Cerebral Palsy

In approximately 10-20% of all sudden deaths, no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachyarrhythmias (CPVT). The resting ECG and the ECG under exercise are pivotal for the diagnosis of ion channel diseases. Molecular genetic screening can reveal underlying mutations in a variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and may identify individuals with incomplete penetration of the disease. In patients with primary electrical diseases, specific clinical triggers for arrhythmic events such as syncope or sudden cardiac death have been identified including exercise, strenuous activity, auditory stimuli, or increased vagal tone. Young, otherwise healthy individuals are likely to be involved in sports activity. Therefore, special attention has to be given to advise these patients. Competitive sports and vigorous exercise are contraindications in almost all patients. Even recreational exercise may have to be avoided in phenotypically overt patients or silent gene carriers depending on the underlying disease.

Background: It is not known whether abnormalities of left ventricular diastolic function are influenced by the various cardiac geometric patterns in Nigerians with newly diagnosed systemic hypertension. Objective: To evaluate the relationship between the parameters of left ventricular diastolic function and the geometric patterns in this group of patients. Methods: Two-dimensional, guided M-mode echocardiography including Doppler was performed in 150 consecutive, newly diagnosed hypertensive individuals and normotensive controls aged between 35 and 74 years. Left ventricular mass index and relative wall thickness were used to classify the hypertensive individuals into four geometric patterns, and the pulsed-wave Doppler parameters obtained were used to categorise the abnormalities of diastolic function. Results: Four left ventricular geometric patterns were identified: 23 (15.3%) had normal left ventricle geometry, 33 (22%) had concentric remodelling, 37 (24.7%) were found to have eccentric hypertrophy, and concentric hypertrophy occurred in 57 (38%) of the hypertensive individuals. Left ventricular diastolic dysfunction occurred more in hypertensives with concentric left ventricular geometric pattern. Increased left ventricular mass index and relative wall thickness were found to be associated with the mitral E-wave, E/A ratio and pulmonary venous flow S-wave in the hypertensives (p < 0.001). Conclusion: In newly diagnosed Nigerian hypertensives, the abnormalities in left ventricular diastolic function varied between the different left ventricular geometric patterns, being worst in those with concentric geometry.

Abnormalities of the skin should be easy to manage… it is all laid out in front of us to observe, measure, touch, diagnose and treat. Cynics may say that most skin problems get better with time, topical corticosteroids and/or topical antifungal cream. The surgically minded may say… ‘if in doubt, cut it out’. Preventive health messages remind us to ‘slip, slop and slap’ to avoid the dangers of harmful ultraviolet (UV) radiation. But it is not always that simple.

PurposePenetrating keratoplasty was performed on the right eye of a 51-year-old patient diagnosed with advanced bilateral keratoconus. Thirteen years later, an 8.5 mm regraft was required as a result of gross vascularisation, a poor epithelium, and suspected recurrent keratoconus. To learn more about the structural basis for graft failure, we examined the removed tissue for the presence of abnormalities in the stroma and limiting membranes.MethodsX-ray scattering and electron microscopy were used to study the failed-graft tissue to provide information on the integrity of the limiting membranes and the diameter, dominant orientation, and distribution of collagen within the corneal stroma. The findings were compared with similar structural data from normal and keratoconus corneas.ResultsIn contrast to the keratoconus cornea, a normal orientation and distribution of collagen was seen throughout most of the failed-graft tissue, although abnormalities were observed in the infero-nasal quadrant at the original graft/host junction. The average diameter of collagen fibrils in the failed-graft button did not differ from that of normal corneas.ConclusionsThe structural abnormalities identified in this case of graft failure were not consistent with those typically seen in keratoconus. The clear demarcation of the graft/host boundary 13 years after surgery suggests that a normal stromal collagen arrangement may never be fully achieved in corneal graft wounds.Eye advance online publication, 3 July 2009; doi:10.1038/eye.2009.159.

OBJECTIVE:: We have previously reported on the point prevalence of ovarian lesions detected by transvaginal ultrasound (TVU) in 515 asymptomatic women at least 5 years postmenopause. The aims of this study were to report, in the same women, on the repeatability of visualization of the ovaries (TVU) and the natural history of ovarian lesions seen at baseline but not treated surgically and to assess whether any women developed new ovarian abnormalities 12 months later. METHODS:: The study involved a cohort of 515 postmenopausal women recruited from the community, at least 5 years past their last period. They were assessed at baseline and again after 12 months with TVU and serum levels of inhibin and CA-125. RESULTS:: The right and left ovaries were seen on both occasions in 80% and 68% of women, respectively. Of the 49 women who had an ovarian lesion at baseline, did not undergo surgery at that time, and had a follow-up TVU, the lesion was unchanged 12 months later in 30 women. Four women developed a new ovarian lesion within the 12 months. None of the 14 women who underwent surgery on the basis of the ovarian appearance at baseline, or the 2 who had surgery on the basis of the ovarian appearance at follow-up, had an ovarian malignancy. CONCLUSIONS:: The use of TVU in women at least 5 years after menopause is problematic because the ovaries cannot be visualized in all women and because TVU has the potential to identify many benign lesions that would otherwise remain undetected. These are important considerations in weighing up the risks and benefits of using TVU as a screening tool.

BACKGROUND:: Impaired erythropoiesis is a key abnormality described in untreated HIV-1 disease. Most of the available data on HIV-associated hematopoietic abnormalities were obtained using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter (and intra)-individual variability in the number of cultured precursors. Aim of this study was to assess the erythropoietic capability of purified CD34 progenitors through a longitudinal analysis of burst-forming units-erythroid (BFU-E) growth before and after antiretroviral therapy (ART). METHODS:: Twelve HIV-infected individuals were studied before and after ART; 31 HIV-uninfected individuals were enrolled as controls. CD34 progenitors were purified from peripheral blood by immunomagnetic sorting and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor, interleukin-3, and erythropoietin. Serum levels of iron, transferrin, transferrin saturation index, soluble transferrin receptor, ferritin, and erythropoietin were also evaluated. RESULTS:: Baseline BFU-E levels were increased in untreated HIV-infected individuals when compared with controls but declined significantly after successful ART. In contrast, serum levels of erythropoietin and soluble transferrin receptor increased significantly after ART. CONCLUSIONS:: These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective erythropoiesis and accumulation of erythroid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of BFU-E levels.

PURPOSE OF REVIEW: To describe current strategies to enhance cardiovascular disease (CVD) prevention in patients with abnormal glucose regulation. RECENT FINDINGS: Early detection of glucose abnormalities and a multifactorial approach to all modifiable risk factors are effective strategies to reduce the burden of CVD in patients with diabetes mellitus. Available evidence suggests that an overly aggressive approach to lowering of glucose may contribute to complications; different hypoglycaemic agents may vary in the likelihood with which their use may give rise to complications. Thus, a decrease of glucose levels below that recommended in available guidelines is not recommended. SUMMARY: Given its increasing prevalence and its substantial concomitant risk for CVD, diabetes mellitus can no longer be perceived as an endocrine disorder only bearing high risk of microvascular complications. Further research involving prospective clinical trials will be necessary to clarify the benefits of early detection and treatment of diabetes in preventing the subsequent development or exacerbation of CVD.

BACKGROUND AND OBJECTIVES:: Patients undergoing liver resection may have marginal preoperative liver function, extensive intraoperative blood loss, and perioperative hepatic dysfunction. We evaluated the prevalence and types of coagulopathic conditions that occur in patients with epidural catheters undergoing hepatic resection. METHODS:: A retrospective chart review was conducted of all patients undergoing hepatic surgery who received epidural analgesia between June 1995 and September 2003 at our institution. Forty-nine surgical cases had an epidural catheter placed preoperatively. Data were collected included age, weight, American Society of Anesthesiologists physical status; preoperative partial thromboplastin time (PTT), international normalized ratio (INR), and platelet count (PLT); estimated blood loss (EBL); and volume of hepatic resection. RESULTS:: Forty-nine cases received an epidural catheter before hepatic resection. Preoperative PTT, INR, and PLTs were within reference ranges in 47 of 49 patients. Twenty-three (47%) of 49 patients were coagulopathic in the postoperative period. The most common abnormality was an INR greater than 1.4 in 16 patients. Nine patients had a PLT of less than 100,000/muL, and 4 patients had a PTT of greater than 40 secs. Patients who developed a hemostatic abnormality were likely to have greater median EBL (400 vs 1400 mL; Mann-Whitney = 100.5, P = 0.0004) and have a greater median volume of liver resected (166 vs 1688 cm; Mann-Whitney = 57.0, P = 0.0004). There was no causal relationship to preoperative laboratory values, age, weight, or American Society of Anesthesiologists classification. DISCUSSION:: A high prevalence of hemostatic abnormalities in patients undergoing major hepatic resection while receiving epidural analgesia occurred. Important considerations may include discussion with the surgical team, measuring coagulation, and heightened clinical monitoring in the postoperative period.

The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure and the quantitative analysis of mtDNA copy number demonstrated an increase. The levels of ATP and TCA cycle metabolites in diabetic oocytes were markedly reduced compared to controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in non-disjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.

Monotherapy with LPV/r maintains blocked viral replication when used as a simplification strategy from antiretroviral therapy with a boosted protease inhibitor and two nucleoside analogs in patients with an undetectable viral load for at least 6 months. This simplification strategy can be recommended to patients in these circumstances and who are able to maintain near perfect adherence. As recommended by the GESIDA guidelines, LPV/r monotherapy could be offered to patients with undetectable viral loads but who show symptoms or laboratory abnormalities attributable to nucleoside analog toxicity, or co-morbidities such as liver disease or nephropathy; LPV/r monotherapy could also be offered to patients who simply wish to take a lower number of pills. This strategy reduces treatment toxicity and costs, without jeopardizing the patient’s future.