Abnormal Serum Chemistry Research Articles

Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft.

BackgroundHemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.MethodsA bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.ResultsNo acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis as intravenous administration of heparin, but failed to inhibit hyperplasia development and stenosis in AVG.

Abstract LB-202: Therapeutic efficacy of coencapsulated cisplatin and arsenic trioxide nanobins in murine models of breast cancer

Abstract We have developed a novel strategy to encapsulate a combination of cisplatin and arsenic trioxide as a precipitate inside 100 nm liposomal nanobins, NB(Pt, As). Cisplatin is a widely used chemotherapeutic but has significant dose-limiting toxicity. Arsenic trioxide (ATO) is a potent FDA-approved therapy for acute promyelocytic leukemia; however, ATO has not been effective in clinical trials of solid tumors. Encapsulation in nanoliposomes can improve the anti-cancer efficacy of chemotherapeutic agents by extending serum half-life, increasing tumor drug delivery and attenuating toxicity. We have tested the therapeutic efficacy of NB(Pt, As) in orthotopic xenograft models of triple negative breast cancer using MDA-MB-231 and MDA-MB-435/LvBr1 cancer cell lines. Treatment with either NB(Pt, As) or cisplatin for three weeks inhibited growth of MDA-MB-231 mammary tumors in vivo. However, the NB(Pt, As) did not cause weight loss in treated animals and did not result in abnormal serum chemistries. NB(Pt, As) was also evaluated for its ability to inhibit lung metastases. Mice inoculated intraductally with highly metastatic MDA-MB-435/LvBr1 cancer cells develop mammary tumors that metastasize and form macroscopic lesions in the lung. Treatment with NB(Pt, As) was initiated when primary tumors reached∼250 mm3. Both NB(Pt, As) and cisplatin inhibited primary tumor growth in this model, whereas only NB(Pt, As) treatment significantly reduced lung metastatic burden. Our results suggest that nanobin encapsulated cisplatin and ATO is a promising nanoscale therapeutic agent for metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-202. doi:10.1158/1538-7445.AM2011-LB-202

Abstract 3619: Tolerability in mice, monkeys, and rabbits of new antibody (MAb)-drug (SN-38) immunoconjugates

Abstract Antibody drug conjugates (ADCs) of the topoisomerase I inhibitor, SN-38, that allowed for a slow release of SN-38 from the ADC over time, were prepared using anti-CEACAM5 MAb, labetuzumab (hMN-14), anti-TROP-2 MAb, hRS7, and other MAbs by thiol-maleimide conjugation chemistry. These were shown previously to have significant anti-tumor activity in human cancer-xenograft models at cumulative doses frequently ≤ 100 mg/kg (≤ 8 mg/kg human equivalent dose; HED) without toxicity. To determine tolerability and dose-limiting toxicity, hRS7-SN-38 was examined in Swiss-Webster (S-W) mice and Cynomolgus monkeys (CMs), and labetuzumab-SN-38 was evaluated in New Zealand White rabbits. CMs do not express CEACAM5, but similarity in tissue cross-reactivity of hRS7 renders toxicity evaluation of hRS7-SN-38 conjugates in CM feasible. Male S-W mice (n = 14; ∼ 40 g) were administered i.p with 0 (control), 250, 500, or 750 mg/kg (0, 4, 8, and 12 mg/kg SN-38 equivalents) of hRS7-SN-38 on days 1 and 4. Half of the animals were necropsied 7 d, and the remainder 15 d, after the last dose. Blood counts, serum chemistry, and histopathology were performed. This ADC was also administered to CMs (3 M + 3 F/group), via i.v. infusion, at 0, 60, or 120 mg/kg (0, 0.96 and 1.92 mg/kg SN-38 equivalents, respectively) on days 1 and 4. Two males and 2 females from each group were euthanized and necropsied day 11, while the remaining animals were terminated on day 32. Blood counts and chemistries were collected pre-study and periodically through termination. The labetuzumab-SN-38 conjugate was examined in rabbits (n = 6-10) at 0, 30, 60, and 90 mg/kg, administered on days 1 and 4. Mice experienced no hematopoietic toxicity, and only transient weight loss of <10%, but there was a transient elevation in ALT and AST 7 days after treatment, which resolved in most animals one week later. There was no evidence of organ damage. Thus, mice tolerated a cumulative dose of 1500 mg/kg (HED ∼120 mg/kg) of the ADC. CMs receiving 2×60 mg/kg (HED = 2×20 mg/kg) had <7.3% weight loss, showed no abnormal serum chemistries, and while blood counts decreased, they remained within normal limits. Histopathological changes in the terminal group ranged from mild to moderate, but trended to normalcy in the recovery group. The 2×120 mg/kg (HED = 2×40 mg/kg) dose resulted in severe GI and hematologic toxicity. Rabbits tolerated labetuzumab-SN-38 conjugate at all the doses (HED up to 2×30 mg/kg), with uneventful histopathology findings. Pharmacokinetic analysis of rabbit serum showed the IgG cleared with a half-life of ∼ 2 d, and SN-38 clearance was consistent with in vitro stability of the ADC in rabbit serum. ADC and free SN-38 were found to have similar mechanisms of action in vitro. These findings, coupled with previous efficacy studies in xenograft models, indicate a favorable therapeutic window for these ADCs and support the clinical evaluation of these agents in their appropriate indications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3619. doi:10.1158/1538-7445.AM2011-3619

Postoperative psychiatric disorders in general thoracic surgery: incidence, risk factors and outcomes

Postoperative psychiatric disorders (PPDs) may complicate the post-surgical outcome. We analysed the types, incidences, risk factors and outcomes of the PPDs in non-cardiac thoracic surgery patients. All patients (n=100) undergoing major non-cardiac thoracic surgery from January 2004 to March 2005 were investigated prospectively. The diagnosis of PPD was made based on the Diagnosis and Statistical Manual of Mental Disorders. The patients were grouped into two according to the presence (group I) or absence (group II) of PPD. Data on pre-, per- and postoperative factors, and the adverse outcomes were analysed. Eighteen patients (18%) developed PPD, including delirium in 44%, adjustment disorders in 22%, panic attack in 17%, minor depression in 11% and psychosis in 6%. The patients who developed PPD were older (58+/-17 vs 50+/-15 years, p=0.05), had a longer operation time (6+/-1 vs 5+/-2h, p=0.015) and hospital stay (13+/-9 vs 8+/-5 days, p=0.019). The morbidity and mortality rates were not significantly different between the groups (67% vs 46%; 11% vs 1%, respectively). The causative factors in the development of PPD were older age, longer operation time, abnormal serum chemistry values of sodium, potassium, calcium and glucose, hypoalbuminaemia, the presence of the postoperative respiratory distress and infection and blood transfusion (p<0.05). PPDs are associated with adverse outcomes including a longer hospital stay, and increased morbidity and mortality rates. The identification, detection and elimination of these risk factors are recommended.

Anaplasma phagocytophilum Infektion bei einer Katze in der Schweiz

The following case report describes the diagnosis and therapy of a cat with an Anaplasma phagocytophilum infection. The cat from the canton of St. Gallen was presented because of lethargy and lack of appetite. The clinical symptoms established were fever and minor exsiccosis. The diagnosis of granulocytic anaplasmosis was established through microscopic evidence of inclusion bodies in neutrophil granulocytes, the detection of pathogen DNA in the blood by PCR and positive IgM and IgG antibody titers by serological testing. Following this diagnosis the cat was treated for 20 days with doxycycline. As the body temperature normalised, the activity of the cat improved while normalisation of food intake was delayed. After therapy Anaplasma phagocytophilum DNA could not be detected by PCR and a complete remission of abnormal serum chemistry and hematological parameters could be shown.

Evidence-based Nutritional Support in the Intensive Care Unit

Over 2 millennia ago ‘‘Hippocrates: Father of Medicine’’ (460? to 377 BC) once said ‘‘If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.’’ That is true even now with various nutrition surveys in hospitals continue to suggest that upwards of 40% to 50% of patients, particularly those in the intensive care unit (ICU), have a moderate to severe degree of malnutrition, with its significant negative impact on clinical outcomes. Malnutrition is a change of body composition in which deficiencies of macronutrients and micronutrients result in progressive decline in body cell mass, various organs dysfunction, and abnormal serum chemistry values. Nutrition support plays a vital role in the prevention and treatment of nutritional deficiencies in at-risk, critically ill patients. Many critically ill patients are hospitalized with various comorbidities such as cardiovascular disease, asthma, and cancer, where they require nutritional supplement while recuperating from their medical

SERUM CHEMISTRY ABNORMALITIES IN CHILDREN WITH UNPROVOKED SEIZURES

Objective Most children brought to the emergency department (ED) for evaluation of seizures undergo an extensive laboratory workup. Since results are usually negative, the value of such routine laboratory workups has been questioned. A group of children with unprovoked seizures was prospectively studied to determine the diagnostic values of routine serum chemistries and to identify risk factors predictive of abnormal findings. Materials & Methods All patients evaluated at the ED of the Ghaem hospital during a consecutive 12 months period between Jan 2004 through Jan 2005 were studied. We collected data for patient's demographics, details of the history of present illness (including vomiting, diarrhea, apnea), medication use, past history of seizures, family history of seizures, metabolic disorders or other chronic medical illnesses, neonatal history and neurological examination as well as nutritional status, type and time of seizure. The role of abnormal serum chemistries as a seizure trigger factor was assessed in patients with a history of seizure. Results A total of 210 patients (mean age 19.2 months) with unprovoked seizures were evaluated. Twenty- three serum abnormalities were noted in the patients (12 cases of hyponatremia, 7 of hypoglycemia, 4 of hypokalemia, 4 of uremia). The incidence of abnormal serum biochemical values was higher in patients with a first seizure, younger patients, and those with gastrointestinal symptoms. Conclusion According to the present study, one can conclude that in children younger than 2 years and having no structural CNS abnormality, electrolyte and glucose screening is recommended only for a first unprovoked seizure, when gastrointestinal symptoms or symptoms suggesting electrolyte disturbances are present. Keywords: Unprovoked, Seizure, Biochemistry, Children

The role of routine serum laboratory tests in children presenting to the emergency department with unprovoked seizures

The role of routine serum laboratory tests in children presenting to the emergency department with unprovoked seizures

Detection of unsuspected normal pregnancy by the abnormal serum chemistry

Detection of unsuspected normal pregnancy by the abnormal serum chemistry

Vitamin E treatment of nonalcoholic steatohepatitis in children: A pilot study

To determine whether supplemental oral vitamin E is effective in lowering serum aminotransferase and alkaline phosphatase levels in children with nonalcoholic steatohepatitis (NASH) associated with obesity. Open-label pilot study enrolling all children <16 years old with chronically elevated serum aminotransferase (alanine aminotransferase and aspartate aminotransferase) levels for greater than 3 months, who demonstrated a diffusely echogenic liver on ultrasonography, had no demonstrable reason for abnormal serum chemistry values other than obesity, and therefore were diagnosed to have NASH. Patients were prescribed oral vitamin E between 400 and 1200 IU per day. Serum chemistry values were monitored monthly during treatment. Eleven subjects with a mean age of 12.4 years were enrolled; treated patients were followed up for 4 to 10 months. The body mass index did not change significantly before and after treatment (32.8 +/- 3.8 kg/m(2) vs 32.5 +/- 4.4 kg/m(2), respectively). Serum alanine aminotransferase decreased from 175 +/- 106 IU/L to 40 +/- 26 IU/L (P <.001, paired Student t test), serum aspartate aminotransferase decreased from 104 +/- 61 IU/L to 33 +/- 11 IU/L (P <.002), and alkaline phosphatase decreased from 279 +/- 42 IU/L to 202 +/- 66 IU/L (P <.003) during treatment. Serum aminotransferase levels remained normal during treatment but returned to abnormal in those electing to stop treatment. Serum alpha-tocopherol levels were within the normal range before the commencement of therapy and increased significantly with supplementation. The liver remained diffusely echogenic during therapy, at the time serum aminotransferase levels were reduced. Daily oral vitamin E administration normalized serum aminotransferase and alkaline phosphatase levels in children with NASH. Obese children with NASH should be encouraged to lose weight as part of a comprehensive weight reduction program and to consider taking supplemental alpha-tocopherol.

Utility of routine admission serum chemistry panels in adult trauma patients.

To determine the frequency of abnormal serum chemistries and whether they provide clinically useful information regarding trauma patients. To identify clinical criteria associated with critical serum chemistry values (CSCVs). The records of all trauma patients admitted to one urban, Level I Trauma Center were retrospectively reviewed for the period (July 1-December 31, 1989). All trauma patients who had had serum chemistry determinations at hospital admission and at least once more prior to discharge were studied. The CSCVs were determined by a panel of experts prior to record review. Serum chemistry values, patient demographics, mechanisms of injury, and outcomes were statistically analyzed. Most (814/913; 89%) trauma patients had abnormal serum chemistry values. However, only 54/913 (6%) had CSCVs and only six of these CSCVs had prompted a change in resuscitation or treatment (therapeutic K+ infusions). Age > 50 years, a history of hypertension therapy, and a Glasgow Coma Scale score < or = 10 were associated with CSCVs; and CSCVs were correlated with increased mortality and critical care unit admission. Routine-admission serum chemistry values, while frequently abnormal for major trauma patients, generally do not provide clinically useful information in the resuscitation and treatment of trauma patients. Hypoglycemia and metabolic acidosis were more rapidly determined using bedside glucose determination and arterial blood gas evaluation. The routine-admission serum chemistry panel described in the study lacked utility for most trauma patients. Selective chemistry panel ordering should be used at the time of hospital admission for major trauma patients.

Screening for Disulfiram‐Induced Liver Test Dysfunction in an Inpatient Alcoholism Program

The objective of this study was to report the frequency of disulfiram-related elevations of four commonly used hepatic screening chemistries using a retrospective record review design. An inpatient alcoholism program was selected for the setting. Patients who had initial laboratory values within the normal range started daily supervised doses of disulfiram, then underwent follow-up testing after 2 and 4 weeks on the drug. The study population consisted of 108 patients receiving disulfiram and 27 patients who did not receive disulfiram (controls). The four screening serum chemistries performed were aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), alkaline phosphatase, and gamma-glutamyl transferase. Twenty-seven (25%) of the 108 patients who were taking 250 mg of disulfiram a day for 2 to 4 weeks had disulfiram-related elevations in alanine aminotransferase above the upper limit of normal, as opposed to one elevation in 27 patients (4%) for whom disulfiram was not prescribed. In the 108 patients (with initially normal serum chemistries) who were prescribed disulfiram, 32 were discontinued from the drug at 2 weeks and an additional 11 were discontinued from the drug at 4 weeks because of one or more abnormal serum chemistries. Alanine aminotransferase was the most specific and sensitive indicator of the four screening chemistries performed.

Serum chemistry of diseased English sole, Parophrys vetulus Girard, from polluted areas of Puget Sound, Washington

AbstractRelationships between selected serum components and microscopically detected idiopathic liver and kidney lesions were evaluated for English sole, Parophrys vetulus, sampled from urban and non‐urban areas of Puget Sound, Washington. The normal range for each serum chemistry parameter was based on English sole with no lesions, or sole with minor parasitic conditions or with lesions in tissues other than liver and kidney which did not significantly affect serum chemistry values. Generally, sole with idiopathic liver lesions had significantly different haematocrit values and levels of serum albumin, calcium, and bilirubin when compared to sole which were free of idiopathic liver and/or kidney lesions. Serum aspartate aminotransferase and alanine aminotransferase activity and serum levels of glucose, total protein, phosphates and magnesium were also abnormal, but appeared to be associated only with certain types of liver lesions. No association between kidney lesions and abnormal serum chemistry values was identified. In addition, English sole sampled from some urban areas of Puget Sound had particular serum chemistry values and liver lesion prevalences which were significantly different from those of sole sampled from non‐urban areas. These findings support the hypothesis that sole near highly urbanized environments may display other signs of impaired health in addition to high prevalences of tissue lesions. Thus, measurements of serum chemistry parameters, in conjunction with histopathological examination, appear to be useful techniques for evaluating the health of English sole.

An Unusual Form of Vitamin D-Dependent Rickets in a Child: Alopecia and Marked End-Organ Hyposensitivity to Biologically Active Vitamin D

A 12-yr-old female patient with an unusual form of vitamin D dependency and alopecia is described. She was a product of consanguineous mating and developed signs and symptoms suggesting vitamin D dependency early in life. Neither 150 microgram/day (6 microgram/kg.day) 1 alpha-hydroxyvitamin D3 nor 5 microgram/day (0.2 microgram/kg.day) 1,25-dihydroxyvitamin D3 proved to have an effect on her abnormal serum chemistry. Seven million international units per day (about 2 x 10(5) IU/kg.day) of native vitamin D restored her serum chemistry to normal and brought about marked improvement on skeletal radiographs, when her serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-di-hydroxyvitamin D were 4250, 4.8, and 35 ng/ml, respectively. Even with the high serum levels of vitamin D metabolites, her intestinal 47Ca absorption rate remained in the lower normal range and urinary calcium excretion was decidedly low. Association of hypoparathyroidism was ruled out. These results suggest that the patient has extreme and-organ (intestine) hyposensitivity, probably of congenital origin, to the biologically active metabolites of vitamin D.