A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition

Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin-Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies.     

Tuberculosis of the knee joint: a case report

Tuberculosis may develop in the skeletal system apart from its primary location, the lungs. A 22-year-old male patient presented with complaints of severe pain and swelling in the left knee and difficulty in walking. The symptoms first appeared 12 years before and he underwent open surgical debridement and arthroscopic debridement at two other centers, at which time aspiration cultures taken from the knee yielded no growth. Physical examination showed a painful left knee with swelling, increased temperature, effusion, and limited range of motion. Based on history, physical examination, radiological studies, and laboratory findings, knee osteoarthritis was considered secondary to nonspecific septic arthritis and knee arthrodesis was performed. At surgery, marked destruction of articular cartilage and synovial hypertrophy were observed. In addition, a cavitary lesion was detected, about 1 x 1 cm in size, in the lateral femoral condyle without articular involvement. Biopsy cultures taken from the lesion showed growth of Mycobacterium tuberculosis in the third week. This enabled a diagnosis of tuberculosis of the knee joint and antituberculous drug therapy was instituted. At six months postoperatively, the patient was on antituberculous treatment and had a painless knee.     

Ectopic lymphoid neogenesis in psoriatic arthritis

BACKGROUND: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). OBJECTIVE: To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates. METHODS: Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor alpha blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates. RESULTS: Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features. CONCLUSIONS: LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.     

Urinary tract infections in renal transplant recipients

Urinary tract infection (UTI) is the most common infectious complication following renal transplantation. The purposes of this study were to determine the causative agents of UTIs among renal transplant recipients and to compare the antibiotic susceptibilities of Escherichia coli strains isolated from renal transplant recipients and complicated community-acquired UTIs. We evaluated 75 episodes of 63 recipients with confirmed UTI who underwent transplantation during the period 1981 to 2006 at our center. Medical records of the patients were reviewed retrospectively. To compare the susceptibility rates of E coli, 226 isolates from nontransplant patients with complicated community-acquired UTIs were also evaluated. Ten episodes (13.3%) occurred in the first month following the transplantation, 11 (14.7%) in the period of the second month to the sixth month, and 54 (72%) after the sixth month of transplantation. Forty-six (61.3%) isolates were E coli. Among these isolates, ciprofloxacin resistance rates were 50% (2/4) in the first month after transplantation, 75% (6/8) in the period of the second month to the sixth month, and 32.4% (11/34) beyond 6 months after transplantation. The resistance rates of trimethoprim/sulfamethoxazole (TMP-SMX) in the same time periods were 100% (4/4), 87.5% (7/8), and 70.6% (24/34), respectively. The rates of resistance to TMP-SMX among E coli isolated from renal recipients were significantly higher than those in community-acquired complicated UTIs. The increased resistance of urinary pathogens to this agent is a major concern. Although high resistance rates of ciprofloxacin against E coli strains were determined in this group, it was not found to be statistically significant.     

Prospective study to evaluate the efficacy of aripiprazole as a monotherapy in patients with severe chronic posttraumatic stress disorder: an open trial

The objective of the study was to assess the efficacy and safety of aripiprazole in outpatients with posttraumatic stress disorder (PTSD) on a 12-week, open-label trial. Twenty-two subjects with DSM-IV diagnosis of PTSD participated; 16 were combat veterans. The primary outcome measure was PTSD symptom severity assessed with the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Positive and Negative Symptoms Scale and the Hamilton Depression and Anxiety Scales. All subjects had a CAPS score of > or = 60 at baseline. Lifetime history of psychotic disorders or bipolar illness was exclusionary. The overall analysis across time was Repeated Measures ANOVA, using Bonferroni corrections. Fourteen subjects completed 12 weeks of treatment. Eight subjects dropped-out due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total, all its subscales, positive symptoms, anxiety and depression scores. Fourteen participants were classified as responders, defined by 20% or greater improvement on CAPS total score. Of the 13 subjects who completed final ratings, CAPS total scores improved significantly (P = .011). Two subjects attained remission of PTSD (CAPS < 20), and three had a final CAPS < or = 26. The mean daily dose of aripiprazole was 12.95 mg. The most common side effects were somnolence (54.5%), restlessness (50%), insomnia (36.4%), and asthenia (31.8%). These results indicate that aripiprazole was effective in about two thirds of subjects that tolerated this medication. The initially high dropout rate may be related to intolerability due to a high starting dose (10 mg), suggesting beginning treatment at lower doses. These preliminary results are encouraging; a double blind study seems warranted.     

Postpartum sacral stress fracture: an unusual case of low-back and buttock pain

Low-back and buttock pain is a common complaint during pregnancy and the postpartum period and is usually attributable to mechanical lesions of the pelvis. Sacral stress fractures are unusual but important causes that should be considered in differential diagnosis. To date, only eight postpartum sacral stress fractures have been reported in the literature. A 32-yr-old woman presented with low-back and right buttock pain that started 15 days after uneventful cesarean section delivery. Imaging studies revealed a right sacral stress fracture. Lumbar spine and femoral neck bone mineral density were normal and, except for pregnancy and lactation, no risk factors for osteoporosis were identified. There was no history of trauma, excessive weight gain, strenuous physical activity, or contribution of mechanical factors. The question remains whether this is an insufficiency fracture or a fatigue fracture. Clinicians should consider sacral fracture during pregnancy and the postpartum period as a diagnostic possibility in patients with low-back and/or buttock pain.     

Case report: a gastrectomized patient under treatment with chemotherapy and radiotherapy

The adjuvant treatment of gastric cancer includes radiotherapy and chemotherapy. The patient underwent gastrectomy on November 10, 2006 and began adjuvant chemotherapy (McDonald scheme) on january 2, 2007, finishing on june 1, 2007. Radiotherapy was started on February 6, 2007 and finished on March 16, 2007. The care plan presented was designed following the Virginia Henderson model and is routinely used at the Reina Sofía Hospital. This care plan follows the NANDA, NOC and NIC taxonomies and is based on the following nursing diagnoses: risk of infection, fear, and disposition to improve knowledge. During the clinical course, two new nursing diagnoses were identified: deterioration of oral mucosa and skin integrity.