Clinical Evaluation of Neck in Patients with Proprioceptive Cervicogenic Dizziness.

OBJECTIVE: To establish a functional connection between neck physical evaluations, dizziness discomfort and image findings among subjects diagnosed with proprioceptive cervical dizziness. METHODS: After exclusion of peripheral vestibular disorders, 20 subjects with proprioceptive cervical dizziness hypothesis were selected. A Visual Analogue Scale (VAS) was used to quantify pain and vertigo. The active neck Range of Motion (ROM) and the Muscle Strength (MS) of the neck region were examined. The manipulation of vertebral bodies by the Maitland method and imaging scan were performed. RESULTS: A positive correlation between pain and vertigo VAS scores was found. The ROM of the cervical spine was limited and vertebral joint movement was restricted, especially at C3 and C5. No loss of MS was noticed. CONCLUSIONS: Proprioceptive cervical dizziness is usually an exclusion diagnosis among episodic chronic vertigos. Characteristically, it is reported by patients as instability or vertigo in crises. It is directly related to the neck ache severity and worsens with neck movements. The common pattern on clinical examination includes restriction and pain during neck flexion without loss of MS. Reduction of joint mobility and pain are also observed, especially at C3 and C54 kHz.

Metabolizing profile of the cytochrome pathway CYP2D6, CYP3A4 and the ABCB 1 transporter in Spanish patients affected by Gaucher disease.

Several therapeutic options are available for type 1 Gaucher disease (GD1), including enzymatic replacement therapy (ERT) and substrate reduction therapy (SRT). Eliglustat is a selective inhibitor of glucosylceramide synthase that is extensively metabolized by CYP2D6 and, to a lesser extent by CYP3A4; it is also an inhibitor of the P-gp transporter. The aim of this study is to evaluate the metabolizer profile of these cytochrome isoforms in 61 GD1 patients, and to analyze interferences with concomitant therapies. Patients were selected from the Spanish Gaucher Disease Registry considering clinical data, GBA genotype, severity score index, comorbidities, concomitant drugs, type and response to therapy and adverse effects. The polymorphisms of CYP2D6, CYP3A4 and three ABCB1 transporter variants were analyzed by Polymerase Chain Reaction (PCR). The most frequent metabolizer profile was extensive or intermediate for CYP2D6, extensive for CYP3A4*1B and CYP3A4*22 and normal activity for ABCB1. Correlations between metabolizer profile and other variables were analyzed by multiple regression study. Twenty-eight patients received ERT, 17 eliglustat and seven miglustat. Forty-two patients (68.8%) had associated diseases and 54.5% were taking daily concomitant medication. Nine patients under eliglustat therapy received concomitant drugs that interact with the CYPs and/or ABCB1, five of these did not reach therapeutic goals and three presented mild or moderate adverse effects (headache and gastrointestinal disorders). Detailed analysis in four patients with TTT haplotype, corresponding to lack of activity of the transporter, was performed. In order to apply personalized medicine and avoid interferences and adverse effects, the individual CYP metabolizer profile and transporter must be considered when choosing the concomitant medication and/or making dose adjustments.

Impaired aerobic exercise capacity and cardiac autonomic control in primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. The aim of our study was to assess aerobic capacity and cardiac autonomic control in PAPS patients. Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill-graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP) and time-to-exhaustion, whereas cardiac autonomic control was assessed by chronotropic reserve (CR) and heart rate recovery at the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). All aerobic capacity indexes were reduced more in PAPS patients than in healthy subjects: VO2peak (30.2 ± 4.7 vs 34.6 ± 4.3 ml.kg(-1).min(-1), p = 0.021), time at VAT (3.0 ± 1.5 vs 5.0 ± 2.0 min, p = 0.016), time at RCP (6.5 ± 2.0 vs 8.0 ± 2.0 min, p = 0.050), time-to-exhaustion (8.5 ± 2.0 vs 11.0 ± 2.5 min, p = 0.010). HRR1min (22 ± 9 vs 30 ± 7 bpm, p = 0.032) and HRR2min (33 ± 9 vs 46 ± 8 bpm, p = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (p = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS.

The present Pyrenean population of bearded vulture (Gypaetus barbatus): its genetic characteristics.

The Pyrenean population of the endangered bearded vulture (Gypaetus barbatus) is the largest natural population in Europe. In this study, its current genetic variability was assessed using 110 animals of the recent population in order to know what the present situation. Sex identification by DNA methodology in the 110 bearded vultures, mitochondrial DNA (mtDNA) and eight microsatellite markers in 87 bearded vultures have been analysed. Our results for sex identification present a number of 49 males and 61 females; no significant differences for number of males and females in this population have been observed. mtDNA studies indicate that nucleotide and haplotype diversities and number of variable sites were low. Tajima's D test and Fu and Li's D* and F* tests suggest that mutations are selectively neutral and the population is expanding. A mean number of alleles per locus and a mean observed heterozygosity have been obtained by microsatellite analysis. FIS is not high, and inbreeding depression could be discarded in the near future. The results suggest that the Pyrenean population of bearded vultures have to be controlled in order to avoid the loss of genetic variability. This data should be taken into account when considering conservation plans for the species.

Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2.

Cell identity is determined by its gene expression programs. The ability of a cell to change its identity and produce cell types outside its lineage is achieved by the activity of transcription controllers capable of reprogramming differentiation gene networks. The synovial sarcoma (SS)-associated protein, SYT-SSX2, reprograms myogenic progenitors and human bone marrow-derived mesenchymal stem cells (BMMSCs) by dictating their commitment to a pro-neural lineage. It fulfills this function by directly targeting an extensive array of neural-specific genes as well as genes of developmental pathway mediators. Concomitantly, the ability of both myoblasts and BMMSCs to differentiate into their normal myogenic and adipogenic lineages was compromised. SS is believed to arise in mesenchymal stem cells where formation of the t(X/18) translocation product, SYT-SSX, constitutes the primary event in the cancer. SYT-SSX is therefore believed to initiate tumorigenesis in its target stem cell. The data presented here allow a glimpse at the initial events that likely occur when SYT-SSX2 is first expressed, and its dominant function in subverting the nuclear program of the stem cell, leading to its aberrant differentiation, as a first step toward transformation. In addition, we identified the fibroblast growth factor receptor gene, Fgfr2, as one occupied and upregulated by SYT-SSX2. Knockdown of FGFR2 in both BMMSCs and SS cells abrogated their growth and attenuated their neural phenotype. These results support the notion that the SYT-SSX2 nuclear function and differentiation effects are conserved throughout sarcoma development and are required for its maintenance beyond the initial phase. They also provide the stem cell regulator, FGFR2, as a promising candidate target for future SS therapy.

Circulating neutrophils may play a role in the host response in cervical cancer.

Neutrophil migration is a key event in the inflammatory response of any origin, and neutrophils may present antitumor activity. We investigated the number and function of circulating neutrophils obtained from patients with cervical neoplasia at different stages. Patients with preinvasive (cervical intraepithelial neoplasia, CIN3, n= 6) or microinvasive ([MICRO] stage IA1, n= 4) neoplasia were evaluated together as CIN/MICRO group (n= 10), while patients at stages II-IV were evaluated as invasive group (INV, n= 12). Healthy women served as controls (n= 15). For patients, analysis of leukogram on diagnosis showed a significant elevated neutrophil count in INV group compared with that in CIN/MICRO group. A neutrophil/lymphocyte ratio >/=5 was observed in 67% patients from INV group compared with only 10% from CIN/MICRO group. Neutrophil migration, assayed in a microchemotaxis chamber in response to the chemoattractants (10(-7) M) N-formyl-l-methionyl-l-leucyl-l-phenylalanine, leukotriene B(4), or interleukin-8, was reduced in INV group than in controls or CIN/MICRO group. Surgical treatment in randomly selected patients from CIN/MICRO group (four CIN, one MICRO) increased neutrophil migration to all chemoattractants compared with time on diagnosis. The serum levels of nitric oxide (NO) metabolites, assayed by the Griess reaction, were higher in patients (n= 19) than in controls (n= 15), without differences related to tumor stage, but were reduced in patients after surgery compared with pretreatment (n= 10). Taken together, the results suggest that neutrophils play a role in the host response in cervical cancer. Soluble circulating mediators released by tumor cells, such as NO, could interfere early in the capacity of neutrophils to migrate, thus impairing host immune response.

[Epidemiological aspects of ciprofloxacin-resistant Escherichia coli at a general hospital]. / Aspectos epidemiológicos de la resistenciade Escherichia coli a ciprofloxacino en un hospital general.

The susceptibility to ciprofloxacin of 7288 Escherichia coli clinical isolates from 5667 patients was determined over a 4-year period (1995-1998). Information about the patients' age, sex, specimen type, date, origin and susceptibility to Escherichia coli isolates was studied, and the c2 test was used for statistical comparison. Overall, 1003 (17.70%) patients out of the 5667 included in the study presented ciprofloxacin resistance. The annual resistance observed over this 4-year period was not considered statistically significant. The resistant isolates were more frequent among men, in urine specimens and in outpatients, and increased with different age groups. The average age of patients with resistant isolates was 61.29 years (SD 21.56) and that of patients with susceptible isolates was 39.76 years (SD 27.41). A similar rate of resistance was observed among outpatients from health centers and those from hospital outpatient services. The higher resistance rates were found in outpatients from the urology department. The resistance to other fluoroquinolones remained the same and was not significant for norfloxacin; it increased starting from 1997 for pefloxacin at the expense of ciprofloxacin-sensitive isolates.

Percutaneous transluminal angioplasty in patients with Takayasu arteritis: five-year experience.

PURPOSE: The authors report their 5-year experience with percutaneous transluminal angioplasty (PTA) for treatment of stenoses related to Takayasu arteritis. PATIENTS AND METHODS: Twenty patients were treated; 12 patients had renovascular hypertension at presentation, three patients had abdominal aortic coarctation syndrome, and five patients had aortoiliac occlusive disease. RESULTS: The initial success rate for patients with renovascular hypertension was 83%, with a 5-year patency of 33.3%. In patients with abdominal aortic coarctation, initial success rate was 100% but 5-year patency was 33.3%. In patients with aortoiliac occlusive disease, the initial success rate was 100%, with a 5-year patency of 60%. CONCLUSION: Despite the high initial success rate for PTA in these patients, the disease recurs in a substantial number of the, due to the fact that this technique does not treat the disease itself but only its consequences.