Conny Arnerlöv

Chlamydia pneumoniae in human abdominal aortic aneurysms

OBJECTIVES To investigate the presence of Chlamydia pneumoniae DNA in the wall of infrarenal abdominal aortic aneurysms, and in the wall of non-aneurysmal infrarenal abdominal aortas. DESIGN Case-control study. MATERIALS AND METHODS The study group consisted of 40 patients operated transperitoneally for an infrarenal abdominal aortic aneurysm (IAAA) (eight females, 32 males; mean age 69 years, median age 68 years). Specimens from the aneurysm wall were taken peroperatively under sterile conditions. The control group consisted of 40 deceased persons without aortic aneurysms (14 females, 26 males; mean age 71 years, median age 70 years). Specimens from the non-aneurysmal infrarenal aortas (NIAA) were collected within 48 h after death. The specimens from both groups were frozen at -70 degrees C immediately after collection. A nested polymerase chain reaction (PCR) method, using two sets of primers designed to detect a fragment of the major outer membrane protein gene of C. pneumoniae, was used. RESULTS The detection of C. pneumoniae-specific DNA was significantly higher in the study group (14/40 = 35%) than in the control group (2/40 = 5%); (p = 0.001). No clinical factor predicting the presence of C. pneumoniae in the aneurysm wall, could be found. CONCLUSION Chlamydia pneumoniae was detected at a significantly higher frequency in the wall of IAAAs than in the wall of NIAAs. Although this finding does not prove that C. pneumoniae causes IAAAs, further studies on the possible role of C. pneumoniae in the pathogenesis of aneurysms should be performed.

Telomerase activity in relation to p53 status and clinico‐pathological parameters in breast cancer

Cell cycle deregulation can occur at different levels in cancer. In human breast cancer it includes overexpression of cyclins D1 and E, down‐regulation of cyclin‐dependent kinase inhibitors and inactivation of the retinoblastoma and p53 tumor suppressor proteins. Telomerase activity is strongly associated with an immortal phenotype and expression of telomerase is linked to the cell cycle. We have recently demonstrated a connection between specific cell cycle defects within the pRB pathway and levels of telomerase activity in breast cancer. In the present study, 106 tumors were investigated for p53 gene and protein status. By single strand conformation polymorphism (SSCP) analysis, 15% showed mutations within exons 5–8 and by immunohistochemistry (IHC), 29% were p53 positive. Tumors with a telomerase activity above median (i.e., telomerasehigh) were significantly associated with p53 protein accumulation (p = 0.004), but not with p53 gene mutations. The strongest telomerase expression was found in tumors with p53 protein accumulation. Morphologic grade, estrogen and progesterone receptor expression differed significantly between the telomerasehigh and telomeraselow groups (p < 0.0001, p = 0.016 and p = 0.046, respectively), but no difference was observed for stage or nodal status. Telomerasehigh tumors were significantly associated with a poor prognosis for node‐negative (N0) patients (p = 0.008), but not for node‐positive (N+) patients, whereas the opposite was demonstrated for tumors with p53 accumulation. The survival data indicated that telomerase expression has biological importance particularly for N0 tumors, suggesting that telomeraselow tumors constitute a group of “pre‐immortalized” tumors with a good prognosis. Int. J. Cancer (Pred. Oncol.) 79:343–348, 1998.

Risk of recurrent stroke before carotid endarterectomy: The ANSYSCAP study

Background Carotid endarterectomy yields greater risk reduction for ipsilateral ischemic stroke when performed within two-weeks of the last cerebrovascular symptom than when performed two-weeks or more after the last symptom. However, additional benefit might be gained if carotid endarterectomy is performed earlier than within two-weeks. Aims To investigate the 90-day risk of ipsilateral ischemic stroke recurrence after amaurosis fugax, retinal artery occlusion, transient ischemic attack, or minor ischemic stroke in patients with 50–99% carotid stenosis before carotid endarterectomy, with emphasis on the first 14 days. Methods Prospective cohort study. 230 consecutive patients with symptomatic 50–99% carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial grading method) who underwent evaluation before carotid endarterectomy. Of these, 183 underwent carotid endarterectomy; the median delay to carotid endarterectomy was 29 days. Blood pressure lowering medication was used by 93% and lipid-lowering medication by 90%. Results The risk of ipsilateral ischemic stroke recurrence before carotid endarterectomy was 5·2% (n = 12) within two-days, 7·9% (n = 18) within seven-days, 11·2% (n = 25) within 14 days, and 18·6% (n = 33) within 90 days of the presenting event. The risk of ipsilateral ischemic stroke recurrence was higher if the presenting event was a stroke (adjusted hazard ratio 12·4, P = 0·015) or transient ischemic attack (adjusted hazard ratio 10·2, P = 0·026) compared with an amaurosis fugax. Discussion The risk of recurrent ipsilateral ischemic stroke was high within the first days of the presenting event. Many recurrences would likely have been avoided if carotid endarterectomy had been performed within the first days of the presenting event.

Cyclin E expression and proliferation in breast cancer

Cyclin E is a part of the cell cycle machinery and aberrantly expressed in several malignancies including breast cancer. Since cyclin E is cell cycle specifically expressed, we wanted to examine the relation between proliferation and expression of cyclin E with special attention to tumours with overexpression of the protein. Seventy-four breast tumours were analysed for the expression of cyclin E by immunohistochemistry and Western blotting and related to the growth fraction determined by Ki-67. Significant correlations were obtained between the growth fraction, the percentage of cyclin E positive cells, the intensity of cyclin E and total amount of cyclin E determined by Western blotting. The majority of the tumours had less cyclin E than Ki-67 positive cells indicating a conserved cell cycle specific expression of the protein which further was supported by flow cytometric analysis of breast cancer cell lines. The cell cycle specificity of cyclin E was found even in tumours with inactivated retinoblastoma protein (pRB) demonstrating the existence of a pRB independent regulation of cyclin E. A fraction of the tumours had considerably elevated cyclin E levels that were not in relation to the proliferative activity as observed for the other tumours. These tumours were in general highly proliferative and considered to overexpress cyclin E. Patients with tumours of high proliferative activity, high total cyclin E levels or disproportionally elevated cyclin E expressions in relation to proliferation had significantly increased risk of death in breast cancer, whereas the intensity of the immunohistochemical cyclin E staining did not affect the survival.

Intratumoral variations in DNA ploidy and s‐phase fraction in human breast cancer

To study intratumoral DNA ploidy heterogeneity and S‐phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.

Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.

Objective: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng·kg−1·min−1 would attenuate such possible negative mesenteric effects. Design: Randomized, experimental, controlled study. Setting: University hospital animal laboratory. Subjects: A total of 31 anesthetized, fluid‐resuscitated pigs with oleic acid lung injury. Interventions: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment‐prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. Measurements and Main Results: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. Conclusions: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

Mammographic growth rate, DNA ploidy, and S‐phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population

Background. The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT).

Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion

This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and &bgr;2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 &mgr;g · kg−1 · min−1) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (Po2 TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal Pco2 (air tonometry), together with blood sampling and end-tidal Pco2 measurements, enabled calculations of pHi and Pco2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and Pco2 gap, whereas Po2 TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.

Effects of positive end-expiratory pressure on intestinal circulation during graded mesenteric artery occlusion.

Background: Reduced gut perfusion is associated with multiple organ failure. Positive end‐expiratory pressure (PEEP) reduces cardiac output (CO) and portal blood flow, and might be detrimental in a situation of already compromised intestinal circulation. The aim of this study was to investigate regional circulatory and metabolic effects of PEEP during graded regional hypoperfusion.

Detection of calcifications in panoramic radiographs in patients with carotid stenoses ≥50%.

OBJECTIVE Carotid stenoses ≥50% are associated with increased risk for stroke that can be reduced by prophylactic carotid endarterectomy (CEA). Calcifications in arteries can be detected in panoramic radiographs (PRs). In a cross-sectional study, we analyzed (1) extirpated plaques for calcification, (2) how often PRs disclosed calcified plaques, (3) how often patients with stenoses ≥50% presented calcifications in PRs, and (4) the additional value of frontal radiographs (FRs). STUDY DESIGN Patients (n = 100) with carotid stenosis ≥50% were examined with PRs and FRs before CEA. Extirpated carotid plaques were radiographically examined (n = 101). RESULTS It was found that 100 of 101 (99%) extirpated plaques were calcified, of which 75 of 100 (75%) were detected in PRs; 84 of 100 (84%) patients presented carotid calcifications in the PRs, in 9.5% contralateral to the stenosis ≥50%. CONCLUSIONS Carotid calcifications are seen in PRs in 84% of patients with carotid stenosis ≥50%, independent of gender. FRs do not contribute significantly to this identification.