YOUR LICENSE AND THE LAW

Rare is the individual respondent in a hearing before the California Board of Medical Examiners who has read the compilation of laws relating to the practice of medicine and surgery before he became involved with the law. Many physicians do not realize that the conviction of either a felony or any offense, misdemeanor or felony involving moral turpitude constitutes unprofessional conduct and that, after being penalized by the civil courts, they then are subject to action by the Board which may revoke the license to practice. During 1960, forty-two hearings on charges of unprofessional conduct were held. Many of these could have been avoided had the doctors involved not been ignorant of the law.     

Conscientious objection,professional duty and compromise: A response to Savulescu and Schuklenk

In a recent article in this journal, Savulescu and Schuklenk defend and extend their earlier arguments against a right to medical conscientious objection in response to criticisms raised by Cowley. I argue that while it would be preferable to be less accommodating of medical conscientious than many countries currently are, Savulescu and Schuklenk's argument that conscientious objection is ‘simply unprofessional’ is mistaken. The professional duties of doctors should be defined in relation to the interests of patients and society, and for reasons set out in this article, these may support limited accommodation of conscientious objection on condition that it does not impede access to services. Moreover, the fact that conscientious objection appears to involve unjustifiable compromise from the objector's point of view is not a reason for society not to offer that compromise. Arguing for robust enforcement of the no‐impediment condition, rather than opposing conscientious objection in principle, may be a more effective way of addressing the harms resulting from an over‐permissive conscientious objection policy.     

Resistance to Arbovirus Challenge in Mice Immediately After Vaccination

Mice vaccinated with a single injection of formalin-inactivated suspensions of mouse brain tissue infected with arboviruses were markedly protected against a challenge injection administered hours later. The protection observed during the first 2 days after vaccination seemed to be nonspecific, in that it appeared not only with the homologous system but also between arboviruses of different antigenic groups; this phase may be associated with an interferon-like activity of the serum. Overlapping the nonspecific phase was one of specific protection, which seemed to be well-established in its own right by day 3 or 4 after vaccination. Serum neutralizing antibodies against the homologous viruses were detected as early as 24 h after vaccination and in almost all instances by day 3.     

Analysis of Your Professional Liability Insurance Policy

The most important lessons for the physician to learn in regard to his professional liability insurance coverage are the following:1. The physician should carefully read his professional liability policy and should secure the educated aid of his attorney and his insurance broker, if they are conversant with this field.2. He should particularly read the definition of coverage and carefully survey the exclusion clauses which may deny him coverage under certain circumstances.3. If the physician is in partnership or in a group, he should be certain that he has contingent partnership coverage.4. The physician should accept coverage only from an insurance carrier of sufficient size and stability that he can be sure his coverage will be guaranteed for “latent liability” claims as the years go along—certainly for his lifetime.5. The insurance carrier offering the professional liability policy should be prepared to offer coverages up to at least $100,000/$300,000.6. The physician should be assured that the insurance carrier has claims-handling personnel and legal counsel who are experienced and expert in the professional liability field and who are locally available for service.7. The physician is best protected by a local or state group program, next best by a national group program, and last, by individual coverage.8. The physician should look with suspicion on a cancellation clause in which his policy may be summarily cancelled on brief notice.9. The physician should not buy professional liability insurance on the basis of price alone; adequacy of coverage and service and a good insurance company for his protection should be the deciding factors.     

Neuronal antigens modulate the immune response associated with experimental autoimmune encephalomyelitis

Rats primed with bovine myelin (BM) in complete Freunds adjuvant, develop acute experimental autoimmune encephalomyelitis (EAE). We have previously described that intraperitoneal administration prior to the active induction of the disease of a bovine synaptosomal fraction (BSF) and BM were effective ways of suppressing EAE. We found that both treatments diminish the incidence of the disease and reduced biochemical and histological alterations of the central nervous system (CNS). To characterize this suppression process, in this study we examined the antigen-specific immune response in animals protected from EAE. Lymph node mononuclear cells derived from sick EAE rats, as well as from those protected by BM and BSF, showed strong myelin basic protein (MBP) proliferation. Analysis of the humoral response against MBP showed a significant diminution of IgG2b anti-MBP titres in protected BM and BSF rats in contrast to sick EAE rats whose condition could be related to a diminished anti-MBP Th1 response. Finally, cells from rats protected by BSF and BM reduced the incidence of EAE when they were adoptively transferred into animals prior to active induction of the disease. These results suggest that a mechanism based on the generation of regulatory cells and immune deviation could account for the EAE suppression mediated by myelin as well as synaptosomal antigens.     

Neutrality at sea in transition: State practice in the gulf war as emerging international customary law∗

Abstract

This paper provides an appraisal of the continuing efficacy of the law of neutrality as it pertains to the balance of interests of belligerents and neutrals in the maritime environment. The author finds that international customary law of naval warfare pertaining to the rights of neutrals is emerging today as a result of State and extra‐State practice in the Gulf War. This is demonstrated by examination of belligerent and neutral conduct in the “Tanker War”; and various authoritative assessments of that conduct by the international community. The examination proceeds from an analysis of the underlying theory of the customary law‐making process and evolutionary nature of the law of neutrality since before World War II. State conduct in the Gulf War, including the employment of war‐exclusion zones, is critically examined against this backdrop. Discerned from this analysis are firm, “baseline”; standards of the law of neutrality against which State practice, belligerent as well as neutral, and ultimately the emerging customary law, may be assessed.     

Summary of the Acre Inaugural Meeting

The charter meeting of the Association of Clinical Researchers and Educators (ACRE) provided a powerful set of arguments against assertions that physician-industry collaboration is harmful and represents a “conflict of interest.” Such collaboration has, in fact, improved medical care for patients, a case made overwhelmingly by patients and patient advocacy groups at the meeting. The contentions that physician-industry collaboration is problematic are not based on evidence. They depend on unjustified generalization from inevitable, sometimes egregious, but vanishingly uncommon adverse outcomes of industry-physician interaction without reference to how so much more commonly these interactions add value. Furthermore, the claim that physician-industry collaboration is unprofessional is refuted by rational scrutiny. Indeed, the term “conflict of interest” itself is vague, inviting subjectivity and deserving to be rejected.The unwarranted success of conflict of interest regulation has prevailed because of the failure of physicians, educators, and innovators, through apathy and intimidation, to pay attention to its fallacies and resist its dangers. It has arisen from activist ambitions and from misalignment between the purposes of medical practitioners, educators, and innovators and those of administrators in medical journals and in academic medical centers. The media and politicians have not appreciated these misalignments and have accepted conflict of interest arguments at face value.Regulation emanating from conflict of interest criticism is confusing, onerous, expensive, disrespectful, and damaging. Prohibitions against speaking about medical products inhibit physician and patient education concerning rapidly emerging and complex therapies. Input by physicians cognizant of compliance requirements into such presentations should be encouraged. Restrictions to the free flow of corporate support of academic health centers, professional societies, and patient organizations threaten to delay medical innovation and education. (Endocr Pract. 2009;15:672-681)     

Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

Induction of a monospecific antiviral CD8+ T cell response may pose a risk to the host due to the narrow T cell response induced. At the individual level, this may result in selection of CD8+ T cell escape variants, particularly during chronic viral infection. Second, prior immunization toward a single dominant epitope may suppress the response to other viral epitopes, and this may lead to increased susceptibility to reinfection with escape variants circulating in the host population. To address these issues, we induced a memory response consisting solely of monospecific, CD8+ T cells by use of DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral variants. Thus, vaccinated mice were protected against chronic infection with LCMV, and no evidence indicating biologically relevant viral escape was obtained. In parallel, a broad and sustained CD8+ T cell response was generated upon infection, and in H-2(d) mice epitope spreading was observed. Even after acute LCMV infection, DNA vaccination did not significantly impair naturally induced immunity. Thus, the response to the other immunogenic epitopes was not dramatically suppressed in DNA-immunized mice undergoing normal immunizing infection, and the majority of mice were protected against rechallenge with escape variants. These findings underscore that a monospecific vaccine may induce efficient protective immunity given the right set of circumstances.     

Identification of a cysteine residue at the active site of Escherichia coli isocitrate lyase.

Escherichia coli isocitrate lyase was inactivated by iodacetate in a pseudo-first-order process. Complete inactivation was associated with the incorporation of only one carboxymethyl group per enzyme subunit. The substrate and products of the enzyme protected against inactivation, suggesting that the reactive group may be located at the active site. Isolation and sequencing of a carboxymethylated peptide showed that the modified residue was a cysteine, in the sequence Cys-Gly-His-Met-Gly-Gly-Lys. The reactivity of isocitrate lyase to iodoacetate declined with pH, following a titration curve for a group of pKa 7.1. The Km of the enzyme for isocritrate declined over the same pH range.     

Bioethics for clinicians: 12. Ethical dilemmas that arise in the care of pregnant women: rethinking "maternal-fetal conflicts".

When a pregnant woman makes a decision or acts in a manner that may be detrimental to the health and well-being of her fetus, her physician may be faced with an ethical dilemma. Is the physician''s primary duty to respect the woman''s autonomy, or to promote behaviour that may be in the best interest of the fetus? The controversial concept of "fetal rights" or the "fetus as a patient" contributes to the notion that the pregnant woman and her fetus are potential adversaries. However, Canadian law has upheld women''s right to life, liberty and security of the person and has not recognized fetal rights. If a woman is competent and refuses medical advice, her decision must be respected even if the physician believes that her fetus will suffer as a result. Coercion of the woman is not permissible no matter what appears to be in the best interest of the fetus.     

Plasmodium berghei berghei: Irradiated sporozoites of the ANKA strain as Immunizing Antigens in mice

Mice were protected against challenge with infective Sporozoites following immunization with X-ray irradiated Sporozoites. The immunity lasted at least 8 weeks. Mice immune against sporozoite challenge remained fully susceptible to challenge with erythrocytic stages. Immunization of mice with extracts of mosquito thorax failed to protect them, indicating that mosquito antigens were not directly responsible for the immunity observed in the basic experiments.     

Role of G proteins and modulation of p38 MAPK activation in the protection by nitric oxide against ischemia-reoxygenation injury

Protein kinase C (PKC)-mediated regulation of the mitogen-activated protein kinases (MAPK) may play a role in the protection afforded by ischemic preconditioning (PC). Nitric oxide (NO) can influence MAPK activation via interaction with PKC or farnesylation of low-molecular-weight (LMWT) G proteins. However, we have recently reported the mechanism of NO-induced cardioprotection to be a PKC-independent process. Therefore, we investigated the role of LMWT G proteins and MAPK signaling in NO-induced cardioprotection against simulated ischemia-reoxygenation (SI-R) injury. Neonatal rat cardiomyocytes treated for 90 min with the NO donor S-nitroso-N-acetyl-l,l-penicillamine (SNAP) 1 mM were protected against 6 h of SI (hypoxic conditions at 37 degrees C with 20 mM lactate, 16 mM KCl at pH 6.2) and 24 h reoxygenation under normal culture conditions. NO-induced protection was blocked by the G protein inhibitor alpha-hydroxyfarnesylphosphonic acid (alphaHFP) 10 microM. We studied the time course of p42/44 and p38 MAPK dual-phosphorylation hourly during SI using phospho-specific antibodies. p38 was phosphorylated during SI and the peak phosphorylation was significantly delayed by SNAP pretreatment. The p38 inhibitor SB203580 1 microM, given during SI, protected against injury. Thus the delay in peak p38 activation may contribute to, rather than be the effect of, NO-induced cardioprotection. We have shown that p38beta does not contribute to the total p38 signal in our extracts. Thus there is no detectable beta isoform. We conclude that the main isoform present in these cells and thought to be responsible for the observed phenomenon, is the alpha isoform.     

Relationships in consultation

The cause of medicine is advanced by the proper exchange of services between general practitioners and specialists. As a medical group and singly, physicians stand to benefit by strengthening their relationships; and the one to benefit most of all by this combination of services is the patient. Any physician of integrity admits that it is impossible for one physician to know all there is to know about every medical subject. The establishment of rules of conduct to be followed by those who get together to solve a medical problem will promote the use of advisory practice.     

RELATIONSHIPS IN CONSULTATION

The cause of medicine is advanced by the proper exchange of services between general practitioners and specialists. As a medical group and singly, physicians stand to benefit by strengthening their relationships; and the one to benefit most of all by this combination of services is the patient.Any physician of integrity admits that it is impossible for one physician to know all there is to know about every medical subject. The establishment of rules of conduct to be followed by those who get together to solve a medical problem will promote the use of advisory practice.     

Effect of potassium depletion of cells on their sensitivity to diphtheria toxin and pseudomonas toxin

When Vero cells were depleted of potassium, the cells were protected against diphtheria toxin. Potassium depletion of Vero cells strongly reduced the binding of the toxin to cell surface receptors. Likewise, potassium depleted L-cells were protected against pseudomonas toxin. Diphtheria toxin binding was completely restored upon addition of potassium to the cells. This restoration was not prevented by inhibition of protein synthesis by cycloheximide. When cells were depleted of potassium in the presence of metabolic inhibitors, and then treated with diphtheria toxin, protein synthesis was reduced to the same extent as in cells with normal intracellular level of potassium. The results indicate that potassium depletion of Vero cells reduces the ability of the cells to bind diphtheria toxin by an ATP requiring process, and that binding, endocytosis and transfer of diphtheria fragment A across the membrane may occur at low intracellular levels of potassium.     

Sexual Therapy of Patients with Cardiovascular Disease

Physical illness or disability inevitably has a damaging effect on sexual relationships. Physicians are usually unaware of the sexual consequences of illness on their patients, and lack experience in treating sexual dysfunctions.The report of treatment of a couple with serious cardiovascular disease illustrates the potential efficacy of brief sex therapy for improving the quality of a patient''s life. If a primary physician lacks the skills to conduct sex therapy, he may collaborate with nonphysician therapists. The physician''s knowledge of the physiological and psychological effects of a specific illness on his patient is essential to successful therapy. Often, simple education, encouragement or reassurance by the physician is enough to overcome the damaging effects of illness on a patient''s sex life.     

Adenoviral augmentation of elafin protects the lung against acute injury mediated by activated neutrophils and bacterial infection

During acute pulmonary infection, tissue injury may be secondary to the effects of bacterial products or to the effects of the host inflammatory response. An attractive strategy for tissue protection in this setting would combine antimicrobial activity with inhibition of human neutrophil elastase (HNE), a key effector of neutrophil-mediated tissue injury. We postulated that genetic augmentation of elafin (an endogenous inhibitor of HNE with intrinsic antimicrobial activity) could protect the lung against acute inflammatory injury without detriment to host defense. A replication-deficient adenovirus encoding elafin cDNA significantly protected A549 cells against the injurious effects of both HNE and whole activated human neutrophils in vitro. Intratracheal replication-deficient adenovirus encoding elafin cDNA significantly protected murine lungs against injury mediated by Pseudomonas aeruginosa in vivo. Genetic augmentation of elafin therefore has the capacity to protect the lung against the injurious effects of both bacterial pathogens resistant to conventional antibiotics and activated neutrophils.     

Pigment Degradation in Discs of the Thermophilic Cucumis sativus as Affected by Light, Temperature, Sugar Application and Inhibitors

Chlorophyll degradation in Cucumis leaf discs was measured at different temperatures between 1 and 25°C in the light and in darkness, and in the presence or absence of sucrose. Two different processes of chlorophyll degradation could be distinguished, a light-requiring process operating at 1 and 5°C and another, light and sucrose enhanced degradation process which was evident at 25°C. Degradation of leaf pigments at low temperatures was of a photo-oxidative nature since there was no degradation in the dark. The chlorophyll a/b ratio was decreased, carotene was degraded at a faster rate than chlorophyll, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and triphenyltetrazolium chloride (TTC) which prevent photo-oxidation, protected against chlorophyll degradation. The light and sucrose enhanced chlorophyll degradation at 25°C was of an enzymatic nature since it occurred in the dark as well as in the light. The chlorophyll a/b ratio was not affected, and carotene and chlorophyll degradation occurred at the same rate. Since DCMU completely inhibited the light enhancement at 25°C and experimentation in a low oxygen atmosphere also protected chlorophyll against the effect of light and sugar application, it is suggested that the enhancement of chlorophyll degradation by light and sucrose at 25°C may be due to increased sugar uptake of the chloroplasts and consequently excessive starch formation in the organelles.     

Evidence that membrane phospholipids and protein are required for binding of diphtheria toxin in Vero cells

Treatment with phospholipase C strongly protected monkey kidney (Vero) cells against diphtheria toxin and reduced the ability of the cells to bind 125I-labelled toxin. Treatment with phospholipase D and with trypsin also protected the cells, although to a lesser extent. Phospholipase A2 had no protective effect. Phospholipase C also protected fetal hamster kidney cells against the toxin. After removal of the enzymes, as well as after treatment of the cells with 4-acetamide 4'-isothiocyanostilbene 2,2'-disulfonic acid, diphtheria toxin binding capability was restored slowly, apparently by a process requiring protein synthesis, since cycloheximide blocked the restoration. The data indicate that both phospholipids and protein are involved in the binding sites for diphtheria toxin.     

Immediate, long-lasting suppression of autoimmune encephalomyelitis by cell-bound neuroantigen

When lymphoid cells from rats recovered from experimental autoimmune encephalomyelitis (EAE) were incubated in vitro for 1 hr with myelin basic protein (BP), then washed and transferred along with anti-BP immune serum to naive recipients, those recipients immediately developed a solid, long-lasting resistance to active induction of EAE. To obtain this high level of suppression, both steps of BP-incubation of cells and transfer of immune serum were found to be essential, i.e., direct transfer of nonincubated cells plus immune serum had no comparable suppressive effect, nor had transfer of BP-incubated cells with nonimmune serum. Specificity of the suppressive effect was indicated by the finding that cells from BP-sensitized donors, incubated with BP, protected against BP-CFA-induced disease but not against disease induced with whole spinal cord homogenate (SCH-CFA). As expected, cells from SCH-CFA-sensitized donors incubated with SCH protected recipients against disease induced with either SCH-CFA or BP-CFA. The suppression appears to act early in the afferent stage of the immune response, since inoculation with incubated cells as little as 24 hr after active challenge was ineffective. There was no suppression of passively induced disease.