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PubMed1994

Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.

PURPOSE: Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS: One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS: After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P < .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P < .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P < .0001) and International Index (P < .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION: In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.

Actuarial Analysis↗
PubMed2002

Correlation between basal signaling and internalization of thyrotropin-releasing hormone receptors: evidence for involvement of similar receptor conformations.

Previous studies have shown that rat thyrotropin-releasing hormone (TRH) receptor type 2 exhibits higher basal signaling activity and internalizes more rapidly upon agonist binding than rat TRH receptor type 1. The mouse TRH receptor type 2 (mR2) was recently cloned and, similar to its rat homolog, shows a higher basal signaling activity than mR1. Taking advantage of the high degree of sequence homology between mR1 and mR2, we used chimeras/mutants of these receptors to gain insight into the properties of the receptors that influence internalization and basal signaling. Chimeric receptors that have the mR1 extracellular and transmembrane domains with the carboxyl terminus and intracellular loops of mR2 (R1/R2-tail; R1/R2-I3,tail; R1/R2-I2,3,tail; R1/R2-I1,2,3,tail) exhibited internalization rates and basal activities that were similar to that of mR1. In contrast, a chimeric receptor with the extracellular and transmembrane domains of mR2 and the carboxyl terminus of mR1 exhibited the more rapid internalization rate and higher basal signaling activity characteristic of mR2. We showed previously that mutation of a highly conserved tryptophan to alanine caused mR1 to exhibit a high basal signaling activity and rapid internalization rate. In contrast, mutation of this tryptophan to alanine in mR2 decreased the rate of internalization and inhibited basal signaling activity. The rates of receptor internalization did not correlate with the binding affinities, coupling efficiencies, or potencies of the receptors. Thus, we observed that receptors with more rapid internalization rates showed relatively higher basal signaling activities, whereas receptors with lower basal signaling activities showed slower internalization rates. These data suggest that similar receptor conformations are required for productive coupling to signaling G proteins and to proteins involved in internalization.

Animals↗
PubMed1998

Agonist-induced endocytosis and recycling of the gonadotropin-releasing hormone receptor: effect of beta-arrestin on internalization kinetics.

This study examined the dynamics of endocytotic and recycling events associated with the GnRH receptor, a unique G protein-coupled receptor (GPCR) without the intracellular carboxyl-terminal tail, after agonist stimulation, and investigated the role of beta-arrestin in this process. Subcellular location of fluorescently labeled epitope-tagged GnRH receptors stably expressed in HEK 293 cells was monitored by confocal microscopy, and the receptor/ligand internalization process was quantified using radioligand binding and ELISA. Agonist stimulation resulted in reversible receptor redistribution from the plasma membrane into the cytoplasmic compartment, and colocalization of internalized GnRH receptors with transferrin receptors was observed. Internalization experiments for the GnRH receptor and another GPCR possessing a carboxy-terminal tail, the TRH receptor, showed that the rate of internalization for the GnRH receptor was much slower than for the TRH receptor when expressed in both HEK 293 and COS-7 cells. TRH receptor internalization could be substantially increased by coexpression with beta-arrestin in COS-7 cells, while GnRH receptor internalization was not affected by coexpression with beta-arrestin in either cell type. Coexpression of the GnRH receptor with the dominant negative beta-arrestin (319-418) mutant did not affect its ability to internalize, and activated GnRH receptors did not induce time-dependent redistribution of beta-arrestin/green fluorescent protein to the plasma membrane. However, the beta-arrestin mutant impaired the internalization of the TRH receptor, and activated TRH receptors induced the beta-arrestin/green fluorescent protein translocation. This study demonstrates that, despite having no intracellular carboxy-terminal tail, the GnRH receptor undergoes agonist-stimulated internalization displaying distinctive characteristics described for other GPCRs that internalize via a clathrin-dependent mechanism and recycle through an acidified endosomal compartment. However, our data indicate that the GnRH receptor may utilize a beta-arrestin-independent endocytotic pathway.

Animals↗
PubMed1999

Role of the rate of internalization of the agonist-receptor complex on the agonist-induced down-regulation of the lutropin/choriogonadotropin receptor.

The extent of agonist-induced down-regulation of the LH/CG receptor (LHR) in human kidney 293 cells transfected with the rat LHR (rLHR) is much lower than in two Leydig tumor cell lines (MA-10 and R2C) that express the rodent LHR endogenously. This difference can not be attributed to differences in the recycling of internalized receptors, or in the replenishment of new receptors at the cell surface. It can be correlated, however, with the half-life of internalization of the bound agonist, which is approximately 60 min in Leydig tumor cells and about 100 min in transfected 293 cells. To determine whether the rate of internalization of the bound agonist affects down-regulation, we compared these two parameters in 293 cells expressing four rLHR mutants that enhance internalization and three mutants that impair internalization. We show that all four mutations of the rLHR that enhanced internalization enhanced down-regulation, while only one of the three mutations that impaired internalization impaired down-regulation. In addition, cotransfections of 293 cells with the rLHR-wt and three constructs that enhanced internalization (G protein-coupled receptor kinase 2, beta-arrestin, and arrestin-3) increased down-regulation, while a related construct (visual arrestin) that had no effect on internalization also had no effect on down-regulation. We conclude that the rate of internalization of the agonist-LHR complex is the main determinant of the extent of down-regulation of the LHR.

Animals↗
PubMed1993

Decreased levels of internalized thyrotropin-releasing hormone receptors after uncoupling from guanine nucleotide-binding protein and phospholipase-C.

Internalization of TRH receptor (TRH-R) is dependent on sequences/structures in the receptor carboxyl-terminal tail. Here, we studied whether coupling to guanine nucleotide-binding protein (G-protein) and phospholipase-C (PLC) is involved in internalization. We constructed two mutant TRH-Rs: delta 218-263 TRH-R, in which most of the residues that form the putative third intracellular loop were deleted, and D71A TRH-R, in which an Asp in the putative second transmembrane helix was mutated to Ala; these TRH-Rs did not activate PLC when expressed transiently in COS-1 cells. In contrast to wild-type (WT) TRH-Rs, approximately 60% of which were internalized at steady state after binding methyl-HisTRH, only approximately 15% of delta 218-263 and D71A TRH-Rs were internalized. Thus, mutant TRH-Rs that do not activate PLC, most likely because they are uncoupled from G-proteins, are internalized to lesser extents than WT TRH-Rs. We also studied the effects of U73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino] hexyl]-1H-pyrrole-2,5-dione), an amino steroid that inhibits receptor-mediated activation of PLC. In COS-1 and AtT-20 cells transfected with WT TRH-Rs and in GH3 cells, U73122 virtually abolished TRH activation of PLC and partially reduced the fraction of WT TRH-Rs internalized. Thus, uncoupling WT TRH-Rs from PLC decreases internalization. We conclude that TRH-R coupling to G-protein and PLC increases the number of TRH-Rs internalized at steady state even though the primary signals for agonist-induced internalization are present in the receptor. These data support the idea that a quaternary complex of TRH/TRH-R/G protein/PLC is normally internalized.

Animals↗
PubMed2003

Cancer knowledge and skills of interns in Australia and New Zealand in 2001: comparison with 1990, and between course types.

OBJECTIVE: To compare the cancer knowledge and skills of interns in 2001 who graduated from graduate medical program (GMP) courses with those from non-GMP courses, and to compare the cancer knowledge and skills of interns in 2001 with those who completed a similar survey in 1990. DESIGN: Questionnaire survey of recently graduated interns in a random sample of Australian and New Zealand hospitals. The questionnaire was designed to allow direct comparison with the 1990 survey, and was guided by the Australian Cancer Society's Ideal Oncology Curriculum for Medical Schools. RESULTS: 443 interns completed the survey (response rate, 62%; 42 were excluded, leaving 401 surveys for analysis: 118 from GMP courses and 283 from non-GMP courses). Interns from GMP courses felt more competent than those from non-GMP courses at discussing death (P = 0.02), breaking bad news (P = 0.04) and advising on smoking cessation (P = 0.02), but less competent at preparing a patient for a hazardous procedure (P = 0.02). More GMP interns would refer a breast cancer patient to a multidisciplinary clinic (83% versus 70%; P = 0.03). Knowledge about cancer risks and prognosis was significantly less in GMP interns, but GMP interns rated their clinical skills, such as taking a Pap smear, higher than non-GMP interns. The GMP and non-GMP groups did not differ in their exposure to cancer patients, but compared with 1990 interns recent graduates had less exposure to patients with cancer. CONCLUSIONS: GMP curricula appear to have successfully introduced new course material and new methods of teaching, but have not always succeeded in producing doctors with better knowledge about cancer. Recent graduates have less exposure to cancer patients than those who trained 10 years ago.

Adult↗
PubMed2002

Internalized racism, body fat distribution, and abnormal fasting glucose among African-Caribbean women in Dominica, West Indies.

The current study examined the relationship of internalized racism to glucose intolerance in a population of Afro-Caribbean women aged 18 to 55. Also of interest was whether this relationship would be differentially influenced by the type of body fat distribution or confounded by the level of hostility. A total of 244 women were selected from a systematic sample of households on the island of Dominica, West Indies. Demographic data together with information on internalized racism were collected by questionnaire. Anthropometric information and fasting blood glucose were also measured. Women with high levels of internalized racism exhibited an increased risk of elevated fasting glucose compared to those with low levels of internalized racism (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.1-5.5). There was no difference in mean body mass index (BMI) by level of internalized racism. However those with high internalized racism had a significantly larger waist circumference after adjusting for age, education, hostility, and elevated fasting glucose status. In multivariate analyses controlling for age, education, hostility, and either weight or BMI, internalized racism remained independently associated with elevated fasting glucose. However, once waist circumference was included in the model, the relationship of internalized racism to elevated fasting glucose was not statistically significant. This study demonstrates a significant relationship between internalized racism and abnormal levels of fasting glucose which may be mediated through abdominal fat. The exact nature of the relationship of internalized racism to glucose intolerance may be an important area of future study.

Adolescent↗
PubMed2004

Preliminary evidence from Queensland that rural clinical schools have a positive impact on rural intern choices.

INTRODUCTION: The unequal and inequitable distribution of the medical workforce between rural and urban parts of Australia has been well documented. Commonwealth and state governments have introduced several significant initiatives in an attempt to address this imbalance, including recruitment of many overseas trained doctors. One longer-term initiative is the funding of university departments of rural health and rural clinical schools in medical schools. OBJECTIVE: To determine the impact of the rural clinical division of the School of Medicine at the University of Queensland (UQ), Australia, on the intern workforce in central and southern Queensland, Australia. METHODS: Time series analysis of first preferences for intern allocation among UQ graduates and source of interns (UQ, interstate and overseas) from 2001-2005, and comparison of trends between Rockhampton and Toowoomba (UQ student placements since 2003) with Mackay (no placements). RESULTS: First preferences for Rockhampton increased from six in 2001 to 10 in 2005, and for Toowoomba from five in 2002 to 12 in 2005, while for Mackay preferences were stable at two. At Rockhampton while two interns came from overseas in 2001 and three were from interstate in 2002, UQ provided all interns in 2004 or 2005. UQ has provided 12/13 interns in 2004 and 13/14 in 2005 for Toowoomba. Mackay continues to source interns from interstate and overseas with UQ providing only 3/5 interns in 2004 and 2005. At Rockhampton, among non-bonded UQ graduates the number of interns choosing to work there increased from zero in 2001 to six in 2005. For Toowoomba, numbers were seven and 10 respectively, while for Mackay it was zero. CONCLUSIONS: UQ's rural clinical division is having a positive impact on the intern workforce in the regional hospitals most closely allied with it.

Journal Article↗
PubMed1992

[Valve injury: a new complication of internal jugular vein cannulation].

Although internal jugular vein cannulation is performed commonly, most physicians are not aware of existence of the internal jugular venous valve. This is the only valve between the right atrium of the heart and the brain, and it has an important role of preventing retrograde blood flow and increased back pressure to the brain. In this study, anatomic appearance of human internal jugular valves is described, and the competence of these valves is assessed. We examined also a safe approach to percutaneous cannulation of the internal jugular vein to avoid this complication. In the cadaveric subjects, the internal jugular vein with its valve was removed at the time of autopsy. In the living subjects, to examine the movement of this valve, endoscopic visualization utilizing the superfine fiberscope, and ultrasound techniques were applied. Next, to detect the competence of the jugular venous valve, transvalvular pressure gradients were measured. Nineteen internal jugular valves were obtained from 20 cadaveric subjects. These valves were situated directly above the termination of the internal jugular vein into the inferior bulb. The opening and closing of the valve were easily visualized with both superfine fiberscope and real-time ultrasound technique. Patients with competent valves showed transvalvular pressure gradients of 50-100 mmHg during cough-induced high intrathoracic pressure. Internal jugular venous valve is located 0.5-2.0 cm above the union of the subclavian and internal jugular veins, and the central approach performed at the summit of the cervical triangle has been shown to have a risk of injuring the internal jugular venous valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization, Peripheral↗
PubMed1992

Internalization of the human insulin receptor. The insulin-independent pathway.

Internalization of the human insulin receptor requires the activation by insulin of the intrinsic kinase of the receptor. However, even in the absence of kinase activation, insulin receptors slowly enter the cells. In the present study, we addressed the question of this insulin-independent pathway of internalization. To that end, we traced insulin receptor internalization with a monoclonal antibody (mAb 83-14) directed against the alpha-subunit of the human insulin receptor. Internalization of this antibody was followed in Chinese hamster ovary (CHO) cells transfected with either normal (CHO.HIRC2) or kinase-deficient (CHO.A1018) human insulin receptors. The internalization rate of 125I-mAb 83-14 was comparable in CHO cells expressing kinase-active or kinase-inactive receptors and was similar to that observed for 125I-insulin in CHO.A1018 cells. Moreover, in CHO.HIRC2 cells, the internalization of 125I-mAb 83-14 was identical with that of its 125I-Fab fragments. Thus, mAb 83-14 represents an appropriate tool to study the constitutive internalization of the insulin receptor. Internalization of insulin receptors tagged with 125I-mAb 83-14 was unaffected by cytochalasin B, which excluded a macropinocytotic process. By contrast, internalization was sensitive to hypertonia, which abrogates clathrin-coated pits-mediated endocytosis. The implication of clathrin-coated pits in this internalization process was directly demonstrated by quantitative electron microscopic autoradiography, which showed that 125I-mAb 83-14 present on the nonvillous domain of the cell surface preferentially associate with clathrin-coated pits at all time points.

Animals↗
PubMed1992

Hm1 muscarinic cholinergic receptor internalization requires a domain in the third cytoplasmic loop.

Selected regions of the Hm1 muscarinic cholinergic receptor were mutated to analyze the molecular mechanisms of agonist-induced receptor internalization (or sequestration). The wild-type and mutant Hm1 genes were expressed, using pSG5, in U293 human kidney cells. Whereas surface receptor density measured with the polar tracer N-[3H]methylscopolamine was rapidly reduced by carbachol exposure, total receptor content measured with [3H]quinuclidinyl benzilate did not decline for at least 24 h, indicating the absence of extensive receptor down-regulation in U293 cells. Carbachol stimulation of phosphatidylinositol turnover paralleled receptor internalization, both with EC50 values of 10-20 microM. Furthermore, a D71N point mutation that prevented receptor activation also abolished carbachol-induced receptor internalization, indicating that receptor activation (but not necessarily second messenger stimulation) was required for internalization. Truncation of the COOH-terminal tail (K447 trunc) and point mutations of several potential Ser and Thr phosphorylation sites to Ala failed to affect receptor activation and internalization. In contrast, partial deletions of the third intracellular loop (i3) (Tyr208-Thr366) resulted in receptor mutants deficient in agonist-induced receptor internalization/sequestration. Various deletions caused either complete loss of internalization (d 232-358) or impaired internalization, ranging from 10 to 30% over 2 h, whereas wild-type Hm1 internalized to approximately 50%. Whereas the reason for the observed differences among the deficient deletion mutants remains unclear, the initial rate of N-[3H]methylscopolamine binding loss from the cell surface was much slower than that of wild-type Hm1 in each case. The deletion of only one single domain, 284-292 (SMESLTSSE), in the middle of i3 was consistently associated with impaired internalization. Domain 284-292 is partially conserved among closely related muscarinic receptors, whereas most of the remainder of i3 is not (except for the i3 membrane junctions), and similar Ser- and Thr-rich regions are present in many other G protein-coupled receptors. We propose that a small receptor domain in the middle of the i3 loop of Hm1 is involved in agonist-induced receptor internalization.

Amino Acid Sequence↗
PubMed2005

[Dutch authors in international medical journals are also authors of publications in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine)].

OBJECTIVES: To determine whether Dutch medical scientists who frequently publish in international journals with high impact factors also publish in Dutch in the Nederlands Tijdschrit voor Geneeskunde (NTvG). DESIGN: Bibliometric study. METHODS: By means of a search in Medline, the Dutch authors were selected who had published the largest number of articles in 20 medical journals with high impact factors from 5 different specialties: general medicine, surgery, dermatology, psychiatry and ophthalmology. Subsequently, it was determined how often these authors had published in the NTvG in the same period. Moreover, a countwas made of the number of articles the first authors of original articles in the NTvG in 1991 and 2000 had published in international journals in 1993-1997 and 1998-2002, respectively. RESULTS: A large proportion of the Dutch investigators with many publications in international journals also published in the NTvG: in 1988-1992, 46 authors wrote 219 international publications and 35 of these published 151 articles in the NTvG; in 1998-2002, 55 authors wrote 326 international publications and 41 of these published 145 articles in the NTvG. The proportion of original articles published by these authors in the NTvG was lower than in the international journals: 83% for the international journals in 1998-2002 versus 39% for the NTvG in 2000. In 2001, 93 original articles by 87 different first authors appeared in the NTvG. Of these 87 authors, 67 (77%) published at least one article and 18 (21%) published more than 10 articles in an international journal in the period 1998 to 2002, as either the first author or a co-author. CONCLUSION: Authors that publish many articles in frequently cited international journals also write articles for the NTvG and, vice versa, the authors of articles in the NTvG also publish in international journals.

Authorship↗
PubMed2006

[How to anticipate specialization at the Examen National Classant (National Entrance Examination) to encourage interns to choose urology].

OBJECTIVES: To analyse the value of an introduction to urology session to recruit interns following the Examen National Classant (ENC) (National Entrance Examination). MATERIALS AND METHODS: Over a 2-year period, interns appointed to surgery in Paris participated in a one-day introduction to urology session before starting work as surgical interns. A questionnaire at the beginning of internship recorded: age, gender, teaching hospital, student attachment in urology and desired specialization as a function of the surgical training programmes proposed by the ENC. Items concerning the desired specialization were resubmitted to the interns at the end of the session. RESULTS: Population. 166 interns, 98 females (59%) and 68 males (41%) with a mean age of 24.8 +/- 5 years (range: 22-31) participated in this study. 110 interns had trained at a Parisian teaching hospital (66.2%) and 56 (33.8%) had trained at a provincial teaching hospital. 31 interns (18.7%) had completed at least one urology attachment during their medical training. Desired specialization: Orthopaedics was the discipline most frequently cited (n=48; 28.9%). Urology was selected by 19 interns (11.4%), 17 of whom had completed an urology attachment during their medical training. At the end of the introduction to urology session, another 15 interns initially oriented towards other specializations were interested in urology training. CONCLUSION: Specialization of certain surgical disciplines during internship could become inevitable in the medium term. In this case, the organization of national introduction to urology sessions in each ENC allocation region would be a solution to encourage motivated interns to immediately choose urology as their surgical speciality by preference rather than by default.

Adult↗
PubMed1992

Effects of dilation with a balloon catheter on the endothelium of the internal thoracic artery.

Controlled dilation of the internal thoracic artery with a balloon catheter has been reported to effectively treat intraoperative arterial spasm. It has been shown in laboratory animals that dilation of the internal thoracic artery at prescribed shear force levels will not cause intimal damage. Using scanning electron and light microscopy, we have examined the effects of calibrated balloon dilation on the endothelium of the human internal thoracic artery. In 10 patients with bilateral internal thoracic artery grafting, the artery was dilated with a Fogarty IMAG balloon catheter (Baxter Healthcare Corporation, Edwards Division, Santa Ana, Calif.) that was withdrawn at tensions of 20 or 30 gm. Arterial segments and nondilated control specimens were prepared for scanning electron microscopy. The intimal surface of each internal thoracic artery was evaluated by assigning a score (from 0 to 3) to 10 examined scanning electron microscopy fields; subsequently the arterial tissue was viewed by light microscopy with paraffin-embedded sections stained for elastic tissue. Arteries were obtained from three additional patients so that the microscopic appearance of the arteries could be observed after rough manipulation or removal of the balloon without shearing. The results of this study are as follows: (1) By scanning electron microscopy, dilated internal thoracic arteries yielded consistently higher scores than the control arteries, reflecting severe, tension-dependent alterations of the endothelium, which included marked desquamation of endothelial cells, with extensive areas of complete denudation and pronounced attachment of platelets to these areas; (2) endothelial injury occurred by inflation alone, without shearing by the inflated balloon; (3) by light microscopy, the internal thoracic arteries showed (a) fenestrations of the internal elastic lamina with occasional transmigration of smooth muscle cells through these gaps and (b) foci of intimal thickening without overt atherosclerotic lesions. We conclude that the endothelium of human internal thoracic arteries is highly vulnerable to balloon dilation, which can severely injure the intimal surface. For this reason we prefer not to include this procedure in our protocol for preparing the internal thoracic artery.

Aged↗
PubMed1966

The international standard for novobiocin.

The National Institute for Medical Research, London, was requested by the WHO Expert Committee on Biological Standardization to arrange a collaborative assay of the International Reference Preparation of Novobiocin in order to define the International Unit of Novobiocin. The collaborative assay showed that the International Reference Preparation was not suitable for use as an international standard, and a second preparation of 400 g of novobiocin acid was obtained in 1962. This second preparation was distributed into ampoules in 100-mg amounts and dried in vacuum. The ampoules were then filled with dry nitrogen and sealed. This material-the proposed international standard for novobiocin-has been assayed biologically in eight laboratories in six countries by means of plate diffusion assays; it has been assayed against the working standard preparation of the US Food and Drug Administration.The variation in the potencies obtained for the second proposed international standard for novobiocin were small and not significant. The material has been established as the International Standard for Novobiocin with a defined potency of 970 International Units per mg, and the International Unit has been defined as the activity contained in 0.001031 mg of the International Standard.

Bacteria↗
PubMed1994

Middle and proximal sections of the human internal mammary artery are not "passive conduits".

Recent studies have shown that blood flow through the internal mammary artery graft is inadequate for maximal exercise and that hypoperfusion may be worsened by high-dose vasopressor therapy that could further reduce arterial graft flow. Histologic studies have suggested that the human internal mammary artery is an elastic "passive conduit" along the majority of its length. However, although the pharmacologic reactivity at the distal section of the internal mammary artery has been extensively studied, this evaluation has never been done at the middle and proximal sections. It is extremely important to understand the contractility at the midsection of the internal mammary artery because, in a critical situation, any contraction may further reduce the internal mammary artery flow. The present study was designed to investigate the following: (1) Is it true that the pharmacologic reactivity of the human internal mammary artery is different among various sections? and (2) Is the human internal mammary artery a nonreactive "passive conduit" at its most important area used as the graft--the middle and the proximal sections? One hundred six human internal mammary artery ring segments taken from patients who underwent internal mammary artery grafting procedures (29 from the proximal, 38 from the middle, and 39 from the distal sections) were studied in the organ bath under a physiologic pressure. Concentration-response curves were established for norepinephrine, endothelin-1, U46619, potassium, and glyceryl trinitrate (precontracted with 10 nmol/L U46619). Contraction forces were standardized (in grams per millimeter circumference) at a pressure of 100 mm Hg. The contraction force was greater in the distal section than in other sections for norepinephrine (p = 0.002) and endothelin-1 (p = 0.04). No differences were seen for potassium, U46619, or glyceryl trinitrate, whereas the effective concentration inducing 50% of maximal response for U46619 was 100-fold lower in the distal than in the middle section (9.06 +/- 0.34 versus 7.06 +/- 0.48 -log M; p = 0.01) indicating higher sensitivity in the distal section. This study for the first time shows various reactivity along the full length of the human internal mammary artery and shows that the distal section is the most reactive part of the graft. However, although the middle and the proximal sections are less reactive to some vasoconstrictors (norepinephrine and endothelin-1), it is not a "passive conduit" and it contracts with all four vasoconstrictors tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1994

Patterns of paging medical interns during night calls at two teaching hospitals.

OBJECTIVE: To assess the patterns of paging medical interns during night calls. DESIGN: Descriptive study; diaries were used to log calls between 7 pm and 7 am for 1 week in February 1991. SETTING: Two teaching hospitals in Halifax. PARTICIPANTS: All 10 interns assigned to the 15 medical units and nurses from 3 representative medical units. MAIN OUTCOME MEASURES: Number and nature of calls. RESULTS: The overall response rate was 90%. A total of 309 calls were logged by the interns and 107 by the nurses. Each intern had 17 calls on average (range 6 to 33) per 12-hour period. Of the calls 27% occurred after midnight, 25% disrupted sleeping, and 19% interrupted direct patient contact. Overall, the most common reasons for paging interns were related to prescribing of medications (42% of the calls), direct patient assessment (25%) and reporting of laboratory results (18%). According to the nurses, there were no delays in the interns' responding to the pages, and 61% of the calls led to a new physician order. CONCLUSIONS: Paging frequently interrupts interns during work and rest on night calls. Assessment of paging patterns may be useful in identifying specific interventions to reduce the number of calls so that interns will have fewer interruptions during patient encounters and more rest. The collection of data from nurses in a routine nursing audit may be useful for evaluating the communication between interns and nurses and, indirectly, for assessing interns' workload.

Data Collection↗
PubMed1993

Internal thoracic artery: prevalence of atherosclerotic changes.

Use of the internal thoracic artery for myocardial revascularization has regained general acceptance because it offers better long-term results than do venous conduits. The aim of this study was to ascertain the prevalence of atherosclerosis in the internal thoracic artery and to correlate the prevalence with other known risk factors. A total of 117 patients (male/female ratio 84:33; mean age 56.8 years) were investigated. Sixty-eight patients had coronary artery disease, 25 had combined coronary artery and valvular heart disease, 14 had acquired valvular heart disease, and 10 had other types of heart disease. All but one patient underwent bilateral semiselective internal thoracic arteriography. Evidence of atherosclerotic change was present in 6.6% of the opacified vessels in 11.1% of the investigated individuals. Although all patients with atherosclerotic lesions in the internal thoracic artery had coronary artery disease, no correlation could be found between coronary artery disease and internal thoracic atherosclerosis. Peripheral vascular disease and hyperlipidemia could be identified as predictors of atherosclerotic changes in the internal thoracic artery. Atherosclerosis is somewhat more prevalent in the internal thoracic artery in this study than in the literature. Although the internal thoracic artery is a protected vessel, there is a certain extent of atherosclerosis, that correlates with known risk factors. Our observations should not preclude use of the internal thoracic artery, but they should be considered for patients who are at risk for atherosclerotic changes of the internal thoracic artery.

Adult↗