Delayed carotid surgery: what are the causes in the north west of England?

INTRODUCTION: Carotid endarterectomy (CEA) should be performed within two weeks of symptoms for patients with carotid stenosis >50%. Whether these standards are being achieved and causes of delay between symptoms and CEA were investigated. DESIGN: An analysis of prospectively collected multi-centre data. MATERIALS: Consecutive data for patients undergoing CEA between January-2006 and September-2010 were collected. Asymptomatic patients and those with no details on the timing of cerebral symptoms were excluded. METHODS: 'Delay' from symptom to CEA was defined as more than two weeks and 'prolonged-delay' more than eight weeks. Univariable and multivariable analyses were used to identify factors associated with these delays. RESULTS: Of 2147 patients with symptoms of cerebral ischaemia, 1522(70.9%) experienced 'delay' and 920(42.9%) experienced 'prolonged delay'. Patients with ischaemic heart disease were more likely to experience 'delay' (OR = 1.56; 95% CI 1.11-2.19, p = 0.011), whereas patients with stroke (OR = 0.77; 95%CI 0.63-0.94, p = 0.011) and those treated at hospitals with a stroke-prevention clinic (OR = 0.57; 95%CI 0.46-0.71, p < 0.001) were less likely to experience 'delay'. Patients treated after the publication of National Institute for Health and Clinical Excellence (NICE) guidelines were less likely to experience 'prolonged delay' (OR = 0.77; 95%CI 0.65-0.91, p = 0.003) but not 'delay'. CONCLUSION: Few patients achieved CEA within two weeks of symptoms. Introducing stroke-prevention clinics with one-stop carotid imaging appears important.

What are the risk factors for renal failure following open elective abdominal aortic aneurysm repair?

OBJECTIVES: Renal failure following abdominal aortic aneurysm (AAA) repair is a common and significant complication. The objective of this study was to identify risk factors for renal failure following open elective AAA repair. DESIGN: A retrospective analysis of prospectively collected multi-centre data. MATERIALS: Consecutive data on patients undergoing open elective AAA repair were collected between January 2000 and December 2010. Patients with pre-operative serum creatinine >200 µmol/L were excluded. METHODS: Renal failure was reported by clinicians and included all patients requiring post-operative renal-replacement therapy. Univariate and multivariate analyses were used to identify renal failure risk factors. A simplified clinical risk score was developed. RESULTS: Post-operative renal failure occurred in 140 (6.0%) of 2347 patients and was associated with age >75 (OR = 1.58, 95%CI 1.11-2.26), symptomatic AAA (OR = 1.77, 95%CI 1.24-2.52), supra/juxta renal AAA (OR = 2.17, 95%CI 1.32-3.57) pre-operative serum creatinine >150 (OR = 2.75, 95%CI 1.69-4.50), treated hypertension (OR = 1.87, 95%CI 1.28-2.74), and respiratory disease (OR = 2.08, 95%CI 1.45-2.97). Patients with post-operative renal failure had significantly higher 30-day mortality (35.0% vs. 4.3%, p < 0.001). CONCLUSIONS: Renal failure following open elective AAA repair was associated with an increased risk of mortality. Risk factors for post-operative renal failure were identified and a simple clinical risk score developed to facilitate focussed care strategies for high-risk patients.

Logistic risk model for mortality following elective abdominal aortic aneurysm repair.

BACKGROUND: The aim was to develop a multivariable risk prediction model for 30-day mortality following elective abdominal aortic aneurysm (AAA) repair. METHODS: Data collected prospectively on 2765 consecutive patients undergoing elective open and endovascular AAA repair from September 1999 to October 2009 in the North West of England were split randomly into development (1936 patients) and validation (829) data sets. Logistic regression analysis was undertaken to identify risk factors for 30-day mortality. RESULTS: Ninety-eight deaths (5·1 per cent) were recorded in the development data set. Variables associated with 30-day mortality included: increasing age (P = 0·005), female sex (P = 0·002), diabetes (P = 0·029), raised serum creatinine level (P = 0·006), respiratory disease (P = 0·031), antiplatelet medication (P < 0·001) and open surgery (P = 0·002). The area under the receiver operating characteristic (ROC) curve for predicted probability of 30-day mortality in the development and validation data sets was 0·73 and 0·70 respectively. Observed versus expected 30-day mortality was 3·2 versus 2·0 per cent (P = 0·272) in low-risk, 6·1 versus 5·1 per cent (P = 0·671) in medium-risk and 11·1 versus 10·7 per cent (P = 0·879) in high-risk patients. CONCLUSION: This multivariable model for predicting 30-day mortality following elective AAA repair can be used clinically to calculate patient-specific risk and is useful for case-mix adjustment. The model predicted well across all risk groups in the validation data set.

Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial--a primary care, type 2 diabetes study.

AIM: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes. METHODS: This was a randomized, 12-week, open-label study comparing vildagliptin (100 mg, n = 1653) and TZD (agent and dose at the investigators' discretion, n = 825) add-on therapy in patients inadequately controlled [haemoglobin A(1C) (HbA(1c)): 7-10%] on a stable dose of metformin (> or =1000 mg/day). The primary objective was to test non-inferiority of vildagliptin to TZDs for the difference in change in HbA(1c) from baseline [established if the upper limit of the two-sided 95% confidence intervals (CI) did not exceed 0.4%]. RESULTS: Mean (+/- s.e.) change in HbA(1c) from baseline to study endpoint was -0.68 +/- 0.02% in the vildagliptin group and -0.57 +/- 0.03% in the TZD group. The difference between groups was -0.11% (95% CI: -0.17% and -0.04%), establishing the non-inferiority of vildagliptin (p = 0.001) after 3 months of treatment. Vildagliptin was non-inferior to TZDs for subgroups of race, age and body mass index. Body weight increased in the TZD group (0.33 +/- 0.11 kg) and decreased in the vildagliptin group (mean: -0.58 +/- 0.09 kg; p < 0.001 for difference). Adverse events occurred in similar proportions of patients in both groups (vildagliptin: 39.5% and TZD: 36.3%) Hypoglycaemia and abnormal changes in liver enzymes were uncommon. CONCLUSIONS: This short-term study suggests that vildagliptin is as effective as TZDs after 3-month treatment as an add-on to metformin in a primary care population that included diverse patient subgroups.

Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study.

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes.

AIM: The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). METHODS: Study 1 was a 12-week, multicentre, randomized, double blind and placebo-controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug-naïve patients with T2DM aged >or=65 years. Study 2 was a 104-week, multicentre, randomized, double blind and active-controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment-naïve patients with T2DM aged >or=65 years. HbA(1c), fasting and postprandial glucose levels, and safety assessments were made. RESULTS: In Study 1, nateglinide significantly reduced HbA(1c) from baseline (7.6 +/- 0.1% to 6.9 +/- 0.1%; Delta = -0.7 +/- 0.1%, p < 0.001) and compared with placebo (between-group difference = -0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA(1c) from baseline (7.8 +/- 0.2% to 6.6 +/- 0.1%; Delta = -1.2 +/- 0.2%, p < 0.001), as did glyburide/metformin (7.7 +/- 0.1% to 6.5 +/- 0.1%; Delta = -1.2 +/- 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin-treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA(1c) (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin-treated patients (Study 2). CONCLUSION: Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.

The design of an observational study of hypertension management, adherence and pressure control in Blood Pressure Success Zone Program participants.

AIMS: The Blood Pressure Success Zone (BPSZ) Program, a nationwide initiative, provides education in addition to a complimentary trial of one of three antihypertensive medications. The BPSZ Longitudinal Observational Study of Success (BPSZ-BLISS) aims to evaluate blood pressure (BP) control, adherence, persistence and patient satisfaction in a representative subset of BPSZ Program participants. The BPSZ-BLISS study design is described here. METHODS: A total of 20,000 physicians were invited to participate in the study. Using a call centre supported Interactive Voice Response System (IVRS), physicians report BP and other data at enrolment and every usual care visit up to 12 +/- 2 months; subjects self-report BPs, persistence, adherence and treatment satisfaction at 3, 6 and 12 months post-BPSZ Program enrolment. In addition to BPSZ Program enrolment medications, physicians prescribe antihypertensive medications and schedule visits as per usual care. The General Electric Healthcare database will be used as an external reference. RESULTS: After 18 months, over 700 IRB approved physicians consented and enrolled 10,067 eligible subjects (48% male; mean age 56 years; 27% newly diagnosed); 97% of physicians and 78% of subjects successfully entered IVRS enrolment data. Automated IVRS validations have maintained data quality (< 5% error on key variables). Enrolment was closed 30 April 2007; study completion is scheduled for June 2008. CONCLUSIONS: The evaluation of large-scale health education programmes requires innovative methodologies and data management and quality control processes. The BPSZ-BLISS design can provide insights into the conceptualisation and planning of similar studies.

Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor: The PERSIST-5 Clinical Trial.

Importance: Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment. The impact of a longer duration of therapy is unknown. Objective: To determine whether adjuvant treatment for primary GIST with imatinib for 5 years is tolerable and efficacious. Design, Setting, and Participants: This prospective, single-arm, phase 2 clinical trial (Postresection Evaluation of Recurrence-free Survival for Gastrointestinal Stromal Tumors With 5 Years of Adjuvant Imatinib [PERSIST-5]) included adult patients with primary GIST (expressing KIT) at 21 US institutions who underwent a macroscopically complete resection and were at intermediate or high risk of recurrence, defined as primary GIST at any site measuring 2 cm or larger with 5 or more mitoses per 50 high-power field or nongastric primary GIST measuring 5 cm or larger. Data were collected from August 5, 2009, through December 20, 2016. Interventions: Imatinib, 400 mg once daily, orally for 5 years or until discontinuation of therapy because of progression or intolerance. Main Outcomes and Measures: The primary end point was recurrence-free survival (RFS). The secondary end point was overall survival. Results: Of the 91 patients enrolled, 48 (53%) were men with a median age of 60 years (range, 30-90 years). Median tumor size was 6.5 cm (range, 2.3-30.0 cm). Median treatment duration was 55.1 months (range, 0.5-60.6 months); 46 patients (51%) completed 5 years of imatinib therapy. Estimated 5-year RFS was 90% (95% CI, 80%-95%), and overall survival was 95% (95% CI, 86%-99%). Recurrence was noted in 7 patients: 1 had disease recur while receiving imatinib (PDGFRA D842V mutation) and died; 6 had disease recur after discontinuation of imatinib therapy. Two additional deaths were unrelated to treatment or tumor progression. Forty-five patients (49%) stopped treatment early because of patient choice (10 [21%]), adverse events (15 [16%]), or other (11 [12%]). All 91 patients experienced at least 1 adverse event, and 17 (19%) experienced grade 3 or 4 adverse events. Conclusions and Relevance: In this first adjuvant trial, to our knowledge, of patients with resected primary GIST who received 5 years of imatinib therapy, no patient with imatinib-sensitive mutations had disease recur during therapy. For patients in whom disease recurred, recurrence was within 2 years of discontinuation of imatinib therapy. Approximately half of the patients discontinued treatment early, most commonly because of patient choice, thus emphasizing the importance of close clinical monitoring to continue imatinib treatment for patients at appropriate risk. Trial Registration: ClinicalTrials.gov identifier: NCT00867113.

Effect of magnesium on the monophasic action potential during early ischemia in the in vivo human heart.

OBJECTIVES: This study sought to examine the effects of magnesium on epicardial action potential duration in patients during early myocardial ischemia. BACKGROUND: Magnesium has been shown to reduce arrhythmias in experimental models of myocardial ischemia. Experimental and clinical observations suggest an effect on repolarization. METHODS: Patients undergoing elective coronary artery bypass surgery were randomized (double blind) to receive intravenous magnesium (n = 10) or placebo (n = 10). Patients were placed on cardiopulmonary bypass and paced at 600 ms, and stable monophasic action potentials were obtained. Ischemia was achieved by aortic cross-clamping for 2 min while normothermia was maintained. RESULTS: Serum magnesium levels increased from 0.60 +/- 0.03 to 1.69 +/- 0.07 mmol/liter (mean +/- SEM) in the magnesium group, with no change in the placebo group. Epicardial temperature was identical in the two groups and did not alter during ischemia. At 90% repolarization, initial action potential prolongation was observed in the placebo group over the first minute of ischemia (282.0 +/- 6.0 to 294.0 +/- 4.8 ms) but not in the magnesium group (278.3 +/- 5.9 to 274.5 +/- 7.4 ms). At 2 min of ischemia, action potential duration was shorter in the magnesium group than in the placebo group (258.1 +/- 5.5 vs. 281.3 +/- 5.9 ms, respectively, p < 0.05). CONCLUSIONS: Intravenous magnesium infusion altered the epicardial action potential response to ischemia in patients. These findings may have important implications in the pathogenesis of arrhythmias in ischemic myocardium.

Hypoglycemic potential of nateglinide versus glyburide in patients with type 2 diabetes mellitus.

Antidiabetic agents that augment insulin secretion can cause hypoglycemia. With the current trend toward early and aggressive treatment of patients with type 2 diabetes, the hypoglycemic potential of insulinotropic agents is of concern. This study aimed to compare the propensity of the "glinide," nateglinide, and the sulfonylurea (SU), glyburide, to elicit hypoglycemia in type 2 diabetic patients with moderately elevated fasting plasma glucose (FPG). Hyperglycemic clamps (target plasma glucose = 11.1 mmol/L) were initiated, and 30 minutes later patients received a single oral dose of nateglinide (120 mg, n = 15) or glyburide (10 mg, n = 12) in a double-blind fashion. At the end of the 2-hour clamp when the glucose infusion was terminated, plasma glucose and insulin levels were measured for 4 additional hours. The minimum plasma glucose level achieved after terminating the glucose infusion (glucose nadir) was used as an index of hypoglycemic potential. The mean (+/-SEM) glucose nadir was significantly lower in patients given glyburide (3.3 +/- 0.2 mmol/L) versus nateglinide (4.4 +/- 0.3 mmol/L, P = .025). Confirmed hypoglycemia (plasma glucose < or = 2.8 mmol/L) occurred in 2 of 12 patients given glyburide and in none of those given nateglinide. Plasma insulin levels were significantly higher from 100 to 240 minutes after clamp termination in patients given glyburide versus nateglinide. Nateglinide has less hypoglycemic potential than glyburide, suggesting that nateglinide may be a more appropriate insulinotropic agent for patients with moderate fasting hyperglycemia, such as elderly patients and those with comorbid cardiac ischemia.

MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure.

In the face of competing tyrosine kinase inhibitors (TKIs), identification of chronic myeloid leukemia (CML) patients expecting favorable response to second-line treatment is warranted. At the time of imatinib resistance, the investigation of multidrug-resistance protein 1 (MDR1) and BCR-ABL yielded the following results: (i) Patients with high MDR1 transcript levels showed superior response at 48 months as compared with low-level MDR1 patients: major molecular response (MMR) in 41% vs 16% (P=0.014), complete cytogenetic response (CCyR) in 58% vs 39% (P=0.044), and progression-free survival (PFS) in 67% vs 46% (P=0.032). (ii) Patients with BCR-ABL(IS) <28% achieved higher MMR rates (48% vs 21%, P=0.009). (iii) PFS at 48 months was associated with in vitro resistance of BCR-ABL kinase domain mutations: 63% (no mutation) vs 61% (sensitive, intermediately sensitive or unknown IC50 (median inhibitory concentration)) vs 23% (resistant, P=0.01). (iv) Single-nucleotide polymorphisms (SNPs) at positions 1236 and 2677 were associated with higher MDR1 expression in comparison to wild type. (v) Nilotinib was able to impede proliferation of MDR1-overexpressing imatinib-resistant cells. High MDR1 gene expression might identify patients whose mode of imatinib resistance is essentially determined by increased efflux activity of MDR1 and therefore can be overcome by second-line nilotinib treatment.

Safety and tolerability of vildagliptin vs. thiazolidinedione as add-on to metformin in type 2 diabetic patients with and without mild renal impairment: a retrospective analysis of the GALIANT study.

OBJECTIVE: This retrospective analysis assessed safety and tolerability of vildagliptin (Vilda) as an add-on to metformin in type 2 diabetes mellitus (T2DM) patients with normal renal function (GFR >80mL/min/1.73m(2)) and mild renal impairment (GFR: >50 to ≤80mL/min/1.73m(2)). METHODS: Adverse events (AE) from this 12-week, randomized, open-label study comparing Vilda 100mg and thiazolidinediones (TZD) as an add-on therapy in patients with T2DM inadequately controlled (HbA(1c): 7-10%) on a stable dose of metformin (≥1000mg/day) were analyzed. RESULTS: Of 2627 randomized patients, 1278 in the Vilda and 635 in the TZD groups had normal renal function; 463 in the Vilda and 230 in the TZD groups had mild renal impairment. Higher incidence of headache and rash was noted in both Vilda groups, whereas those with mild renal impairment receiving TZD experienced a higher incidence of peripheral edema and URI. Fewer patients in the Vilda group discontinued the study due to AEs compared to TZD group. Serious AEs were greater in TZD groups (normal: 2.4%; mild renal impairment: 3.0%) compared to Vilda groups (normal: 1.6%; mild renal impairment: 2.4%). CONCLUSION: The safety profile of Vilda or TZD as an add-on to metformin was similar in patients with mild renal impairment and normal renal function.

Comparative efficacy and safety of amlodipine/benazepril combination therapy and amlodipine monotherapy in severe hypertension.

This multicentre, double-blind, trial in subjects with severe hypertension compared the efficacy and tolerability of two parallel drug regimens: A/B (amlodipine/benazepril: 5/20 or 10/40 mg daily, if necessary) with A (amlodipine: 5 or 10 mg daily, if necessary). The principal dependent variable was the proportion of patients achieving goal blood pressures (BP<140/90 mm Hg or BP<130/80 mm Hg in diabetes or chronic kidney disease) in the two groups within 6 weeks. In the 259 randomized subjects, BP control rates were higher with A/B at 2, 4 and 6 weeks (10.5, 22, and 33.6%, respectively) compared with A (5.7, 16, and 25.8 %, respectively). Corresponding trended BP reductions from baseline at 2, 4 and 6 weeks were about 5 mm Hg greater with A/B (-21+/-16, -26+/-17 and -30+/-17 mm Hg, respectively, compared with A (-16+/-17, -23+/-18 and 25+/-19 mm Hg, respectively, P<0.01). Both regimens were well tolerated; incidences of peripheral oedema at weeks 4 and 6 were similar (A/B: 13 and 20% versus A: 20 and 22%, P=not significant). We conclude that titration of amlodipine and benazepril in single-pill combinations is more effective than titration of amlodipine alone for rapid BP control in patients with severe hypertension.

Effectiveness of initiating treatment with valsartan/hydrochlorothiazide in patients with stage-1 or stage-2 hypertension.

This prospective, 6-week, multicenter, double-blind study examined the benefits of initiating treatment with combination valsartan/hydrochlorothiazide (HCTZ) compared with initial valsartan monotherapy for 648 patients with stage-1 or stage-2 hypertension (age=52.6+/-10 years; 54% male; baseline blood pressure (BP)=161/98 mm Hg, 32% stage 1). Patients were randomized to valsartan 80 mg (V-low), valsartan 160 mg (V-high) or valsartan/HCTZ 160/12.5 mg (V/HCTZ), and electively titrated after weeks 2 and 4 to the next dosage level (maximum dose valsartan/HCTZ 160/25 mg) if BP remained >140/90 mm Hg. At end of the study, patients initiated with V/HCTZ required less titration steps compared with the initial valsartan monotherapy groups (63 vs 86% required titration by study end, respectively) and reached the target BP goal of <140/90 mm Hg in a shorter period of time (2.8 weeks) (P<0.0001) vs V-low (4.3 weeks) and V-high (3.9 weeks). Initial combination therapy was also associated with higher BP control rates and greater reductions in both systolic and diastolic BP from baseline (63%, -27.7+/-13/-15.1+/-8 mm Hg) compared with V-low (46%, -21.2+/-13/-11.4+/-8 mm Hg, P<0.0001) or V-high (51%, -24.0+/-13/-12.0+/-10 mm Hg, P<0.01). Overall and drug-related AEs were mild to moderate and were similar between V/HCTZ (53.1 and 14.1%, respectively) and the two monotherapy groups, V-low (50.5 and 13.8%) and V-high (50.7 and 11.8%). In conclusion, initiating therapy with a combination of valsartan and low-dose HCTZ results in early, improved BP efficacy with similar tolerability as compared with starting treatment with a low or higher dose of valsartan for patients with stage-1 and stage-2 hypertension.

A statistical model for inter-temporal causal dynamics of glucose production and disposal with insulin level in diabetic patients.

This paper provides a useful tool to examine inter-temporal behaviour in glucose and insulin level in diabetic patients. The primary thrust of this paper is to model inter-temporal causal dynamics of endogenous and ingested glucose production and disposal with insulin in diabetic patients. A short-run compartmental dynamics of glucose and insulin was introduced with their stochastic relationship through a vector autoregressive (VAR) scheme. This study also aims to develop glucose variability indices and test for their independence, homogeneity and symmetry at steady-state condition. The model also empirically identifies the significant prognostic factors and other exogenous variables affecting the dynamics. An empirical application provides more compelling evidence of such dynamics. The estimated model reconfirms the fact that pre-prandial PM glucose level has statistically significant effects on post-prandial PM glucose level in diabetic patients. Also, pre-prandial PM insulin level shows a significant impact on post-prandial PM insulin in this study. In addition, results also indicate statistical significance of body mass index (BMI) and haemoglobin on post-prandial PM glucose level. It is interesting to note that the pattern of glucose variability indices in pre- and post-prandial AM time points is different from those at PM period. The results also show interdependence between the glucose variability indices. Only the pre- and post-meal PM variations of glucose are homogenous to its pre- and post-meal AM variations.

Disturbances in cellular features and elemental homeostasis in the integument of a freshwater fish Channa punctatus (Bloch) in relation to hydrogen ion concentration of polluted water.

Scanning electron microscopy revealed that the cellular and morphological defects in the integument of Channa punctatus, associated with heavy metal and other environmental pollution was related to a significant extent to the hydrogen ion concentration of the water. At low pH, the epidermis showed severe lesions, and the scale lost its attachment with the skin, due to lepidontal alterations of the circuli. Atomic absorption spectroscopic analysis of the tissue indicated disturbances in the homeostasis of several elements, which probably played a major role in causing the cellular and morphological defects. Experimental monitoring of the pH of the polluted water to near-neutral, reduced significantly the extent of cellular and morphological defects and disturbances in elemental homeostasis.