Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.

OBJECTIVES: The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM). PATIENTS AND METHOD: Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment. RESULTS: 85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline). CONCLUSIONS: Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

[Low vitamin B12 levels in elderly patients cured within one week by oral cobalamin therapy]. / Posologie de cyanocobalamine orale corrigeant en une semaine les hypovitaminoses B12 du sujet agé.

OBJECTIVE: Non-dissociation of vitamin B12 from its carrying proteins is the most frequent cause of vitamin B12 deficiency in the elderly. The aim of this study was to determine the initial dose of oral cyanocobalamin that would correct the B12 vitamin deficiency within one week. METHODS: This was an open, prospective, study on 30 elderly patients suffering from vitamin deficiency (B12 < 0.20 microg/L) induced by food-cobalamin malabsorption. Ten patients (group I) were treated with a daily dose of 1000 microg of oral cyanocobalamin (from D1 to D8), 10 (group II) with 1000 microg every other day (D1, D3, D5 and D7), 5 (group III) with 1000 microg every 4 days (D1 and D5) and 5 (group IV) with 1000 microg only on D1. The biological response was assessed by control measurement of vitamin B12 serum levels on the 8th day. RESULTS: Mean vitamin B12 serum levels had significantly increased (p < 0.01) in groups I, II and III, but not in group IV. The dose-effect, assessed by the mean increase in vitamin B12 serum levels, was significantly greater (p < 0.05) in groups I (0.25 microg/L) and II (0.18 microg/L), than in groups III and IV (0.09 microg/L). CONCLUSION: This prospective study shows that an oral dose of 1000 microg of cyanocobalamin every 4 days, which corresponds to 250 microg per day, was sufficient to correct B12 vitamin deficiency induced by food-cobalamin malabsorption within one week. However, initial doses of 1000 microg per day or every other day would be preferable because of the greater dose-effect with daily doses higher than 500 microg. A randomised study is warranted to validate these preliminary results.

[Cogan's syndrome revealed by haemorrhagic glairous diarrhoea]. / Syndrome de Cogan révélé par une diarrhée glairo-sanglante.

INTRODUCTION: Cogan's syndrome is defined by the combination of non syphilitic interstitial keratitis and inner ear dysfunction, similar to Meniere's disease. OBSERVATION: Cogan's syndrome was revealed by haemorrhagic glaireous diarrhoea in a 21 year-old woman whose medical history included Hirschsprung's disease. Cerebral MRI revealed viral-like bilateral neuritis of the eighth cranial nerve, never described in the literature before. The auditory and visual disorders regressed after treatment with corticosteroids. CONCLUSION: The early diagnosis of Cogan's syndrome permits the cure of the visual and auditory and notably inner ear symptoms with corticosteroid therapy.

Hyperammonaemic encephalopathy induced by a commercial very-low-energy diet in a neglected ornithine-carbamoyltransferase-deficient woman.

This case report describes a 31-year-old woman with a neglected ornithine carbamoyltransferase deficiency, admitted for a hyperammonaemic encephalopathy induced by a commercial very low-energy diet. To our knowledge, this is the first reported case and it underlines the potential risk of such a diet in patients with undiagnosed or neglected ornithine carbamoyltransferase deficiency.

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.

[Sub-clinical hypothyroidism, towards the end of a controversy?]. / Hypothyroïdie fruste, vers la fin d'une controverse?

DEFINING THE PROBLEM: Sub-clinical hypothyroidism, defined as a moderate and isolated increase in TSH levels, is a common syndrome and is the first phase of a progressive disease. However its treatment remains controversial. Some anamnestic, clinical and biological (anti-thyroperoxidase antibodies) parameters contribute in identifying the patients most likely to progress towards overt hypothyroidism. WHAT CAN BE EXPECTED OF TREATMENT? Several clinical studies have described cardiovascular, neuromuscular and lipid disorders in these patients, but administration of levothyroxine has provided varying results and does not enable the distinction between a pharmacological-like intrinsic effect of the thyroid hormone and the true benefits imputable to the correction of TSH, in the absence of any large interventional study. More studies are required to better identify the patients who will benefit most from hormone replacement.

Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients.

BACKGROUND: It has been suggested that oral cobalamin (vitamin (B12)) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption. However, the duration of this treatment was not determined. PATIENTS AND METHOD: In an open-label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption, who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month. ENDPOINTS: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. RESULTS: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 x 10(6)/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). CONCLUSION: Our findings suggest that crystalline cyanocobalamin, 250-1000 microg/day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.

Primary hepatic anaplastic large cell Ki-1 non-Hodgkin's lymphoma and hereditary hemochromatosis: a fortuitous association?

We report here a case of primary hepatic anaplastic large cell Ki-1 non-Hodgkin's lymphoma in a 60 year old patient followed for hereditary hemochromatosis.

[Vitamin B12 deficiency with normal Schilling test or non-dissociation of vitamin B12 and its carrier proteins in elderly patients. A study of 60 patients]. / Carences en vitamine B12 avec test de Schilling normal ou syndrome de non-dissociation de la vitamine B12 de ses protéines porteuses chez le sujet âgé. Etude de 60 patients.

PURPOSE: Approximately 15% of people over 60 years old have a cobalamin (Cbl) deficiency in relation with a food-cobalamin malabsorption (FCM). But to date, only case reports or small series have been reported. The aim of this study was to describe the clinical characteristics of the FCM in old subjects. METHODS: Sixty patients, at least 65 years old, presenting a Cbl deficiency related to FCM, were extracted from a cohort study of the Hôpitaux universitaires de Strasbourg, France (n = 169). All these patients had an established diagnosis of Cbl deficiency and met the Carmel's criteria of FCM. Their clinical data were retrospectively analysed. RESULTS: The median age of the 60 patients was 75 years and the female/male ratio was 2.3. The principal clinical symptoms were peripheral neuropathy (35%), confusion and dementia (30%) and anemia-related manifestations such as asthenia and edemas of the legs (20%). Average hemoglobin was 10.7 +/- 2.5 g/dl and average mean erythrocyte cell volume was 95.5 +/- 13.8 fl. There was an anemia, a leucopenia, a thrombocytopenia and a pancytopenia in respectively 27%, 18%, 15% and 8% of the cases. Average serum vitamin B(12) and homocystein levels were with 138 +/- 42 pg/ml and 22.5 +/- 15.2 micro mol/l. No patient had anti-intrinsic factor antibody and the Schilling's test was normal in all patients. Main disorders associated with FCM were atrophic gastritis (59%), long-term metformin or antiacid intake (17%), chronic alcohol intake (8%) and idiopathic FCM (n = 10). Sixteen patients have been successfully treated with oral crystalline cyanocobalamin (500 +/- 280 micro g/d). CONCLUSIONS: This study shows that: firstly, the Cbl deficiency related to FCM may be responsible of severe neurological and hematologic manifestations in approximately 20% of the elderly patients; secondly, the disorders associated with the FCM are multiple in old age, with mainly atrophic gastritis; and thirdly, in clinical practice, oral cyanoCbl treatment may be successful.

[Gastroplasty: complications and their prevention]. / Gastroplastie: complications et mesures préventives.

Bariatric surgery is now frequently proposed for the treatment of morbid or complicated obesity since the introduction of minimally invasive laparoscopic anti-obesity operations such as the adjustable silicone gastric binding gastroplasty. However this reversible procedure in not always as safe as presumed and the results in weight loss may be sometimes disappointing. Side effects are common and early or late complications occured in more than 20% out of the patients. They are favoured by post operative eating disorders. Nutritional consequences are probably underestimated and are not limited to uncomfortable digestive symptoms. Some deficiencies in micronutriments have been described. The worsening of previous eating disorders or psychosocial abnormalities are not seldom. Gastroplasty is not an harmless procedure. A good selection in patients, a regular follow up, nutritional advices and psychosocial management by a multidisciplinar team are required to reduce complications after gastroplasty.

[Development and long-term prognosis of unexplained persistent inflammatory biologic syndromes]. / Evolution 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.

[DHEA: an unknown star]. / DHEA: célèbre et méconnue.

PURPOSE: To clarify the physiological function of dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, which remains poorly understood. To analyse the beneficial effects of a supplementation in order to alleviate its decrease in ageing and improve well-being. CURRENT KNOWLEDGE AND KEY POINTS: DHEA (and its sulfate) acts on peripheral tissues as an androgenic and estrogenic precursor. It is also considered as a neurosteroid. DHEA administration in several pathological animal models is promising, especially in metabolic diseases such as obesity and insulin resistance. It appears like a factor of immunomodulation and facilitates cognitive acquisition. In humans there is little evidence that DHEA may be useful in characterized pathologies apart from adrenal insufficiency. An interesting effect was also noted in severe systemic lupus erythematosus. The effects on cognitive and neuropsychiatric diseases such as midlife dysthymia are not yet convincing. Prospective studies of supplementation versus placebo indicate inconstant improvement in well-being in the post-menopausal state. DHEA is not a panacea against ageing despite there being a well-established aging-related decrease of DHEA. Contrary to some assertions there are no proven relations between cardiovascular or cancer risk. FUTURE PROSPECTS AND PROJECTS: Until now adrenal insufficiency has been the only well-documented indication of an oral DHEA supplementation. However, DHEA may be a good way for androgen supplementation in menopausal men. Further investigations are needed to better know the anti-inflammatory and immunomodulation properties of DHEA. At the least, prospective studies on large populations are necessary to assess the true benefits and dangers of DHEA in prevention of ageing.

Ten-year trends of dietary intake in a middle-aged French population: relationship with educational level.

OBJECTIVE: To compare dietary intakes at a 10 y interval of a population aged 35-64 living in France. Trends in nutrient intake and food consumption were examined with a special emphasis on the relationships between educational level and dietary behaviour. DESIGN: Two independent surveys conducted in 1985-1987 (S1) and 1995-1997 (S2) in the framework of the WHO MONICA project. Dietary intake was assessed with a 3-day record method and a food frequency questionnaire. The samples analysed included 416 men and 446 women for S1, 393 men and 409 women for S2. RESULTS: A significant improvement of the quality of fat intake was observed between S1 and S2, independently of educational level, with an increase of the age adjusted P/S ratio from 0.42 to 0.50 in men (P=10(-4)) and from 0.41 to 0.50 in women (P=10(-4)), whereas the daily cholesterol intake dropped from 552.0 to 466.9 mg and from 447.2 to 384.6 mg in men and women, respectively (P=10(-4)). These variations were associated with a decrease in the consumption of high-fat foods and an increase in that of low-fat products (poultry, low-fat dairy foods, fish) in all educational classes. By contrast, the consumption of fruit and vegetables, which was highly associated with educational level, varied little over time. CONCLUSIONS: Our results indicate slight improvement in fat quality, independently of educational level, while fruit and vegetable intake, which appeared more dependent on educational level, was only poorly modified over the 10 y interval.

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.

Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis.

Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA. Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count <0.5x10(9)/l) were extracted from a cohort study of DIA patients (n=110). G-CSF (300 microg/day subcutaneously) was used where the neutrophil count was <0.1x10(9)/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07+/-0.1x10(9)/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs. 11.6+/-5; 7.5+/-3.8 days vs. 12+/-4.5; and 7.3+/-4.8 days vs. 13+/-6.1, respectively (all p<0.05). G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.

[Adult Still's disease: an unrecognized cause of acute febrile hepatic cytolysis. Study of twelve patients]. / Maladie de Still de l'adulte: une cause méconnue de cytolyse hépatique aiguë fébrile.

OBJECTIVE: Certain liver test abnormalities have been described in adult Still's disease. The objective of the present study was to analyze their type and frequency. PATIENTS: In a 10 year retrospective study, patients were included if they fulfilled Kahn's and/or Yamaguchi's diagnostic criteria (median follow-up: 6.5 years). RESULTS: Twelve patients were selected. The median age was 25 years old and the sex ratio H/F was 2.7. Fever was present in 100% of patients and hepatomegaly in 41%. Liver test abnormalities were identified in 92% of patients: moderate cytolysis (level of transaminases between 2 and 5 N) (83%), severe cytolysis (level of transaminases > 5 N) (17%), cholestasis (elevated levels of GGT and/or alkaline phosphatase) (75%), and an increase in the LDH level (41%). All these liver abnormalities resolved spontaneously or during treatment (83%), within a median of 18 days. CONCLUSION: Our study confirms the high frequency of liver test abnormalities (> 2/3 of the patients) in adult Still's disease. These abnormalities are generally moderate and asymptomatic (3/4 of the cases), but severe cytolysis may exist. This emphasizes the need to consider a diagnosis of adult Still's disease in the presence of fever and elevated transaminase activity.