Lateral Ge Diffusion During Oxidation of Si/SiGe Fins.

This Letter reports on the unusual diffusion behavior of Ge during oxidation of a multilayer Si/SiGe fin. It is observed that oxidation surprisingly results in the formation of vertically stacked Si nanowires encapsulated in defect free epitaxial strained SixGe1-x. High angle annular dark field scanning transmission electron microscopy (HAADF-STEM) shows that extremely enhanced diffusion of Ge occurs along the vertical Si/SiO2 oxidizing interface and is responsible for the encapsulation process. Further oxidation fully encapsulates the Si layers in defect free single crystal SixGe1-x (x up to 0.53), which results in Si nanowires with up to -2% strain. Atom probe tomography reconstructions demonstrate that the resultant nanowires run the length of the fin. We found that the oxidation temperature plays a significant role in the formation of the Si nanowires. In the process range of 800-900 °C, pure strained and rounded Si nanowires down to 2 nm in diameter can be fabricated. At lower temperatures, the Ge diffusion along the oxidizing Si/SiO2 interface is slow, and rounding of the nanowire does not occur, while at higher temperatures, the diffusivity of Ge into Si is sufficient to result in dilution of the pure Si nanowire with Ge. The use of highly selective etchants to remove the SiGe could provide a new pathway for the creation of highly controlled vertically stacked nanowires for gate all around transistors.

Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population.

BACKGROUND: The aim of this study was to determine the incidence and patterns of failure following potentially curative surgery of colonic cancer. METHODS: Data were obtained from the cancer registry of the Côte-d'Or (France). Data on 2657 patients who had resection for cure of colonic cancer between 1976 and 2000 were analysed. Local and distant failure rates were calculated using the actuarial method and multivariable analysis was performed using a Cox model. RESULTS: The 5-year cumulative rate was 12.8 percent for local recurrence and 25.6 percent for distant metastases. Five-year cumulative local recurrence rates were 4.9 percent for stage I, 11.0 percent for stage II and 23.5 percent for stage III tumours (P<0.001). The corresponding rates for distant metastases were 6.4, 21.4 and 48.0 percent (P<0.001). The 5-year cumulative rates for distant metastases were 31.7 percent for the period 1976-1980 and 21.1 percent for 1996-2000, and the local recurrence rates were 17.6 and 9.0 percent respectively. The decreases in rates of local recurrence and distant metastases were significant in multivariable analysis. Cancer extension and presenting features were related to patterns of failure. Tumour location was significantly associated with risk of local recurrence, whereas age and gross features were associated with risk of distant metastasis. CONCLUSION: Recurrence following resection of colonic cancer remains a substantial problem. Follow-up is of particular importance in the 3 years after surgery.

Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

Incidence and management of malignant digestive endocrine tumours in a well defined French population.

BACKGROUND AND AIMS: Little is known about the epidemiology of malignant digestive endocrine tumours. The aim of this study was to report on their incidence and management in a well defined population. METHODS: Data were obtained from the population based Digestive Cancer Registry of Burgundy (France) over a 24 year period. Incidence rates were calculated by sex, age groups, and period of diagnosis. Treatment and stage at diagnosis were also investigated. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. RESULTS: Between 1976 and 1999, 229 cases were recorded. Age standardised incidence rates were 0.76/100,000 for men and 0.50/100,000 for women. They increased over time in both sexes. The resectability rate was 74.1%. Among recorded cases, 26.6% did not extend beyond the organ, 20% had lymph node metastases, and 53.3% had visceral metastases or were unresectable. There was no improvement in the resection rate or in the stage at diagnosis over the study period. The overall relative survival rate was 66.9% at one year, 50.4% at five years, and 40.6% at 10 years. Stage at diagnosis, age at diagnosis, and subsite were independent significant prognostic factors. CONCLUSIONS: Although their incidence is increasing, malignant digestive endocrine tumours remain a rare cancer, representing 1% of digestive cancers. Stage at diagnosis and prognosis at a population level are worse than those reported in hospital series. In the short term, new therapeutic possibilities represent the best way to improve their prognosis.

The use of inferior vena cava filter as a treatment modality for massive pulmonary embolism. A case series and review of pathophysiology.

The use of inferior vena cava (IVC) filter for massive pulmonary emboli (PE) with cardiopulmonary instability has not been clinically studied. We present a case series of six such patients who received an IVC filter with anticoagulation rather than thrombolysis because of high risk of bleeding. Acute pulmonary embolectomy was considered, but was not possible for a variety of individual clinical situations. These six hospitalized patients prospectively followed during their admission. They were triaged to three medical intensive care units (ICUs) and one surgical ICU in three university teaching hospitals. One patient was transferred from another institution. All six patients had severe hypoxia and tenuous cardiopulmonary status. All required high inspiratory oxygen and hemodynamic support; two required mechanical ventilation and vasopressors. An IVC filter was placed emergently and anticoagulation was started immediately All six patients had resolution of pulmonary thromboemboli (PTE) on anticoagulation while the IVC filter prevented further PE. All six patients were discharged home in their pre-critical illness state. None ofthe patients suffered complications from this therapy and had excellent resolution ofcardiopulmonary collapse. The IVC filter placement prevented further major embolic events while the PTE resolved with anticoagulation. An IVC filter should be considered as an adjunct to anticoagulation therapy for those patients with massive PE and cardiopulmonary instability who are not candidates for thrombolysis, and acute pulmonary embolectomy is not readily available or is of very high risk.

Biased expression of T cell receptor genes characterizes activated T cells in multiple sclerosis cerebrospinal fluid.

To better characterize the inflammatory response that occurs in the nervous system in multiple sclerosis (MS), T-cell receptor (TCR) gene expression was quantified from cerebrospinal fluid (CSF) cells of 21 patients with active disease. Unstimulated CSF cells expressed each of 22 different TCR beta chain variable region (V beta) gene families in proportion to their expression in simultaneously sampled peripheral blood. When CSF cells from individuals with MS were expanded by in vitro culture in T-cell growth factor/interleukin 2 and 4-containing medium (TCGF/IL2/IL4), restricted numbers of V beta genes were expressed. In many subjects, expanded CSF cells expressed predominantly V beta 2. In contrast to CSF, expansion of corresponding peripheral blood mononuclear cells (PBMC) in TCGF/IL2/IL4 resulted in persistent expression of all V beta gene families. Within individuals, different V beta genes were overexpressed by PBMC compared with CSF cells. No effect of the HLA haplotype of the individual on CSF V beta gene expression was observed. Expanded CSF cells retained their capacity to respond to mitogen stimulation, but the proliferative response to myelin basic protein (MBP) was not enhanced. Finally, freshly obtained CSF cells stimulated directly with MBP also expressed a limited number of V beta genes, although these were generally different from patterns observed following stimulation with TCGF/IL2/IL4. Thus, restricted populations of T cells capable of responding to TCGF/IL2/IL4, presumably reflecting in vivo activated cells, are compartmentalized in the nervous system in MS.

The family of LAMP-2 proteins arises by alternative splicing from a single gene: characterization of the avian LAMP-2 gene and identification of mammalian homologs of LAMP-2b and LAMP-2c.

The two lysosome-associated membrane proteins, LAMP-1 and LAMP-2, are major integral membrane proteins of the lysosomes. They also occur in the plasma membrane, where they have been discovered independently as principal lactosaminoglycan-bearing glycoproteins and as tumor antigens. Avian LAMP-2 has recently been shown to be encoded by at least three transcripts resulting in variant transmembrane and cytoplasmic domains (Hatem et al., 1995). We report isolation and characterization of chicken genomic clones indicating that the three transcripts are the result of alternative splicing of a single LAMP-2 gene. Only a single LAMP-2, homologous to chicken LAMP-2a, has been described in mammals. To ascertain whether multiple forms of LAMP-2 also occur in mammals, we cloned cDNAs encoding LAMP-2 variants homologous to avian LAMP-2b and LAMP-2c from mouse brain cDNA libraries. Thus, the family of LAMP-2 proteins is conserved from bird to mammals and the diversity is generated by alternative splicing of a single LAMP-2 gene.

Multiple mRNAs encode the avian lysosomal membrane protein LAMP-2, resulting in alternative transmembrane and cytoplasmic domains.

Lysosomal membranes are enriched in extensively glycosylated transmembrane proteins, LAMP-1 and LAMP-2. LAMP-1 proteins have been characterized from several mammalian species and from chickens, but no non-mammalian homologues of LAMP-2 have been described, and no splice variants of either protein have been reported. Here we report the characterization of three cDNA clones encoding chicken LAMP-2. The nucleotide sequences of the cDNAs diverge at their 3' ends within the open reading frame, resulting in sequences that code for three different transmembrane and cytoplasmic domains. Southern analysis suggests that a single gene encodes the common region of chicken LAMP-2. The position of the divergence and the identity of the common sequence are consistent with alternative splicing of 3' exons. Analysis of the mRNAs present in adult chicken tissues suggests tissue-specific expression of the three chicken LAMP-2 variants, with LAMP-2b expressed primarily in the brain. The cytoplasmic domain of LAMP-type proteins contains the targeting signal for directing these molecules to the lysosome. Using chimeras consisting of the lumenal domain of chicken LEP100 (a LAMP-1) and the transmembrane and cytoplasmic domains of the LAMP-2 variants, we demonstrate in transfected mouse L cells that all three LAMP-2 carboxyl-terminal regions are capable of targeting the chimeric proteins to lysosomes. Levels of expression, subcellular distribution, and glycosylation of the LAMP proteins have all been shown to change with differentiation in mammalian cells and to be correlated with metastatic potential in certain tumor cell lines. Alternative splicing of the LAMP-2 transcript may play a role in these changes.

Unusual organization of the human T-cell receptor beta-chain gene complex is linked to recombination hotspots.

Two rare Sfi I polymorphisms of 360 kb and 280 kb present within the human T-cell antigen receptor beta-chain gene complex were revealed by pulsed-field gel electrophoresis. They represent allelic variants of the polymorphic 330- and 300-kb Sfi I fragments previously described. The 360-kb polymorphism results from duplication of the 30-kb DNA fragment responsible for the 330/300-kb insertion/deletion-related polymorphism. The 280-kb polymorphism results from a 20-kb deletion from the 300-kb SfiI allele. The rare polymorphisms also map on either side of a Sal I site located near a recombination hotspot, suggesting that germline duplications and deletions arose from nonhomologous crossover events.

The major nucleoside triphosphatase in pea (Pisum sativum L.) nuclei and in rat liver nuclei share common epitopes also present in nuclear lamins.

The major nucleoside triphosphatase (NTPase) activities in mammalian and pea (Pisum sativum L.) nuclei are associated with enzymes that are very similar both biochemically and immunochemically. The major NTPase from rat liver nuclei appears to be a 46-kD enzyme that represents the N-terminal portion of lamins A and C, two lamina proteins that apparently arise from the same gene by alternate splicing. Monoclonal antibody (MAb) G2, raised to human lamin C, both immunoprecipitates the major (47 kD) NTPase in pea nuclei and recognizes it in western blot analyses. A polyclonal antibody preparation raised to the 47-kD pea NTPase (pc480) reacts with the same lamin bands that are recognized by MAb G2 in mammalian nuclei. The pc480 antibodies also bind to the same lamin-like bands in pea nuclear envelope-matrix preparations that are recognized by G2 and three other MAbs known to bind to mammalian lamins. In immunofluorescence assays, pc480 and anti-lamin antibodies stain both cytoplasmic and nuclear antigens in plant cells, with slightly enhanced staining along the periphery of the nuclei. These results indicate that the pea and rat liver NTPases are structurally similar and that, in pea nuclei as in rat liver nuclei, the major NTPase is probably derived from a lamin precursor by proteolysis.

The human T-cell receptor beta-chain repertoire: longitudinal fluctuations and assessment in MHC matched populations.

The influence of the environment and of the major histocompatibility complex (MHC) in shaping the human T-cell receptor beta-chain variable region (TCRBV) repertoire has not been systematically studied. Here, expression of TCRBV gene families was estimated by a sensitive polymerase chain reaction (PCR)-based method. Serial studies of peripheral blood, performed at 2-week intervals over a 3-month period, revealed that fluctuation in the expression of many TCRBV genes occurred in healthy individuals and in the absence of clinically evident infections. Fluctuation of TCRBV4, TCRBV5.2, TCRBV9, and TCRBV13.1 genes were present in all subjects. Additional TCRBV genes fluctuated in some but not in other individuals. Comparison of the TCRBV repertoire between these unrelated individuals indicated differences in the mean expression of TCRBV5.1, TCRBV9, TCRBV11, TCRBV15, TCRBV17, and TCRBV20 genes. For any TCRBV gene, intersubject differences were generally of a magnitude of twofold or less. Larger differences characterized the TCRBV repertoire of CD4 compared to CD8 cells. Some differences, for example over-representation of TCRBV2 and TCRBV5.1 on CD4, and TCRBV10, TCRBV14, and TCRBV16 on CD8 cells, were present in most subjects. Individuals homozygous for DR2- or DR3-bearing extended MHC haplotypes displayed similar individual variability of TCRBV expression. These data indicate that the circulating TCRBV repertoire in humans is both dynamic and diverse. Both environment and MHC effects contribute to the diversity of TCRBV expression.

Ca(2+)-regulated serine protease associated with the nuclear scaffold.

The nuclear scaffold (NS) is a proteinaceous network of orthogonally arrayed intermediate filament proteins, termed lamins, which is responsible for nuclear structure. Recent work has demonstrated that a subset of lamins A/C is proteolytically cleaved to produce an ATP-binding protein. This proteolytic cleavage is accomplished by a NS protease activity, which shows a considerable selectivity for lamins A/C and is stringently regulated by Ca2+ in vitro, suggesting that it might also participate in control of NS breakdown in various scenarios. Here, we identify the major NS protease as a novel serine protease with a predominantly chymotryptic-like substrate preference, and we show that even transient perturbations in cytosolic Ca2+ have significant effects on the NS protease activity. This NS protease activity shows extensive similarities to the multicatalytic proteinase complex. In addition to a potential role in control of NS breakdown at mitosis and/or under pathological conditions, this NS protease is also strategically located for other functions, such as inactivation of various oncogenic proteins or maturation-promoting factor.

Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity.

Human immunodeficiency virus type I encodes a regulatory protein, termed Rev, which is associated with the appearance of unspliced and partially spliced viral RNAs in the cytoplasm. Rev is believed to function via interaction with a sequence element in the env region of the viral RNA, termed the Rev-responsive element (RRE). In this study, we use a stably transfected, Rev-producing mouse cell line to show that low, functional levels of Rev are associated with the nuclear scaffold (NS). Immunohistochemical studies localize Rev to the NS. Furthermore, immunoblot analyses demonstrate the presence of Rev in NS preparations isolated from Rev-producing cells and document binding of purified Rev protein to isolated NS or to cloned lamin C in vitro. Results with an in vitro RNA transport assay suggest that Rev is associated with a significant defect in transport of RNAs which lack RRE, whereas transport of RRE-containing transcripts proceeds efficiently. This Rev-induced transport defect appears to be mediated via direct inhibition of NS nucleoside triphosphatase, an enzyme thought to be involved in the nucleocytoplasmic transport process. NS preparations isolated from Rev-producing cells show a significantly lower nucleoside triphosphatase activity than those from control preparations. Addition of Rev protein to isolated NS produces a significant inhibition of NS nucleoside triphosphatase activity, which is specifically reversed by addition of RRE transcripts. These data suggest that a major aspect of Rev function may involve selective modulation of host cell nucleocytoplasmic transport mechanisms via interaction with the NS.

Alterations in nuclear scaffold constituents during carbon tetrachloride-induced liver regeneration.

Liver regeneration was induced in rats by treatment with CCl4, which results in substantial regenerative activity with a sharp mitotic response 2 days after intoxication. Closely paralleling the mitotic index, we observed fourfold increases in nuclear scaffold nucleoside triphosphatase, an activity thought to participate in nucleocytoplasmic RNA transport and in the 46 kD putative enzyme and its selective photolabeling. Because previous work has indicated that the 46 kD protein may be proteolytically derived from lamins A/C by cleavage at a tyrosine residue at aa376, we investigated the response of lamin A/C transcripts during this regeneration. Surprisingly, Northern blot analyses after CCl4 administration showed low levels of lamin A/C transcripts (which appeared to be predominantly poly[A]-), and we found a decrease in immunoprecipitable lamins A/C from in vitro translation of poly(A)- selected RNA. To circumvent potential problems with such analyses, we used reverse transcription/polymerase chain reaction amplification of lamin A/C transcripts from total cytoplasmic RNA. These assays showed a transient, comparatively minor increase in lamin A/C transcripts 1 day after treatment, but levels rapidly declined from 1 to 3 days and were decreased at 3 to 5 days. However, nuclear scaffold protease activity, which shows a considerable selectivity for lamins A/C and may be involved in derivation of the 46 kD protein, increased in parallel to the mitotic response and increases in nucleoside triphosphatase, as assessed using a nonspecific (Azocoll) protease assay. Assays with a specific tyrosine-containing substrate (Z-Y-Sbenzyl) showed an increase that mirrored that observed with the nonspecific substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Demethylation of ribosomal RNA by hepatocyte microsomal preparations.

Previous work has shown that hypomethylation of rRNA is an important control for protein synthesis in rat hepatocytes, and that the net hypomethylation appears to arise from cytoplasmic events. Here we show that demethylation of rRNA is catalyzed by microsomal preparations. The rRNA demethylation is dependent upon NADPH and is almost completely inhibited by carbon monoxide. Demethylation appears to increase following galactosamine intoxication, a hepatotoxin which induces hypomethylation of rRNA and inhibition of protein synthesis.

The Mr 46,000 nuclear scaffold ATP-binding protein: identification of the putative nucleoside triphosphatase by proteolysis and monoclonal antibodies directed against lamins A/C.

Previous work suggested that the major Mr 46,000 ATP-binding protein [a putative nucleoside triphosphatase (NTPase)] found in rat liver nuclear scaffold (NS) may be proteolytically derived from lamins A/C. To definitively establish this identification, we undertook a series of photolabeling, proteolysis, and immunoprecipitation experiments. Mice were immunized with human lamin C expressed in bacteria, and monoclonal antibody-producing hybridomas were obtained. The purified monoclonal antibodies all recognized lamins A and C on immunoblots of NS, as well as Mr 46,000 or 34,000 proteolytic fragments as minor components. The Mr 46,000 photolabeled band was the only major NS component photolabeled with low concentrations of azido-ATP, and it was immunoprecipitated with anti-lamin monoclonal antibodies. To preclude the possibility that the photolabeled Mr 46,000 protein represented a minor component which comigrated with the Mr 46,000 lamin fragment and which specifically associated with lamins A/C during immunoprecipitation, a series of proteolytic digestions were undertaken. Digestion of the photolabeled Mr 46,000 peptide with chymotrypsin and staphylococcal protease V8 produced a limited number of photolabeled fragments, all of which comigrated with major stainable fragments produced from the Mr 46,000 lamin fragment. Cyanogen bromide cleavage of the photolabeled Mr 46,000 polypeptide, followed by polyacrylamide gel electrophoresis or high performance liquid chromatography/amino acid analyses, defined the COOH-terminal cleavage site as the Y residue at amino acid 376 and localized the photolabeled site to the COOH-terminal region (amino acids 372-376). In support of this proposed proteolytic cleavage site, specific assays with tyrosine-containing thiobenzyl ester substrate documented the presence of NS protease activity which cleaves at tyrosine residues; this activity shows a Km of 0.2 mM and a Kcat of approximately 250/s. Parallel experiments with mildly proteolyzed cloned lamin C preparations showed selective photolabeling of an Mr 34,000 fragment, which corresponds to a proteolytic breakdown product of the Mr 46,000 NS polypeptide; this Mr 34,000 photolabeled fragment was also immunoprecipitated with anti-lamin monoclonal antibodies and contained the same photolabeled site as the Mr 46,000 peptide. Cloned lamin C preparations were inactive in NTPase assays but did exhibit substantial ATP binding with an apparent KD = 4 x 10(-5) M ATP. These results indicate that the major Mr 46,000 photoaffinity-labeled protein in NS, which represents the putative NTPase thought to participate in nucleocytoplasmic transport, is derived from lamin A or lamin C by NS proteolytic activity which exposes a cryptic ATP-binding site near the highly conserved end of coil-2.(ABSTRACT TRUNCATED AT 400 WORDS)

Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.

Assessing clinical skills of residents with standardized patients.

Current techniques do not provide a reproducible, reliable, or valid basis for assessing clinical skills. The need for large-scale direct observation and standardized assessment procedures has precluded development of better techniques. A project using standardized patients presenting with common clinical problems evaluated the skills of 336 internal medicine residents at 14 New England residency programs in 1289 standardized patient and resident encounters. Results indicated that reproducible assessment of the clinical skills could be achieved in approximately 1 day of testing time using standardized patients. Resident performance improved with years of training, and senior residents and those from programs with stronger reputations performed better and were more homogeneous in ability. Low correlations between standardized-patient-based measures of clinical skills and other evaluation techniques suggested that standardized patients provided unique information. Reactions of residents and faculty to standardized-patient-based evaluations were favorable.

Comparing ambulatory care practices of primary care and traditional medicine residents.

Although special residency programs preparing internists for primary care have been in existence for a decade, little is known about whether these tracks have achieved their goals. As part of a multicenter evaluation of ambulatory care at four university hospitals, 1,040 patient care encounters were reviewed for 16 primary-care and 41 traditional medicine residents. Using a chart-based audit, the authors examined 16 discrete items of patient care to assess resident management in the following areas: screening for colorectal carcinoma, management of hypertension, benzodiazepine drug prescribing, and management of chronic lung disease. Their hypothesis that primary care residents would score higher than traditional medicine residents in the areas of screening, prevention, and prescribing of drugs was not supported. There was no association between type of training and performance of a task with the following exception: second-year primary care residents screened for colorectal carcinoma in 86% (126) of patients whose charts were audited, while second-year traditional medicine residents did so in 77% (160) (P less than 0.025). This difference was not maintained when the residents were reaudited 1 year later. Both groups of residents scored high in all areas with the following exceptions: documentation of the amount of sedative dispensed and immunization of susceptible patients against pneumococcus and influenza. The ambulatory practices of both groups of residents exceeded expectations, probably because of the wider influence of primary care training.