Isolated growth hormone deficiency in Chilean patients: clinical and molecular analysis

Isolated growth hormone deficiency (IGHD) is a disorder that leads to short stature. It has been classified into types IA, IB, II and III. GH gene mutations and growth hormone releasing hormone (GHRH) receptor gene mutations have been described in patients with IGHD. We report here a clinical and molecular study of 27 Chilean patients with IGHD. We performed GH stimulation tests with GHRH and GHRP, and segregation and molecular analysis of the GH, GHRH and GHRH receptor genes. We describe four patients with IGHD IA bearing a 7 kb mutation (13%), and two IGHD II patients who showed two different splice site point mutations (6.8%). In 21 patients, we did not find a mutation in any of the three genes examined. These results led us to conclude that the molecular causes of IGHD involve other genes besides those analyzed in this report, as has been reported previously in patients of different ethnic origins.     

Therapeutic drug monitoring of anticonvulsant drugs by micellar HPLC with direct injection of serum samples

BACKGROUND: We developed a micellar liquid chromatographic (MLC) procedure for the determination of three extensively monitored antiepileptics in serum samples: carbamazepine, phenobarbital, and phenytoin. METHODS: We determined the composition of the mobile phase after modeling the elution behavior of the antiepileptics in hybrid micellar mobile phases of sodium dodecyl sulfate (SDS) with different organic modifiers (propanol, butanol, or pentanol) in an experimental design that used five mobile phases, a C(18) column, and ultraviolet detection. In the micellar chromatographic system, the serum samples can be injected directly. RESULTS: The optimum mobile phase was 70 mL/L butanol in 0.05 mol/L SDS, pH 7, in which the three antiepileptics were resolved in <10 min. Intra- and interday precision was evaluated at four different drug concentrations within the therapeutic range (n =10); CVs were <2.1%. The method was applied to the analysis of 120 serum samples, and results were similar to those obtained by the TDx method. CONCLUSIONS: The MLC method allows chromatographic determination of three antiepileptics, using an interpretative strategy of optimization, without pretreatment of the serum samples and with direct injection in a hybrid micellar mobile phase of SDS-butanol. The method provides complete resolution and quantification of mixtures of two and three antiepileptics.     

Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats

This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.     

CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers

OBJECTIVE: This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. METHODS: Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C9*2 and *3 was carried out with PCR-RFLP. RESULTS: The frequencies of CYP2C9*1, *2, and *3 alleles were 0.74 (95%CI: 0.68-0.80), 0.16 (95%CI: 0.11-0.21) and 0.10 (95%CI: 0.06-0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3'-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C9*1/*3 (0.83+/-0.4, n=14, 95% CI for the difference: 0.02-0.4) and CYP2C9*2/*3 (1.10+/-0.5, n=4, 95% CI for the difference: 0.16-0.8) genotypes compared to CYP2C9*1/*1 (0.62+/-0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C9*3 variant. CONCLUSIONS: The frequencies of CYP2C9*1, *2, and *3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C9*3 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied     

Acute reversible paraparesis secondary to probable fibrocartilaginous embolism

Fibrocartilagenous embolism (FCE) of the intervertebral disc represents a very rare cause of spinal infarct. Up to now only 33 others cases in human beings have been reported in the literature, most of them diagnosed post mortem. We present a 14-year-old boy who developed acute dorsal back pain after lifting a heavy gate, followed by progressive paraparesis. An MRI of the spine showed a degenerative disc at D10-D11 without compromise of the spinal canal lumen associated with an acute Schmorl's nodule situated in the superior endplate of D11. A week later, a second MRI disclosed an intraxial spinal cord lesion at D7-D8 vertebral level involving the vascular territory of the anterior spinal artery. It also showed an abnormal signal located in the posterior third of the D8 vertebral body. These clinical and neuro-radiological findings are similar to those mentioned in the literature and support the diagnosis of an anterior spinal infarct secondary to a probable fibrocartilaginous embolism. This case highlights the importance of considering this etiology among the causes of spinal cord infarct, especially in young people, and underlines the utility of MRI in its diagnosis in vivo.     

Misogyny in the nursing world? A historical overview

Through history, there have been men and women who have cared for injured warriors, attended to expectant mothers, cared for those most unprotected or attended to the health of children and sick older people. This is a fact which the History of Nursing does not ignore. Nonetheless, it is no less certain that since their origins, surgical practices and therapeutic specialties in the hands of men have enjoyed an enormous social recognition while those treatment practices and care tasks which have women as their main protagonists frequently fall into a forgotten and silent place. Now the question is to what is due such an asymmetric and sexual evaluation of these tasks? How are these differences among men and women and among doctors and nurses expressed and explained? Basically these are viewed through a dense network of images, symbols and social stereotypes which codify their behaviors, regulate their activities, prescribe their expectations and construct their tastes. All this is a subtle, polymorphic strategy for androcentric normalization of feminine reality which, as is to be expected, does not escape being designated as specific roles for female caretakers either. The authors examine the Florence Nightingale model to ascertain whether or not this model is capable to overcome, eliminate or transform some of the androcentric patterns described in the previous article or, to the contrary, whether or not these patterns still persevere and are transmitted to present day, even though only in a deceptive manner.     

Risk factors for amputation in periprosthetic knee infection

Treatment for prosthetic knee replacement is becoming more common. Infection is an arthroplasty-related complication leading to prolonged hospitalization, multiple surgical procedures, permanent loss of the implant, impaired function, impaired quality of life and even amputation of the limb. Previous studies have evaluated the risk factors associated with periprosthetic knee infection, but scarce information related to risk factors associated with amputation in this group of patients is available. The purpose of this study was to identify risk factors for amputation in periprosthetic infected knee through a case–control study, analyzing patients treated from January 2012 to November 2016 in a hospital with a high incidence of this diagnosis. We included 183 patients with periprosthetic knee infection; 23 required amputation as definitive management (cases). We found that patients with surgical time >120 min (p = 0.01), surgical risk higher than two points according to the American Society of Anesthesiology score (p = 0.00), smokers (p = 0.04), obesity and diabetes mellitus (p = 0.00) had an increased risk of amputation.