99mTc-thymine scintigraphy may be a promising method in the diagnosis of breast cancer

OBJECTIVE:

Mammography has been established as the gold standard for the detection of breast cancer, and imaging techniques such as ultrasonography, magnetic resonance imaging, scintigraphy and positron emission tomography may be useful to improve its sensitivity and specificity. The objective of this study with breast scintigraphy was to evaluate the uptake of 99mTc-thymine in mammary lesions.

METHODS:

A total of 45 patients were included in this study. Thirty-three patients (73%) were subjected to surgery or percutaneous biopsy, providing histopathological data. The other 12 patients who remained under surveillance received clinical examinations and biannual mammography with a normal follow-up of at least three years, the data from which were used for comparison with the scintimammography results.

RESULTS:

The majority of patients (64.4%) had clinically impalpable lesions with a mammogram diagnosis of microcalcifications, impalpable nodules, or focal asymmetry. Of the studied lesions, 87% were smaller or equal to 20 mm in diameter, and 22% had malignant histopathological findings. Scintigraphy with 99mTc-thymine had a sensitivity of 70%, a specificity of 85.7%, positive and negative predictive values of 58.3% and 90.9%, respectively, and an accuracy of 82.2%.

CONCLUSIONS:

The results of this study are consistent with those previously reported by other authors. The good specificity and high negative predictive value of this technique and the absence of uptake in the heart indicate that it may be a promising complementary method in clinical practice and that it may contribute to reducing unnecessary benign biopsies.     

Patient-reported outcomes and low-level residual HIV-RNA in adolescents perinatally infected with HIV-1 after switching to one-pill fixed-dose regimen

The choice of an antiretroviral regimen can often impact on adherence, treatment satisfaction and therefore influence on clinical outcome. These concerns are particularly true in adolescents. In this setting, adherence is usually affected by multifactor events and biopsychosocial factors, which connect and changeover time. We evaluated the effect of a switch to a single-pill fixed-dose regimen on patient-reported outcomes, virologic and immunologic outcomes, and safety in a cohort of adolescents with perinatal HIV-1 infection. In addition, we evaluated the effect on low-level residual HIV-RNA. An open-label, non-randomised study was performed: 12 adolescents with a confirmed viremia <50 copies/mL treated with lamivudine or emtricitabine, tenofovir and efavirenz were switched to one-pill fixed-dose regimen of emtricitabine/tenofovir/efavirenz. At the end of follow-up, the new regimen was associated with improvements in treatment satisfaction, HIV-symptoms, whereas adherence remained high. No immunological or virological significative changes were observed. No side-effects were registered. Moreover, the low-level residual HIV-RNA was <3 copie/mL in all patients. One-pill fixed-dose regimen is an added value that favours adherence, reduces HIV-symptoms, improves patients' satisfaction and could better control of HIV-RNA in adolescents, too.     

Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20?mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2?years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.     

Pharmacology and Pharmacogenetics of Pediatric ADHD with Associated Aggression: A Review

Attention deficit hyperactivity disorder (ADHD) is often associated with symptoms of aggression in children and adolescents. Clinically, this is complex because aggression can be from hyperactivity and impulsivity, or could be a distinct symptom from a comorbid diagnosis. Past research has recommended first treating the primary disorder of ADHD. Stimulants are the most common treatment for pediatric ADHD, which can be helpful in decreasing aggressive behaviors. Alpha-adrenergic agonists and atomoxetine (ATX) are non-stimulant medications for ADHD and aggression, but more research is necessary to compare these drugs to stimulants. If aggressive symptoms do not improve from treating the primary disorder, aggression can be treated separately. Risperidone, lithium, valproic acid, clonidine, and guanfacine have shown positive results in reducing aggression, but studies including children with aggression and ADHD are limited. The variability in treatment tolerability in patients has stimulated research in pharmacogenetics for ADHD. Although this field is still emerging, research has found evidence supporting a link between the response rate of methylphenidate and the dopamine transporter (DAT1) and a link between the metabolism rate of atomoxetine and hepatic cytochrome 450 isozymes. Pharmacogenetics may be relevant to ADHD and associated aggression. Further research in pharmacogenetics will strive to identify patterns of genetic variations that can tailor individual treatments.     

DAT genotype modulates striatal processing and long-term memory for items associated with reward and punishment

Previous studies have shown that appetitive motivation enhances episodic memory formation via a network including the substantia nigra/ventral tegmental area (SN/VTA), striatum and hippocampus. This functional magnetic resonance imaging (fMRI) study now contrasted the impact of aversive and appetitive motivation on episodic long-term memory. Cue pictures predicted monetary reward or punishment in alternating experimental blocks. One day later, episodic memory for the cue pictures was tested. We also investigated how the neural processing of appetitive and aversive motivation and episodic memory were modulated by dopaminergic mechanisms. To that end, participants were selected on the basis of their genotype for a variable number of tandem repeat polymorphism of the dopamine transporter (DAT) gene. The resulting groups were carefully matched for the 5-HTTLPR polymorphism of the serotonin transporter gene. Recognition memory for cues from both motivational categories was enhanced in participants homozygous for the 10-repeat allele of the DAT, the functional effects of which are not known yet, but not in heterozygous subjects. In comparison with heterozygous participants, 10-repeat homozygous participants also showed increased striatal activity for anticipation of motivational outcomes compared to neutral outcomes. In a subsequent memory analysis, encoding activity in striatum and hippocampus was found to be higher for later recognized items in 10-repeat homozygotes compared to 9/10-repeat heterozygotes. These findings suggest that processing of appetitive and aversive motivation in the human striatum involve the dopaminergic system and that dopamine plays a role in memory for both types of motivational information. In accordance with animal studies, these data support the idea that encoding of motivational events depends on dopaminergic processes in the hippocampus.     

Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease

Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.     

Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.