Nicholas Kontos

Intramuscular Administration of Very High Dose of a-Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.

Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by intraperitoneal administration of (−)-Epigallocatechin-3-gallate

The aim of this study was to evaluate the effect of ( − )-epigallocatechin-3-gallate (EGCG), a natural antioxidant, on liver and lungs after warm intestinal ischemia/reperfusion (I/R). Thirty male Wistar rats were equally divided into a sham-operation group, an intestinal I/R group and an intestinal I/R group pretreated with EGCG intraperitoneally. Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 120 min. Immediately after reperfusion, liver, lung and blood samples were collected and analyzed. Results showed that intestinal I/R increased the levels of aspartate (AST) and alanine (ALT) transaminase in serum to 987 and 752 IU/l, respectively. Malondialdehyde (MDA) increased in liver to 1.524 nmol/g in the group subjected to intestinal I/R compared to 0.995 nmol/g in the sham operation group. MDA was also increased in lungs to 1.581 nmol/g compared to 0.896 nmol/g in the sham operation group. Myeloperoxidase (MPO) increased in liver, after intestinal I/R, to 5.16 U/g compared to 1.59 U/g in the sham operation group. MPO was also increased in lungs to 3.89 U/g compared to 1.65 U/g in the sham operation group. Pretreatment with EGCG decreased serum levels of AST and ALT to 236 and 178 IU/l, respectively. It also decreased mean MDA levels in liver and lungs to 1.061 and 1.008 nmol/g, respectively, and mean MPO levels in liver and lungs to 1.88 and 1.71 U/g, respectively. Light microscopy and transmission electron microscopy examinations showed significant alteration in liver and lungs and protection of liver and lung parenchyma in the animals treated with EGCG.

Bipolar spectrum disorder: a pilot study.

Objective: To assess depressive features of a proposed definition of bipolar spectrum disorder (BSD). Methods: Thirty-six patients with bipolar disorder type I or II were compared to 37 patients with unipolar major depressive disorder through patient interview and chart review. Results: Univariate analysis suggests that 7 of 12 (recurrent major depressive episodes, brief major depressive episodes, atypical depressive symptoms, early age of onset, family history of bipolar disorder, antidepressant tolerance, and antidepressant-induced mania) features of major depressive episodes were more likely to occur in bipolar versus unipolar patients. After adjustment in a multivariable regression model, however, the five most powerful predictors of bipolar disorder were brief major depressive episodes, early age of onset, antidepressant- induced mania, postpartum depression, and atypical depressive symptoms. Conclusions: This preliminary study supports the idea that bipolar disorder is characterized by some depressive features less likely to be found in unipolar depression. Further prospective study needs to be conducted comparing BSD with unipolar depression.

Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (−)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.

Discharges Against Medical Advice

In their Viewpoint about discharges against medical advice, Drs Alfandre and Schumann1 asked, “Why would you discharge a patient against medical advice?” Until this question is answered, they argued, “continued use of the practice does not seem justified.” We believe the authors conflated 3 different scenarios, a clarification of which may help to answer their question.

Severe total hepatic ischemia and reperfusion: Relationship between very high α-tocopherol uptake and lipid peroxidation

Reperfusion injury of the liver occurs in liver transplantation and in major hepatectomies. It triggers a severe oxidative stress that leads to increased lipid peroxidation. In our study we examined the effect of parenteral supranutritional administration of α-tocopherol, a vitamin that plays a key role in the endogenous antioxidant system, to rats subjected to severe ischemia/reperfusion (I/R) injury of the liver. α-Tocopherol was administered to the animals at doses of 30 and 300mg/kg bw, whereas total hepatic ischemia was induced for 60 min followed by 120 min reperfusion. Tissue and blood samples were collected for malonyldialdehyde (MDA) and serum α-tocopherol assay, respectively. In the sham operation group, mean MDA level in liver was 1.14nmole/g wet tissue in the control subgroup, and 1.01 or 0.74nmole/g wet tissue in the subgroups given 30 or 300mg/kg α-tocopherol. In the I/R group, mean MDA level was 1.57nmole/g wet tissue in the control subgroup, and 0.97 and 0.77nmole/g wet tissue in the subgroups given 30 or 300mg/kg α-tocopherol. Mean levels of α-tocopherol in serum (μmole/l) were 10.20 and 1.80 in the control subgroups, 25.28 and 11.25 in the subgroups treated with 30 and 300mg/kg bw of α-tocopherol, and 31.00 and 13.02 in the subgroups treated with 30 and 300mg/kg bw of α-tocopherol, within the sham-operation and I/R groups, respectively. A significant decrease of MDA accompanied by a significant increase of serum α-tocopherol was documented in the α-tocopherol-treated rats within both groups. Ischemia/reperfusion triggered a significant increase of the MDA level in the liver of the rats not treated with α-tocopherol as compares with the treated animals.

Perspective: biomedicine--menace or straw man? Reexamining the biopsychosocial argument.

More than 30 years after its introduction by George Engel, the biopsychosocial model exerts a major influence on the rhetoric and intentions of academic medicine. However, advocates of the model do not feel that it has significantly altered the practice of physicians, whom they portray as tightly clinging to a biomedical approach. Using Engels original writings, those of his successors, and the work of medical historians, the author asserts that biopsychosocial advocates use clinical biomedicine as a straw man to support their argument. Proceeding from that point, the author attempts to demonstrate that excessive focus on this straw man has inhibited critique of the biopsychosocial model and the argument supporting it. He identifies failures to address clinical medicines functional specificity and relationship with broader social trends as contributors to the biopsychosocial models stagnation. The author proposes that it would be more productive to view clinical biomedicine as an epiphenomenon of the human traits of overenthusiasm and the need for security. Recognizing that medicine is made up of heterogeneous tasks, he observes that no one model, including the biopsychosocial model, tends to all of them. The biopsychosocial model would be best served by shedding the biomedical straw man and modifying its ambitions.

The Muddles of Medicine: A Practical, Clinical Addendum to the Biopsychosocial Model

Background The commonly-accepted “biopsychosocial model” does not always lend itself to the kind of pragmatic decisions that many clinical situations demand of physicians. Objective The authors attempt to identify and close gaps in the biopsychosocial model that hinder its application in certain real-life clinical situations. Method The authors review some of the current and historical literature on the development and application of the biopsychosocial model, and argue the shortcomings of this modality in various clinical situations. Results The authors present three dicta to guide clinicians toward relevant areas of inquiry: 1) Think neuroanatomically; 2) Think existentially; and 3) Think “dirty;” that is, understand that patients and physicians sometimes work toward different goals. Discussion These dicta form an addendum to the biopsychosocial model, identifying and filling three specific, commonly-encountered gaps in that paradigm, which, ironically, is usually considered all-inclusive.

Morgellons Disease, or Antipsychotic-Responsive Delusional Parasitosis, in an HIV Patient: Beliefs in The Age of the Internet

“Which was worse, the real condition or the self-created one; and did it matter?” — Don DeLillo: “White Noise” Viking Press

The Assessment and Management of Agitation and Delirium in the General Hospital

The Psychiatric Consultation Service at Massachusetts General Hospital (MGH) sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. Such consultations require the integration of medical and psychiatric knowledge. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss the diagnosis and management of conditions confronted. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry. Dr Stern is chief of the Psychiatric Consultation Service at MGH and is a professor of psychiatry at Harvard Medical School (HMS); Drs Celano and Gross are clinical fellows in psychiatry at HMS and fellows in adult psychiatry at MGH and McLean Hospital; Dr Huffman is director of Inpatient Psychiatry Services at MGH; Drs Freudenreich, Kontos, and Nejad are attending physicians on the Psychiatric Consultation Service at MGH; Ms Repper-DeLisi is a psychiatric nurse clinician on the Nursing Consultation Service at MGH; Dr Thompson is director of the Medical Intensive Care Unit at MGH and an associate professor of medicine at HMS. Dr Stern is an employee of the Academy of Psychosomatic Medicine; has served on the speakers board of Reed Elsevier; is a stock shareholder in WiFiMed (Tablet MD); and has received royalties from Mosby/Elsevier and McGraw Hill. Dr Freudenreich has served as a consultant to Beacon Health Strategies and has received grant/research support from Pfizer and honoraria from Reed Medical Education. Drs Celano, Gross, Huffman, Kontos, Nejad, and Thompson and Ms Repper-DeLisi report no financial or other affiliations relevant to the subject of this article.