Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate.

The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.

The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that these supplements were well tolerated.

Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs.

ABSTRACT This investigation was undertaken to evaluate the therapeutic efficacy and safety of glycosylated undenatured type II collagen (UC-II) alone or in combination with glucosamine HCl and chondroitin sulfate in arthritic dogs. Twenty dogs divided into four groups (n = 5) were daily treated orally for 120 days: group I, placebo; group II, 10 mg UC-II; group III, 2,000 mg glucosamine + 1,600 mg chondroitin; group IV, UC-II (10 mg) + glucosamine (2,000 mg) + chondroitin (1,600 mg), followed by a 30-day withdrawal period. On a monthly basis, dogs were examined for overall pain, pain upon limb manipulation, and exercise-associated lameness. Serum samples were analyzed for markers of liver function (ALT and bilirubin) and renal function (BUN and creatinine). Body weight was also measured at a monthly interval. Dogs in group I exhibited no change in arthritic conditions. Dogs receiving UC-II alone showed significant reductions in overall pain within 30 days (33%) and pain upon limb manipulation and exercise-associated lameness after 60 days (66% and 44%, respectively) of treatment. Maximum reductions in pain were noted after 120 days of treatment (overall pain reduction, 62%; pain reduction upon limb manipulation, 91%; and reduction in exercise-associated lameness, 78%). The overall activity of the dogs in the UC-II supplemented with glucosamine and chondroitin group (group IV) was significantly better than the glucosamine + chondroitin-supplemented group (group III). Glucosamine and chondroitin alleviated some pain, but in combination with UC-II (group IV) provided significant reductions in overall pain (57%), pain upon limb manipulation (53%), and exercise-associated lameness (53%). Following withdrawal of supplements, all dogs (groups II to IV) experienced a relapse of pain. None of the dogs in any groups showed any adverse effects or change in liver or kidney function markers or body weight. Data of this placebo-controlled study demonstrate that daily treatment of arthritic dogs with UC-II alone or in combination with glucosamine and chondroitin markedly alleviates arthritic-associated pain, and these supplements are well tolerated as no side effects were noted.

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

Cholinergic and noncholinergic brain biomarkers of insecticide exposure and effects.

The objective of this investigation was to determine the distribution of cholinergic and noncholinergic biomarkers in discrete brain regions (cortex, stem, striatum, hippocampus, and cerebellum) of rats treated with dimethyl sulfoxide (DMSO, controls), and insecticides such as carbofuran (CARB, 1.5 mg/kg, sc), or methyl parathion (MPTH, 5 mg/kg, ip). Both insecticides produced characteristic signs of anticholinesterase nature within 5-7 min after injection. In controls, analyses of the brain regions revealed a wide variability in the values of cholinergic (acetylcholinesterase, AChE) and noncholinergic (creatine kinase, CK; and lactic dehydrogenase, LDH, and their isoenzymes) biomarkers. The highest activities of AChE and LDH were found in the striatum (1661+/-23 micromol/g/h and 57,720+/-478 IU/l, respectively) and lowest in the cerebellum (118+/-6 micromol/g/h) and 39,480+/-918 IU/l, respectively). However, the activity of CK was found highest in the cerebellum (742,560+/-798 IU/l) and lowest in the hippocampus (353,400+/-11,696 IU/l). Each brain region showed a characteristic profile of CK and LDH isoenzymes. Among the CK isoenzymes, activity of CK-BB was highest (77.5-89.3%), followed by CK-MM (6.7-15.6%), and least CK-MB (0-6.9%). The cerebellum had no CK-MB activity. In all brain regions, CK-MM isoenzyme had only the CK-MM3 subform. Among the LDH isoenzymes, activity of LDH-4 was highest in all brain regions (23-40%), except the cerebellum in which LDH-1 was highest (29%). Compared to the brain, control serum contained very little CK and LDH activity, but serum had three distinct CK and five distinct LDH isoenzymes. Unlike brain regions, serum had three CK-MM subforms. Each insecticide induced characteristic alterations in brain biomarkers. AChE activity was maximally inactivated in cortex (90. 6%) with CARB, and in cerebellum (95.3%) with MPTH. With either insecticide, the least inhibition of AChE occurred in the striatum. Unlike AChE, carboxylesterase (CarbE) did not show brain regional variability in controls, and its activity was uniformly inhibited in all brain regions by CARB and comparatively greater by MPTH. CARB- or MPTH-induced characteristic alterations in CK, LDH, and their isoenzymes in the brain, which were also reflected in serum, as a result of their leakage from the brain by increased permeability due to depletion of ATP (38-57% and 33-47%, respectively) and phosphocreatine (PCr, 23-42% and 56-65%, respectively).

Comparison of the effect of histidine-rich glycoprotein and 6-aminohexanoic acid on plasmin production and fibrinolysis in vitro.

Because histidine-rich glycoprotein binds to the kringle 1-3 domain of plasminogen, it may affect fibrinolysis by reducing fibrin-dependent plasmin production, and in this way it could be mechanistically analogous to 6-aminohexanoic acid. We tested this hypothesis by comparing the effects of histidine-rich glycoprotein and 6-aminohexanoic acid in an in vitro assay of fibrin-dependent plasmin production mediated by tissue plasminogen activator. Whereas 1 mM of 6-aminohexanoic acid increased the K(m) of the reaction from approximately 0.22 microM to approximately 1.7 microM, 2 microM of histidine-rich glycoprotein had no discernible effect. Similar results were obtained in an assay based upon fibrin clot lysis. Therefore, we could not document an effect of histidine-rich glycoprotein on the rate of fibrin-dependent plasmin production.

Role of high-energy phosphates and their metabolites in protection of carbofuran-induced biochemical changes in diaphragm muscle by memantine.

A combined antidotal treatment with memantine HCI (MEM, 18 mg/kg, s.c.) and atropine sulfate (ATS, 16 mg/kg, s.c.) provided complete protection against acute carbofuran toxicity (1.5 mg/kg, s.c.) in rats by multiple mechanisms. Carbofuran, in addition to inhibiting serine-containing esterases, also perturbed the activities of mitochondrial/cytoplasmic biomarker enzymes (creatine kinase, CK; and lactic dehydrogenase, LDH) in diaphragm muscle. The observed changes in the activity of biomarker enzymes were reflected in serum as a result of their leakage from the diaphragm due to a depletion of high-energy phosphates, such as adenosine triphosphate (ATP, 27%) and phosphocreatine (PCr, 33%) and their metabolites (ADP, 36%; AMP, 35%; and Cr, 38%). Combined treatment with MEM and ATS provided protection and reversal of the induced changes in biomarkers by preventing depletion of high-energy phosphates and thus maintaining normal cell membrane characteristics, including permeability and integrity. These results, along with those reported previously, indicate that MEM antagonizes carbofuran toxicity by multiple mechanisms.

Accuracy of electrocardiogram reading by family practice residents.

OBJECTIVES: This study evaluated the electrocardiogram (EKG) reading skills of family practice residents. METHODS: A multicenter study was carried out to evaluate the accuracy of EKG reading in the family practice setting. Based on the frequency and potential for clinical significance, we chose 18 common findings on 10 EKGs for evaluation. The EKGs were then distributed to residents at six family practice residencies. Residents were given one point for the identification of each correct EKG finding and scored based on the number correct over a total of 18. RESULTS: Sixty-one residents (20 first year, 23 second year, and 18 third year) completed readings for 10 EKGs and were evaluated for their ability to identify 18 EKG findings. The median score out of 18 possible points for all first-, second-, and third-year residents was 12, 12, and 11.5, respectively. Twenty-one percent of residents did not correctly identify a tracing of an acute myocardial infarction. Data analysis showed no statistically significant difference among the three groups of residents. CONCLUSIONS: We evaluated the accuracy of EKG reading skills of family practice residents at each year of training. This study suggests that EKG reading skills do not improve during residency, and further study of curricular change to improve these skills should be considered.

Polar Plasmodium falciparum lipids induce lipogenesis in rat adipocytes in vitro.

Previous studies have shown that 'toxic malarial antigens' released by Plasmodium yoelii can induce hypoglycaemia in mice and act synergistically with insulin in stimulating lipogenesis in rat adipocytes in vitro. In this study, it was shown that similar bioactivity could be detected in Plasmodium falciparum culture supernatant, and the molecular basis of this activity was further investigated. Boiled spent culture medium from P. falciparum cultures ('BS-Pf') (exclusively released into the culture supernatant when schizonts rupture) acts in synergy with insulin to increase lipogenesis in a rat adipocyte assay by more than 250% (P < 0.001). Control preparations prepared from non-parasitized erythrocytes grown under similar conditions had no effect (P < 0.001). While contamination with mycoplasma has previously been shown to interfere with the interpretation of data obtained with other molecules thought to be released from P. falciparum in culture, including those inducing TNF-alpha and NO production by macrophages, such contamination was unequivocally ruled out here. BS-Pf alone did not stimulate the lipogenesis in short-term assays (less than 4 h), while long-term exposure of rat adipocytes to BS-Pf alone (12-24 h) caused a stimulation of lipogenesis at a level comparable to that observed with insulin. Furthermore, lipogenesis-inducing activity was also detected in the serum of squirrel monkeys infected with different species of malaria parasites (P. vivax, P. falciparum and P. brasilianum). Preliminary biochemical characterization showed that the biological activity was found in the solvent-extracted polar lipid fraction of boiled supernatant of P. falciparum cultures. All the different polar lipid fractions, collected from silica gel column chromatography, showed a comparable lipogenesis-inducing activity. Enzymatic treatment by phospholipase C of the lipid fraction, which co-migrated with the phosphatidylcholine standard, showed that the activity of the fraction was associated with the 1,2-diacylglycerol (1,2-DAG) moieties released from polar lipids. When this exogenous 1,2-DAG was added to the adipocyte cultures (short- and long-term cultures), it induced stimulation of lipogenesis in rat adipocytes, while no lipogenic activity was obtained from bacterial polar lipids and 1,2-DAG isolated from unparasitized erythrocytes. The importance of these findings is discussed with reference to other toxic malarial antigens and also to the potential role of these molecules in the induction of hypoglycaemia in the severe forms of malaria.

Reversible nonthrombocytopenic palpable purpura associated with metoclopramide.

OBJECTIVE: To report a case of reversible nonthrombocytopenic palpable purpura associated with metoclopramide. CASE SUMMARY: A 72-year-old white man was admitted for worsening palpable purpura over a two-day period. Two days prior to admission, metoclopramide 10 mg orally three times per day was started for a gastrointestinal condition. Upon admission, all drugs were continued except metoclopramide. Over the next two days, the purpura began to resolve. Platelet count was within normal limits on admission and the patient developed no serious consequences because of the purpura. DISCUSSION: According to the literature, reversible nonthrombocytopenic palpable purpura has not been previously reported with metoclopramide. A search of MEDLINE (1966 to November 1998) and International Pharmaceutical Abstracts (1970 to November 1998) did not reveal a similar case. Although a rechallenge was not tried, this case appears to demonstrate a temporal relationship between the initiation and discontinuation of metoclopramide and the onset and resolution of symptoms. Similar cases of this reaction have been reported with procainamide, which is structurally similar to metoclopramide. CONCLUSIONS: Metoclopramide may cause reversible nonthrombocytopenic vascular-type palpable purpura. Discontinuation of the drug appeared to be responsible for the resolution of symptoms.

Risk factors for urinary incontinence after radical prostatectomy.

PURPOSE: We identified risk factors associated with urinary incontinence after radical retropubic prostatectomy. MATERIALS AND METHODS: The time from operation until urinary continence was achieved was determined by chart review and questionnaire in 581 patients who were continent before undergoing radical retropubic prostatectomy between 1983 and 1994. Using univariate and multivariate analyses of data gathered prospectively, we examined risk factors associated with incontinence in these patients. RESULTS: The actuarial rate of urinary continence at 24 months was 91% for the entire patient population and 95% for those treated after 1990. Many factors were associated with the risk of incontinence in univariate Cox proportional hazards regression analysis (patient age and weight, degree of obstructive voiding symptoms, prior transurethral resection of the prostate, clinical stage, intraoperative blood loss, resection of neurovascular bundles, postoperative anastomotic stricture and technique of vesicourethral anastomosis). However, in a multivariate analysis the factors that were independently associated with increased chance of regaining continence were decreasing age, a modification in the technique of anastomosis (introduced in 1990), preservation of both neurovascular bundles and absence of an anastomotic stricture. With introduction of the new surgical technique in 1990 the median time to continence decreased from 5.6 to 1.5 months and the rate of continence at 24 months increased from 82 to 95%. CONCLUSIONS: While the risk of urinary incontinence after radical prostatectomy is related to the uncontrollable factor of patient age, it is also sensitive to the surgical technique used.

The role of digital rectal examination, biopsy Gleason sum and prostate-specific antigen in selecting patients who require pelvic lymph node dissections for prostate cancer.

OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation and prostate-specific antigen (PSA) level, alone and in combination, to predict regional nodal metastases in individual patients with localized prostate cancer. PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy Gleason sum and PSA, alone and in combination, to predict nodal metastases in an individual patient was examined. The study included 689 patients who had laparoscopic or open pelvic lymph node dissection for clinical stage T1-3 prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test and logistic regression were used for continuous, ordinal, categorical, and multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage, DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were significant predictors of lymph node status in a multivariate analysis. However, based on a receiver operating characteristic curve, a model with satisfactory sensitivity and specificity could not be obtained. CONCLUSION: Current estimations of primary prostate cancer biology using pre-operative PSA level, clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict nodal metastases, and pelvic lymphadenectomy remains the definitive method of detection.

Radical retropubic prostatectomy: limited benefit of autologous blood donation.

PURPOSE: We determine whether autologous blood donation significantly decreases the need for homologous transfusions after radical prostatectomy. MATERIALS AND METHODS: The effects of estimated blood loss and autologous donation on the rate of homologous transfusions were analyzed in 3 groups of 100 consecutive patients treated between 1983 and 1992. RESULTS: Overall, donors were less likely than nondonors to receive homologous blood. As median estimated blood loss decreased from 1,200 to 800 cc from groups 1 to 3 (p < 0.05), the incidence of nondonors requiring homologous blood decreased from 62 to 11% and that of autologous units transfused decreased from 96 to 19%. CONCLUSIONS: With decreasing blood loss, safe but stringent criteria for transfusion and improved safety of the blood supply, autologous donation is an inefficient method to lower the slight risk of complications following homologous transfusion during radical prostatectomy.

The frequency of apoptosis correlates with the prognosis of Gleason Grade 3 adenocarcinoma of the prostate.

BACKGROUND: Although localized carcinomas are predominantly moderately differentiated (Gleason Grade 3), they demonstrate markedly different rates of progression. Previously, the authors reported a correlation between apoptosis and the malignant characteristics of carcinoma in the mouse prostate reconstitution model system and between apoptosis and Gleason grade in the human tumor. This study was undertaken to determine whether the frequency of apoptosis correlates with prognosis and to compare the prognostic significance of the apoptotic index with other prognostic features in Gleason Grade 3 carcinomas. METHODS: The apoptotic and mitotic indices of malignant and nonmalignant epithelium in 28 consecutive radical prostatectomy specimens were determined for a carcinomas composed entirely of Gleason sum 6 (primary Grade 3, secondary Grade 3) with a clinical stage T2 classification. Each patient was followed for 5-9 years (median 6, years). The indices, defined as the number of apoptotic and mitotic bodies in an H & E-stained section per 100 grids delineated by an ocular measuring field, were determined. The actuarial time to progression, defined as a sustained rise in the serum prostate specific antigen level greater than or equal to 0.4 ng/ml, was correlated with the apoptotic index, the mitotic index, tumor volume, and pathologic stage. RESULTS: Neither pathologic stage nor tumor volume differed significantly between the group of 19 patients (68%) with no progression and the other 9 whose tumor progressed. The median apoptotic index of the carcinomas was 0.87 (range, 0.12-3.91). For patients with a low apoptotic index (< 0.87), the actuarial progression rate at 5 years was 7% +/- 14% (+/- 2 SE) compared with 50% +/- 26% for those with a high apoptotic index (P < 0.007). Mitotic index had no prognostic significance. CONCLUSIONS: In carcinoma of the prostate, apoptosis can be recognized in standard H & E sections and quantitated by light microscopy. The apoptotic index may provide additional prognostic information in the predominant grade of early stage carcinoma. Cancer 1995; 75:522-9.

Can radical prostatectomy alter the progression of poorly differentiated prostate cancer?

A favorable outcome after radical prostatectomy for early stage prostate cancer has sometimes been attributed to the relatively benign natural history of the disease rather than the beneficial effects of treatment. Poorly differentiated tumors, however, are recognized as inherently aggressive and progress rapidly when managed conservatively. We determined the actuarial rate of treatment failure after radical prostatectomy for clinically localized (stages T1 to T3) poorly differentiated cancer, using as an end point an increase in the serum level of prostate specific antigen (PSA) to assess whether treatment altered the rapid progression expected of these cancers. Of 500 patients treated with radical prostatectomy, regardless of grade, the actuarial nonprogression rate was 76 +/- 5% at 5 years and 73 +/- 6% at 10 years. Poorly differentiated cancer, defined as Gleason score 7 or greater in the radical prostatectomy specimen, was present in 268 patients (54%) who had a nonprogression rate at 5 years of 55 +/- 12% compared to 92 +/- 4% for the 232 patients with a well or moderately differentiated (Gleason score less than 7) cancer (p < 0.00005). The extent of the cancer (confined or not confined) was strongly associated with progression (p < 0.00005). Only 76 of the 268 poorly differentiated tumors (28%) were confined to the prostate and the prognosis was excellent. At 5 years 85 +/- 18% of the patients had no evidence of progression, compared to 46 +/- 12% with poorly differentiated cancer extending outside the gland (p < 0.0001). In a multivariate analysis neither the grade nor volume of the tumor influenced the rate of progression when the cancer was confined to the prostate. Impalpable tumors detected by an elevated PSA level were as likely to be poorly differentiated as palpable disease (56% versus 63%) but were significantly more likely to be confined to the prostate (44% versus 24%, p < 0.01). Poorly differentiated cancers usually extend outside of the prostate by the time they are detected, and they progress rapidly. PSA increases the detection of impalpable high grade cancer confined to the gland. When these tumors are detected while still confined, most can be controlled by radical prostatectomy.

Cholinergic and noncholinergic changes in skeletal muscles by carbofuran and methyl parathion.

The objective of this investigation was to determine the distribution of cholinergic (acetyl-cholinesterase, AChE) and noncholinergic markers in slow-, fast-, and mixed-fiber containing muscles (soleus, SOL; extensor digitorum longus, EDL; and diaphragm, DIA, respectively). Noncholinergic markers included high-energy phosphates (adenosine triphosphate, ATP; phosphocreatine, PCr; and their metabolites), and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) and their isoenzymes and subforms. All three types of muscles had only one CK isoenzyme, CK-MM, which totally consisted of MM3 subform. Levels of these determinants were highest in EDL followed by DIA and least in SOL. Another objective was to determine alterations of these markers under the influence of acute carbofuran (1.5 mg/kg) or methyl parathion (MPTH, 5 mg/kg) toxicity. Rats receiving either insecticide showed cholinergic signs with maximal severity including muscle fasciculations and convulsions within 15-30 min that lasted for about 2 h. At 1 h postinsecticide injection, when AChE was maximally inhibited (81-96%), significant depletion of ATP and PCr was evident in muscles (DIA > SOL > EDL), and activities of CK-MM and LDH were elevated in muscles and consequently in serum. Serum CK-MM3 activity was markedly reduced with sequential increase in MM2 and MM1 subforms, probably due to induced higher carboxypeptidase activity. These findings suggested that (1) the differences in levels of biochemical constituents in muscles depend upon the fiber type, (2) anticholinesterase insecticide-induced increased muscle activity produces characteristic changes in CK and LDH isoenzymes patterns, and (3) leakage of these enzymes/isoenzymes into serum is due to depletion of ATP and PCr, which are required to maintain the cell membrane permeability.

In vivo acute effects of carbofuran on protein, lipid, and lipoproteins in rat liver and serum.

The objective of this investigation was to determine the changes in proteins, lipids, and lipoproteins in liver and serum of rats acutely intoxicated with carbofuran (1.5 mg/kg sc). Under the influence of carbofuran acute intoxication, analysis of globulin fractions revealed remarkable changes: In liver, the levels of alpha-2, alpha-3, and gamma were significantly elevated while alpha-1 was reduced; in serum, alpha-1 and alpha-3 fractions were elevated while alpha-2, beta, and gamma remained unchanged. A transient increase in total protein and albumin was noted only in liver. Carbofuran produced significant increases in triglycerides and cholesterol in liver that were also seen in serum. In both the liver and serum the levels of low-density-lipoprotein cholesterol (LDL-C) were reduced while the values of very-low-density-lipoprotein cholesterol (VLDL-C) were elevated. The concentration of high-density-lipoprotein cholesterol (HDL-C) was drastically reduced in liver (23% of control) with a proportional rise in serum (176%). In liver, carbofuran caused marked depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) (38% and 22% of controls, respectively), resulting in increased cell membrane permeability, thereby allowing leakage of cell constituents. It was concluded that carbofuran, directly or indirectly, produced perturbations in lipoprotein metabolism.

Dobutamine two-dimensional transesophageal echocardiographic stress testing for detection of coronary artery disease.

Atrial pacing and dipyridamole transesophageal echocardiography have been shown to be sensitive and specific tests for the detection of coronary artery disease. However, the sensitivity and specificity of dobutamine transesophageal echocardiography have not been reported. The purpose of this study was to determine the feasibility, sensitivity, and specificity of dobutamine transesophageal echocardiography for the detection of coronary artery disease. Transesophageal echocardiographic assessment of left ventricular function was performed in 81 adult patients aged 62 +/- 12 years during stepwise infusion of dobutamine from 5.0 to 40 micrograms/kg/min. Ischemia was diagnosed by the development of severe hypokinesis, akinesis, or dyskinesis of a previously contractile left ventricular segment. Coronary artery disease was defined by angiography as a reduction in luminal diameter of > or = 70% of an epicardial or > or = 50% of the left main coronary artery. In patients who had undergone coronary artery bypass graft surgery, a stenotic bypass graft was defined as a reduction in luminal diameter of > or = 70%. In patients without previous CABG, significant coronary artery disease was present in 21 patients: 5 with single-vessel disease, 7 double-vessel disease, 8 triple-vessel disease, and 1 left main coronary disease. Dobutamine transesophageal echocardiography had a sensitivity of 90% (19 of 21) and specificity of 94% (49 of 52) for the detection of coronary artery disease. In patients with previous CABG (n = 8), the sensitivity and specificity for the detection of bypass graft stenosis were 100% (4 of 4) and 75% (3 of 4), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-dimensional transesophageal echocardiographic determination of mitral valve area in adults with mitral stenosis.

Two-dimensional transthoracic echocardiography has been shown to be a reliable and accurate method of measuring stenotic mitral valve orifice area. Little data exist on the role of two-dimensional transesophageal echocardiography for this purpose. Thus in 45 adult patients with mitral stenosis mitral valve area was determined by direct planimetry with the use of two-dimensional transesophageal and transthoracic echocardiography. Transesophageal was less feasible than transthoracic echocardiography in the 45 patients (69% vs. 89%, p < 0.025). In 14 patients, two-dimensional transesophageal echocardiography was not feasible, primarily because of leaflet dropout. In 30 patients, transesophageal and transthoracic echocardiography were feasible, and measurements of mitral valve area by the two techniques correlated well (r = 0.91, SEE = 0.33 cm2, p < 0.0001). Mean mitral valve orifice area determined by transesophageal echocardiography (1.54 +/- 0.75 cm2; range 0.56 to 3.49 cm2) and by transthoracic echocardiography (1.55 +/- 0.78 cm2; range 0.62 to 3.68 cm2) did not differ (p = NS). The absolute (0.24 +/- 0.22 cm2) and percent (19% +/- 21%) differences between mitral valve area determined by transesophageal versus transthoracic echocardiography were small. These data show that mitral valve area in patients with mitral stenosis can be accurately measured by direct planimetry with two-dimensional transesophageal echocardiography. Technical refinements such as lateral-gain-compensation features may improve the feasibility of two-dimensional transesophageal echocardiography for measurements of mitral stenosis area, and this technique may become an adjunct to transthoracic echocardiography in the assessment of severity of mitral stenosis.