In memoriam: Clayton Daniel Mote, MD (1905-95)

Clayton Mote had a long career as a teacher, scholar and practitioner of medicine. He was noted for his diagnostic skills and rigorous approach to bedside teaching, with emphasis on the physical examination. The author's attitude towards him was a mixture of admiration for his talents and anxiety that one could never quite meet his expectations. People of his kind still have a place in modern academic medicine: they can be leaders and role models, they can integrate the new and the old, and they can inspire those under their tutelage to return to hands-on medicine.     

Donor hematopoietic cells from transgenic mice that express GFP are immunogenic in immunocompetent recipients

OBJECTIVE: To study the immunogenicity of hematopoietic cells marked with green fluorescence protein (GFP) while avoiding the potentially confounding effects of viral gene transduction, marked cells from GFP+ transgenic mice were tracked after transplantation into unconditioned immunocompetent recipients. MATERIALS AND METHODS: Marrow was harvested from GFP+ transgenic mice that had been crossed onto a BALB/cByJ background. Unconditioned marrow transplantation involved infusion of sex-matched or sex-mismatched cells into female BALB/cByJ hosts. Engraftment and contribution to circulating nucleated blood cells were compared to recipients of donor cells that were not GFP-marked. Donor cells were detected by flow cytometry (GFP) and fluorescence in situ hybridization (FISH) for Y-chromosome sequences. RESULTS: Donor cells from mice of the same genetic background that did not express GFP were detected for more than four-weeks in unconditioned recipients. In contrast, GFP-marked cells in the blood peaked at one-week, declined to undetectable levels by two-weeks and were not detected in the marrow at sacrifice. In sex-mismatched studies, detection of male GFP+ donor cells by FISH yielded levels similar to those observed by flow cytometry, in contrast to the levels detected for many weeks in mice infused with male cells that did not express GFP. In immunocompetent recipients immunized with irradiated GFP-expressing cells, rechallenge with GFP+ cells resulted in the accelerated loss of donor cells. CONCLUSION: Donor marrow cells from GFP+ transgenic mice were lost after infusion into unconditioned immunocompetent mice and sensitization studies infer an immunologic mechanism. These results are similar to studies of virally transduced cells. Thus, infusion of cells with optimum engraftment potential could not compensate for the loss of donor cells due to immunogenicity.     

Limitations of Potassium Cardioplegia during Cardiac Ischemic Arrest: A Phosphorus 31 Nuclear Magnetic Resonance Study

Cold K⁺ cardioplegia is commonly used to preserve the myocardium during surgical ischemia. Since the K⁺-induced membrane depolarization could cause a Ca²⁺-mediated breakdown of adenosine triphosphate, this study compared the influence of different electrolytes on high-energy phosphate metabolism during cardioplegic arrest and subsequent recovery of mechanical function. An isolated working heart was subjected to hypothermic ischemia for one hour. Metabolic studies were assessed on phosphorus 31 nuclear magnetic resonance (NMR). Results show that (1) K⁺ cardioplegia is harmful when the Ca²⁺ content is equal to 2 mEq/L; (2) deleterious effects of K⁺ are markedly reduced by lowering the Ca²⁺ content; (3) the most adequate preservation is provided by a Mg²⁺-rich–Ca²⁺-poor perfusate; (4) this protection is not enhanced by addition of K⁺. Finally, ³¹P NMR appears particularly appropriate for evaluating myocardial protection techniques since it allows noninvasive serial monitoring of high-energy phosphate content and subsequent correlation with functional recovery after ischemia.     

Results and complications of intraaortic balloon pumping in surgical and medical patients

The intraaortic balloon was attempted for therapy in 94 patients and successfully placed in 86. The balloon catheter could not be passed through the femoral or iliac artery in 12 patients (13 percent) of the group; in 4 of these the balloon was inserted through an aortic arch graft. The medical indications were cardiogenic shock and preinfarction angina. Ten of the 14 patients in the group with shock survived when treated with an aortic balloon without emergency surgery. Indications for balloon pumping in the surgical group included inability to wean the patient from the pump-oxygenator, postoperative shock and prophylactic placement of the balloon for poor ventricular function. Inability to remove a patient from pump-oxygenator support was the most common surgical indication, and 47 percent of patients were long-term survivors. Only 1 of the 17 patients for whom balloon pumping was used prophylactically died. Complications occurred in 17 percent of the entire group of 86 patients although the rate for medical patients with cardiogenic shock was 50 percent. The most common complication was arterial insufficiency requiring removal of the balloon. Four patients had permanent damage to the legs from ischemia, one patient requiring bilateral amputation. The overall incidence of serious arterial obstruction was 10 percent. Other complications included balloon displacement with arterial obstruction and pericardial tamponade from anticoagulant agents resulting in death.     

Activation of XII motoneurons and premotor neurons during various oropharyngeal behaviors

Neural control of tongue muscles plays a crucial role in a broad range of oropharyngeal behaviors. Tongue movements must be rapidly and accurately adjusted in response to the demands of multiple complex motor tasks including licking/mastication, swallowing, vocalization, breathing and protective reflexes such as coughing. Yet, central mechanisms responsible for motor and premotor control of hypoglossal (XII) activity during these behaviors are still largely unknown. The aim of this article is to review the functional organization of the XII motor nucleus with particular emphasis on breathing, coughing and swallowing. Anatomical localization of XII premotor neurons is also considered. We discuss results concerned with multifunctional activity of medullary and pontine populations of XII premotor neurons, representing a single network that can be reconfigured to produce different oromotor response patterns. In this context, we introduce new data on swallowing-related activity of XII (and trigeminal) motoneurons, and finally suggest a prominent role for the pontine K?lliker-Fuse nucleus in the control of inspiratory-related activity of XII motoneurons supplying tongue protrusor and retrusor muscles.     

Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously. Contrary to our hypothesis, there was a significant increase in polypharmacy between 1998 and 2001. The predominant use of second generation antipsychotics became standard in schizophrenia treatment. In this context the decrease of concomitant anticholinergic medication is notable. Doses of conventional antipsychotics like haloperidol as well as doses of risperidone decreased whereas doses of other second generation antipsychotics increased. All in all, the pharmacological management of schizophrenia patients is increasingly in tune with current treatment guidelines.     

Microsurgical varicocelectomy for infertile couples with advanced female age: natural history in the era of ART

Varicocele represents the most common cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative to varicocelectomy for the management of couples with a varicocele. The age of the female partner is important in the decision-making process; however, the true influence of female age on pregnancy outcome following varicocelectomy or ART in these couples is unknown. We evaluated the outcomes of 2 cohorts of infertile men with a varicocele and a female partner 35 years of age or older; one group selected varicocelectomy and the other a nonsurgical approach. We reviewed a group of consecutive infertile men who underwent microsurgical varicocelectomy and whose partners are 35 years of age or older (n = 110). We also reviewed a consecutive group of men with varicoceles who elected not to have surgery and whose partners are 35 years of age or older (n = 94). The outcome measures included changes in semen parameters, pregnancy rates (assisted and unassisted), and use of ART. The surgical and nonsurgical groups had comparable semen parameters and female ages. Mean sperm concentration and motility increased significantly after varicocelectomy (P < .05). At a mean of 30 months follow-up, 35% of couples in the surgical group achieved a spontaneous pregnancy and an additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In the nonsurgical group, 25% achieved a spontaneous pregnancy and an additional 16% achieved a pregnancy with ART (40% of this group attempted ART). This study on the natural history of infertile men with varicocele and advanced female age suggests that the surgical and nonsurgical approaches offer comparable pregnancy outcome (combined assisted and unassisted pregnancy rates are about 40%). Overall, these data suggest that varicocelectomy is an acceptable option for couples with advanced female age, but other female factors must be considered in the decision-making process.