Values and ethics: a collection of curricular reforms for a new generation of physicians.

In recent years, medical educators have expressed concern that the reductionist-positivist mode of medical education fails to equip physicians with the skills and attitudes to meet the full range of patients' physical and emotional needs. Indeed, the authors suggest that neither patients nor physicians are satisfied. Among the factors responsible are a pervasive industrialization of clinical practice, a progressive segmentation of patient care, and a deepening shortage of both primary care and specialty physicians. But underlying these system issues is a lack of adequate schooling in the values, ethics, and culture of caring. Today's physicians must simultaneously be analytical, perceptive, and self-reflective. They must have the capacity to see their patients as individuals with differing psychological, social, and historical natures. And they must have insight into their own values and behaviors. All of this contributes to making a competent and humane physician. To aid medical students in achieving these characteristics, the authors contend that medical education must be radically restructured so that knowledge and skills are taught within the context of values and ethics. This commentary explores such reform through the lens of three articles published in the current issue of Academic Medicine, by Litzelman and Cottingham, Kanter and colleagues, and Dobie. These articles are the product of a national call that resulted in more than thirty abstracts, testimony to the fertile thinking already being applied to this problem. It is the authors' hope that this series of papers will stimulate still more thinking and lead to the curricular reform that future generations of physicians deserve.     

Development and Evaluation of a PCR-Based Assay for Detection of Haemobartonella felis in Cats and Differentiation of H. felis from Related Bacteria by Restriction Fragment Length Polymorphism Analysis

The 16S rRNA gene of Haemobartonella felis was amplified by using universal eubacterial primers and was subsequently cloned and sequenced. Based on this sequence data, we designed a set of H. felis-specific primers. These primers selectively amplified a 1,316-bp DNA fragment of the 16S rRNA gene of H. felis from each of four experimentally infected cats at peak parasitemia. No PCR product was amplified from purified DNA of Eperythrozoon suis, Mycoplasma genitalium, and Bartonella bacilliformis. Blood from the experimental cats prior to infection was negative for PCR products and was greatly diminished or absent 1 month after doxycycline treatment. The overall sequence identity of this fragment varied by less than 1.0% among experimentally infected cats. By taking into consideration the secondary structure of the 16S rRNA molecule, we were able to further verify the alignment of nucleotides and quality of our sequence data. In this PCR assay, the minimum detectable number of H. felis organisms was determined to be between 50 and 704. The potential usefulness of restriction enzymes DdeI and MnlI for distinguishing H. felis from closely related bacteria was examined. This is the first report of the utility of PCR-facilitated diagnosis and discrimination of H. felis infection in cats.     

Genomic structure of PIR-B, the inhibitory member of the paired immunoglobulin-like receptor genes in mice

Abstract: The genes encoding the murine paired immunoglobulin-like receptors PIR-A and PIR-B are members of a novel gene family which encode cell-surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and their non-inhibitory/activatory counterparts. PIR-A and PIR-B have highly homologous extracellular domains but distinct trans-membrane and cytoplasmic regions. A charged arginine in the transmembrane region of PIR-A suggests its potential association with other transmembrane proteins to form a signal transducing unit. PIR-B, in contrast, has an uncharged transmembrane region and several ITIMs in its cytoplasmic tail. These characteristics suggest that PIR-A and PIR-B which are coordinately expressed by B cells and myeloid cells, serve counter-regulatory roles in humoral and inflammatory responses. In the present study we have determined the genomic structure of the single copy PIR-B gene. The gene consists of 15 exons and spans approximately 8 kilobases. The first exon contains the 5' untranslated region, the ATG translation start site, and approximately half of the leader peptide sequence. The remainder of the leader peptide sequence is encoded by exon 2. Exons 3–8 encode the six extracellular immunoglobulin-like domains and exons 9 and 10 code for the extracellular membrane proximal and transmembrane regions. The final five exons (exons 11–15) encode for the ITIM-bearing cytoplasmic tail and the 3' untranslated region. The intron/exon boundaries of PIR-B obey the GT-AG rule and are in phase I, with the notable exception of the three boundaries determined for ITIM-containing exons. A microsatellite composed of the trinucleotide repeat AAG in the intron between exons 9 and 10 provides a useful marker for studying population genetics.     

Benefit of nasal CPAP in obstructive sleep apnea is due to positive pharyngeal pressure

The purpose of this study was to determine if the mechanism of nasal continuous positive airway pressure's (CPAP's) effectiveness is to act as a pneumatic splint or to increase functional residual capacity (FRC) and consequently, upper airway caliber. Four subjects with obstructive sleep apnea underwent 3 nights of polysomnography: night 1, control; night 2, nasal CPAP; night 3, external subatmospheric pressure (ESAP). ESAP, a negative pressure body suit, increases FRC. We measured the changes in FRC with nasal CPAP and ESAP using the weighted spirometer technique. The dose used for the ESAP night was the dose that produced the same FRC as the subject's prescribed nasal CPAP dose. The mean number of arousals and the respiratory events index were higher on ESAP and control nights. Less severe oxygen desaturation occurred during non-rapid-eye-movement sleep on the nasal CPAP and ESAP nights. These preliminary results show that increasing FRC alone does not account for the effectiveness of nasal CPAP, and splinting of the collapsible upper airway is necessary.     

Homozygosity for autosomal dominant Marfan syndrome.

Marfan syndrome is an autosomal dominant condition with varying phenotypic manifestations. Affected persons are usually heterozygotes. A family is presented in which the gene for this syndrome is segregating in a large number of members. Two sibs suffered from unusually severe, identical, and fatal manifestations from birth, their parents having mild cardiovascular and somatic symptoms common in Marfan syndrome. Investigation of collagen biosynthesis in fibroblasts revealed no abnormalities in fibronectin and procollagen I and III synthesis and secretion or in the procollagen to collagen conversion. We suggest that these two sibs are examples of homozygosity for the Marfan syndrome gene, based on the large number of affected members, the absence of additional consanguinity, manifestation of the syndrome in both parents, and the severity of the disease in the two sibs.     

Visceral pleural invasion in lung cancer: recognizing histologic parameters that impact staging and prognosis

Visceral pleural involvement (VPI) is a critical component in the staging of non-small cell lung carcinoma (NSCLC). Tumors < or =3 cm that involve the visceral pleura are classified as T2 lesions, underscoring the prognostic significance of this histologic parameter. Accurate staging of small NSCLCs depends on appropriately assessing the presence or absence of VPI. Elastic stains can be instrumental in detecting disruptions of the visceral pleural elastic layer by tumor, a finding that has prognostic and staging implications similar to tumor that is present on the visceral pleural surface.     

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.     

New classification for mental disorders with management guidelines for use in primary care: ICD-10 PHC chapter five.

A primary care version of the International classification of diseases (10th revision) chapter five for mental and behavioural disorders (ICD-10 PHC chapter five) has been developed. This provisional version focuses on 24 conditions which are frequently seen in primary care and which can be managed effectively by general practitioners. The classification is accompanied by a flipcard for each of the conditions. The cards have diagnostic guidelines on one side and management guidelines on the other. The latter provide information which should be given to the patient, advice on the content of counselling, the available treatment methods, and indications for specialist referral. This classification system is also supported by diagnostic decision making aids, medication cards, and patient leaflets to facilitate the recognition and management of patients with mental disorders in primary care settings. The draft version of ICD-10 PHC chapter five will be finalized after field trials which will test the applicability and usefulness of the system in different primary care settings in various countries.     

A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Anger-coping styles and blood pressure in black and white males: Buffalo, New York

Data from a random survey of household residents in the urban area of Buffalo, stratified by race and education, showed relations between anger-coping styles and age-weight adjusted blood pressure (BP) among males (N = 720). Findings show that older black males with a high reflective mode of anger (constrain anger and try to solve the problem) had significantly lower blood pressure than those with low scores on this mode. In contrast, older black males with a high Anger-out mode (impulsive anger strongly expressed) had significantly higher blood pressure than those low on this mode. This Anger-out pattern was also found for older white men; but for younger whites, only higher alcohol and lower education were significantly related to higher BP levels. An Anger-in mode (impulsive anger not expressed) was not significantly related to blood pressure. The limitations of the Anger-in measures are examined. and a concept of a resentful anger style is discussed and presented for further research.