[Thiamine-responsive megaloblastic anemia or Rogers syndrome: A literature review]. / L'anémie mégaloblastique thiamine dépendante ou syndrome de Rogers : une revue de la littérature.

Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive disease characterized by three main components: megaloblastic anemia, diabetes mellitus and sensorineural deafness. Those features occur in infancy but may arise during adolescence. Diagnosis relies on uncovering genetic variations (alleles) in the SLC19A2 gene, encoding for a high affinity thiamine transporter. This transporter is essentially present in hematopoietic stem cells, pancreatic beta cells and inner ear cells, explaining the clinical manifestations of the disease. Based on a multidisciplinary approach, treatment resides on lifelong thiamine oral supplementation at pharmacological doses, which reverses anemia and may delay development of diabetes. However, thiamine supplementation does not alleviate already existing hearing defects.

Cannabis use and risk of schizophrenia: a Mendelian randomization study.

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.

[CoLaus: diabetes and dyslipidemia, there is always something new!]. / CoLaus: diabète et dyslipidémie, il y a toujours du nouveau!

Cardiovascular diseases remain the first cause of mortality in our country. They are associated with well known risk factors such as diabetes and dyslipidemia. Herein we summarize main results of the CoLaus study regarding, first the prevalence and characteristics of the treatment of these risk factors. Then we present recent discoveries of new genetic determinants associated with these risk factors. Finally, we discuss whether this knowledge changes our current clinical management of our patients.

Electrical colonic stimulation reduces mean transit time in a porcine model.

Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.

Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease.

BACKGROUND: Major amputation is a dreaded event with high mortality and morbidity. However, few studies have investigated the epidemiology of amputation in the elderly over time, in the face of evolving management and prevention efforts. METHODS: We undertook a retrospective study to determine the incidence rate, etiology and prognosis of major lower limb amputations (transtibial or higher) in elderly patients (> 65 years). Cases were identified over a 10-year period in the Geneva (Switzerland) area, where all amputations are performed in a single center and reliable demographic data are available. RESULTS: The rate of amputation varied from 1.8 to 11.4/10000 patients/year, increasing with age and male gender. Diabetes was present in 48% patients, and conferred a 10 times higher risk of amputation. Severe peripheral arterial disease (PAD) was present in > 94% patients. The prognosis remains poor, 47% patients had died after two years and only 53% patients could be equipped with a prosthetic limb. Over 10 years we found a progressive increase in age at amputation; this encouraging increase was mostly accounted for by diabetic patients (> 6 months per year). CONCLUSIONS: The rate of amputation observed among elderly patients was low. Neither the rate nor the prognosis improved over the decade studied. However, the age at amputation increased by > 6 months/year, particularly in diabetic amputees, suggesting that current management successfully delays amputation. Amputations were almost exclusively performed for severe PAD. Further reduction in the rate of amputation will require progress in the prevention and management of PAD.

Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up.

BACKGROUND: Diabetic foot lesion is associated with increased morbidity and high resource use. Although early amputation has been advocated in case of osteomyelitis, conservative treatment is a more attractive alternative. OBJECTIVE: To identify criteria predictive of failure of conservative treatment of diabetic foot ulcer at time of admission to the hospital. METHODS: We conducted a 5-year retrospective cohort study with prospective long-term follow-up of all diabetic patients admitted for a foot lesion at a large (1600-bed) teaching institution. Predetermined criteria were used for the diagnosis and classification of diabetic foot lesions (Wagner classification). Study variables included patient demographics and clinical parameters related to infection and diabetes. The average follow-up after hospital discharge was 2 years. Failure of conservative treatment was the main outcome measure. Independent predictor variables were selected by logistic regression analysis. RESULTS: A total of 120 diabetic patients were admitted for foot lesions; complications of contiguous osteomyelitis, deep tissue involvement, and/or gangrenous lesions occurred in 78 (74%) of the 105 patients for whom charts were available. Fourteen patients (13%) underwent immediate amputation. Conservative treatment was successful for 57 (63%) of the 91 remaining patients. Success was achieved in 21 (81%) of 26 patients presenting with skin ulcer, 35 (70%) of 50 patients with deep tissue infection or suspected osteomyelitis, and 1 (7%) of 15 patients with gangrene (P<.001, chi2 for trend). Independent factors predictive of failure were the presence of fever (odds ratio [OR]=1.1 per degrees Celcius; 95% confidence interval [CI], 1.0-1.2) and increased serum creatinine level (OR=1.002 per micromoles per liter; 95% CI, 1.0020-1.0021) on admission, prior hospitalization for diabetic foot lesion (OR=1.4; 95% CI, 1.2-1.6), and gangrenous lesion (OR=1.8; 95% CI, 1.5-2.2). Other patient characteristics, demographics, duration of diabetes mellitus, neutrophil count, or the anatomical site of the lesion failed to predict outcome. CONCLUSIONS: Conservative treatment, including prolonged, culture-guided parenteral and oral antibiotics, is successful without amputation in a large proportion of diabetic patients admitted for a foot skin ulcer or suspected osteomyelitis. Future studies comparing early amputation with novel therapeutic strategies for severe diabetic foot infection should take into account currently identified factors that predicted failure of conservative treatment on admission to the hospital.

[Cost of training a diabetes mellitus patient. Effects on the prevention of amputation]. / Coût de la formation du patient atteint d'un diabète sucré. Effets sur la prévention des amputations.

Cost of disease is a complex notion: financial cost, psychological cost for those who have cope with a chronic disease. But there is also another cost which has not yet sufficiently been taken into account: the cost of resistance to change. It has largely been shown that patient education could result in major cost-saving as well as improvement of quality of life. Why is there such a resistance from health care providers, health policy planners for implementation of patients education programs? These resistances may well be part of the real cost of efficient control of a disease and like in the case of diabetes, prevention of acute and chronic complications. Education and training of patients has enabled us to decrease markedly lower extremities amputations: 12 times less above knee amputations, reduction by half of below knee amputations and a four fold decrease of toe amputations at the University Hospital of Geneva, Switzerland.

Metabolic and clinical consequences of changing from high-glucose to high-fat regimens in parenterally fed newborn infants.

To evaluate the metabolic and clinical consequences of changing from high-glucose to high-fat regimens during initiation of parenteral nutrition, we performed 22 studies in 11 newborn infants (birth weight (mean +/- SD) 2.54 +/- 0.54 kg, gestational age 37 +/- 3 weeks, postnatal age 8 +/- 3 days) maintained in a constant thermal environment. In a paired design, two isoproteinic (2.4 +/- 0.2 gm/kg/day) and isocaloric (64 +/- 6 kcal/kg/day) regimens differing by source of energy (high glucose vs high lipid) were infused on consecutive days. Environmental and body temperatures were recorded during a 4-hour period, and 24-hour urinary excretions of catecholamines, nitrogen, and C peptide were measured. Despite constant incubator and average skin temperatures, the rectal and interscapular temperatures rose significantly when the high-glucose regimen was changed to a high-lipid regimen. The specific locations of these changes in body temperature suggested brown fat activation. A significant drop in nitrogen retention (63 +/- 9% vs 56 +/- 10%) during the lipid infusion could be further evidence of a metabolic adaptation to the rapid change in energy substrates.

Environmental temperature control in very low birth weight infants (less than 1000 grams) cared for in double-walled incubators.

To evaluate the effect of fluctuations in environment and body temperatures on preterm infants, we recorded these variables in very immature newborn infants (birth weight less than 1000 gm) cared for in double-walled incubators (Air-Shields model C-100 and Ohio model IC). Both incubators maintained environmental temperatures corresponding overall to the set point, despite incubator openings. Under skin temperature servocontrol, however, environmental temperature fluctuations were greater than 2 degrees C even in strictly controlled conditions. The pattern of incubator temperature fluctuations depended on the set point rather than on the type of incubator (conventionally heated or heated by warm air blown between the double walls). The long-term clinical significance of the incubator temperature variability remains to be determined; the choice between air and skin servocontrolling should depend in part on the need for environmental stability.

[Determination of the amputation level by transcutaneous PO2 measurement and distal arterial systolic pressure]. / Détermination du niveau d'amputation par la mesure transcutanée de la PO2 et la pression artérielle systolique distale.

Transcutaneous oxygen partial pressure measurement (TcPO2) using a polarographic probe heating the skin at 44 degrees C provides informations about the capacity of blood to supply skin with oxygen. As oxygen is necessary for tissue survival, TcPO2 could constitute an adequate parameter for the determination of an amputation level. Among 67 amputations performed between 1983 and, 1984, we included in this study 34 patients (35 amputations), in whom TcPO2 was preoperatively measured (24 males, 10 females, mean age 67 years, range 19-86 years). Twenty two were diabetics. Twenty patients suffered from severe ischemia (stage Fontaine 4); 13 patients suffered from chronic diabetic lesions or/and osteomyelitis and two patients suffered from frostbite. The follow-up period lasted until operative wound was healed or a more proximal amputation was undertaken (mean 2.5 months, range 15 days to 10 months). Five operative wounds did not heal, so that a more proximal amputation was undertaken. TcPO2 was below 20 mm Hg in 3 of these 5 patients. TcPO2 was above 20 mm Hg in 24 among 30 patients in whom operative wound healed. When TcPO2 is above 20 mm Hg, the probability of operative wound healing is 92%. When TcPO2 is below 20 mm Hg, the risk of a more proximal amputation is 33%. Distal systolic blood pressure has no predictive value. It is concluded than when TcPO2 is above 20 mm Hg, the probability of healing of operative wound is clinically acceptable. When TcPO2 is below 20 mm Hg, 1 of 3 patients will be reamputated at a more proximal level, but healing does occur in 66% of patients.

[Disarticulation of the knee. Surgical technic--prosthesis fitting]. / La désarticulation du genou. Technique opératoire--appareillage.

The authors describe a modified technique for knee joint disarticulation surgery. Their approach provides two flaps, one medial and one lateral, which result in a posterior, longitudinal scar that remains outside the contact areas of the prosthesis. They abrade the lateral and posterior aspect of each condyle, peeling out the articular cartilage and re-covering the condyles with the joint capsule. This technique allows a satisfactory stability in prosthetic rotation, and improves the appearance of the artificial limb. For post-operative rehabilitation the authors use a tridimensional alignment jig and a prosthetic ankle with three degrees of freedom: flexion-extension, lateral-medial motion and rotation, making easier the swing phase while maintaining the obvious advantages of a pilon-type prosthesis.