Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study.

Introduction: The effectiveness of gastric lavage in organophosphorus (OP) poisoning has not been established. We assessed the ability of gastric lavage to remove OP insecticides as a preliminary stage in assessing effectiveness. Patients and methods: Organophosphorus poisoning patients presenting within 6 hours were included, irrespective of prior gastric lavage. A nasogastric tube was placed and gastric contents aspirated, followed by at least three cycles of gastric lavage with 200 mL of water. Samples from the initial aspirate and the first three lavage cycles were sent for identification and quantification of the OP compounds. Patients were monitored for complications of gastric lavage. Results: Around 42 patients underwent gastric lavage. Eight (19.0%) patients were excluded from the study because of a lack of analytical standards for ingested compounds. Insecticides were detectable in the lavage samples of 24 of 34 (70.6%) patients. Lipophilic OP compounds were detected in 23 of 24 patients, while no hydrophilic OP compounds could be detected in six patients with reported ingestion of hydrophilic compounds. For chlorpyrifos poisoning (n = 10), only 0.65 mg (SD 1.2) of the estimated ingested amount (n = 5) of 8,600 mg (SD 3,200) was recovered by gastric lavage. The mean proportion of the compound removed by initial gastric aspirate was 79.4% and subsequent three cycles removed 11.5, 6.6, and 2.7%. Conclusion: Lipophilic OP insecticides could be quantified in the stomach contents of OP poisoning patients with the first aspiration or lavage being most effective. The amount removed was very low; hence, routine use of gastric lavage for OP poisoning patients arriving within 6 hours is unlikely to be beneficial. How to cite this article: Mathansingh AJ, Jose A, Fleming JJ, Abhilash KPP, Chandiraseharan VK, Lenin A, et al. Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study. Indian J Crit Care Med 2023;27(6):397-402.

Role of hyperhomocysteinemia and Vitamin B12 deficiency in central and hemi-central retinal vein occlusion: A case-control study.

BACKGROUND: Retinal venous occlusive diseases have been recognized as a major cause of ocular morbidity. Hyperhomocysteinemia could be a potentially modifiable risk factor. OBJECTIVE: To determine the association of hyperhomocysteinemia with central and hemi-central retinal vein occlusion (CRVO and HCRVO), the correlation of serum levels of homocysteine with Vitamin B12 and folate levels and the association of Vitamin B12 deficiency with hyperhomocysteinemia. METHODS: In this case-control study, patients with CRVO and HCRVO, and age- and gender-matched controls without CRVO and HCRVO, who met the eligibility criteria, were enrolled after obtaining informed consent. Data obtained from participants using a questionnaire, complete ophthalmological examination and relevant investigations, including estimation of serum homocysteine, Vitamin B12 and folate levels, were collated and analyzed. RESULTS: Thirty-nine cases with CRVO and HCRVO and 39 age- and gender-matched controls were studied. We found a significant association of hypertension (P < 0.01), hyperlipidemia (P = 0.01), and abnormal blood profile (P < 0.01) with retinal vein occlusion. There was no statistically significant association of hyperhomocysteinemia with CRVO and HCRVO (P = 0.81). However, we found a high prevalence of both hyperhomocysteinemia (43.58% of cases and 53.84% of controls; P = 0.81) and Vitamin B12 deficiency (23.08% of cases and 38.46% of controls; P = 0.14) in cases and controls, without a statistically significant difference between the two groups with respect to both parameters. Our study also found a negative correlation of serum levels of homocysteine with Vitamin B12 (Pearson correlation co-efficient - 0.3874, P = 0.0005), and folate (Pearson correlation coefficient - 0.3886, P = 0.0004) of the study participants. Among the study participants (n = 78), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (2.26-21.72) times those of patients without Vitamin B12 deficiency (P = 0.001). Similarly, among the cases (CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (1.22-40.09) times those of patients without Vitamin B12 deficiency (P = 0.029). In the control group also (non-CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 6.67 (1.47-30.21) times those of patients without Vitamin B12 deficiency (P = 0.014). CONCLUSION: Hyperhomocysteinemia was not found to be an independent risk factor for retinal vein occlusion in our study. However, we found a high prevalence of hyperhomocysteinemia and Vitamin B12 deficiency in both cases and controls, without a statistically significant difference between the two groups with respect to both parameters. We also found a negative correlation of serum homocysteine levels with Vitamin B12 and folate levels. The odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were seven times those of patients without Vitamin B12 deficiency. Hypertension, hyperlipidemia, and abnormal blood profile had a significant association with CRVO and HCRVO. Many of the systemic risk factors for retinal vein occlusions are found to be associated with elevation of serum homocysteine levels, which may be part of a final common pathway in bringing about a state of accelerated atherosclerosis, leading to CRVO or HCRVO. Therefore, lowering serum levels of homocysteine by Vitamin B12 and folate supplementation could have a role in the prevention of these diseases.

Clinical presentation of type 1 and type 2 pyrethroid poisoning in humans.

BACKGROUND: It is unclear if the clinical presentation of poisoning with type 1 and type 2 pyrethroid compounds is different. This study was undertaken to detail the clinical profile and outcome of patients presenting with pyrethroid poisoning and to quantify serum pyrethroid levels. PATIENTS AND METHODS: In this prospective study, patients were categorised as poisoning with type 1 pyrethroids or type 2 pyrethroids. Blood samples were sent for compound identification and quantification. Clinical features and outcomes were compared between the two groups. Factors associated with moderate and severe toxicity were explored using univariate logistic regression analysis and presented as odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Type 1 pyrethroids were implicated in 16 patients and type 2 in 43 patients. The incidence of nausea and vomiting (81.2% vs. 81.3%) and tremor (37.5% vs. 32.6%) were similar in type 1 and type 2 poisoning; paraesthesia (6.2% vs. 32.6%, p = 0.04), hypersalivation (0% vs. 20.9%, p = 0.04), seizures (0% vs. 7%, p = 0.29) and depressed sensorium (0% vs. 18.6%, p = 0.03.) were observed more frequently in type 2 pyrethroid poisoning. Pyrethroids were detected in the serum samples of 24 patients; quantification was possible in 22 patients in whom serum levels ranged from 1.1 to 453 µg/ml. The compounds were undetectable in 35 patients. Two patients (lambda-cyhalothrin poisoning and cypermethrin poisoning) required intubation for low sensorium and respiratory distress. The median (interquartile range) duration of hospitalization was 12 (12-24) hours. All patients survived. Factors associated with moderate and severe toxicity included ingestion of a type 2 pyrethroid, lambda-cyhalothrin (OR 7.81, 95%CI 1.55-39.37, p = 0.01) and volume ingested (OR 1.01, 95%CI 1.00-1.02, p = 0.02). CONCLUSION: Patients with pyrethroid poisoning present predominantly with mild to moderate symptoms. Paraesthesia and hypersalivation are more frequent in type 2 poisoning. A favourable outcome can be expected.

Urinary Neutrophil Gelatinase Associated Lipocalin - A Sensitive Marker for Urinary Tract Infection in Children.

Early antibiotic treatment for urinary tract infection (UTI) in young children can prevent renal scarring. Sensitivity of pyuria and positive urine nitrite test as indicators of UTI are low, whereas results of urine culture, the gold standard for diagnosing UTI, may not be available for 48--72 h. Novel markers for rapid and accurate diagnosis of UTI would help in the early initiation of treatment in children with suspected UTI. We studied the utility of urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of UTI. This study included 100 children between 3 months and 5 years with suspected UTI. After parental consent, a midstream clean catch or suprapubic aspirate urine specimen was sent for culture and NGAL analysis. Sensitivity and specificity of urine NGAL as a marker of UTI were estimated. Of the 100 children evaluated, urine culture was positive in 34%. Median urine NGAL values were higher in culture-positive children than in culture-negative children (223.20 vs 13.65, P = 0.0001). Receiver operating curve analysis showed an optimal cutoff level of 27 ng/ml for urine NGAL (odds ratio, 8.2, 95% confidence interval, 3.1--22.1) correlating best with culture positivity. Sensitivity and specificity of urine NGAL estimation were significantly better (79.4% and 68.2%) when compared with urine white blood cell estimation (70.6% and 53%). Urine NGAL is a sensitive and specific marker to predict UTI in children with a cutoff level of 27 ng/ml. It may serve as a screening test for detecting simple, uncomplicated UTI in young children.

An association between crypt apoptotic bodies and mucosal flattening in celiac disease patients exposed to dietary gluten.

BACKGROUND: Celiac disease (CD) is characterized histologically by inflammation and villous atrophy. Villous atrophy is thought to result from a disruption of epithelial cellular proliferation and death. Epithelial cells in intestinal mucosa normally proliferate in the crypts and migrate towards the lumen, eventually dying. Apoptotic bodies in crypts are usually abnormal and are associated with certain disease states. The presence of crypt apoptosis in celiac disease has not been thoroughly examined by routine histologic assessment of crypt apoptotic body count (ABC). METHODS: We quantified the ABC in duodenal biopsies from celiac patients before and after initiation of a gluten-free diet (GFD). We examined twenty-three duodenal biopsies from adult patients with celiac disease at diagnosis and following GFD and determined the maximum ABC in 10 consecutive crypts. Fourteen biopsies from heartburn patients served as controls. RESULTS: Mean duration between paired biopsies was 2.9 (0.5-8.5) years. Mean maximum ABC in active celiac disease was 5.44 per crypt and decreased to 2.60 with GFD (p = <.0001). The mean maximum ABC in controls was 1.79, lower than both active celiac disease and GFD (p = <.0001 and p = .019 respectively). Flat lesions with total villous atrophy (mean: 6.44) showed a higher ABC compared to non-flat lesions (mean: 4.87); p = .04. CONCLUSIONS: Crypt ABC is markedly elevated in active celiac disease and decreases significantly with GFD, however it does not achieve normalcy. Total villous atrophy is associated with a higher ABC than all other lesions. Crypt apoptosis is likely a significant contributor to villous atrophy in celiac disease and can be appreciated by routine histologic examination.

Effects of Fluoride on Bone in an Animal Model of Vitamin D Deficiency.

We investigated the combined effect of fluoride exposure and Vitamin D deficiency in causing bone damage as a precursor to development of Fluorotoxic Metabolic Bone Disease. Thirty-six male Sprague-Dawley rats were divided into 6 groups of six; 3 groups received a Vitamin D deficient diet whereas the other 3 received a Vitamin D adequate diet. Serum total 25-hydroxyvitamin D (25OHD), calcium, phosphorus, creatinine, Alkaline phosphatase (ALP), albumin, Parathyroid hormone (PTH), Osteocalcin and C terminal telopeptide (CTx) were measured following exposure to varying levels of fluoride in drinking water (< 1.0, 15 and 50 ppm). Full body Dual-energy X-ray Absorptiometry (DXA) scans were used to examine changes in bone morphology pre and post exposure to fluoride. Renal tubular function was assessed using serum creatinine and urine Cystatin C. Histopathological examination of sections of bone and kidney tissues were also performed. Prior to fluoride exposure, DXA scans revealed a significant decrease in Bone Mineral Density (BMD) and Bone Mineral content (BMC) (p < 0.05) but a significant increase in fat mass (p < 0.05) and fat percentage (p < 0.01) among Vitamin D deficient rats, with no significant change in biochemical parameters. Following exposure to fluoride, BMD was significantly increased (p < 0.05) in both groups with a corresponding increase in serum ALP, bone fluoride content, Osteocalcin, CTx and urine fluoride with increasing levels of fluoride exposure. Serum creatinine calcium and phosphate and urinary cystatin C levels showed no significant changes. Light microscopy examination revealed mild thickening and increased osteoid in 80% of the Vitamin D deficient rats exposed to high levels of fluoride but renal tubular changes were found only in one experimental and one control animal. Fluoride deposited in rat bone affects both osteoblastic and osteoclastic activity. Also, these effects are accentuated in the presence of Vitamin D deficiency.

Expression of Metallothionein after Administration of Aspirin, Vitamin C or Zinc Supplement in the DMH Induced Colon Carcinoma in Rat

Background: Chemoprevention refers to the use of specificnatural or synthetic chemical agents to suppress the development and progression to carcinoma. The purpose of this study was to assess the effect of aspirin, vitamin C or zinc on the metallothionein (MT) mRNA gene expression as well as MT protein content byimmunohistochemistry andradioimmunoassay (RIA) in 1, 2-dimethyl hydrazine (DMH) induced cancerous colonic tissuein rats. Methods: Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) group 3 (zinc), each of which was further sub divided into two groups and given subcutaneous injections of DMH (30 mg/kg body weight) twice a week for 3 months and sacrificed at either 4 months (A-precancer model) or at 6 months (B-cancer model).The control groups were administered 0.5 ml saline subcutaneously. All the 3 groups were simultaneouslyadministered aspirin, vitamin Cor zinc supplement respectively from the beginning till the end of the study. Results: It was observed that rats co-treated with aspirin, vitamin C or zinc resulted in a significant increase in the colonic MT mRNA expression in the precancer and cancer model as compared to the saline only controls. MT protein expression showed a 60%, 64% and 78% immunopositivity in the co-treated groups respectively.The mean MT content in the precancer and the cancer model was restored to near normal levels in all the three co-treated groups. Conclusion: These results suggest that co-administration of aspirin, vitamin C or zinc resulted in a significant increase in MT mRNA gene expression, MT protein expression and MT protein content which could possibly be one of the reasons for a chemo protective effect against progression to colonic cancer in a chemically induced DMH model in rat.Zinc supplement had a greater effect on metallothionein expression than aspirin or vitamin C.

Validating a High Performance Liquid Chromatography-Ion Chromatography (HPLC-IC) Method with Conductivity Detection After Chemical Suppression for Water Fluoride Estimation.

A variety of methods, including the Ion Selective Electrode (ISE), have been used for estimation of fluoride levels in drinking water. But as these methods suffer many drawbacks, the newer method of IC has replaced many of these methods. The study aimed at (1) validating IC for estimation of fluoride levels in drinking water and (2) to assess drinking water fluoride levels of villages in and around Vellore district using IC. Forty nine paired drinking water samples were measured using ISE and IC method (Metrohm). Water samples from 165 randomly selected villages in and around Vellore district were collected for fluoride estimation over 1 year. Standardization of IC method showed good within run precision, linearity and coefficient of variance with correlation coefficient R2 = 0.998. The limit of detection was 0.027 ppm and limit of quantification was 0.083 ppm. Among 165 villages, 46.1% of the villages recorded water fluoride levels >1.00 ppm from which 19.4% had levels ranging from 1 to 1.5 ppm, 10.9% had recorded levels 1.5-2 ppm and about 12.7% had levels of 2.0-3.0 ppm. Three percent of villages had more than 3.0 ppm fluoride in the water tested. Most (44.42%) of these villages belonged to Jolarpet taluk with moderate to high (0.86-3.56 ppm) water fluoride levels. Ion Chromatography method has been validated and is therefore a reliable method in assessment of fluoride levels in the drinking water. While the residents of Jolarpet taluk (Vellore distict) are found to be at a high risk of developing dental and skeletal fluorosis.

Arsenicosis, possibly from contaminated groundwater, associated with noncirrhotic intrahepatic portal hypertension.

BACKGROUND AND AIMS: Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH), a chronic microangiopathy of the liver caused by arsenicosis from use of contaminated groundwater, was reported from Asia. This study aimed to see, if in the twenty-first century, arsenicosis was present in NCIPH patients at our hospital and, if present, to look for groundwater contamination by arsenic in their residential locality. METHODS: Twenty-seven liver biopsy proven NCIPH patients, 25 portal hypertensive controls with hepatitis B or C related cirrhosis and 25 healthy controls, matched for residential locality, were studied. Eighty-four percent to 96 % of study subjects belonged to middle or lower socioeconomic category. Arsenicosis was looked for by estimation of arsenic levels in finger/toe nails and by skin examination. Arsenic levels in nails and in ground water (in NCIPH patients with arsenicosis) was estimated by mass spectrometry. RESULTS: Nail arsenic levels were raised in five (10 %) portal hypertensive study subjects [two NCIPH patients (both had skin arsenicosis) and three portal hypertensive controls]. All of these five patients were residents of West Bengal or Bangladesh. Skin arsenicosis was noted in three NCIPH patients (11 %) compared to none of disease/healthy controls. Ground water from residential locality of one NCIPH patient with arsenicosis (from Bangladesh) showed extremely high level of arsenic (79.5 µg/L). CONCLUSIONS: Arsenicosis and microangiopathy of liver, possibly caused by environmental contamination continues in parts of Asia. Further studies are needed to understand the mechanisms of such 'poverty-linked thrombophilia'.

Partner Burden: A Common Entity in Celiac Disease.

BACKGROUND: Caregiver burden is documented in several chronic diseases, but it has not been investigated in celiac disease (CD). AIMS: We aim to quantify the burden to partners of CD patients and identify factors that affect the perceived burden. METHODS: We surveyed patients with biopsy-proven CD and their partners. Patients completed CD-specific questions, including the validated Celiac Symptom Index (CSI) survey. Partners completed the validated Zarit Burden Interview (ZBI) and questions regarding sexual and relationship satisfaction. Univariable and multivariable analyses were used to assess the association between demographics, CD characteristics, and partner burden. RESULTS: In total, 94 patient/partner pairs were studied. Fifteen patients (16 %) reported a CSI score associated with a poor quality of life, and 34 partners (37 %) reported a ZBI score corresponding to mild-to-moderate burden. Twenty-two partners (23 %) reported moderate-to-low overall relationship satisfaction, and 12 (14 %) reported moderate-to-low sexual satisfaction. The degree of partner burden was directly correlated with patient CSI score (r = 0.27; p = 0.008), and there were moderate-to-strong inverse relationships between partners' burden and relationship quality (r = -0.70; p < 0.001) and sexual satisfaction (r = -0.42; p < 0.001). On multivariable logistic regression, predictors of mild-to-moderate partner burden were low partner relationship satisfaction (OR 17.06, 95 % CI 2.88-101.09, p = 0.002) and relationship duration ≥10 years (OR 14.42, 95 % CI 1.69-123.84, p = 0.02). CONCLUSIONS: Partner burden is common in CD, with more than one-third of partners experiencing mild-to-moderate burden. Partner burden is directly correlated with patient symptom severity, and it increases with poorer sexual and relationship satisfaction. Healthcare providers should address relationship factors in their care of patients with CD.

Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat.

AIM: Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats. MATERIALS AND METHODS: Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA. RESULTS: MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls. CONCLUSION: This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.

Estimation of Monocrotophos renal elimination half-life in humans.

INTRODUCTION: Monocrotophos, implicated in about 1/4th of organophosphate poisonings in our centre, is associated with the highest mortality (24%). Yet data on its pharmacokinetics in humans is limited. We estimated the renal elimination half-life of monocrotophos. PATIENTS AND METHODS: Consecutive patients presenting with monocrotophos overdose over a 2-month period who had normal renal function were recruited. Monocrotophos in plasma and urine were quantitated by high-performance liquid chromatography. Urine was obtained from catheterised samples at 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 h. Plasma specimens were collected at the time of admission, and at the midpoint of the urine sample collections at 1, 3, 5, 7, 10, 15 and 21 h. Renal elimination half-life was calculated from the cumulative amount excreted in the urine. RESULTS: The cohort of 5 male patients, aged 35.8 ± 2.94 years, presented with typical organophosphate (cholinergic) toxidrome following intentional monocrotophos overdose. All patients required mechanical ventilation; one patient died. Plasma data was available from 5 patients and urine data from 3 patients. The median renal elimination half-life was 3.3 (range: 1.9-5.0 h). Plasma monocrotophos values, as natural log, fell in a linear fashion up to around 10 h after admission. After the 10-hour period, there was a secondary rise in values in all the 3 patients in whom sampling was continued after 10 h. CONCLUSION: A renal elimination half-life of 3.3 h for monocrotophos is consistent with a water-soluble compound which is rapidly cleared from the plasma. The secondary rise in plasma monocrotophos values suggests possible re-distribution. Determining the elimination profile of this compound will help develop better strategies for treatment.

Early treatment of food-induced anaphylaxis with epinephrine is associated with a lower risk of hospitalization.

BACKGROUND: Food-induced anaphylaxis (FIA) is potentially life threatening. Prompt administration of epinephrine is universally recommended by current treatment guidelines. OBJECTIVE: To identify factors associated with early epinephrine treatment for FIA and to specifically examine the association between early epinephrine treatment and hospitalization. METHODS: A chart review study conducted at Hasbro Children's Hospital/Rhode Island Hospital. By using the International Classification of Diseases, Ninth Revision codes, we identified all patients who presented to the emergency department with FIA between January 1, 2004, and December 31, 2009. Early epinephrine treatment was defined as receipt of epinephrine before arrival to the emergency department. The independent association between early epinephrine treatment and hospitalization was assessed using logistic regression. RESULTS: Among the 384 emergency department visits for FIA identified during the study period, 234 patients received epinephrine (61%). Among this subset, most (164 [70%]) received early epinephrine treatment, whereas a smaller number of patients (70 [30%]) first received epinephrine in the emergency department (late treatment). Patients who received early epinephrine treatment were older (7.4 vs 4.3 years; P = .008), were more likely to have a known food allergy (66% vs 34%; P < .001), and were more likely to own an epinephrine autoinjector (80% vs 23%; P < .001). Patients treated early were less likely to be hospitalized (17% vs 43%; P < .001). After adjusting for age, sex, and race, the patients who received early epinephrine treatment remained at significantly decreased risk of hospitalization compared with those who received late epinephrine treatment (odds ratio 0.25 [95% CI, 0.12-0.49]). CONCLUSIONS: In this population, early treatment of FIA with epinephrine was associated with significantly lower risk of hospitalization. Accordingly, this study supports the benefit of prompt administration of epinephrine for the treatment of FIA.

Protective role of aspirin, vitamin C, and zinc and their effects on zinc status in the DMH-induced colon carcinoma model.

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma.

BACKGROUND & OBJECTIVES: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. METHODS: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. RESULTS: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 µg/day had a low sensitivity and uNMN >600 µg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. INTERPRETATION & CONCLUSIONS: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

Caregiver expectations of clinicians during the asthma diagnostic process in young children: thematic analysis of focus groups.

OBJECTIVE: Asthma is difficult to diagnose in young children, and the subjective experience of caregivers varies. Clinicians' ability to meet caregiver expectations during the diagnostic process improves the caregiver-clinician relationship, and effectiveness of disease management strategies. METHODS: We performed thematic analysis of seven focus groups (FGs) with 38 caregivers of children 1-6 years old diagnosed with asthma in the preceding 12 months. Caregivers were classified as satisfied or dissatisfied with clinicians during the asthma diagnostic process. Differential themes in these two groups identified caregiver expectations that determined satisfaction with the diagnostic process. RESULTS: Caregiver expectations during the asthma diagnostic process included (1) provision of a diagnostic strategy, (2) acknowledgment of caregiver advocacy, (3) addressing caregiver's beliefs about treatment with asthma medications before a diagnosis was confirmed, and (4) discussing asthma specialist involvement in the diagnosis. Higher perceived severity of a child's illness made caregiver expectations more difficult to meet. CONCLUSIONS: We conclude that clinicians considering an asthma diagnosis in young children must include a diagnostic strategy that is congruent with the caregiver's beliefs about the underlying illness, use of medication, and asthma specialist involvement. Perceived illness severity must also be accounted for when designing a diagnostic strategy.

Zinc and zinc related enzymes in precancerous and cancerous tissue in the colon of dimethyl hydrazine treated rats.

Trace element zinc deficiency or excess is implicated in the development or progression of some cancers. The exact role of zinc in the etiology of colon cancer is unclear. To cast light on this question, an experimental model of colon carcinogenesis was applied here. Six week old rats were given sub cutaneous injections of DMH (30 mg/kg body weight) twice a week for three months and sacrificed after 4 months (precancer model) and 6 months (cancer model). Plasma zinc levels showed a significant decrease (p<0.05) at 4 months and a greater significant decrease at 6 months (p<0.01) as compared with controls. In the large intestine there was a significant decrease in tissue zinc levels (p<0.005) and in CuZnSOD, and alkaline phosphatase activity (p<0.05) in the pre-cancerous model and a greater significant decrease in tissue zinc (p<0.0001), and in CuZnSOD and alkaline phosphatase activity (p<0.001), in the carcinoma model. The tissue zinc levels showed a significant decrease in the small intestine and stomach (p<0.005) and in liver (p<0.05) in the cancer model. 87% of the rats in the precancer group and 92% rats in the cancer group showed histological evidence of precancerous lesions and carcinomas respectively in the colon mucosa. This study suggests that the decrease in plasma zinc, tissue zinc and activity of zinc related enzymes are associated with the development of preneoplastic lesions and these biochemical parameters further decrease with progression to carcinoma in the colon.