (PMSI). Administrative and medical diagnosis was established after discharge and consisted parameters are collected and used to classify each hospital mainly of chronic inflammatory diseases. In the remaining stay into a case-mix system, similar to the American third, the inflammatory syndrome persisted in clinically diagnosis-related groups (DRG). The French equivalent of asymptomatic patients [1]. the DRG, called the ‘homogeneous group of patients’ The 67 hospital stays were classified into 27 GHMs. (GHM in French), describes hospital stays that are similar Forty-five percent of the stays were classified according to in terms of cost and resources. Each GHM corresponds to the following main GHMs: an activity synthetic index value (ISA value in French) that is used to classify the GHMs using a scale of relative costs. GHM 671: signs and symptoms with complications or The ISA value of 1000, assigned to the GHM 540, which comorbidities, which was assigned an ISA value of 1608. regroups uncomplicated normal vaginal deliveries, is conGHM 672: signs and symptoms without complications sidered to be the reference value. or comorbidities, valued at 945. In order to explore whether the diagnostic activity in GHM 675: other factors that influence health coninternal medicine is adequately represented by the medicodition, valued at 749. economic indices currently in use, we carried out a GHM 823: factors that influence health condition and retrospective study that described a group of patients other reasons to resort to health services (one-day hospitalized in a Department of Internal Medicine for an hospitalization), valued at 241. inflammatory syndrome. The study population comprised 46 patients (15 men and 31 women) with a mean age of The ISA value was recorded for each hospital stay. The 62619 years (median 67 years, range 21–90 years). The mean ISA value was 10746768.2 (median 945, range total number of hospital stays was 67 (15 ‘one-day’ 225–4644). Sixty-five percent of the GHMs were valued at lower than 1000. In 30% of cases, the ISA value was between 1000 and 2000, and it was greater than 2000 in *Corresponding author. Tel.: 133-3-8812-7600; fax: 133-3-8812the remaining 5%. 7596. These findings suggest an inadequacy in the existing E-mail address: anne-elisabeth.perrin@chru-strasbourg.fr (A.-E. Perrin). DRG system in evaluating diagnostic activity. The difficul-