Nanosized Anti-Stokes Phosphors for Antitumor Drug Delivery and Solid Tumor Theranostics.

Abstract-Theranostics is the direction in modern biomedicine aimed at developing drugs that combine the capabilities of diagnosis and therapy of tumors in one agent. Upconversion nanophosphors (UCNPs) are inorganic crystalline materials that can be used to create a nanoplatform providing diagnostic and therapeutic modalities. They have been proposed as luminescent markers for optical imaging of biological tissue due to their anti-Stokes luminescence, lack of photodegradation and low toxicity. In this article, UCNPs as a theranostic agent for both optical imaging and delivery of anticancer drugs have been offered. To obtain biocompatible nanocomplexes, UCNP surface with a core/shell structure of NaYF4:Yb3+Tm3+/NaYF4 was modified with polylactic acid in the presence of various stabilizers (dextran, polyvinyl alcohol, and poly-N-vinylpyrrolidone). To give the therapeutic modality to the nanocomplex, the antitumor antibiotic doxorubicin was loaded into the polymer shell. The loading efficiency was up to 0.1 mg per 1 mg UCNPs. The toxicity and the intracellular accumulation of nanocomplexes were evaluated in vitro. It was concluded that the modification of UCNPs with polylactic acid provides the transport of doxorubicin, allowing the combination of diagnostic and therapeutic modalities in one agent.

Long-term follow-up of persistent truncus arteriosus: Kuwait experience.

OBJECTIVE: To evaluate the long-term results of patients in Kuwait who were operated for persistent truncus arteriosus (PTA). SUBJECTS AND METHODS: The following data were collected for retrospective analysis from 24 medical records of consecutive patients with PTA in Kuwait between August 1993 and August 2009: demographics, morphology, management and outcome. Major associated abnormalities included interrupted aortic arch in 1 patient and abnormal coronary artery anatomy in 2. RESULTS: Of the 24 patients, 16 underwent total intracardiac repair. The age at operation ranged from 15 days to 5 years (mean 166.19 ± 438.63 days) and weight ranged from 2.5 to 15 kg (mean 4.3 ± 3.01 kg). The right ventricle to pulmonary artery continuity was established with aortic homograft in 11, pulmonary homograft in 4 and by implantation of a Contegra conduit in 1 patient. Four patients had moderate truncal valve regurgitation requiring concomitant truncal valve repair. After a mean follow-up period of 81.81 ± 61.58 months (range 3-166) there was no death. Eight of the 16 (50%) patients underwent redo homograft operations. One patient who had concomitant truncal valve repair subsequently underwent aortic valve replacement. CONCLUSION: The data showed that complete repair of PTA in the neonatal and early infancy period was the treatment with the best potential for survival. The homograft remained one of the conduits of choice to establish continuity between the right ventricle and the pulmonary artery in spite of the high incidence of conduit redo operations.

Homozygous familial hypercholesterolemia with generalized arterial disease.

OBJECTIVE: This report describes the clinical features and management of an 11-year-old boy with end-stage homozygous familial hypercholesterolemia (hoFH) and generalized arterial disease. CLINICAL PRESENTATION AND INTERVENTION: The patient presented with recurrent anginal episodes. On examination, he was found to have multiple planar and tendinous xanthomas, an (LDL) cholesterol level of 24.6 mmol/l and family history of hypercholesterolemia. Resting electrocardiogram showed ST depression in the anterior and inferior leads. Coronary angiogram outlined 70% stenosis of the left main coronary, ostial stenosis of the right coronary artery and extensive atherosclerotic disease of the aorta and all its major branches. The lipid profile was grossly abnormal, but the other biochemical and hematological parameters were normal. The patient was managed with metoprolol 12.5 mg twice daily, nitroglycerin infusion, antithrombotics (aspirin 75 mg once daily and heparin infusion 150 units per hour), cholesterol-lowering drugs (simvastatin 10 mg once a day, cholestyramine 4 g twice a day) and analgesics. CONCLUSION: This case report emphasizes the need to diagnose early familial hypercholesterolemia in families with heart disease and the need to test the partners of affected persons so that the risk of conceiving children with hoFH can be counseled.

Impact of the Gulf war on congenital heart diseases in Kuwait.

BACKGROUND: There has been concern over the increase in the number of babies born with congenital heart diseases (CHD) in Kuwait after the Gulf War. METHODS: We evaluated retrospectively the number of Kuwaiti infants who were diagnosed to have CHD within the first year of life. The comparison was made between those presented from January 1986 to December 1989 (preinvasion) and those presented after the liberation of Kuwait (from January 1992 to December 2000). The number of cases was considered per 10,000 live births in that year. RESULTS: The numbers of cases were 2704 (326 before the invasion and 2378 after liberation). The mean annual incidence of CHD was 39.5 and 103.4 (per 10,000 live births) before and after the Gulf War, respectively (P<0.001). There was an increase in the number of babies with CHD during the immediate 3 years postliberation with a relative reduction in the trend from 1995 to 2000, in some types of CHD. CONCLUSIONS: In our series, there was an increased incidence of CHD almost immediately following the end of the Gulf War period. The cause of this increase remains relatively obscure. Environmental pollution may be a contributing factor; others such as possible psychological trauma remain subject to speculation.

Familial truncus arteriosus: a possible autosomal-recessive trait.

Truncus arteriosus is a relatively uncommon congenital malformation. It accounts for approximately 1% of congenital heart diseases. The defect occurs sporadically but 22q11 deletion is frequently noted in such patients with conotruncal defects. We studied six cases of TA in four closely related families. Analysis of karyotypes in these cases was normal. Family 1 has one affected male infant who was born in 1998. Family 2 has two affected children (one male and one female) who were born in 1989 and 1995, respectively. They have four other normal children. Family 3 has two affected children (one male and one female) who were born in 1981 and 1984, respectively. They have three other normal children. Family 4 has one affected male born in 1998 and another healthy child. All parents of all affected children are double cousins. The data in this study are compatible with an autosomal-recessive inheritance, but multifactorial inheritance may also play a role.

Do we have a less severe form of Kawasaki disease or is it the gammaglobulin effect?

This study was undertaken to evaluate the incidence of coronary artery aneurysms (CAA) in Kawasaki disease (KD). We reviewed the clinical and echocardiographic findings of 135 children who presented to our center with KD between December 1986 and December 1997. The age of onset ranged between 3months to 13 years (median 2 years). The male to female ratio was 1.54:1. All patients received intravenous Gammaglobulin (IVGG) during the acute stage. The echocardiogram, which was done between 2-3 weeks of the onset of fever, was normal in 106 patients (78.5%). Follow-up studies over a period of 6 months to 1 year remained normal. Minimal right or left coronary artery wall ectasia without dilatation or aneurysm formation was seen in 16 (11.85%). Follow-up of these patients showed disappearance of these changes over 6 weeks to 6 months. One patient (0.74%) had generalised dilatation of all the coronary arteries during the acute stage. This has normalized over a period of 9 months. A total of 10 (7.4%) had CAA during the acute stage. On follow-up of 8 of these patients for an average 3 months to 1.5 years all CAA regressed completely. One patient had residual Giant CAA after 1 year follow-up. One patient with CAA was lost to follow-up. One patient (0.74%) had pericardial effusion and another one (0.74%) had mitral incompetence during the acute stage only, both had no coronary involvement. None of our patients had cardiac failure, arrhythmia, myocardial infarction or death. We conclude that coronary artery changes due to KD are less common and less severe in our patients than those seen in other studies. We speculate that this can be related partly to the early administration of IVGG. The difference in incidence of CAA secondary to KD among different racial groups warrants more detailed genetic studies.