Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery.

BACKGROUND: Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. RESULTS: TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. CONCLUSION: It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

Retraction: Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

The above article, published in print in the Jan 2018 issue of the Journal of Child Psychology & Psychiatry and online in Wiley Online Library (wileyonlinelibrary.com), has been retracted by the JCPP Editor-in-Chief, Edmund Sonuga-Barke, and John Wiley & Sons. Following a series of communications from readers highlighting concerns about the paper (now published on the journal website), the journal editors requested that the authors send them the raw data from the trial. In response the authors informed the editors that; (i) the electronic data base had been lost following a computer outage and (ii) that they could send only 95 out of 120 hard-copy participant data sheets as one site had closed and was no longer contactable. The substantial data loss in and of itself posed a serious difficulty in verifying the correctness of the data presented in the paper. The JCPP then analysed the data from the 95 cases itself. A number of significant discrepancies emerged between the re-analysis and the findings reported in the paper both in terms of means and standard deviations of key outcome variables across the trial. These involved very substantial differences that we judged to be extremely unlikely to have arisen due to variations in composition of the original and re-analysed samples. We also discovered previously unidentified/reported problems with missing data and recording irregularities regarding changes in treatment regimen and subject identifiers. As a result of these issues the Editors no longer have confidence in the findings reported in the original paper. Based on all these matters combined and following published guidance from the Committee on Publishing Ethics (COPE) and Wiley's Best Practice Guidelines on Publishing Ethics, we have decided that the only course of action available to us is to retract the paper.

An elderly male with tubercular osteomyelitis of the chest wall.

Primary tuberculosis of the ribs is rare. A 70-year-old male presented with a 6-month history of a chest wall swelling that ruptured over few weeks to lead to a chronic discharging sinus. He had been administered multiple antibiotics, but the discharge continued. Clinical examination revealed anaemia, cervical lymphadenopathy and a 2-cm splenomegaly. Investigations revealed a normochromic and normocytic anaemia (Hb 7.0 g/dl), an ESR of 60 and a positive tuberculin sensitivity test of 25 mm. Surgical excision of the sinus along with the underlying revealed a caseous rib with histopathological features of a caseating granuloma. The patient was put on antitubercular therapy and is doing well on follow-up.

Early results of oesophagectomy for carcinoma oesophagus in 1008 cases.

OBJECTIVE: To determine the early results of 1008 oesophagectomies done for carcinoma oesophagus over a 9 years period. METHODS: This observational descriptive study was conducted at Department of Cardiothoracic Surgery, Lady Reading Hospital, and Khyber Medical Centre Peshawar from June 2002 to June 2011. All patients had apart from routine investigations, Barium studies, Endoscopy and biopsy, CT thorax/upper abdomen with oral and I/V contrast and abdominal ultrasound. The operative approaches included left thoracolaparotomy with left neck anastomosis, transhiatal, left thoracolaparotomy with Roux en-Y, McKeown with right decortication, Ivor Lewis and left thoracolaparotomy with left decortication. All operations were done by one surgical team. The hospital records and operation reports of these patients were carefully analysed for demographic feature; operative approach and outcome. RESULTS: Out of 1008 cases, 698 were males and 310 were females with a mean age of 51.6 years. The age range was 17-80 years. Out of 1008 cases 611 (60.61%) cases had lower one third tumours, 384 (38.09%) cases had middle one third tumours while 13 (1.28%) tumours were just below the thoracic inlet. Of the 611 lower 1/3 tumours stomach involvement was present in 271 (44.35%) cases. Adenocarcinoma was present in 516 (51.19%) cases, squamous cell carcinoma was present in 485 (48.11%), adenosquamous was 6 (0.59%) and carcinoma in situ was present in 1 case (0.09%). Morbidity was 63/1008 (6.25%), and comprised anastomotic leaks 15, aspiration pneumonia 13, wound infection 13, hoarseness 8, and strictures 14, 30-day mortality was 23/1008 (2.28%) and causes included aspiration pneumonia-respiratory failure (5), myocardial infarction (4), anastomotic leak (6), tracheal injury (2), and presumed pulmonary embolism (6). CONCLUSION: More than 1000 cases in 9 years is a very high oesophageal workload for malignancy. Morbidity of 6.25% and mortality of 2.28% shows that such major operations can be done safely in thoracic centres.

Milk composition changes--a simple and non-invasive method of detecting ovulation in lactating women.

OBJECTIVE: To assess the possibility of detecting ovulation through observing changes in composition of milk and using this as a simple and non-invasive method. METHOD: Twenty five normal lactating women (menstruating and non-menstruating), varying in age from 18-35 years and taking no hormonal contraceptives were included in this study. Hormonal estimation was done by radioimmunoassay and changes in milk composition were observed by measuring the concentration of Na+, Cl-, K+ and lactose. RESULTS: Changes were observed in milk composition of four menstruating women (ovulatory), characterized by significant increase in concentration of Na+ and Cl- and decrease in concentration of lactose and K+. However, in one non-menstruating woman who was found to have ovulation, these findings could not be observed. CONCLUSION: Results show that the determination of Na+, K+, Cl- and lactose in milk of lactating women have a high value for detection of ovulation.

Concentration of heavy metals in drinking water of different localities in district east Karachi.

BACKGROUND: Several heavy metals are present in drinking water that play important roles in the body provided their level remains within the specified range recommended by WHO. But now due to the industrialization and rapid urbanization, the problems of pollution have surfaced. This study was designed to ascertain the contents of some heavy metals and then their variations if any in drinking water in different localities of district East of Karachi, Pakistan. METHODS: Drinking water samples were collected from different sources and localities of district East of Karachi. The concentration of the heavy metals i.e. Lead, Arsenic, Copper, Iron, Mercury, Chromium, Manganese, Nickel, Cadmium and Zinc were determined by Atomic Absorption Spectrophotometry. PH was estimated by pH meter. Total dissolved solids (TDS) were calculated by formula. These concentrations of heavy metals, pH and TDS were compared with the standards set by WHO. RESULTS: Concentrations of lead and nickel were found to be significantly elevated as compared to WHO recommended levels in all the three sources of water (Piped water, Hand pump water and Tanker water supply). Chromium was found to be raised in hand pump water. Arsenic and Mercury were not detected in any source of water. Copper, iron, manganese, cadmium and zinc were found to be within the safe limits in all the three sources of water. pH was found to be within the range of WHO recommended level in all the three sources of water. TDS was found to be elevated in hand pump water and tanker water. CONCLUSION: Concentrations of lead and nickel were found to be significantly elevated as compared to WHO recommended levels in all the three sources of water in district East of Karachi.

Increased malondialdehyde levels in coronary heart disease.

OBJECTIVE: To assess and compare the status of lipid peroxidation, both in control subjects and in coronary heart disease patients. METHODS: Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and malondialdehyde levels were determined in 46 patients with coronary heart disease and 50 age matched control healthy subjects. 29 male coronary heart disease patients were divided into smoker (n = 19) and nonsmoker (n = 10) groups, to observe the effect of smoking on lipid peroxidation in coronary heart disease patients. RESULTS: Malondialdehyde and lipid parameters were found significantly high (P < 0.001) with the exception of high-density lipoprotein cholesterol which was significantly low (P < 0.001) in coronary heart disease patients. Smokers with coronary heart disease showed significantly increased (P < 0.025) malondialdehyde levels as compared to nonsmokers with coronary heart disease. CONCLUSION: Elevated serum levels of malondialdehyde indicate increase in the level of production of oxygen free radicals, suggesting their possible role in atherogenesis, leading to coronary heart disease.

Lipoprotein(a) status in coronary heart disease.

OBJECTIVE: To compare the magnitude of lipid, and lipoproteins, especially the lipoprotein(a) [Lp(a)], in controls and patients with coronary heart disease (CHD). METHODS: Serum total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apo A1, apo B, and Lp(a) levels were determined in 37 patients with CHD and 25 age matched control subjects. RESULTS: A significant difference (P < 0.001) in lipid and apolipoprotein ratios were found. Lp(a) and other lipid parameters were found significantly high (P < 0.001) with the exception of HDL-C and apo B which were significantly low (P < 0.001) in CHD patients. CONCLUSIONS: Elevated levels of Lp(a) suggest not only its role in atherogenesis, leading to CHD, but also that Lp(a) should be given due consideration while assessing CHD risk.

Magnitude of lipoprotein (a) in diabetes mellitus.

One hundred and three patients, 76 with diabetes mellitus alone (48- Non-Insulin dependent diabetes and 28 Insulin dependent diabetes) and 27 diabetics having coronary heart disease (CHD) and 27 normal control subjects were included in this study. All the 27 diabetics with CHD were Non-Insulin dependent. The patients and the controls were investigated for serum Lp (a), triglycerides, cholesterol, VLDL-C, LDL-C, HDL-C, apo A1 and apo B. The objective was to assess and compare the level of lipoproteins, especially the lipoprotein (a), in diabetic and non-diabetic subjects and to compare the level of the aforementioned parameters in diabetics with and without CHD. The Lp (a) and other lipid parameters were significantly raised (P < 0.001) except HDL-C and apo A1 that were significantly decreased (P < 0.001) both in diabetic patients with and without CHD, as compared to the control group. The diabetics with CHD showed significantly elevated (P < 0.001) Lp (a) and lipid profile, and significantly low (P < 0.001) HDL-C and apo A1 levels as compared to the patients having diabetes alone. No significant difference was observed in the levels of the above parameters when NIDDM patients were compared with IDDM group. In both NIDDM and IDDM patients significantly low (P < 0.001) HDL-C level and significantly high (P < 0.001) Lp (a) level along with the aforementioned lipid parameters was observed as compared to control group. Elevated levels of Lp (a) and lipid profile in diabetic subjects suggest their involvement in atherogenesis and subsequent development of CHD.

Thrombocytopenia in preeclampsia: an earlier detector of HELLP syndrome.

Platelet count was determined in eighty four pregnant women by direct visual method. Among them thirty normal pregnant women were taken as control. Twenty-seven were preeclamptic and twenty seven eclamptic women. There was significant (P < 0.01) reduction in platelet count of preeclamptic and highly significant (P < 0.001) in eclamptic women as compared to controls. It is concluded that there is need to do platelet count in all pregnancy induced hypertensive women, which can be an earlier detector for HELLP syndrome.

Hematologic effect of vitamin A supplementation in anemic Pakistani children.

To assess the prevalence of vitamin A deficiency in anemic Pakistani children and investigate the hematologic response to vitamin A supplementation, 4-8 year old primary school children from the slum areas of Karachi were surveyed for anemia. Of 101 anemic children selected, 16% had low level of vitamin A ( < 20 micrograms/dl) and an additional 2% had deficient level ( < 10 micrograms/dl). Serum Retinol level showed positive associated with serum iron, ferritin, hemoglobin, hematocrit and Mean cell hemoglobin concentration. A non-randomized control trial was then carried out. Oral vitamin A capsules were given to 42 children and 53 children served as controls. After 6 weeks, there were significant differences between the two groups for Retinol, Retinol-Binding-Protein and Hematocrit. However, no significant difference could be found for Hemoglobin, RBC count, Mean Corpuscular Volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Serum iron, ferritin or transferrin. A single vitamin A supplement improved the hematocrit in 6 weeks. Long-term studies are needed to find if the WHO recommended periodic massive doses of vitamin A besides improving the morbidity and mortality will also improve the overall picture of anemia in children.

Thyroid hormone in hyperemesis gravidarum.

OBJECTIVE: Several studies have suggested that nausea and vomiting in early pregnancy are related to the levels of thyroid hormones and human chorionic gonadotropin (hCG). To ascertain this relationship, we investigated 60 pregnant women (30 subjects each with morning sickness and hyperemesis gravidarum) and compared them with 30 control subjects (by enzyme immunoassay method). METHODS: Serum T3, T4 and TSH were determined in all the subjects while serum hCG was assayed in pregnant women only. Group comparison was done by applying Student's t-test and the relationship between various parameters was evaluated by calculating coefficient of correlation, "r". RESULTS: Serum T4 and hCG levels were significantly increased in hyperemesis gravidarum while TSH demonstrated a significant decline in the same group. Correlation analysis showed a direct relationship between serum T4 and hCG and an inverse relationship between serum TSH and hCG in pregnancy with morning sickness. CONCLUSION: Our results are suggestive of the involvement of these variables in the pathogenesis of morning sickness and hyperemesis gravidarum not only because their levels were significantly altered but the extent of increase or decrease in their level correlated well with the severity of symptoms in the study subjects.

A study on serum triglyceride and lipoproteins cholesterol in coronary heart disease patients.

Sera obtained from 42 patients of myocardial infarction, 28 of unstable angina and 25 healthy control subjects was assayed for total triglycerides, cholesterol, LDL cholesterol (LDL-C), HDL Cholesterol (HDL-C) and VLDL Cholesterol (VLDL-C). The level of cholesterol was also determined among the sub-fractions of HDL. The levels of total triglycerides, cholesterol, LDL-C and VLDL-C were significantly raised in both groups of patients. Total high density lipoprotein cholesterol was low in patients, which was highly significant in HDL2-C and not in HDL3-C. These results suggest that serum lipids are directly correlated with the severity of coronary heart disease (CHD). Total cholesterol when measured in major lipoprotein classes and further partitioned into subfractions, increase their sensitivity, specificity and hence their predictive value as sensitive markers for the assessment of CHD risk.

Carbohydrate metabolism in liver cirrhosis.

Patients with cirrhosis of liver are more prone to have accompanying diabetes mellitus. The present study was conducted to investigate various biochemical parameters in patients with hepatic cirrhosis without diabetes. In these patients blood pyruvate, total bilirubin and globulin levels were elevated as compared to normal individuals. In contrast serum albumin level declined significantly whereas no significant change was observed in the concentrations of blood glucose, total proteins, total lipids, urea and serum cholesterol. These studies confirm the previous reports that carbohydrate metabolism is deranged in hepatic cirrhosis which may lead to diabetes mellitus.

Adrenocortical response during examination.

The stressful effect of a written and oral examination was studied in twenty-two doctors sitting a postgraduate examination. The rise in the plasma cortisol was not significant in the written examination and reverted to normal values after an hour. On the other hand, there was a significant rise in the plasma cortisol during the oral examination with a pre-entry rise in blood sugar and a fall in alpha-amino nitrogen. It is concluded that whereas a written examination is not a stressful situation, an oral examination is stressful enough to be comparable to rowing and flying.