Temperature-induced change of variant surface antigen expression in Paramecium involves antigen release into the culture medium with considerable delay between transcription and surface expression.

We analyzed temperature-induced changes of variant surface antigen (vsAg) expression in Paramecium primaurelia, using immuno-techniques and mRNA determinations. Upon a 23 degrees C to 33 degrees C shift, the old vsAg, type 156G, remains on the cell surface for a time, when already mRNA for the new form, 156D, is expressed. A considerable amount of 156D-specific mRNA is formed 45-48 h after the temperature shift, while 156D surface expression reaches maximal levels only after >72 h. A new aspect of these experiments is that, during this transition, the old vsAg is steadily released in high-molecular-weight form into the culture medium, as found by dot blot and Western blot analysis of concentrated culture medium. The new vsAg form is first inserted into the somatic cell membrane, before it spreads also into cilia. In the reverse transition, 33 degrees C to 23 degrees C, the adaptation on the level of transcription and surface expression is considerably faster. While we had previously shown, under steady-state conditions (constant temperature), the occurrence of a degradation pathway by endocytotic and phagocytotic ingestion of vsAg this may proceed in parallel to the steady release of old vsAg from the cell surface into the medium. Altogether these combined processes may facilitate the installation of the new vsAg type.

Laparoscopic Roux-en-Y gastric bypass: defining the learning curve.

BACKGROUND: Increasing numbers of laparoscopic surgeons are performing laparoscopic Roux-en-Y gastric bypass (LGB). Our aim was to determine the length of the learning curve for a skilled laparoscopic surgeon. METHODS: The study population consisted of the first 225 consecutive LGB procedures attempted by one laparoscopic surgeon (HJS). Outcome parameters included mortality, morbidity, operative time, and conversion to an open procedure. RESULTS: Average operative time decreased from 189 min (first 75 patients) to 125 minutes (last 75 patients). Most of the improvement in operative time occurred over the first 75 patients. The perioperative complication rate decreased from 32% (first 75 patients) to 15% (second and third groups of 75 patients). Complication rates did not significantly decrease after the first 75 patients. Low mortality and conversion rates were achieved early in the series. CONCLUSION: Low mortality rates and low conversion rates can be achieved early in the learning curve for LGB. Complication rates plateau after approximately 75 LGBs, and operative times decrease substantially over the initial 75 cases. Operative times continue to decrease at a slower rate beyond 75 cases.

M-cone opsin gene number does not correlate with variation in L/M-cone sensitivity.

Molecular genetic studies demonstrate that the human cone opsin gene array on the q-arm of the X-chromosome typically consists of one long-wave-sensitive (L) cone opsin gene and from one to several middle-wave-sensitive (M) cone opsin genes. Although the presence of the single L-cone opsin gene and at least one M-cone opsin gene is essential for normal red-green colour discrimination, the function of the additional M-cone opsin genes is still unclear. To investigate whether any variations in phenotype correlate with differences in the number of M-cone opsin genes, we selected 13 normal trichromat males, for whom four independent molecular techniques have exactly determined their number of M-cone opsin genes, ranging from one to four. Their phenotype was characterized by estimating their foveal L- to M-cone ratio from heterochromatic flicker photometric (HFP) thresholds, by measuring the wavelength corresponding to their 'unique yellow', and by determining their L- and M-cone modulation thresholds (CMTs). No correlation was found between these psychophysical measures and the number of M-cone opsin genes. Although, we found a reasonably good correlation between the L/M-cone ratios based on HFP and on CMT, we did not find any correlation between the estimated L/M-cone ratios and the settings of 'unique yellow'. Our results accord with previous molecular genetic studies that suggest that only the first two genes in the X-linked opsin gene array are expressed.

Macroscopic magnetization jumps due to independent magnons in frustrated quantum spin lattices.

For a class of frustrated spin lattices including the Kagomé lattice we construct exact eigenstates consisting of several independent, localized one-magnon states and argue that they are ground states for high magnetic fields. If the maximal number of local magnons scales with the number of spins in the system, which is the case for the Kagomé lattice, the effect persists in the thermodynamic limit and gives rise to a macroscopic jump in the zero-temperature magnetization curve just below the saturation field. The effect decreases with increasing spin quantum number and vanishes in the classical limit. Thus it is a true macroscopic quantum effect.

Structuring student learning in the primary care setting: where is the evidence?

Over the past two decades, the majority of medical schools in the USA have embarked upon curricular initiatives to enhance the teaching of ambulatory or office-based primary care. Identifying characteristics of these primary care experiences that make for the most effective learning is a top priority in medical education research. In this paper we examine what is known about the influence of variability in the structure of primary care experiences on student learning outcomes. We examine the questions of how rotations are scheduled, who does the teaching and where the teaching takes place. Given the variability in curricula across the 125 accredited medical schools in the USA and the absence of agreed-upon objectives, outcomes or assessment measures for primary care education, it is not surprising that the current literature has fallen short in providing definitive answers. There is much debate about the benefits of community vs. campus sites, longitudinal vs. block experiences, and the influence of specialty training of the preceptor, but little in the current literature to guide and substantiate a programme's choice. What can be concluded with relative confidence is that clinics currently offer more active student experiences than do private offices, that students may be more satisfied with rural experiences than with urban or suburban experiences, and that longitudinal and block experiences have different learning advantages. Research in primary care medical education will benefit from the current movement towards a cross-institutional consensus on educational objectives and outcome measures and on the general application of a more rigorous research methodology.

Error patterns of 3rd-year medical students on the cardiovascular physical examination.

BACKGROUND: Recent research documents widespread deficits in the physical examination skills of practicing physicians. PURPOSE: This study explored physical examination skills of 3rd-year medical students after completion of a course in physical diagnosis. METHODS: Standardized patient physical examination checklist data were analyzed for a cohort of 2,038 medical students for a patient presenting with classic signs and symptoms of an acute myocardial infarction. A follow-up paper case and survey explored reasons underlying omissions. RESULTS: Students systematically omitted 3 of 10 component maneuvers critical to the evaluation of a patient with shortness of breath and chest pain. The same pattern of omissions was observed across 8 medical schools and over 2 successive years. The paper case follow-up study ruled out time constraints and performance anxiety as the cause. Survey data revealed that students may omit a maneuver due to inability to recall pertinence (blood pressure in both arms) or difficulty discriminating findings (heart sounds at different locations), or because of inadequate technical mastery (percussion of the lungs). CONCLUSIONS: These data suggest fundamental inadequacies in the current paradigm for teaching physical examination skills. Standardized patient checklist data can provide an informative window into the efficacy of teaching practices.

[Cardiotoxicity of 5-fluorouracil. Clinical relevance of palliative radiochemotherapy of malignant head-neck tumors]. / Kardiotoxizität des 5-Fluorouracil. Klinische Relevanz bei palliativer Radiochemotherapie von malignen Kopf-Hals-Tumoren.

BACKGROUND: In the past cardiotoxicity has been increasingly reported as 5-fluorouracil is widely used as well in curative adjuvant as in palliative chemotherapy of malignant neoplasms. METHODS: We report on two cases of 5-fluorouracil-associated cardiotoxicity on palliative treatment of head and neck cancer and evaluate the importance of intensive drug monitoring. RESULTS: 5-fluorouracil-associated cardiotoxicity occurs with an incidence of 1.1-4.5%. Ischaemic cardiopathy due to vasospasms is believed to be the most common manifestation. CONCLUSIONS: Since most patients with head and neck cancer have risk factors for cardiovascular disease, 5-fluorouracil-associated cardiotoxicity should not be underestimated and patients should be monitored carefully.

The effects of patient characteristics and practice settings on students' participation in a primary care clerkship.

PURPOSE: To explore the effects of practice, patient, and encounter variables on students' participation in a third-year primary care clerkship. METHOD: In 1995-96, 154 students, randomly assigned to ambulatory teaching sites, completed for each patient encounter a scannable card indicating the patient's age range, gender, and insurance type, the setting of care, the type of visit, whether it was a repeat or first visit to the student, and the student's level of participation. Conventional measures of students' satisfaction (post-clerkship survey) and performance (preceptor ratings, USMLE Step 2, standardized-patient examination scores) were examined. RESULTS: The students reported significantly higher levels of participation for patient encounters taking place in clinic and emergency room settings than for those in private offices; for repeat rather than for first visits; for patients over 12 years old than for those 12 years old or younger; and for sick visits rather than for follow-ups or checkups. Students' participation had a modestly positive correlation with students' satisfaction and performance. CONCLUSION: Several practice and patient variables influence the level of students' participation in the care of ambulatory patients. The strongest predictor of active student participation is the clinical setting of the encounter. Monitoring students' self-reported levels of participation is an important tool for tracking the impact of practice variability on the quality of the learning environment in ambulatory clerkships.

The Toxic Symbiont Caedibacter caryophila in the Cytoplasm of Paramecium novaurelia.

Endosymbiotic bacteria were observed to inhabit the cytoplasm of the freshwater ciliate Paramecium novaurelia. Transmission electron microscopy and toxicity tests with sensitive paramecia showed that the endosymbionts belong to the genus Caedibacter. The bacteria conferred a killer trait to their host paramecia. The production of a proteinaceous inclusion body ("R-body") in the bacterial cell makes them toxic to other paramecia after they become enclosed in food vacuoles. R-bodies of Caedibacter sp were associated with phages, which are known in most other Caedibacter species to code for the R-body proteins. The killer-effect of P. novaurelia on sensitive P. caudatum strains was of the "paralysis" type, which is a characteristic of the symbiont species Caedibacter caryophila. Until now C. caryophila was known to inhabit the macronucleus of Paramecium caudatum only. Sequencing of the 16S rRNA-gene proved that Caedibacter sp from the cytoplasm of P. novaurelia belongs to the species C. caryophila as well. The rDNA-sequence of 1695 bp length differed in a total of only 1 bp from the corresponding gene in C. caryophila from the macronucleus of P. caudatum. The results indicate that the infection of specific host cell compartments may depend on host genes, but not on different traits of the infecting symbiont species. The occurrence of killer and sensitive paramecia strains together in one pond is discussed with respect to the competitive advantage of the killer trait.

Intra- and intercellular communication systems in ciliates.

Intracellular signaling and cell-cell interactions are basic features of living organisms. Ciliated protozoa show complex mechanisms of intracellular signaling, as is demonstrated for the phagosomal pathway. Although unicellular, ciliates also communicate with other cells, for example, with invading or symbiotic micro-organisms, some of which are dwelling in the nuclei. In predator-prey interactions chemical signals (kairomones) released by certain predators induce defensive morphological or behavioral changes in the prey ciliates. In intercellular communication sensu strictu ciliate cells communicate with each other, for example, in sexual propagation. A variety of sexual signals have been found to function in preconjugant interaction. Many phenomena of cellular communication in ciliates appear to be similar to those found in multicellular organisms.

The habit of humanism: a framework for making humanistic care a reflexive clinical skill.

While many have voiced the need for increased humanism in the practice of medicine, few approaches exist for explicitly and systematically permeating the medical culture with humanistic thinking and behavior. This article describes the central importance of developing a "habit" of humanistic communication, decision making, and behavior. The habit comprises three essential tasks: (1) identifying the multiple perspectives in any clinical encounter; (2) reflecting on how these perspectives might converge or conflict; and (3) choosing to act altruistically. Teaching this model can enhance students' and medical professionals' abilities to think and act humanely and is a valuable way to make humanistic care a reflexive clinical skill.

Direct visual resolution of gene copy number in the human photopigment gene array.

PURPOSE: To visualize by direct fluorescent in situ hybridization the entire human visual pigment gene array on single X-chromosome fibers and to compare the results with values obtained by other molecular techniques. METHODS: The size of the opsin gene array on the X-chromosome in eight male subjects was investigated by (i) direct visual in situ hybridization (DIRVISH) on elongated DNA fibers: (ii) quantitation of genomic restriction fragments after Southern blot hybridization; (iii) quantitation of restriction fragment length polymorphism after PCR amplification (PCR/RFLP), and (iv) sizing of NotI fragments by pulsed field gel electrophoresis and Southern blot detection. Each male subject's color vision was assessed by Rayleigh matches on a Nagel Type 1 anomaloscope. RESULTS: The number of genes resolved by the DIRVISH protocol, which ranges from 1 to 6, agrees exactly with the gene array sizes obtained in the same male subjects from pulsed field gel electrophoresis, but differs from the estimates derived from the commonly used indirect Southern blot hybridization and PCR/RFLP quantitation methods. In particular, the PCR/RFLP method overestimates the copy number in all but the smallest arrays. CONCLUSIONS: Visualization of the X-chromosome opsin gene array by DIRVISH provides a new, direct method for obtaining exact copy numbers and helps to resolve the controversy about the range and the average visual pigment gene number in the human population in favor of smaller average array sizes.

Learning primary care in medical school: does specialty or geographic location of the teaching site make a difference?

PURPOSE: The Liaison Committee on Medical Education mandates a core curriculum in primary care but does not specify its content or structure. In this study, we explored the question of whether primary care specialty or geographic location affects student learning and satisfaction. METHODS: From 1994 to 1996, 294 third-year medical students at one medical school in New York state were randomly assigned to multiple teaching sites for a required 5-week primary care clerkship. Independent predictor variables were primary care specialty of the preceptor (family medicine, medicine, pediatrics, or joint medicine and pediatrics) and geographic location of the site (urban, suburban, rural). Outcome measures included four areas of student satisfaction, one of patient volume, and two of student performance. RESULTS: Primary care specialty had no detectable association with the outcome measures, except for a lower rating of patient diversity in pediatric experiences (P <0.001). Geographic location of the site had a significant association with all measures of student satisfaction and patient volume (all P values <0.001). Students at rural sites rated the experience more highly and saw on average 15 more patients per rotation. Ratings of student satisfaction remained high after adjusting for patient volume. Primary care specialty and geographic location did not influence student performance in the clerkship or scores on standardized patient examination. CONCLUSIONS: Rural geographic location of teaching site, but not primary care specialty, was associated with higher student satisfaction. However, higher student satisfaction ratings did not correspond to better student performance. Provided that all sites meet the screening criteria for inclusion in a teaching program, these findings support the continued development of high-quality, heterogeneous, interdisciplinary, primary care experiences.

Extraperitoneal laparoscopic inguinal hernia repairs.

Totally extraperitoneal herniorrhaphy (TEP) is a highly technical procedure with a long learning curve for surgeons. It demands extra skills and may be frustrating, even to the experienced laparoscopic surgeon. The main eriticisms have been the higher costs, the need for general anesthesia, and the prolonged operating room time. When properly performed, TEP provides satisfaction to all involved, namely the patient, the surgeon and the third party payer. The initial concerns of safety, efficacy and efficiency are no longer valid issues as TEP has proved to be safe in numerous randomized trials. We find that there is increasing patient demand for this procedure.

Elevating clinical licensing examinations to professional testing standards.

Clinical licensure examinations for graduates have increasingly come under criticism. Studies question whether licensing examinations can discriminate between prepared and unprepared candidates for independent practice. A study at Columbia showed no correlation between student performance on in-school clinical examinations and NERB examinations. The results question whether the NERB clinical examinations meet concurrent validity standards. A recent steep rise in the regional failure rate on the prosthodontics manikin examination questions the reliability of that examination. The authors urge immediate action to bring clinical licensing examinations into line with recent (1992) national guidelines for dental licensing agencies.

A model to structure student learning in ambulatory care settings.

Providing students with an explicit framework for conducting patients' follow-up visits can ease students' transition into ambulatory care settings and enhance their learning. The authors describe a model that structures and defines students' tasks for a follow-up office visit. The model gives priority to the organization of patient care issues, the efficient use of patient and preceptor time, and the student's identification of a learning agenda for each patient encounter. In a rapidly expanding managed care world where physician and practice productivity are paramount, this model has the potential to enhance standardization of learning across diverse clinical sites and to increase the cost-effectiveness of teaching medical students in ambulatory settings. The authors have introduced this model in a half-day orientation for a primary care clerkship. Initial feedback suggests that the model is useful in preparing students to function more effectively in an ambulatory care setting.

Molecular characterization of the D surface protein gene subfamily in Paramecium tetraurelia.

When Paramecium tetraurelia expresses the D serotype, detectable by serum tests, high molecular mRNA could be isolated, which corresponds to the molecular mass of the D surface protein. Using this D specific mRNA as a probe for screenings in different genomic libraries a subfamily of five very similar genes was found, named alpha-51D, gamma 1-51D, gamma 2-51D, delta-51D, and epsilon-51D. Each of them is about 8-kb long, they show regions of identity to each other, and there is no evidence that any are defective genes or pseudogenes. Up to now serotype D is the only known serotype showing this phenomenon. Another novel feature is that two of the D isogenes are closely linked. The sequence for the entire coding region of the alpha-51D gene has been determined, as well as the upstream and downstream noncoding regions. Its deduced amino acid sequence shows the same characteristic cysteine periodicity displayed by all other immobilization antigen (i-ag) genes from Paramecium. However, in contrast to most other such genes, tandem repeats are missing from the 7599-bp long coding region of the alpha-51D gene. When the sequences of the type 51D genes are compared to each other, the similarity is very high and extends to coding as well as to noncoding regions. Similarity within noncoding regions is usually only observed for allelic i-ag genes. We conclude that the type D genes constitute a family of isogenes that are nonallelic. They contain slightly different consensus sequences with possible functions as regulatory regions.

A cotton rat model of effectors of immunity to respiratory syncytial virus other than serum antibody.

A model for studying effectors of immunity to respiratory syncytial virus (RSV) was developed. Paris of inbred cotton rats (Sigmodon hispidus) were joined surgically using the technique of parabiosis. One week later, one animal of each pair was primed intranasally with a small volume of RSV suspension. Fourteen days after priming, both animals of each pair were bled for determination of serum neutralizing antibody titers, and challenged intranasally with a standard dose of RSV suspension. Single, unprimed cotton rats were challenged concomitantly and served as controls. Four days after challenge, all animals were sacrificed for virus titration of nasal tissues and lungs. Parabiosed cotton rats were surgically separated at varying intervals between priming and challenge (days 7, 9, 12, or 14 after priming) or were kept joined until sacrificed (day 18). Significant transfer of nasal and pulmonary immunity from primed to unprimed parabionts began 9 days after priming, gradually increasing through 18 days. Resistance to RSV challenge in spite of low levels of serum neutralizing antibody suggests that non-antibody immunologic mediators were responsible for the transferred immunity. Evidence is presented for three broad categories of RSV immunologic effectors: systemic, local with a transient systemic phase, and local without a systemic phase. These categories are now amenable to further study using the described model.