Evaluation of the ankle brachial index and toe brachial index for peripheral arterial disease diagnosis in patients over 70 years with lower limb ulcers.

OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of the ankle brachial index using pulsed Doppler, and the toe brachial index using laser Doppler, in comparison with the arterial Doppler ultrasound of the lower limbs as a reference test, in a population of non-diabetic subjects over 70 years old with lower limb ulcers and without chronic renal failure. METHODS: We included 50 patients, 100 lower limbs from the vascular medicine department of the Paris Saint-Joseph hospital from December 2019 to May 2021. RESULTS: We found a sensitivity of 54.5% for the ankle brachial index and a specificity of 67.6%. Regarding the toe brachial index, the sensitivity was 80.3% and the specificity 44.1%. We could explain the low sensitivity of the ankle brachial index in our population by the mediacalcosis of elderly subjects, avoidable with the measurement of the toe blood pressure index, which had a better sensitivity. CONCLUSION: In a population of subjects over 70 years of age with a lower limb ulcer, without diabetes and without chronic renal failure, it would seem judicious to use the ankle brachial index in association with the toe brachial index for the diagnosis of peripheral arterial disease, followed by an arterial Doppler ultrasound of the lower limbs in order to evaluate the lesion profile of patients with a result of less than 0.7 of toe brachial index.

Reduction of Extended-Release Tacrolimus Dose in Low-Immunological-Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor-Specific Antibodies: A Randomized Study.

The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid-free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0 ) >3 µg/L; group B had no change in TacER dose (TacER C0 7-12 µg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent-to-treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0 was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 µg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 µg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti-HLA donor-specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0 should be maintained >7 µg/L during the first year after transplantation in low-immunological-risk, steroid-free KTRs receiving a moderate dose of mycophenolic acid.

Hypogammaglobulinemia and risk of severe infection in kidney transplant recipients.

BACKGROUND: Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post-transplant infections. METHODS: We analyzed the risk factors of HGG and the relationship between HGG and the risk of severe infection in a cohort of 318 kidney transplant recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig) concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12 (M12), and month 24 (M24) post transplant. RESULTS: The prevalence of IgG HGG was 56% and 36.8% at D15 and M6, respectively. Age was the sole identified risk factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6 IgG HGG were the presence of D15 IgG HGG (OR 6.41, P < 0.001) and treatment of acute rejection (OR 2.63, P = 0.014). Most infections occurred between D15 and M6 post transplant. Only age (hazard ratio 1.03, P < 0.001) was identified as a risk factor of infection between D15 and M6 post transplant. Survival free of infection (overall infections and bacterial or viral infections) did not differ significantly between patients with or without D15 IgG HGG. Only septicemia occurring between M6 and M12 post transplant was more frequently observed in patients with HGG. The low prevalence of severe HGG (<400 mg/dL) did not allow conclusions on the infectious risk associated with this patient subgroup. CONCLUSIONS: This study does not support the existence of a strong link between post-transplant HGG and the risk of severe infections in KTR. Correction of HGG to minimize the risk of severe infections in KTR is thus questionable and needs to be reevaluated in prospective studies.

Severe episodes of extra cellular dehydration: an atypical adult presentation of cystic fibrosis.

Cystic fibrosis (CF) is usually diagnosed during childhood by respiratory or gastro-intestinal symptoms. Hyponatremic hypochloremic dehydration with metabolic alkalosis is a rare but typical presentation of CF in infants. In contrast, only 3 cases have been described in adults. We report a case of CF in a 33-year-old Caucasian female presenting with a severe sodium and chloride depletion caused by inappropriate sweating. She experienced three episodes of severe dehydration before the diagnosis was suspected. Sweat chloride test was pathological and mild pulmonary involvement was found on CT scan. Delta F508 mutation and a rare mutation (3849+40 A/G) on the intron 19 of CFTR gene were found. Interestingly, our patient has a heterozygote twin sister, carrier of the same mutations of CFTR gene who also developed CF but with a different phenotype. We suspect modifier genes to be implicated in the differences observed between the two phenotypes. We discuss the physiopathology of electrolyte disturbance and review the other similar adults cases.

Different effects of hypothermia on amino acid incorporation and on amino acid uptake in the brain in vivo.

The temperature dependence of the incorporation of amino acids into cerebral proteins and that of the transport of amino acids through the blood-brain barrier were studied. We measured the protein synthesis rate in vivo over a wide temperature range (14 degrees C-38 degrees C) in male Sprague-Dawley rats using a flooding dose of labeled valine. There was a linear dependence of the protein synthesis rate on temperature. The temperature quotient expressed as per cent decrease per 1 degree C was somewhat lower at the lower temperatures, a decrease from 7.8% in the 37.7-32.5 degrees C range to 6.7% in the 25.5-14 degrees C range. The transport of the three amino acids phenylalanine, lysine, and alanine, representing three transport systems, through the blood-brain barrier showed no temperature dependence in vivo. The results show that in hypothermia cerebral metabolic rates are lowered to a great extent, while some aspects of metabolic transport are not affected.

Amino acid uptake systems in lizard and chick brain cells.

The uptake of seven amino acids, alpha-aminoisobutyric acid (AIB), cyclo-leucine (cyclo-Leu), gamma-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu), lysine (Lys), and taurine (Tau), representatives of different amino acid transport systems, was studied in slices of brain from Tokay lizards and White Leghorn chicks. In descending order, the rate of the initial uptake of the amino acids in both species was Glu greater than Gly greater than GABA greater than Cyclo-Leu greater than AIB greater than Lys greater than Tau. The substrate specificities and the differences in sodium and temperature dependence of the uptake of the amino acids indicate the presence of several distinct amino acid transport systems, some sodium-dependent and some sodium-independent. The structural specificity of amino acid transport classes in the brain of these species is similar to that in other vertebrate brain preparations.

Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice.

Adult male C57BL/6By and BALB/cBy mice were housed either in large groups (20 per cage) or individually, and levels of plasma testosterone were measured in samples taken in the morning (9 to 10 A.M.) and in the evening (9 to 10 P.M.). No significant strain differences were found in testosterone levels, but the mean testis weight was significantly higher in the BALB/cBy strain. Two-way analysis of variances of pooled plasma testosterone data showed that social isolation of males results in a significant increase in A.M. (but not P.M.) testosterone concentrations and increased testis weight in both strains. Our results suggest that differential housing of a social species can affect testicular function. Since testicular function can also be influenced by the time of day, the question is raised whether the expression of circadian variation in plasma testosterone level is dependent on population density.

In vivo rates of protein synthesis in brain, muscle, and liver of five vertebrate species.

To compare cerebral protein metabolism rates in vivo, protein synthesis rates of three organs of five vertebrate species were measured after a single i.p. injection of a flooding dose of [1-14C]valine. In muscle, brain, and liver, the respective average protein synthesis rates, expressed as percent of total protein-bound valine replaced per hour, that is, percent synthesis per hour, in goldfish at 22 degrees C body temperature, were 0.07, 0.23, and 0.57%; in the bullfrog at 20 degrees C, 0.06, 0.18, and 0.55%; in the white Leghorn chicken at 39 degrees C, 0.24, 0.70, and 2.17%; and in the mouse at 38 degrees C, 0.22, 0.65, and 2.0%. In the Tokay lizard at different body temperatures, the synthesis rates were 0.04, 0.13, and 0.43% at 26 degrees C; 0.05, 0.20, and 0.63% at 32 degrees C; and 0.07, 0.27, and 0.81% at 38 degrees C. The results demonstrate differences in protein synthesis rates in organs of the various species examined. The differences among the species seem to be due, to a major extent, to differences in body temperature; rates in lizard are below those in other species at temperatures tried. Protein synthesis rates in brain in all species are almost three times lower than those in liver and almost three times higher than those in muscle.

A simplified radioimmunoassay of plasma nortriptyline in depressed patients compared with high-pressure liquid chromatography and gas-liquid chromatography.

Antiserum to nortriptyline was generated in male New Zealand rabbits innoculated with n-succinylnortriptyline-bovine serum albumin conjugates. The antiserum was used at a final dilution of 1:4000 and tritiated imipramine was used as the label antigen. An accurate, sensitive, and specific radioimmunoassay of depressed patients' plasma or serum nortriptyline is described. The accuracy was good with a recovery range of 90-100% with a mean of 94%. The method can be used to measure nortriptyline concentration in the range of 0.1 microgram/liter to 100 micrograms/liter without prior extraction and purification of plasma or serum. Results of this method correlate well with those obtained by high-pressure liquid chromatography (r = 0.979) and by gas-liquid chromatography (r = 0.98). The specificity of the antiserum was examined by studying the cross-reactivity of 20 different psychopharmacological compounds, including nortriptyline's metabolites.

Short column chromatographic separation of 11-deoxy- and 11-oxy-17-oxogenic steroids as dinitrophenylhydrazone derivatives.

A method for the determination of urinary 17-oxogenic steroids in two fractions (11-deoxy-17-oxogenic and 11-oxy-17-oxogenic steroids) is described. The method is based on initial reduction with borohydride and on oxidation with sodium metaperidate, followed by the formation of dinitrophenylhydrazone derivatives and the separation of the derivatives on short columns of alumina eluted by amyl alcohol to toluene. The assay is robust, reliable, and suitable as a simple laboratory measurement of the integrated adrenocortical function over time. Such analysis should be useful in any situation where cortisol metabolism is changed. Some suggested areas of applicability are in cases of Cushing's syndrome and in the diagnosis and treatment of congenital adrenal hyperplasia.

Comparison of the use of inorganic and organic bases in the Zimmermann reaction for 17-oxosteroids.

A comparison has been made between inorganic and organic bases proposed for use in the Zimmermann reaction for 17-oxosteroids. The use of inorganic base in pyridine solution is preferred for large scale liquid chromatography because of its high sensitivity and its better wetting characteristics. Several of the organic bases tested have desirable characteristics when used for total group assays and may be preferred by some for such assays.

The specificity of multi-column liquid chromatography of neutral urinary steroids as evaluated by comparison with parallel gas chromatography and mass spectrometry.

The use of gas chromatography/mass spectrometry is advocated as the best currently available methodology for the validation of a routine assay for steroid analysis. This is documented by comparative studies by gas chromatography/mass spectrometry and spectrophotometry of peak material obtained in routine assays by multi-column liquid chromatographic techniques.

Multi-column chromatography and the use of isotopes in the study of steroid metabolism.

Multi-column liquid chromatography is demonstrated to be a technique well suited for isotope experiments involving administration of labelled cortisol. It has potential for secretion rate determinations, for dynamic studies of cortisol metabolism and for work with stable isotopes.

Multi-column chromatography of urinary steriods and adrenocortical dysfunction.

The potential of the multi-column assay for urinary neutral steroids in work with samples from patients with adrenocortical pathology is demonstrated through analyses performed on urine samples from Cushing and congenital adrenal hyperplasia cases, after modification of the routine methodology to include the quantitation of additional steroids of particular importance for pathological samples.

Multi-column chromatography of urinary 17-ox osteroids as their 2,4-dinitrophenylhdrazones.

The use of 2,4-dinitrophenylhydrazones in the multi-column chromatography of 17-oxosteroids from urinary extracts has been possible on mixed columns of alumina and silica gel. Preliminary results indicate agreement with values obtained using the Zimmermann reaction. The hydrazones have the advantage of color stability, when compared with the Zimmermann reaction, and the analysis is simpler and cheaper to perform.

General methodology for the estimation of common neutral urinary steroids by multi-columin liquid chromatography.

A method is described for the estimation of common neutral urinary steroids by multi-column liquid chromatography. Hydrolysis is performed in two steps: enzymatically, using beta-glucuronidase, followed by solvolysis. Initial short column chromatography separates the neutral steroids into three fractions according to polarity: 17-oxosteroids, corticosteriods less polar than cortolones, and cortolones and cortols. The cortolone, cortol fraction is oxidized and the different steroid groups are chromatographed on capillary aluminum oxide and silica gel columns. A computerized, spectrophotometric system is used for the quantitation procedure.