Intracranial interhemispheric osteochondrolipoma: Diagnostic and surgical challenges in an extremely rare entity

Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.5‐years‐old male child which was detected antenatally, in association with corpus callosum agenesis. The lesion progressively increased in size with resulting compression of surrounding structures, and was subjected to microsurgical decompression. To the best of our knowledge, this is the first case of intracranial interhemispheric osteochondrolipoma in the existing medical literature. Peculiarities of this case and the diagnostic and surgical challenges are discussed.     

Nephrocalcinosis in rabbits – correlation of ultrasound, computed tomography, pathology and renal function

Objective. The purpose of this study was to induce nephrocalcinosis (NC) in rabbits with phosphate, vitamin D, oxalate and furosemide, to determine the effect on renal function and to correlate detection on ultrasound (US) and computed tomography (CT) with pathology. Materials and methods. Seventy-five immature New Zealand white rabbits were divided into five groups of 15. In each group, 5 animals were controls and 10 were given oral phosphate, furosemide, vitamin D or oxalate. Unilateral nephrectomy was performed at 3–6 weeks, and 5 rabbits of each test group were withdrawn from the substance. Weekly US was performed as well as US, CT and measurement of serum creatinine at the time of nephrectomy and prior to planned demise. Results. A total of 140 kidneys in 75 rabbits had both pathological and US correlation, with CT correlation in 126. Forty rabbits developed nephrocalcinosis with early (post nephrectomy at 3–6 weeks) or late (post demise at 12–20 weeks) pathological correlation obtained in 53 kidneys. Forty-one of these kidneys were from test animals: 23 developed NC early, 18 late. Twelve controls developed NC: 4 early, 8 late. Comparing US and CT to pathology, the sensitivity was 96 % for US, 64 % for CT. Specificity was 85 % for US and 96 % for CT. In 109 kidneys, information on serum creatinine level was available to correlate with pathology. The mean creatinine level was 138 mmol/l for those with NC and 118 mmol/l for those without NC (P < 0.001). Conclusion. In this study, the presence of NC was significantly associated with increasing serum creatinine. Overall, US was more sensitive and CT was more specific in the detection of NC. Received: 20 August 1996 Accepted: 12 August 1997     

Cardiac extracorporeal life support: state of the art in 2007

Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease.A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation.As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile "Berlin Heart" ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support "urgently" rather than "emergently", before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability.     

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Antifeedant and Insecticidal Activity of Plant Extracts Against <Emphasis Type="Italic">Spodoptera litura</Emphasis> (Fab.) and <Emphasis Type="Italic">Lipaphis erysimi</Emphasis>

The solvent extracts of four plants, viz. Polyalthia longifolia (Sonn.) Thw. (PL), Paederia foetida (PF), Limonia acidissima L. (LA) and Balanites aegyptiaca (L.) Del. (BA), from different families, were screened for their antifeedant, insecticidal and insect growth regulatory potential against important crop pests. The solvent extracts, namely methanol, petroleum ether, chloroform and water, of all four plants were tested for their bio-activity against lepidopteran insect pest, Spodoptera litura; and sucking insect pest, L. erysimi (mustard aphid). It was observed that Polyalthia longifolia (methanol extract) exhibited maximum potency with least concentration of 0.1 % (~1080 ppm) to give 50 % antifeedancy, followed by P. longifolia (petroleum ether) with a value of 0.2 % (~2360 ppm) and Limonia acidissima (methanol) and L. acidissima (petroleum ether). The least active compound for antifeedancy was found in the aqueous extract of Balanites aegyptica. Out of 16 plant extracts bio-assayed, methanol showed potential antifeedancy when compared with chloroform, water and petroleum ether extracts. But chloroform and petroleum ether extracts of all four plants gave very promising insecticidal activity against aphids, in comparison to other two extracts. L. acidissima (water), B. aegyptica (methanol), P. longifolia (methanol) and P. foetida (water) did not give any insecticidal activity with 50 % lethal concentration (LC₅₀) up to 0.1 % as maximum concentration.     

Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes

OBJECTIVE

Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A−β+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (“provoked,” with progressive β-cell function loss over time) or no precipitant (“unprovoked,” with sustained β-cell functional reserve). These three A− KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown.

RESEARCH DESIGN AND METHODS

Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A−β− (n = 7), provoked A−β+ (n = 15), and unprovoked A−β+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes–associated HLA class II alleles.

RESULTS

Provoked A−β+ and A−β− KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A−β+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed.

CONCLUSIONS

Provoked A−β+ KPD and A−β− KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A−β+ KPD lacks both humoral and cellular islet autoimmunity.Ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA) in patients lacking the typical features of autoimmune type 1 diabetes, is a heterogeneous syndrome (1,2). A validated classification scheme for KPD, based on the presence or absence of β-cell autoantibodies (“A+” or “A−”) and presence or absence of β-cell functional reserve (“β+” or “β−”) (3) includes two autoantibody-negative A− phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Long-term longitudinal follow-up of a large cohort of A−β+ KPD patients has revealed that this phenotype comprises two distinct subtypes distinguished by whether the index DKA episode had a defined precipitant (“provoked” A−β+) or no precipitant (“unprovoked” A−β+) (4). Provoked A−β+ KPD patients have progressive loss of β-cell function after initial recovery from the DKA episode, with relapse to insulin dependence, no sex predominance, and an increased frequency of the HLA class II alleles DQB1*0302 and DRB1*04 associated with susceptibility to autoimmune type 1 diabetes. In contrast, unprovoked A−β+ KPD patients have sustained preservation of β-cell function after recovery from the DKA episode, prolonged insulin independence, male predominance, and an increased frequency of the protective allele DQB1*0602 (4). The unique clinical features and natural histories of these two subtypes of A−β+ KPD patients suggest distinctive underlying pathophysiologic processes for each. Although an underlying “occult” autoimmune element is suggested in the provoked A−β+ subtype by progressive β-cell loss and the presence of type 1 diabetes–associated HLA susceptibility alleles, the unprovoked A−β+ subtype could represent a truly nonautoimmune syndrome of KPD.We have previously shown that the T cells of a significant proportion of individuals with an apparent phenotype of type 2 diabetes react strongly to islet antigens, despite lacking β-cell autoantibodies, and that this reactivity is associated with low C-peptide levels, indicating underlying cellular immune damage to β-cells (5,6). This finding expands the range of diabetic phenotypes—including those labeled as having “type 2” diabetes—with a potential pathophysiologic basis in islet autoimmunity. In the current study, we extended these findings to the unique, emerging forms of A− KPD. Specifically, we hypothesized that differences in cellular immune responses might distinguish the three A− KPD subtypes (A−β−, unprovoked A−β+, and provoked A−β+) with regard to a cellular autoimmune etiology. To test this hypothesis, we measured islet-specific T-cell responses using the validated cellular immunoblotting assay and islet autoantibody responses to determine the presence of islet autoimmunity in patients carefully phenotyped for these three KPD subtypes. We further assessed the percentage of proinflammatory (CD14+CD16+) monocytes in the peripheral blood of the three KPD subtypes.In healthy subjects, 90–95% of classical monocytes express high levels of the cell surface marker CD14 (CD14+), without expression of CD16 (CD16−). Inflammation and infection are associated with the emergence of a distinct monocyte population characterized by coexpression of CD14 and CD16 (CD14+CD16+). CD14+CD16+ monocytes secrete high levels of proinflammatory tumor necrosis factor-α and low levels of anti-inflammatory interleukin-10, leading to their designation as proinflammatory monocytes (7).Our results demonstrate that 1) provoked A−β+ KPD, associated with progressive loss of β-cell function, is associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations; 2) unprovoked A− KPD is a distinct syndrome of reversible β-cell dysfunction lacking evidence of humoral or cellular islet autoimmunity; and 3) a substantial proportion of A−β− KPD patients, who resemble patients with type 1 diabetes but lack autoantibodies, have evidence of cellular islet autoimmunity.     

The effect of Baroque music on behavioural disturbances in patients with dementia

Aim: To study the effect of Baroque music in people with dementia. Methods: Patients in a multicultural dementia‐specific aged care facility were subjected to Baroque music in a cross‐over study. Results: There were significantly more behavioural disturbances during the weeks when Baroque music was played compared to control periods (0.2 more episodes per week, P= 0.01), and more episodes in the afternoon shift compared to evening shift (1 more episode per week, P= 0.001). Conclusion: These results confirm that music can influence behaviour but is contrary to previous results.     

Serum placental growth factor as a predictor of early onset preeclampsia in overweight/obese pregnant women

The purpose of this study was to analyze whether maternal serum placental growth factor (PlGF) could predict early onset preeclampsia (<32 weeks of gestation) in overweight/obese pregnant women, and whether it could do it more effectively than in normal/underweight pregnant women. A prospective cohort study was conducted on 1678 pregnant women with singleton pregnancies, who were grouped as underweight, normal, overweight, and obese on the basis of body mass index, followed by serum PlGF estimation at 20 to 22 weeks of gestation. A cut-off value of <144 pg/mL for PlGF was determined by Receiver Operating Characteristic curve analysis to identify risk of early onset preeclampsia. Univariate logistic regression analysis revealed significantly stronger association between PlGF <144 pg/mL and early onset preeclampsia in overweight/obese pregnant women (odds ratio 7.64; 95% confidence interval 5.34–10.12; P = .000) than in normal/underweight pregnant women (odds ratio 2.95; 95% confidence interval 1.74–4.26; P = .007). Weight and PlGF levels in study women had a significant negative correlation (r = 0.663; P = .002). Serum PlGF in early second trimester could be an effective predictor of early onset preeclampsia in overweight/obese pregnant women and may be more effective than in normal/underweight pregnant women.     

Neurocognitive impairment in obstructive sleep apnea

Obstructive sleep apnea syndrome (OSAS) is a common disorder with far-reaching health implications. One of the major consequences of OSAS is an impact on neurocognitive functioning. Several studies have shown that OSAS has an adverse effect on inductive and deductive reasoning, attention, vigilance, learning, and memory. Neurocognitive impairment can be measured objectively with tests such as the Wechsler Adult Intelligence Scale-Revised, the Psychomotor Vigilance Task, the Steer Clear Performance Test, and tests of repetitive finger tapping. In children, OSAS may cause attention-deficit hyperactivity disorder in addition to behavioral problems and learning disabilities. Risk factors for cognitive impairment include increasing age, male sex, apolipoprotein E ε4 allele positivity, current cigarette smoking, obesity, hypertension, diabetes mellitus, metabolic syndrome, Down syndrome, hypothyroidism, significant alcohol consumption, stroke, and the use of psychoactive medications. At a cellular level, OSAS likely causes cognitive impairment through intermittent hypoxia, hormonal imbalance, and/or systemic inflammation, either independently or via the resultant endothelial dysfunction that occurs. Excessive daytime sleepiness should be measured and minimized in all studies of neurocognitive impairment. Recent studies have used functional and structural neuroimaging to delineate the brain areas affected in patients with OSAS with neurocognitive dysfunction. A common finding in several of these studies is decreased hippocampal volume. Other affected brain areas include the frontal and parietal lobes of the brain, which show focal reductions in gray matter. These changes can be reversed at least partially with the use of CPAP, which highlights the importance of early recognition and treatment of OSAS. The currently available data in this field are quite limited, and more research is needed.     

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.