Assessment of whole blood coagulation with a microfluidic dielectric sensor.

Essentials ClotChip is a novel microsensor for comprehensive assessment of ex vivo hemostasis. Clinical samples show high sensitivity to detecting the entire hemostatic process. ClotChip readout exhibits distinct information on coagulation factor and platelet abnormalities. ClotChip has potential as a point-of-care platform for comprehensive hemostatic analysis. SUMMARY: Background Rapid point-of-care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders. Objective To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation. Methods The ClotChip is a three-dimensional, parallel-plate, capacitive sensor integrated into a single-use microfluidic channel with miniscule sample volume (< 10 µL). The ClotChip readout is defined as the temporal variation in the real part of dielectric permittivity of whole blood at 1 MHz. Results The ClotChip readout exhibits two distinct parameters, namely, the time to reach a permittivity peak (Tpeak ) and the maximum change in permittivity after the peak (Δεr,max ), which are, respectively, sensitive towards detecting non-cellular (i.e. coagulation factor) and cellular (i.e. platelet) abnormalities in the hemostatic process. We evaluated the performance of ClotChip using clinical blood samples from 15 healthy volunteers and 12 patients suffering from coagulation defects. The ClotChip Tpeak parameter exhibited superior sensitivity at distinguishing coagulation disorders as compared with conventional screening coagulation tests. Moreover, the ClotChip Δεr,max parameter detected platelet function inhibition induced by aspirin and exhibited strong positive correlation with light transmission aggregometry. Conclusions This study demonstrates that ClotChip assesses multiple aspects of the hemostatic process in whole blood on a single disposable cartridge, highlighting its potential as a POC platform for rapid, comprehensive hemostatic analysis.

The role of a novel fungal strain Trichoderma atroviride RVF3 in improving humic acid content in mature compost and vermicompost via ligninolytic and celluloxylanolytic activities.

AIMS: With the rising concerns about indiscriminate use of chemical fertilizers and accumulation of agro-industrial wastes in huge quantities, the present experiment was conducted to elucidate the effect of a novel fungal strain of Trichoderma atroviride in hastening the compost/vermicompost production process and for the production of humic acid (HA) rich compost and vermicompost. METHODS AND RESULTS: Rice (Oryza sativa) straw and distillation waste of geranium (Pelargonium graveolens), two important agricultural/industrial crop wastes were subjected to composting and vermicomposting. T. atroviride strains GVF10 (cellulase and xylanase producing), and RVF3 (ligninase and celluloxylanase producing) were inoculated alone or in combination. The HA content was found to increase maximally in rice vermicompost treated with ligninase producing strain RVF3 (85% with respect to HA standard) followed by geranium vermicompost + RVF3. The addition of the strain GVF10 increased HA content to about 35-62% with respect to HA standard. The addition of the fungal inoculum reduced the composting/vermicomposting time from 110 to 90 days. CONCLUSIONS: Our results indicate that the use of selected fungal strain(s) hold potential to produce qualitatively superior compost and vermicompost with high HA content in a shorter period. SIGNIFICANCE AND IMPACT OF THE STUDY: Use of appropriate fungal strains may increase the efficiency of composting/vermicomposting processes producing compost and vermicompost with higher HA content, and alleviating the problems of solid waste accumulation and declining soil fertility.

Peripheral neuropathy in diabetes.

Peripheral neuropathy is common complication of diabetes. The prevalence of peripheral neuropathy among diabetic patients on the basis of loss of vibration sensation had been studied. Detailed clinical history of each patient including age, gender, duration of diabetes, foot ulcer and biothesiometry was recorded in 211 diabetic patients between 20 and 80 years of age. It was observed that all patients under 30 years age (n = 8) felt vibration below 15 volts (no risk zone); 77% (24 out of 31) of the patients in the age group of 30-39 years were in the no risk zone, and 23% (n = 7) had mild peripheral neuropathy. Sixty per cent of the patients between 40 and 50 years (n = 44) were in the no risk zone, while 32% (n = 24) had mild peripheral neuropathy, 5% (n = 4) had moderate neuropathy and 3% (n = 2) had severe peripheral neuropathy. Amongst patients above 50 years of age, 31% (n = 31) were in no risk zone, 34% (n = 34) had mild peripheral neuropathy, 22% (n = 20) had moderate peripheral neuropathy and 13% (n = 13) had severe peripheral neuropathy. Of the patients with diabetes for less than 5 years, 58% had no neuropathy, and only 3% had severe neuropathy. Of the patients with diabetes for 5 to 15 years, 50% had no neuropathy, 30% had mild, and 10% had severe peripheral neuropathy. When patients with diabetes for over 15 years were studied, only 6% had no neuropathy and 19% had severe peripheral neuropathy. The study re-establishes that the severity of peripheral neuropathy increases with age and vibration perception decreses progressively with increased duration of diabetes. Vibration perception threshold testing helps to identify the high risk subjects who require special counselling and education to protect their feet.

A clinical study to compare the efficacy and safety of pregabalin sustained release formulation with pregabalin immediate release formulation in patients of diabetic peripheral neuropathic pain.

OBJECTIVE: To compare the efficacy and safety of sustained release (SR) formulation of pregabalin with immediate release (IR) formulation in patient with diabetic peripheral neuropathic pain. MATERIALS AND METHODS: In this open label, randomized, comparative, multicentric study, the primary efficacy measure was reduction in visual analogue scale (VAS) of short form McGill pain questionnaire (SF-MPQ) score from baseline to last visit. The secondary evaluation measures included reduction in SF-MPQ descriptive score and present pain intensity score and change in clinical global impression - improvement of illness (CGI-I) and clinical global impression - severity of illness (CGI-S) from baseline to last visit. Total duration of the study was 12 weeks. Safety evaluation was done by recording treatment emergent adverse events and laboratory investigations at baseline and end of treatment. RESULTS: Of 265 randomized patients, 133 received pregabalin SR tablets and 132 pregabalin IR. Patients randomized to both treatments responded to respective treatments. The least square means of VAS score in both the groups were reduced significantly (P <0.01). Reduction in both groups was similar (P = ns). At the end of the trial in both the groups, there was a significant reduction in the SF-MPQ descriptive score (P <0.01), severity of illness as well as clinically significant improvement in the symptoms. Difference between the groups for CGI-I (P = 0.37) and CGI-S (P = 0.41) score was not statistically significant. Treatment in both the groups was found safe and well tolerated. CONCLUSION: The study shows that the pregabalin SR is safe and effective in patients of diabetic peripheral neuropathic pain. The results of the study demonstrated that pregabalin SR has comparable efficacy and safety as pregabalin IR.

Awareness of diabetic retinopathy among physicians and optometrists in a district of West Bengal.

A cross sectional study was done to ascertain the current knowledge among physicians and optometrists regarding diabetic retinopathy in a district of West Bengal. We obtained response from 242 physicians and 36 optometrists working in government health units. The questionnaire comprised of three sections covering magnitude of problem, risk factors and management. The responses were analysed and graded. In different sections, knowledge of 74 - 78% physicians and 83 - 86% optometrists was graded as not acceptable. Existing lack of knowledge among physicians and optometrists regarding diabetic retinopathy needs correction.

Hyperthyroidism.

Hyperthyroidism is a clinical situation where there is excess thyroid hormones in the circulation due to increased synthesis of hormone from a hyperactive thyroid gland. Common causes are Graves' disease, toxic multinodular goitre and toxic solitary nodule. Excess thyroid hormones in the circulation are also found in thyroiditis (hormone leakage) and excess exogenous thyroxine intake. Thyrotoxicosis is the term applied when there is excess thyroid hormone in the circulation due to any cause. Thyrotoxicosis can be easily diagnosed by high serum level of thyroxine (T4) and triiodothyronine (T3) and low serum level of thyroid stimulating hormone (TSH). Hyperthyroidism is confirmed by high isotope (I 131 or Tc99) uptake by the thyroid gland, while in thyroiditis it will be low. Treatment of hyperthyroidism depends on the underlying cause. Antithyroid drugs, 1131 therapy and surgery are the options of treatment of hyperthyroidism. Surgery is the preferred treatment for toxic adenoma and toxic multinodular goitre, while 1131 therapy may be suitable in some cases. Antithyroid drugs and 1131 therapy are mostly preferred for Graves' disease. Beta-adrenergic blockers are used for symptomatic relief in most patients of thyrotoxicosis due to any cause. Other rare causes of hyperthyroidism like, amiodarone induced thyrotoxicosis, choriocarcinoma, thyrotropin secreting pituitary tumour are difficult to diagnose as well as to treat.

Subclinical thyrotoxicosis.

Subclinical thyrotoxicosis as a definite entity has been recognised with the development of highly sensitive immunometric TSH assays. The condition is characterised by suppressed TSH in presence of normal T3 and T4. It may be due to exogenous or endogenous causes. The risks may be osteoporosis and atrial fibrillation. Exogenous subclinical thyrotoxicosis must be prevented by optimising laevothyroxine dosage. Endogenous subclinical thyrotoxicosis may or may not be treated depending upon the clinical situation and existing comorbidities.

Prevalence of diabetes in various habitats of West Bengal, India.

The epidemiological profile data were collected for diabetes mellitus from the people living in three habitats (rural, industrial and urban) having considerable difference in their lifestyle and socio-economic status. Every 5th (occasionally 4th or 6th) member from each habitat was sampled; no restriction regarding age was kept during screening; OGTT (oral glucose tolerence test) was performed 2 hours after 75 g glucose, in those whose FBS (fasting blood sugar) was >90 mg/dl. Diagnosis of diabetes mellitus was ascertained, if the FBS was >120 mg/dl and/ or postglucose value was >200mg/dl. The per cent prevalence (among all aged people) of diabetes mellitus in rural, industrial and urban habitats were found to be: 1.66 +/- 0.58 (male 1.99 +/- 0.88, female 1.3 +/- 0.75); 3.00 +/- 0.74 (male 3.17 +/- 1.04, female 2.80 +/- 1.04) and 4.8 +/- 0.98 (male 5.31 +/- 1.43, female 4.27 +/- 1.32) respectively.

Exercise in prediabetes.

Exercise as a therapeutic modality in the management of type 2 diabetes is well established. However, exercise has emerged as an important tool to prevent, or at least, to delay the onset of type 2 diabetes. This has been borne out by a few recent clinical trials. Exercise improves insulin sensitivity besides having beneficial effects on many cardiovascular risk factors. A sedentary adult at high risk for developing diabetes may benefit from at least 30 minutes of daily moderate-intensity exercise.

Prevention of type 2 diabetes in the prediabetic population.

Prevention of diabetes has been tried by several groups with varying degree of success. Prediabetic population are the ideal target for the purpose. In this study, prediabetic subjects are selected from the high-risk groups, like those having obesity, family history of diabetes, past history of gestational diabetes, hypertension, dyslipidaemia; and are included in the study when their fasting plasma glucose was found to be below 110 mg/dl and 2 hours postglucose (75g) plasma glucose remained between 110 and 200 mg/dl. After giving advice for lifestyle changes to all for a period of 3 months, those who had their blood glucose values in the impaird glucose tolerance (IGT) range were given either metformin, rosiglitazone or acarbose, the rest continued with diet and exercise only. Total follow-up period was 3 years. All groups maintained blood sugar in the euglycaemic range till the end of the 3-year period.

Prevention of microvascular and macrovascular complications in diabetes mellitus.

Microvascular and macrovascular complications in relation to diabetes mellitus are responsible for major morbidity and mortality condition. Prevention of these complications should be the aim while managing diabetes. Retinopathy, nephropathy and neuropathy are microvascular complications and macrovascular complication affects heart, brain and foot. In preventing retinopathy, glycaemic and blood pressure control is essential. Laser photocoagulation therapy can prevent loss of vision in non-proliferative or proliferative diabetes mellitus. The aim of preventing nephropathy lies on meticulous glycaemic control, dietary protein limitation and vigorous control of blood pressure. The highest priority at present to prevent diabetic neuropathy is the education of patients and their physicians about the potential for detection and treatment of early neuropathy. Glycaemic control is beneficial in reducing the frequency of progression of neuropathy. Macrovascular complication (cardiovascular, cerebrovascular, peripheral vascular) can be prevented with some intervention strategies eg, discouraging smoking habit, proper diet, regular physical activity, strict glycaemic and blood pressure control, lowering low density lipoprotein cholesterol level and aspirin therapy. Amputation in diabetic foot can be dealt with a number of prevention strategies eg, careful self examination, to use specially fitted shoes, minimisation of trauma, earlier detection and aggressive management by local debridement, provision of special support and early antibiotic therapy.

Mason diabetes--report of a family.

A 48-year-old Hindu housewife was presented with increased appetite, thirst, frequency of micturition, weakness, cramps in the legs, tingling in the fingers, decline in bladder-bowel control and dimness of vision. She was a patient of diabetes. On investigations and history, she was diagnosed as a case of type 2 diabetes transmitted in three generations as an autosomal dominant trait.

Simultaneous expression of guinea pig UDP-glucuronosyltransferase 2B21 and 2B22 in COS-7 cells enhances UDP-glucuronosyltransferase 2B21-catalyzed morphine-6-glucuronide formation.

Although UDP-glucuronosyltransferases (UGTs) act as an important detoxification system for many endogenous and exogenous compounds, they are also involved in the metabolic activation of morphine to form morphine-6-glucuronide (M-6-G). The cDNAs encoding guinea pig liver UGT2B21 and UGT2B22, which are intimately involved in M-6-G formation, have been cloned and characterized. Although some evidence suggests that UGTs may function as oligomers, it is not known whether hetero-oligomer formation leads to differences in substrate specificity. In this work, evidence for a functional hetero-oligomer between UGT2B21 and UGT2B22 is provided by studies on the glucuronidation of morphine in transfected COS-7 cells. Cells transfected with UGT2B21 cDNA catalyzed mainly morphine-3-glucuronide formation although M-6-G was also formed to some extent. In contrast, cells transfected with UGT2B22 cDNA did not show any significant activity toward morphine. When UGT2B21 and UGT2B22 were expressed simultaneously in different ratios in COS-7 cells, extensive M-6-G formation was observed. This stimulation of M-6-G formation was not observed, however, when microsomes containing UGT2B21were mixed with those containing UGT2B22 in the presence of detergent. Furthermore, this effect was not very marked when human UGT1A1 and UGT2B21 were coexpressed in COS-7 cells. This is the first report suggesting that UGT hetero-oligomer formation leads to altered substrate specificity.

Congenital lobar emphysema: experience with 21 cases.

A retrospective study of all cases (n = 21) of congenital lobar emphysema (CLE) treated at the Royal Hospital, Muscat, from September 1988 to August 1999 was performed. The presentation, diagnosis, treatment, and outcome are reviewed. All 21 patients were nonwhite. Thirteen had left-upper-lobe, 7 right-middle-lobe, and 1 right-upper-lobe involvement. Of the 14 upperlobe cases, 10 had severe symptoms whereas only 2 of the 7 middle-lobe cases had severe symptoms. Mildly symptomatic cases on conservative treatment invariably needed surgery if infected. It is concluded that CLE is not limited to white infants, upper-lobe disease is more severe than middle-lobe disease, and nonoperative measures are likely to be useful in mildly symptomatic cases involving the middle lobe.

Fetus-in-fetu: a case report and review of the literature.

A unique case of intraperitoneal fetus-in-fetu attached to an ovary is presented. An asymptomatic newborn girl was found to have a mobile cystic mass in right side of her abdomen. Radiological investigations showed fetus-in-fetu. During laparotomy, an intraperitoneal fetus-in-fetu was found attached to right ovary and vascular pedicle to ovarian vessels. Only 79 cases of fetus-in-fetu have been reported, and this is the first such case attached to an ovary.

Paediatric adrenocortical neoplasia - a study of 25 cases.

We reviewed our experience of 25 children with adrenocortical tumours from January 1980 to December 1994. Their ages ranged from 7 months to 15 years; there were 16 girls and 9 boys. Truncal obesity, moon facies, hypertension, and virilisation were the most common clinical features. Establishment of the diagnosis of Cushing's syndrome was accomplished by hormonal and radiological studies. Eighteen patients had adrenocortical carcinomas, but 2 of them refused operation; 7 had adrenocortical adenomas. Twenty-three patients were treated by surgery; 6 with carcinomas are still alive after periods of 6 months to 3 years. The results of treatment of adrenocortical carcinoma have been poor, but the prognosis is excellent for benign lesions.