Possible role of a radiation-induced p53 mutation in a Nelson’s syndrome patient with a fatal outcome

Nelson’s syndrome (NS) is characterized by the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for the treatment of Cushing’s disease. Such corticotroph macroadenomas respond poorly to currently available therapeutic options which include surgery, radiotherapy and chemotherapy. P53 protein accumulation may be detected by immunohistochemistry in pituitary corticotroph adenomas and it has been suggested that it might be causally related to tumor development. Wild type P53 protein plays an important role in the cellular response to ionizing radiation and other DNA damaging agents and is mutated in many human tumors. In this study we report an adult male patient with NS who underwent both transsphenoidal and transcranial pituitary surgeries, conventional and stereotaxic radiotherapy and brachytherapy. Despite of the efforts to control tumor mass and growth, this macroadenoma displayed relentless growth and aggressive behavior. DNA extracted from the first two surgical samples, as well as DNA from peripheral blood leukocytes disclosed normal p53 sequence. DNA extracted from tumor samples obtained at surgeries performed after pituitary irradiation carried a somatic heterozygous mutation, consisting of a deletion of four cytosines between nucleotides 12,144–12,149 in exon 4 of the p53 gene. This frameshift mutation creates a stop codon in exon 4 excluding the expression of a functional protein from the defective allele. These data demonstrate a possible association between the P53 protein loss of function induced by radiotherapy and the aggressive course of the disease in this patient.     

Protective role of DDAH2 (rs805304) gene polymorphism in patients with myocardial infarction

The purpose of the present study was to establish the role of DDAH gene polymorphisms in the risk of developing myocardial infarction (MI) in a clinical cohort of Mexican patients. One polymorphism (rs1498373) in the DDAH1 and three in the DDAH2 (rs805304, rs3131383, and rs805305) genes were performed by TaqMan genotyping assays in 473 patients with MI and 447 healthy unrelated controls. Similar distribution of DDAH1 and DDAH2 polymorphisms was observed in MI patients and healthy controls. Under a recessive model adjusted for age, gender, and obesity, the rs805304 C allele was associated with decreased risk of MI (OR = 0.70, 95% CI = 0.51–0.96, P = 0.030). The effect of the polymorphisms on various cardiovascular risk factors was analyzed. Under a recessive model adjusted for age and gender, the DDAH2 rs805304 C allele was associated with decreased risk of obesity (OR = 0.35, 95% CI = 0.22–0.57, P = 0.001). The three DDAH2 polymorphisms were in strong linkage disequilibrium. Our results suggest that the rs805304 C allele was associated with decreased risk of MI and decreased risk of obesity.     

Mycotic aneurysm of the tibioperoneal trunk: a first manifestation of an infected endocarditis

Infrapopliteal mycotic aneurysm resulting from endocarditis is rare, with only a few reported cases. We describe the case of a 28-year-old male patient who was suffering with pain and edema in the right leg. The ultrasound revealed an aneurysm of the right tibioperoneal trunk and a deep vein thrombosis (DVT). The patient was admitted and developed acute congestive heart failure, being diagnosed with possible endocarditis. A pseudo-aneurysm was revealed by arteriography. Aggressive antibiotic treatment was initiated, and open surgery confirmed a mycotic pseudo-aneurysm of the tibioperoneal trunk. To our knowledge, this is the 8th case reported of an infected aneurysm in this particular location.     

Frailty and respiratory impairment in older persons

BackgroundAmong older persons, the association between frailty and spirometry-confirmed respiratory impairment has not been evaluated yet.MethodsBy using data on white participants aged 65 to 80 years (Cardiovascular Health Study, N = 3578), we evaluated cross-sectional and longitudinal associations between frailty and respiratory impairment, including their combined effect on mortality. Baseline assessments included frailty status (Fried phenotype: non-frail, pre-frail, and frail) and spirometry. Outcomes included development of frailty features (pre-frail or frail) at year 3 and respiratory impairment (airflow limitation or restrictive pattern) at year 4, and death (median follow-up, 13.2 years).ResultsAt baseline, 48.3% of participants were pre-frail, 5.8% of participants were frail, 13.8% of participants had airflow limitation, and 9.3% of participants had restrictive pattern; 46.1% of participants subsequently died. At baseline, pre-frail and frail were cross-sectionally associated with airflow limitation (adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.29-2.04 and adjusted OR 1.88; 95% CI, 1.15-3.09) and restrictive pattern (adjusted OR, 1.80; 95% CI, 1.37-2.36 and adjusted OR, 3.05; 95% CI, 1.91-4.88), respectively. Longitudinally, participants with baseline frailty features had an increased likelihood of developing respiratory impairment (adjusted OR, 1.42; 95% CI, 1.11-1.82). Conversely, participants with baseline respiratory impairment had an increased likelihood of developing frailty features (adjusted OR, 1.58; 95% CI, 1.17-2.13). Mortality was highest among participants who were frail and had respiratory impairment (adjusted hazard ratio, 3.91; 95% CI, 2.93-5.22), compared with those who were non-frail and had no respiratory impairment.ConclusionFrailty and respiratory impairment are strongly associated with one another and substantially increase the risk of death when both are present. Establishing these associations may inform interventions designed to reverse or prevent the progression of either condition and to reduce adverse outcomes.     

Can fasting plasma glucose and glycated hemoglobin levels predict oral complications following invasive dental procedures in patients with type 2 diabetes mellitus? A preliminary case-control study

OBJECTIVE:

To evaluate the effects of the levels of glycemic control on the frequency of clinical complications following invasive dental treatments in type 2 diabetic patients and suggest appropriate levels of fasting blood glucose and glycated hemoglobin considered to be safe to avoid these complications.

METHOD:

Type 2 diabetic patients and non-diabetic patients were selected and divided into three groups. Group I consisted of 13 type 2 diabetic patients with adequate glycemic control (fasting blood glucose levels <140 mg/dl and glycated hemoglobin (HbA1c) levels <7%). Group II consisted of 15 type 2 diabetic patients with inadequate glycemic control (fasting blood glucose levels >140 mg/dl and HbA1c levels >7%). Group III consisted of 18 non-diabetic patients (no symptoms and fasting blood glucose levels <100 mg/dl). The levels of fasting blood glucose, glycated HbA1c, and fingerstick capillary glycemia were evaluated in diabetic patients prior to performing dental procedures. Seven days after the dental procedure, the frequency of clinical complications (surgery site infections and systemic infections) was examined and compared between the three study groups. In addition, correlations between the occurrence of these outcomes and the glycemic control of diabetes mellitus were evaluated.

RESULTS:

The frequency of clinical outcomes was low (4/43; 8.6%), and no significant differences between the outcome frequencies of the various study groups were observed (p>0.05). However, a significant association was observed between clinical complications and dental extractions (p = 0.02).

CONCLUSIONS:

Because of the low frequency of clinical outcomes, it was not possible to determine whether fasting blood glucose or glycated HbA1c levels are important for these clinical outcomes.