Showing papers by "Jewish Hospital published in 1999"

The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene

Abstract: The goal of this study was to interrogate the role of inducible NO synthase (iNOS) in the late phase of ischemic preconditioning (PC) in vivo. A total of 321 mice were used. Wild-type mice preconditioned 24 h earlier with six cycles of 4-min coronary occlusion/4-min reperfusion exhibited a significant (P < 0.05) increase in myocardial iNOS protein content, iNOS activity (assessed as calcium-independent l-citrulline formation), and nitrite + nitrate tissue levels. In contrast, endothelial NOS protein content and calcium-dependent NOS activity remained unchanged. No immunoreactive neuronal NOS was detected. When wild-type mice were preconditioned 24 h earlier with six 4-min occlusion/4-min reperfusion cycles, the size of the infarcts produced by a 30-min coronary occlusion followed by 24 h of reperfusion was reduced markedly (by 67%; P < 0.05) compared with sham-preconditioned controls, indicating a late PC effect. In contrast, when mice homozygous for a null iNOS allele were preconditioned 24 h earlier with the same protocol, infarct size was not reduced. Disruption of the iNOS gene had no effect on early PC or on infarct size in the absence of PC. These results demonstrate that (i) the late phase of ischemic PC is associated with selective up-regulation of iNOS, and (ii) targeted disruption of the iNOS gene completely abrogates the infarct-sparing effect of late PC (but not of early PC), providing unequivocal molecular genetic evidence for an obligatory role of iNOS in the cardioprotection afforded by the late phase of ischemic PC. Thus, this study identifies a specific protein that mediates late PC in vivo.

Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.

Abstract: In 43 amenorrheic women with polycystic ovary syndrome (PCOS), 31 (74%) with fasting hyperinsulinemia (> or =20 microU/mL), our aim was to determine whether Metformin (Bristol-Myers Squibb, Princeton, NJ), which reduces hyperinsulinemia, would reverse the endocrinopathy of PCOS, allowing resumption of regular normal menses. A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function, and to determine if there were different responses to Metformin between those who lost weight and those who did not. A third aim was to assess associations between PCOS, 4G/5G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene (PAI-1 gene), and PAI activity (PAI-Fx). Of the 43 women, 40 (93%) had normal fasting blood glucose and 37 had normal hemoglobin A1C (HgA1C); onlythree (7%) had type 2 diabetes mellitus. Metformin (1.5 to 2.25 g/d) was given for 6.1+/-5.1 months (range, 1.5 to 24), to 16 patients for less than 3 months, to 12 for 3 to 6 months, and to 15 for at least 6 months. On Metformin, 39 of 43 patients (91%) resumed normal menses. The percentage of women resuming normal menses did not differ among treatment duration groups (P .1). The body mass index (BMI) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin (P=.0008). Of 43 patients, 28 (67%) lost weight (1 to 69 pounds), with nine (21%) losing at least 12 pounds. On Metformin, the median fasting serum insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from 61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001). Metformin-induced improvements in ovarian function were independent of weight loss (testosterone decrease, P .05) between those who lost weight and those who did not, excepting Lp(a), which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not (P = .003). The change in response variables on Metformin did not differ among the five quintiles of weight loss, excepting fasting glucose (P or =22 U/mL, 28% v3%, chi(2)=10.1, P=.001). Metformin reduces the endocrinopathy of PCOS, allowing resumption of normal menses in most (91%) previously amenorrheic women with PCOS.

Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome.

Abstract: In 41 women with at least one pregnancy drawn from a group of 149 (108 never-pregnant) women with polycystic ovary syndrome (PCOS), our specific aim was to determine whether hypofibrinolysis mediated by high plasminogen activator inhibitor activity (PAI-Fx) is an independent risk factor for miscarriage. The 41 women had 77 total pregnancies with 34 miscarriages (44%) and 42 live births (55%). There were 12 women with at least one pregnancy, at least one miscarriage, and no live births (16 pregnancies and 16 miscarriages). There were 15 women with at least one pregnancy, no miscarriages, and at least one live birth (25 pregnancies and 28 live births). Of 12 women with only miscarriages and no live births, 67% had PAI-Fx greater than 16.4 U/mL (normals' 95th percentile), versus 29% of 15 women with no miscarriages and all live births (chi2 = 3.8, P = .052). By stepwise logistic regression, the number of pregnancies (P = .0001) and PAI-Fx (P = .016) were significant positive explanatory variables for the number of miscarriages. Age, 4G/5G polymorphisms of the PAI gene, factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) gene mutations, androstenedione, testosterone, sex hormone-binding globulin, the Quetelet index, and fasting serum insulin and glucose were not significant variables in the logistic regression model. In a separate stepwise logistic regression, three nonoverlapping groups of women (12 with > or = 1 pregnancy, > or = 1 miscarriage, and 0 live births, 10 with > or = 1 pregnancy, > or = 1 miscarriage, and > or = 1 live births, and 15 with > or = 1 pregnancy, 0 miscarriages, and > or = 1 live births) were the dependent variables. PAI-Fx was positively associated (P = .05) with the group with the worst pregnancy outcome (> or = 1 pregnancy, > or = 1 miscarriage, and 0 live births). The 41 women with PCOS and at least one pregnancy were more likely than healthy normal controls to have heterozygosity and homozygosity for the 4G/5G polymorphism of the PAI-1 gene (P = .028), but did not differ from normals for factor V Leiden (P > .10) or MTHFR (P > .09) mutations. PAI-Fx is a predominant independent significant positive reversible risk factor for miscarriage in women with PCOS.

The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis.

Abstract: In 59 patients with osteonecrosis of the hip, four genes associated with thrombophilia or hypofibrinolysis along with coagulation tests were studied to determine the pathoetiologic associations of heritable coagulation disorders with osteonecrosis. Patients did not differ from healthy control subjects for the thrombophilic Factor V Leiden, prothrombin, or methylenetetrahydrofolate reductase mutations. The plasminogen activator inhibitor-1 gene was shifted toward homozygosity for the 4G polymorphism; 41% of patients with osteonecrosis were homozygous for the 4G/4G polymorphism versus 20% of 40 healthy control subjects. The gene product of the 4G polymorphism, hypofibrinolytic plasminogen activator inhibitor activity, was higher in patients than in control subjects (median 19.2 versus 6.3 U/mL); 61% of patients had high plasminogen activator inhibitor activity (> or = 16.4 U/mL) versus 5% of control subjects. Stimulated tissue plasminogen activator activity (inhibited by plasminogen activator inhibitor activity) was lower in patients than in control subjects (3.10 versus 5.98 IU/mL); 31% of patients had low stimulated tissue plasminogen activator activity (< 2.28 IU/mL) versus 3% of control subjects. Heritable hypofibrinolysis conferred by the 4G/4G mutation of the plasminogen activator inhibitor-1 gene seems to be a major pathoetiology of primary osteonecrosis.

Hyperoxia-induced cell death in the lung--the correlation of apoptosis, necrosis, and inflammation.

Abstract: Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries.These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents. Simple strategies to mitigate hyperoxia-induced ALI might not be effective by virtue of merely reducing or augmenting the extent of apoptosis of pulmonary cells. Identification of the specific cell types undergoing apoptosis and further understanding of the precise timing of the onset of apoptosis may be necessary in order to gain a greater understanding of the connection between apoptosis and tolerance to hyperoxia and ALI. Attention should also be focused on other forms of non-apoptotic programmed cell death.

Heritable Thrombophilia and Hypofibrinolysis: Possible Causes of Retinal Vein Occlusion

Abstract: Objective To determine whether heritable thrombophilia and hypofibrinolysis were risk factors for retinal vein occlusion. Design Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain reaction assays were performed for 3 thrombophilic gene mutations (factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activator inhibitor activity, and polymerase chain reaction analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation measures were performed in 17 patients with retinal vein occlusions with comparison with serologic coagulation measures and polymerase chain reaction assays in 40 and 234 healthy normal volunteers as controls, respectively. Results Of 14 patients with retinal vein occlusion with measures of dilute Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6 (43%) had abnormal results (>38.8 seconds) compared with 1 (3%) of 30 controls ( P =.002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233 controls ( P =.02). Of 17 patients with vein occlusion, 2 (12%) had normal alleles ( 5G/5G ) for the plasminogen activator inhibitor gene promoter; the other 15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism ( P = .03). Patients with vein occlusion were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity. These levels were high (>22 U/L) in 6 (38%) of 16 patients with vein occlusion compared with 1 (2%) of 40 controls (χ 2 =12.8; P =.001). Patients with vein occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic Lp(a) (>35 mg/dL) than controls (5/40 [13%]; χ 2 =9; P =.003). The median Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62 mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype ( P =.05). Conclusion Thrombophilia and hypofibrinolysis are possible causes of retinal vein occlusion.

Abnormal lung growth and the development of pulmonary hypertension in the Fawn-Hooded rat.

Abstract: The Fawn-Hooded rat (FHR) strain develops accelerated and severe pulmonary hypertension when exposed to slight decreases in alveolar P O 2 . We recently observed that adult FHR lungs showed a strik...

Effect of exogenous estrogen on atherothrombotic vascular disease risk related to the presence or absence of the factor V leiden mutation (resistance to activated protein C)

Abstract: Estrogen replacement therapy (ERT), which produces acquired resistance to activated protein C when superimposed on heritable resistance to activated protein C (the mutant Factor V Leiden trait), may promote venous and arterial thrombosis. In a cross-sectional study of 423 women referred for hyperlipidemic therapy (93 of whom [22%] were on ERT), our specific aim was to determine whether ERT and heterozygosity for the Factor V Leiden mutation and/or resistance to activated protein C interacted as risk factors for atherothrombosis. Of the 423 women, 168 (40%) had atherothrombosis, 19 (4%) were heterozygous for Factor V Leiden mutation or had resistance to activated protein C or =2 (Factor V Leiden mutation-). By stepwise logistic regression, positive explanatory variables for atherothrombosis included hypertension (p = 0.002), age (p = 0.003), relatives with atherothrombosis (p = 0.002), anticardiolipin antibody immunoglobulin-M (p = 0.02), and a Factor V Leiden mutation*ERT interaction term where atherothrombosis events were more likely in 2 subgroups of women (ERT- and Factor V Leiden mutation-) or (ERT+ and Factor V Leiden mutation+) (p = 0.02). High-density lipoprotein cholesterol was inversely associated with atherothrombosis (p = 0.004). In a separate logistic regression model for the 213 women with a polymerase chain reaction measurement of the Factor V gene, ERT was protective (p = 0.008); the Factor V Leiden mutation was positively associated with atherothrombosis (p = 0.05). The atherothrombosis odds ratio risk for ERT (yes vs no) was 0.36 (95% confidence intervals [CI] 0.16 to 0.74, p = 0.007). The atherothrombosis risk odds ratio in women heterozygous for the Factor V Leiden mutation (vs normal) was 2.00 (95% CI 1.02 to 4.22, p = 0.05). ERT may be protective against atherothrombosis when the Factor V Leiden mutation is absent, whereas the Factor V Leiden mutation may increase risk for atherothrombosis, particularly in the presence of ERT. We suggest that the Factor V Leiden mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the Factor V Leiden mutation (4%), in whom ERT is relatively or absolutely contraindicated because of increased risk for atherothrombosis and thromboembolism. A second, much larger group of women will also be identified without the factor V Leiden mutation (96%), in whom ERT may reduce the risk for atherothrombosis.

Recognition of Staff Nurse Job Performance and Achievements: Staff and Manager Perceptions

Abstract: Recognition for job performance is central to staff nurse morale. However, little research has been done to identify recognition methods most valued by nurses themselves. The authors report results of a multisite survey conducted to compare staff and manager perceptions of meaningful recognition behaviors. They provide data for developing management interventions that may help to improve morale and increase retention. Given the financial constraints of the current environment, the nonmonetary recognition practices identified are of particular significance.

Evidence that anticardiolipin antibodies are independent risk factors for atherosclerotic vascular disease.

Abstract: Thrombophilic anticardiolipin antibodies (ACLAs) are independent risk factors for atherosclerotic vascular disease. We suggest that ACLAs IgG and IgM be routinely measured as ancillary atherothrombotic risk factors in all patients with atherosclerotic vascular disease events, in those at high risk for atherosclerotic vascular disease, and in those in whom thrombosis is a major pathoetiology.

The role of the psychiatrist in organ transplantation.

Abstract: The psychiatrist has multiple roles on the transplant team, beginning with the transplantation psychiatry consultation (TPC). It addresses such issues as risks of exacerbation or recurrence of a psychiatric illness, pharmacokinetic and pharmacodynamic considerations due to organ failure, potential drug interactions involving psychotropic and immunosuppressant medications, adequacy of support system, history of medical compliance, emotional and cognitive preparedness for transplantation, mental status findings supplemented by standardized cognitive testing and psychosocial rating instruments, and decision-making capacity. The consultation concludes with an overall assessment of the patient's psychosocial strengths and limitations, and recommended interventions to optimize his or her candidacy for transplantation. The consultation findings aid the psychiatrist and the transplant team in striving for fairness and the ideal of "neutrality" in an effort to serve the needs of the patient, other transplant candidates, and society with regard to optimal organ stewardship.

Achieving femoral artery hemostasis after cardiac catheterization: a comparison of methods

Abstract: BACKGROUND Cardiac catheterization is a common procedure that involves the introduction of a small sheath (5F-8F) into the femoral artery for insertion of other diagnostic catheters. After cardiac catheterization, local compression of the femoral artery is required to prevent bleeding and to achieve hemostasis. Traditional methods of achieving hemostasis require significant time and close supervision by medical personnel and can contribute to patients' discomfort. VasoSeal is a recently developed device that delivers absorbable collagen into the supra-arterial space to promote hemostasis. OBJECTIVES To compare outcomes between patients receiving a collagen plug and patients in whom a traditional method of achieving hemostasis was used after diagnostic cardiac catheterization. METHODS An outcomes tracking tool was used to analyze the medical records of 95 patients in whom a traditional method was used (traditional group) and 81 patients in whom VasoSeal was used (device group) to achieve hemostasis. Complications at the femoral access site, patients' satisfaction, and times to hemostasis, ambulation, and discharge were compared. RESULTS Hematomas of 6-cm diameter occurred in 5.3% of the traditional group; no complications occurred in the device group. The device group also achieved hemostasis faster and had earlier ambulation (P < .001). Patients in the device group were discharged a mean of 5 hours sooner than patients in the traditional group (P < .05). No significant differences were found in patients' satisfaction. CONCLUSIONS VasoSeal is a safe and effective method of achieving hemostasis after cardiac catheterization that can hasten time to hemostasis, ambulation, and discharge.

Hyperoxia in cell culture. A non-apoptotic programmed cell death.

Abstract: Here we discuss the morphological features and our current understanding of the pathways involved in non-apoptotic cell death from O2 toxicity. Preliminary data on hyperoxic signaling indicate that NF-kappa B translocation (and presumptive activation) is not a result of the p42/p44 MAPK pathway, but a likely downstream consequence of activation of the JNK pathway. Our observations suggest the existence of multiple signal transduction pathways in hyperoxia-induced cell death: one involved in the stress response which appears to be NF-kappa B-dependent and another in cell death.

Sessile polypoid gastric heterotopia of rectum: A report of 2 cases and review of the literature

Abstract: Objective.—The term heterotopia, a term derived from Greek, implies “other place.” It refers to the finding of normal tissues at foreign sites. Heterotopic gastric tissue rarely involves the large bowel. We report 2 cases of this rare entity. Data Sources.—Case reports of 2 patients with sessile polypoid lesion in the rectum, with a review of the available literature, using both MEDLINE and relevant bibliographies of published articles. Results.—Biopsies of the rectal lesions in our 2 cases reveled the presence of gastric tissue. Only 27 other such cases have been reported in the English literature. Conclusions.—Patients with rectal gastric heterotopia usually present with bleeding, but other presentations and complications are possible. Endoscopic or surgical excision is the treatment of choice, although the lesions also respond to histamine 2 receptor blockers.

Parents Call for Concerned and Collaborative Care

Abstract: Parents' perceptions and expectations of health care providers within the context of the pediatric lung transplant experience were investigated using a phenomenological approach. Fifteen parents of 12 children were interviewed. Two theme clusters, concerned care and collaborative care, were formulated. Themes that reflected parents' perceptions of concerned care included: being treated as an individual, seeing familiar faces, feeling that their children really mattered, and conversely, experiencing a feeling of abandonment. Parents' perceptions of collaborative care included: being part of the team, and conversely, feeling caught in the middle. The theme cluster, concerned care, reflected the value parents place on continuity of care. Humanistic nursing theory provided the link between study results and nursing practice.

Contribution of fasting hyperinsulinemia to prediction of atherosclerotic cardiovascular disease status in 293 hyperlipidemic patients.

Abstract: In a cross-sectional study of 293 nondiabetic patients (169 men and 124 women) referred for the diagnosis and treatment of hyperlipidemia, our specific aim was to determine whether fasting serum insulin independently contributes to the prediction of atherosclerotic cardiovascular disease (ASCVD) status. Of the 169 men and 124 women, 65 (38%) and 44 (35%), respectively, had ASCVD with at least one of the following: unstable angina, myocardial infarction (MI), angioplasty, coronary artery bypass graft (CABG), cluadication, transient ischemic attack, or ischemic stroke. In addition, 42% and 38% had fasting hyperinsulinemia (≥20 μU/mL). Fasting serum insulin of 20 μU/mL or higher was very in women (59% to 100%) and men (67% to 88%) when hypertension, obesity, top-decile triglyceride (TG), and bottom-decile high-density lipoprotein cholesterol (HDLC) were concurrent in various combinations. ASCVD events (present or absent) were dependent variables in a stepwise logistic regression model with explanatory variables including age, gender, race, hypertension, cigarette smoking, ASCVD in first-degree relatives at age 55 years or less, Quetelet Index, fasting serum insulin, a gender × insulin interaction term, anticardiolipin antibodies (ACLAs) IgG and IgM, total cholesterol to HDLC ratio. TG, lipoprotein(a) [Lp(a)], and homocysteine. The risk odds ratio for ASCVD (109 events and 184 nonevents) for subjects with top-decile insulin (v the bottom nine deciles was 3.71 with a 95% confidence interval (CI) of 1.62 to 8.9 (P = .002). For patients with MI and/or CABG and/or angioplasty ([MCA] 63 events and 184 nonevents), the risk odds ratio for top-decile insulin versus the rest was 5.07 (95% CI, 1.83 to 14.8, P = .002). For patients with MCA at age 55 or less, the gender × insulin interaction term was significant (P = .0004); the risk odds ratio for men with top-decile insulin was 13.28 (95% CI, 3.82 to 51.65, P = .0001). Hyperinsulinemia is very common in nondiabetic hyperlidemic women and men. Fasting serum insulin, a crude, simple, practical, and inexpensive measure, independently and uniformly improved the prediction of ASCVD status beyond traditional risk factors and lipid variables in patients referred for treatment of hyperlipidemia.

Fast estimation of arterial vascular parameters for transient and steady beats with application to hemodynamic state under variant gravitational conditions.

Abstract: Numerous parameter estimation techniques exist for characterizing the arterial system using electrical circuit analogs These techniques are often limited by requiring steady-state beat conditions and can be computationally expensive Therefore, a new method was developed to estimate arterial parameters during steady and transient beat conditions A four-element electrical analog circuit was used to model the arterial system The input impedance equations for this model were derived and reduced to their real and imaginary components Next, the physiological input impedance was calculated by computing fast Fourier transforms of physiological aortic pressure (AoP) and aortic flow The approach was to reduce the error between the calculated model impedance and the physiological arterial impedance using a Jacobian matrix technique which iteratively adjusted arterial parameter values This technique also included algorithms for estimating physiological arterial parameters for nonsteady physiological AoP beats The method was insensitive to initial parameter estimates and to small errors in the physiological impedance coefficients When the estimation technique was applied to in vivo data containing steady and transient beats it reliably estimated Windkessel arterial parameters under a wide range of physiological conditions Further, this method appears to be more computationally efficient compared to time-domain approaches

Impact of troponins on the evaluation and treatment of patients with acute coronary syndromes.

Abstract: Cardiac troponins possess superior sensitivity and specificity for the detection of cardiac injury. They can be used successfully to replace measurements of MB isoenzyme of creatine kinase or lactate dehydrogenase for the retrospective diagnosis of myocardial infarction. Measurement of these proteins confers powerful prognostic information that can be used to triage patients. An increasing body of data suggests that measurement of troponin proteins can be useful to guide therapeutic decisions in patients with acute coronary artery syndromes, especially regarding treatment with low-molecular-weight heparin or IIB/IIIA inhibitors. The absence of troponins in the circulation does not necessarily indicate the absence of coronary artery disease. With current assays, a significant diagnostic difference does not appear to exist between cardiac troponin I and T in patients with acute coronary artery syndromes.

Editorial: Nutrition and Fat Cell Differentiation

Abstract: Over the past decade, there has been an explosion of knowledge about obesity and a great focus on the complex program involved in fat cell differentiation. The temporally orchestrated dance between transcription factors that leads to lipid loading and enhanced insulin sensitivity is fascinating and has increased our understanding of cell fate determination for adipocytes, as well as serving as a model for understanding other cellular differentiation programs (1). It is believed that elucidation of adipocyte biology will facilitate development of strategies to combat obesity, a major problem in the U.S. and worldwide. Additionally, because increased adiposity is associated with insulin resistance and type 2 diabetes, the fat cell could be the key to unlocking the pathophysiology of those diseases as well. The article by Wang et al. in this month’s journal demonstrates the importance of understanding normal adipocyte biology as a backdrop for the examination of pathophysiology (2). The authors demonstrate that metabolic signals (glucose and insulin) in excess are capable of down-regulating CCAAT enhancer binding protein a (C/EBPa), a transcription factor essential for maintenance of a fully differentiated adipocyte phenotype (2–4). This is a critical observation because loss of complete differentiation correlates with increased insulin resistance and leads to a cavalcade of metabolic derangements. It also provides some insight into the mechanism whereby fat cell differentiation agents, peroxisome proliferator activated receptor g (PPARg) agonists, lead to improvement in insulin sensitivity in the setting of hyperglycemia.

Laparoscopic diagnosis and management of malignant ascites.

Abstract: Malignancy is the second most common cause of ascites. Tissue diagnosis is often difficult because the cytology of ascitic fluid is positive in only 57% of cases. Peritoneovenous shunting is often used as palliation in such patients and has proven superior to nonoperative management for some patients. We present three cases of malignant ascites with negative cytologies managed by using laparoscopic biopsies to confirm intraperitoneal cancer and assist in the placement of a peritoneovenous shunt. Results suggest that exploratory laparoscopy and shunt placement is a valuable procedure in these patients with a limited life expectancy and is preferable to open laparotomy.

Different responses of human anti‐HLA and anti‐αgal antibody to long‐term intravenous immunoglobulin therapy

Abstract: Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose alpha1-3 galactose (alphaGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-alphaGal IgG. Levels of PRA, anti-alphaGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-alphaGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alphaGal IgG, catabolism of anti-alphaGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-alphaGal IgG level it would be necessary to use IVIG depleted of this antibody.

Comparison of Tacrolimus Concentrations Measured by the IMx Tacrolimus II vs the PRO-TRAC II FK506 ELISA Assays

Abstract: Contemporary practice in the therapeutic monitoring of the immunosuppressant tacrolimus has required increasingly rapid and more sensitive assays. To this end, the two most commonly used immunoassay formats, IMx Tacrolimus II (Tacrolimus II) and PRO-TRAC IITM FK506 (ProTrac II) have undergone extensive revision, leading to changes in the measured drug concentration relative to the original assay format (1)(2)(3). Multiple studies have compared the original microparticle enzyme immunoassay (MEIA) and second-generation Tacrolimus II methods [e.g., Refs. (2)(3)], one report has compared the original MEIA and the second-generation ProTrac II method (1), and two preliminary reports have compared the ProTrac II method with the Tacrolimus II method (4)(5). In each of these reports, the ProTrac II method consistently yielded lower tacrolimus concentrations than the Tacrolimus II assay. The aim of this study was to further characterize the correlation between the Tacrolimus II method and the ProTrac II ELISA. Tacrolimus II controls were kindly provided by Abbott Laboratories (Abbott Park, IL). Pure tacrolimus powder was a courtesy of Fujisawa USA (Chicago, IL). Tacrolimus stock solutions in whole blood at concentrations of 5.0, 10.0, and 20.0 μg/L were prepared from tacrolimus powder. Tacrolimus powder was initially dissolved in methanol, followed by sequential dilution with drug-free human whole blood. Tacrolimus assays were performed according to manufacturers instructions. Correlation data were analyzed by Deming regression [Medsnap program (6)]. Differences between the two methods were analyzed by the methods of Bland and Altman (7)(8). Fifty-five whole blood specimens from 39 transplant patients [heart (n = 9), lung (n = 9), kidney (n = 7), liver (n = 10), and bone-marrow (n = 4); human studies approval UHSC 35-97] were initially assayed for tacrolimus with the ProTrac II method (PRO-TRAC II FK506 Kit). The specimens were …

Use of spasmography to assess the effects of botulinum toxin type A in patients with lower‐limb spasticity

Abstract: Lower-limb spasticity is one of the main features of advanced multiple sclerosis (MS), and botulinum toxin type A (BTX-A) is known to be effective in the treatment of lower-limb spasticity. Two hundred randomly selected MS outpatients were analysed for spasticity using clinical scores. Of the 200 randomly selected MS outpatients, 23% had marked or severe spasticity. Hence, the aims of this study were to investigate the effect of BTX-A injections in MS patients with lower-limb spasticity refractory to conventional treatment, and to evaluate the new method of spasmography for analysing muscle tone. Fifteen MS patients (mean MS duration, 11.2 years) with spasticity of the lower limbs were injected with BTX-A (BOTOX®) into the affected muscles. A control group of 15 healthy volunteers was analysed by spasmography. In the 15 MS patients, the Modified Ashworth Scale scores for the left and right legs were significantly lower than baseline values (P < 0.05) at 3 and 6 weeks post-treatment. At 6 weeks post-treatment, the spasmography measures (n= 12) of mean muscle tone and mean maximum muscle tone of both legs in passive mode were significantly reduced (P < 0.05) compared with baseline. The time to walk 10 m (n = 9) was significantly reduced compared with baseline (P < 0.05) at 3 and 6 weeks post-treatment. No adverse events were reported for any patients treated with BTX-A. These data indicate that BTX-A is effective and safe in the treatment of lower-limb spasticity, and that spasmography is a useful method for assessing therapeutic intervention in Spasticity.