Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases.

Concordant response to pharmacotherapy in monozygotic twins with schizoaffective disorder.

BACKGROUND: Schizoaffective disorder (SAD) represents one of the most confusing and controversial concepts in psychiatry. Prevalence is less than 1%, but despite that it has a major influence on an individual and community. There is an increased risk for schizophrenia and mood diorders in first degree relatives with SAD, according to DSM IV. This paper describes the concordant clinical response of a pair of monozygotic twins with SAD when treated with risperidon and valproic acid. We found that their clinical symptoms were very similar and both brothers expressed hipomanic and depressive episode prior to full onset of SAD-psychotic symptoms with correlations of elevated mood, and first psychiatric hospitalization at the age of 19 (patient A) and 18 (patient B). Their response to the combined treatment with risperidon and valproic acid has been also similar both in intensity and in the pattern of symptoms that have improved.

Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis.

OBJECTIVE: To assess the correlation between cognitive impairment and overall vs regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI tractography in multiple sclerosis (MS). METHODS: Brain dual-echo, T1-weighted, and DT MRI data were acquired from 82 patients with MS. DT tractography was used to produce maps of white matter (WM) tracts involved in cognition. The sensory thalamocortical projections and optic radiations were studied as "control" WM tracts. The contribution of global brain damage (T2 lesion volume, normalized brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal-appearing WM and GM damage) and damage to selected WM tracts to overall cognitive impairment and to impairment at individual neuropsychological tests was assessed using a random forest (RF) analysis. RESULTS: Thirty-three patients had cognitive impairment. The majority of MRI measures differed significantly between cognitively impaired and cognitively preserved (CP) patients. Significant correlations were found between performance in the majority of neuropsychological tests and global or regional brain damage (r ranging from -0.60 to 0.57). The RF analysis showed a high performance in classifying cognitively impaired vs CP patients, with a classification (C)-index = 76.8, as well as in classifying patients' impairment in individual neuropsychological tests (C-index between 75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather than measures of normal-appearing WM damage in the same tracts or global brain/WM/GM damage, resulted in the highest classification accuracy. CONCLUSIONS: Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.

CT volumetry of normal pancreas: correlation with the pancreatic diameters measurable by the cross-sectional imaging, and relationship with the gender, age, and body constitution.

PURPOSE: The purpose of this study was to estimate the volume of normal pancreas in adults using the CT volumetry (summation of the areas technique), analyze the correlation between the volume and the diameters of pancreas, which are measurable by the cross-sectional imaging, and assess the relationship with the gender, age, and body constitution. METHODS: 220 CT examinations were analyzed retrospectively (102 females, 118 males; age 16-82, average 56). Following diameters were measured: cranial-caudal-CC(pancreas), CC(body&tail), CC(body), CC(head); anterior-posterior--AP(tail), AP(body), AP(head); lengths--LL(head), L(body&tail); and maximal transversal diameter of the L1 vertebral body (LL(L1)) and thickness of the abdominal subcutaneous fat (AP(ASF)), as markers of body constitution. RESULTS: The average volume of the pancreas was 79.2 ± 24.1 cm3 (ranging from 37.4 to 168.2 cm3). Pancreatic volume strongly correlated with all measured diameters of the pancreas (P < 0.0001). Pancreatic volume significantly correlated with gender (M:F = 86.1:72.8 cm3, P = 0.002) and the LL(L1) (r = 0.185, P = 0.008), and did not correlate with the age (r = -0.110, P = 0.151) and the AP(ASF) (r = -0.115, P = 0.104). Correlation of vertebral body-pancreas volume ratio of each subject and the age was strongly negative (r = -0.202, P = 0.006). CONCLUSIONS: Marked individual variations in normal pancreas volume were observed. Pancreatic volume could be computed using the diameters measurable by the cross-sectional imaging employing the formula: V = (AP(tail) + AP(body))/2 × L(body&tail) × CC(body) + (AP(head)/2)2 × 3.14 × CC(head).

[Computerized tomography in postoperative monitoring of patients with the Whipple operation--characteristics of CT findings].

We presented the postoperative CT findings of patients after the Whipple's operation (cephalic pancreaticoduodenectomy), performed for the pancreatic head cancer, or ampullary carcinoma. Technique of the Whipple's operation is described, and normal and pathological postoperative CT findings, which are characteristic for the immediate (early) and delayed (late) follow-up period, are presented. In addition, difficulties in differentiation of afferent jejunal loop from the recurrent tumor by CT are discussed, and references from the literature about the possibilities of successful visualization of the afferent jejunal loop are cited. Possible locations and CT appearances of the tumor recurrences are presented. An overview of the literature is provided.

The impact of sexual dysfunction on the quality of life measured by MSQoL-54 in patients with multiple sclerosis.

OBJECTIVE: Sexual dysfunction (SD) is a common but often overlooked symptom in multiple sclerosis (MS). The aim of this study was to estimate the frequency, type, and intensity of SD in our patients with MS and to investigate its influence on all the domains of quality of life. METHODS: The study population comprised a cohort of 109 patients with MS (McDonald's criteria, 2001). SD was quantified by a Szasz sexual functioning scale. Health-related quality of life was measured by a disease-specific instrument MSQoL-54 (Serbian version). RESULTS: The presence of at least one symptom of SD was found in about 84% of the men and in 85% of the women. The main complaints in women were reduced libido, difficulties in achieving orgasm, and decreased vaginal lubrication; in men, the main complaints were reduced libido, incomplete erections, and premature ejaculation. In women, statistically significant negative correlations between the presence and level of SD and quality of life domains were reached for all subscales (P < 0.01), except for the Pain subscale (P = 0.112). In men, negative correlations were also observed for all domains, but they were statistically significant for physical health, physical role limitations, social function, health distress, sexual function, and sexual function satisfaction (P < 0.01). We found that the presence of all the analyzed types of sexual problems statistically significantly lowered scores on the sexual function and the sexual function satisfaction subscales in both men and women (P < 0.01). The most prominent impact on both domains was observed for the total loss of erection in men and for anorgasmia in women. CONCLUSIONS: Our results reveal that frequent occurrence of SD in MS patients prominently affects all aspects of their quality of life.

CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.

[Clinical study of administration of abciximab--a monoclonal antibody to platelet glycoprotein IIb/IIIa in percutaneous intracoronary interventions]. / Klinicka studija o primeni monoklonskog antitela protiv IIb/IIIa glikoproteina trombocita--abciksimaba kod bolesnika sa perkutanom intrakoronarnom intervencijom.

During the last 10 years a new group of drugs was developed--platelet glycoprotein IIb/IIIa blockers that is nowadays largely and efficiently used as for the prevention of percutaneous coronary intervention complications as well as in the treatment of acute coronary syndromes. In the period February-June 2000--19 patients (18 males, 1 female, of average age 53.3 years) were administered Abciximab in the bolus dose of 10 mg immediately before the intervention and afterwards 10 mg by 12-hour infusion. All patients received aspirin and ticlopidine hydrochloride if the stent was introduced and heparin by the standard protocol. Elective intervention was done in 17 patients (non-Q infarction in 3 patients, unstable angina pectoris in 5 patients, postinfarction angina pectoris in 2 patients, acute myocardial infarction at least 1 month before the intervention in 6 patients and 1 patient with myocardiopathy) and in 2 patients the intervention was performed during the myocardial infarction. In 15 patients (79%) intracoronary stent was introduced and in 5 patients (21%) the intervention was performed on 2 arteries. Maximal immediate effect of the dilatation was achieved in 18 patients (94.7%). In the first 60 days of the follow-up 1 patient (5%) died of some other disease, and in no patients symptomatic myocardial ischemia was found. No adverse effects were observed.

[Hemodynamic significance of fluoroscopic diagnosis of coronary artery calcification]. / Hemodinamski znacaj fluoroskopski otkrivenih kalcifikacija u koronarnihm arterijama.

The onset of coronary arterial calcification is an active, organized, metabolically regulated process that occurs only when the initial changes of atherosclerosis are present. Coronary arterial calcification may represent an attempt to protect the arterial wall mechanically. Determination of hemodynamic significance in detecting coronary heart disease was the aim of the study. 110 patients with suspected angina pectoris were performed fluoroscopy and coronary angiography after-wards. In 77 patients (70%) was determined coronary arteriosclerosis using coronary angiography, and in 33 (30%), finding was normal. Out of 77 (70%) patients with positive funding in 44 patients (57.14%) calcifications were detect using fluoroscopy, while in 33 (42.86%) were not. Out of 33 (30%) patients without arteriosclerosis calcifications were detected in 5 (15.15%) patients, and in 28 (84.85%) were not. According to our results and literature review, the calcification finding confirms the presence of already existing significant stenosis on the coronary artery or a high risk for hemodynamic disorder within the next two to five years.

[Coronarography in the diagnosis of left atrial thrombosis]. / Koronarografija u dijagnostici tromboze leve pretkomore.

Thrombosis of left atrium is frequent in the patients with mitral defect. Systemic embolism that generates by separated thrombus parts is a possible complication during the disease. Echocardiography is routinely used in the diagnosis of left atrial thrombosis. On the basis of angiographic experience, we have set the hypothesis: coronary angiography has a great sensitivity, but small specificity in the diagnosis of left atrial thrombosis. The presence of thrombus in left atrium was analyzed in 60 operated patients with mitral valve disease. During the surgery, thrombus was found in 13, and not found in 47 patients. Coronary angiography was preoperatively performed in all patients. In 9 out of 13 patients with intraoperatively observed left atrial thrombus, thrombus was also found by angiography. In 47 patients thrombus was found neither intraoperatively, and in 45 nor by angiography. The sensitivity of angiography in the diagnosis of left atrial thrombosis is 69%, specificity is 97%, and the accuracy is 90%. Positive index of anticipation is 81%, and negative index of anticipation is 91%.

Informational and psychosocial needs of women choosing conservative surgery/primary radiation for early stage breast cancer.

Recent advances in the treatment of early stage breast cancer give women a choice of treatments. Prospective and retrospective studies demonstrate the comparable efficacy of treatment with a modified radical mastectomy and treatment with conservative surgery and primary radiation. While the number of women with early stage breast cancer choosing the latter treatment continues to increase, there is a paucity of information in the nursing literature assessing the informational and psychosocial needs of this group. This article reports the results of a questionnaire assessing the informational and psychosocial needs of patients choosing breast conservation surgery, and the future implications of these results for the nursing profession.

[2 cases of ovarian struma]. / Povodom dva slucaja strume ovarija.

The authors present two patients, aged 48 and 54 respectively, treated surgically for the alleged tumor of the ovary which histologically proved to be the struma of the ovary. In one patient the tumor behave as a benign one, while in the other there was also ascites--simpto mof malignant tumour. After surgery all disorders disappeared in both patients.