Early spermatogenesis changes in traumatic complete spinal cord-injured adult patients.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on the spermatogenesis of patients studied in the early subacute stage and ensuing months. SETTING: National hospital for SCI patients. METHODS: A prospective follow-up study was conducted on 28 male patients with complete SCI who were evaluated in the early subacute phase (~1 month), and 3 and 6 months after the injury. At each time point, fine needle aspiration biopsy samples were taken from the testes for cytological assessment, and serum levels of relevant hormones were measured. At the end of the study period, ejaculation was attempted for standard semen analyses. RESULTS: Cytological patterns indicative of defective spermatogenesis were found in 61%, 52% and 20% of the patients at 1, 3 and 6 months after SCI, respectively, suggesting an improvement over time. Serum hormone analyses showed a steady elevation of estradiol levels above the reference range, and increasing levels of testosterone, inhibin B and prolactin throughout the study period. Prolactin levels were above the reference range at all time points. Only 2 out of the 10 patients who were able to ejaculate at 6 months post injury showed normal sperm parameters. CONCLUSION: A majority of the patients showed impaired spermatogenesis soon after the injury, which in most cases recovered over time. That was accompanied by parallel increases in serum levels of inhibin B, testosterone and prolactin, possibly driving or reflecting the spermatogenesis recovery. Further studies are needed to elucidate the biological mechanisms underlying these changes.

Concordance of the ACR TI-RADS.

BACKGROUND: Ultrasonography (US) is the method of choice for evaluating thyroid nodules. In 2017, the American College of Radiology (ACR) created a classification system based on US characteristics. For the system to be adopted, it must be reproducible. OBJECTIVES: To determine the intraobserver and interobserver variability of the ACR TI-RADS. METHODS: Cross-sectional study; three radiologists with different levels of experience used the ACR TI-RADS to classify 100 nodules on two occasions one month apart, and we calculated the intraobserver and interobserver variability. RESULTS: Regarding intraobserver variability, the first radiologist had nearly perfect concordance for composition, echogenicity, shape, and margins and substantial concordance for echogenic foci; the second radiologist had nearly perfect concordance for composition, echogenicity, shape, and margins and substantial concordance for echogenic foci, and the third radiologist had nearly perfect concordance for composition, echogenicity, and shape and substantial concordance for margins and echogenic foci. The interobserver concordance was calculated for the two readings; the concordance was substantial except for shape in the first reading and for echogenicity and margins in the second reading, which had moderate concordance. CONCLUSIONS: The ACR TI-RADS classification system is reproducible.

Concordance of the ACR TI-RADS. / Concordancia del TIRADS-ACR.

BACKGROUND: Ultrasonography (US) is the method of choice for evaluating thyroid nodules. In 2017, the American College of Radiology (ACR) created a classification system based on US characteristics. For the system to be adopted, it must be reproducible. OBJECTIVES: To determine the intraobserver and interobserver variability of the ACR TI-RADS. METHODS: Cross-sectional study; three radiologists with different levels of experience used the ACR TI-RADS to classify 100 nodules on two occasions one month apart, and we calculated the intraobserver and interobserver variability. RESULTS: Regarding intraobserver variability, the first radiologist had nearly perfect concordance for composition, echogenicity, shape, and margins and substantial concordance for echogenic foci; the second radiologist had nearly perfect concordance for composition, echogenicity, shape, and margins and substantial concordance for echogenic foci, and the third radiologist had nearly perfect concordance for composition, echogenicity, and shape and substantial concordance for margins and echogenic foci. The interobserver concordance was calculated for the two readings; the concordance was substantial except for shape in the first reading and for echogenicity and margins in the second reading, which had moderate concordance. CONCLUSIONS: The ACR TI-RADS classification system is reproducible.

Current management of breakthrough cancer pain according to physicians from pain units in Spain.

PURPOSE: Current evidence suggests the need to improve the management of breakthrough cancer pain (BTcP). For this reason, we aimed to assess the opinion of a panel of experts composed exclusively of physicians from pain units, who play a major role in BTcP diagnosis and treatment, regarding the key aspects of BTcP management. METHODS: An ad hoc questionnaire was developed to collect real-world data on the management of BTcP. The questionnaire had 5 parts: (a) organizational aspects of pain units (n = 12), (b) definition and diagnosis (n = 3), (c) screening (n = 3), (d) treatment (n = 8), and (e) follow-up (n = 7). RESULTS: A total of 89 pain-unit physicians from 13 different Spanish regions were polled. Most of them agreed on the traditional definition of BTcP (78.9%) and the key features of BTcP (92.1%). However, only 30.3% of participants used the Davies' algorithm for BTcP diagnosis. Respondents preferred to prescribe rapid-onset opioids [mean 77.0% (SD 26.7%)], and most recommended transmucosal fentanyl formulations as the first option for BTcP. There was also considerable agreement (77.5%) on the need for early follow-up (48-72 h) after treatment initiation. Finally, 65.2% of participants believed that more than 10% of their patients underused rapid-onset opioids. CONCLUSIONS: There was broad agreement among pain experts on many important areas of BTcP management, except for the diagnostic method. Pain-unit physicians suggest that rapid-onset opioids may be underused by BTcP patients in Spain, an important issue that need to be evaluated in future studies.

[An analysis of the causes, characteristics, and consequences of reexposure to a drug or compound responsible for a hepatotoxicity event]. / Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxidad.

INTRODUCTION: reexposure to a causal agent represents a potentially serious event in hepatotoxicity. OBJECTIVES: to assess the characteristics and outcome of cases with positive reexposure. MATERIAL AND METHODS: a retrospective study of cases with evidence of positive reexposure included in Registro Español de Hepatopatías Asociadas a Medicamentos, and an analysis of their relation to demographic and clinical variables, causality, course, and consequences. RESULTS: of a total of 520 cases 31 (6%) met reexposure criteria. Fatal outcomes, needs for admission, and mean recovery time were all higher for hepatocellular-type toxic injury. The most commonly identified drug class was antibiotics. On most occasions (73%) reexposure to the causal compound escaped notice because of: absence of index case diagnosis, lack of information to patients and their physicians, and (12%) development of cross reactions between structurally similar drugs. CONCLUSIONS: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is common and may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflecting diagnostic suspicion in the initial episode s record may reduce the incidence of this iatrogenic event.

[Protected penetrating keratoplasty: surgical technique and endothelial response]. / Queratoplastia penetrante protegida: técnica quirúrgica y respuesta del endotelio.

PURPOSE: To describe the technique and to evaluate the safety of protected penetrating keratoplasty (PPK). METHODS: A technique for penetrating keratoplasty is described. The postoperative endothelial cell counts of 17 eyes in which this operative technique was used were compared with those in 24 eyes in whom the standard operative technique for penetrating keratoplasty (PK) was used. The post-operative time periods were grouped as follows: 3-6 months, 7-12 months and >12 months. For statistical analysis, the Mann-Whitney U non-parametric test was employed. RESULTS: There was no case where tissue extrusion occurred during the procedure. The endothelial cell count was similar in both groups for the 3-6 month period (PK = 2,086, DS 566; PPK = 1,858, DS 671; p = 0.2702) and >12 months period (PK = 1,574, DS 745; PPK = 1,419, DS 810; p = 0.2882). There was a significant difference in the 7-12 month period (PK = 2,255, DS 831; PPK = 1,569, DS 623; p = 0.0397). CONCLUSIONS: The described technique of PPK may reduce the risk of per-operative complications. Damage to the endothelium is not increased compared with that seen following the standard PK procedure.

Maxillary sinus balloon lifting and deferred implantation of 50 osseointegrated implants: a prospective, observational, non-controlled study.

The aim of this study was to assess the effectiveness of minimally invasive antral membrane balloon elevation (MIAMBE). Twenty-seven patients with severe resorption of the posterior maxilla were treated by balloon catheter-assisted sinus lift procedure with deferred implant placement. Panoramic radiographs and computed tomography scans were obtained prior to surgery and at 6 months after surgery, before implantation. Data collected following surgery included inflammation, pain, bleeding, infection, and haematoma. Pain and inflammation were recorded using a six-point verbal rating scale (VRS). The patients were followed up for an average of 15 months. The initial sinus floor height was measured for each planned implant and compared with the height at 6 months post-surgery. The average bone height gain was 8.10±3.45mm (range 0.5-13.95mm). Inflammation on the VRS ranged from 0 to 3 (mean 0.97±0.85), while pain ranged from 0 to 4 (mean 0.87±1.19). There was a perforation of the Schneiderian membrane smaller than 2mm in one case. In another case, the balloon lift procedure had to be aborted and changed to the conventional Tatum technique due to breakage of the balloon inside the sinus. The results of this study show the balloon sinus lift technique to be an easy procedure to perform, with apparently low rates of inflammation and pain, and to provide sufficient quantity and quality of bone for the placement of osseointegrated implants.

Effects of baclofen on temperature perception in humans.

The aim of this study was to evaluate the effect of chronic consumption of the GABAB agonist baclofen on temperature perception in humans. We investigated temperature perception thresholds to detect warm and cold stimuli in a group of 21 patients with spinal cord injury, who were chronically consuming oral baclofen at different daily doses to treat spasticity. Temperature perception thresholds were assessed above the level of the lesion, using a psychophysical approach based on the ability of the subjects to perceive precisely quantified sensory stimuli (quantitative sensory testing, QST). The data were compared with a control group of healthy subjects, not receiving baclofen. We found that chronic baclofen consumption increased temperature perception thresholds for both cold and warm stimuli in a dose-dependent manner. Temperature perception thresholds did not depend on the level of the lesion nor on the duration of baclofen treatment, suggesting that our finding represent normal GABAB-mediated modulation in spared nervous structures. We conclude that GABAB therefore plays a role in temperature perception in humans.

Steady-state carbamazepine plasma concentration-dose ratios in epileptic patients.

The distribution of carbamazepine plasma concentration-dose ratio was studied in 322 samples from patients undergoing long term treatment. Data have been grouped according to: age--3 to 6, 7 to 9, 10 to 14, and above 15 years old; number of drugs used in the treatment--mono- and polytherapy; dose--less than or equal to 10, 10.1 to 14.9, 15 to 19.9, and greater than or equal to 20 mg/kg; and plasma concentration found--less than 4, 4 to 8, 8.1 to 12, and greater than 12 mg/L. From the results it is concluded that the carbamazepine concentration-dose ratio increases with age in children, but is less than in adults, is higher in monotherapy than in polytherapy, and decreases as the dose increases.

Pseudomonas attachment to new hydrogel contact lenses.

The adhesion of two strains of Pseudomonas aeruginosa to unworn hydrogel contact lenses (CLs) was studied by scanning electron microscopy. New daily-wear polymacon lenses (38.6% water content) and extended-wear lidofilcon A lenses (70% water content) were exposed to a suspension of 10(8) colony-forming units per milliliter of P aeruginosa for 2, 5, 15, 30, and 60 minutes. Increasing numbers of bacteria were found to attach to the lenses with time, and no significant differences between CL types were demonstrated. Attachment was considered to be irreversible since washing did not remove the bacteria. We conclude that P aeruginosa can actively attach to new, unworn hydrogel CLs.

Cyst of accessory lacrimal gland.

We present a case of an epithelial cyst of the conjunctiva caused by the dilatation of an accessory lacrimal gland. The case is peculiar in regard to the size of the cyst and the absence of traumatic or inflammatory factors to explain the retention of fluid.

Corneal dioptric power after penetrating keratoplasty.

The dioptric power of the cornea (spherical equivalent) was studied in 60 eyes operated on for penetrating keratoplasty. In order to determine the possible influence of (1) the underlying pathology, (2) the presence of neovascularisation, or (3) the size of the graft the sample was divided into four groups, with the following results: group A (keratoconus, same-sized graft) = 42.25 D; group B (keratoconus, oversized graft) = 45.16 D; group C (keratopathy with minimal or no vascularisation) = 45.34 D; group D (keratopathy with significant vascularisation) = 45.36 D. The results showed that donor-receptor disparity is the main factor determining the outcome of the postoperative corneal spherical power. There was no demonstrable influence from underlying pathology or the presence of vessels in the receptor cornea.

Idiopathic lipid corneal degeneration.

Two patients with no history of eye disease or systemic disorder exhibited bilateral corneal lipid annular infiltrates, together with deep stromal vascularization. Penetrating keratoplasty was performed on one eye of each patient, and one patient presented with an acute graft rejection.

Hydrogel contact lens-induced Pseudomonas keratitis in a rabbit model.

Unused soft contact lenses (SCL) containing 38.6% water (polymacon) and 70% water (lidofilcon A) were exposed to Pseudomonas aeruginosa (10(8) CFU/ml) for 60 min and washed. The contaminated lenses were used on rabbit eyes under the following conditions: for 1 h on a scratched corneal epithelium (16 eyes, four infected), for 24 h on normal cornea (eight eyes, none infected), and for 7 days on normal cornea (eight eyes, three bacterial infections and two noninfected epithelial defects). A control group of rabbits used an uncontaminated lens for 7 days (eight eyes, four noninfected epithelial defects). The control group and groups that wore contaminated lenses for 24 h and 7 days underwent tarsorrhaphy to keep the contact lens in place. In addition, three drops of the bacterial suspension were instilled in eyes with normal corneal epithelium (eight eyes, none infected) and scratched corneal epithelium (16 eyes, 13 infected). Results suggest that Pseudomonas-contaminated SCL give rise to keratitis only on an injured corneal epithelium and that a bacterial suspension is more pathogenic to the rabbit cornea than is a similar amount of bacteria on an SCL.

Protective effect of GABA and sodium valproate on stress-induced gastric lesions in guinea-pigs.

gamma-Aminobutyric acid (GABA) and sodium valproate (VPA) inhibit the formation of stress-induced gastric ulcers in guinea-pigs. The present study was conducted to evaluate the effect of these drugs on the development of cold- and restraint-induced gastric ulcers in guinea-pigs. In control saline-pretreated animals, a 3 h exposure to cold and restriction resulted in the production of gastric ulcers in 9 out of 10 animals. GABA (200 mg kg-1 oral, i.p.) completely prevented the development of gastric ulcers. VPA (100 and 200 mg kg-1 i.p.) exerted no significant effects on the development of gastric ulcers. GABA (100 mg kg-1 oral and i.p.) and VPA (oral) also exhibited partially protective activity. It is suggested that GABA may participate in a physiological modulation of the gastric mucosal barrier, by increasing its resistance to stress-induced lesions.

Factors modifying valproate plasma level/dose ratio: age, sex, dose and plasma level.

Valproate plasma level/dose (L/D) ratios obtained from 155 outpatients under long-term monotherapeutic regimen have been studied. Analytical data were obtained by enzymatic immunoassay (EMIT) from paired samples taken before the morning drug dosage. L/D ratios were increased with age and plasma level and decreased with dose. There were no sex differences in L/D in the different age, dose and concentration groups. L/D ratios were higher than those found by other researchers in our country.

Phenobarbital plasma level/dose ratio in monotherapy. Influence of age, sex and dose.

Phenobarbital plasma level/dose ratio (L/D) has been studied in 536 outpatients distributed in groups according to age, sex and drug dosage. Samples were obtained prior to the first morning dose. Plasma levels that correspond to the steady-state phase were determined by homogeneous enzymatic immunoassay (EMITR). From the results it must be pointed out: 1) An increase of L/D as the age increases within each group; 2) A decrease of L/D as the dose of phenobarbital increases in the overall sample; 3) Sex does not affect L/D in any of the subgroups studied; 4) For a given dose higher blood levels are reached in children 7 to 15 years old in our sample than in other comparable studies in Spain.

Total and free valproic acid: plasma level/dose ratio in monotherapy.

Free plasma level/dose ratio of valproic acid (L/D-F) can be more effective than total plasma level/dose ratio (L/D-T) in adjusting dosage regimens. The influence of age, dose, and plasma concentration have been studied on L/D-T and L/D-F ratios. L/D-T and L/D-F ratios from 67 outpatients under long-term monotherapy were obtained. Analytical data was carried out by fluorescent polarized immunoassay. L/D-T and L/D-F ratios do not vary according to age. L/D-T and L/D-F ratios decreased while the dosage increased; both ratios increased with an increase in total plasma level of valproic acid. Significant differences were found between L/D-T and L/D-F ratios. Dose and interindividual variations are the factors which most influence L/D ratios of valproic acid.

Factors affecting the free plasma fraction of phenytoin in patients with epilepsy.

The variability and possible factors modifying the free plasma fraction of phenytoin were investigated in 134 patients with epilepsy undergoing long-term treatment. The total and free plasma concentrations of phenytoin were determined using fluorescent polarisation immunoassay. Concentrations of albumin, bilirubin and creatinine were also obtained. The free plasma concentration was separated by ultrafiltration, at 25 degrees C, using Centrifree((R)) filters. Factors related to the free plasma fraction of phenytoin (free plasma concentration/total plasma concentration) were gender, age, dose, therapeutic regimen, total plasma concentration and the biochemical parameters mentioned. The mean of free plasma fraction was 9.1% with a very high variability (between 3.3 and 37%). No significant relationship was found between the free plasma fraction and dose, age, gender, total plasma concentration or the biochemical data. The only variable with a significant effect (p < 0.05) on the free plasma fraction was polytherapy with valproic acid. The variability in the free plasma fraction of phenytoin was high in epileptic patients, and was poorly related to the clinical or analytical variables studied. In the absence of pathologies that modify phenytoin binding (uraemia, hypoalbuminaemia), the only factor predictive of a possible alteration in the binding of phenytoin to plasma proteins was polytherapy with valproic acid.

[Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature]. / Hepatitis aguda por ticlopidina. Presentación de 12 casos y revisión de la literatura.

OBJECTIVE: To analyze the characteristics of hepatotoxicity due to ticlopidine. PATIENTS AND METHODS: We describe all the case of hepatotoxicity attributed to ticlopidine and reported to the Register of drug associated hepatopathies. We also obtained data from MEDLINE and the Spanish Medical Index regarding cases reported during the period 1982 2001. RESULTS: We reported twelve cases of hepatopathy related to the use of ticlopidine. These made up 5% of all the cases notified to the Register. Eighty three percent of the patients were male, and of an average age of 68 years. Sixty six percent required hospital admission. The latent period varied between 2 and 13 weeks. The liver lesion was of cholestatic type in 75% of the cases, hepatocellular in 16.6% and mixed in 8.3%. Twenty five percent of the patients had received sub therapeutic doses. CONCLUSIONS: Ticlopidine is often related to hepatotoxicity. This seems to be due to an idiosyncratic mechanism and is mainly cholestatic. The use of lower dosage than that recommended means that the desired therapeutic effect is not attained but does not protect against the development of hepatotoxicity. Doctors who use this drug should be aware of this so as to establish the true risk benefit relation.