Biomedical subjects

T Holm

Publications and source records attributed to T Holm.

At least 19 recordsLinked to original sources

PubMed2002

The surgeon as a prognostic factor after the introduction of total mesorectal excision in the treatment of rectal cancer.

BACKGROUND: With conventional blunt surgical resection of rectal cancer, local recurrence rates are high and the individual surgeon putatively influences patient outcome. With total mesorectal excision (TME) local recurrence rates have been reduced and intersurgeon variability may be less important. The 'TME project' was a collaborative project that included surgical workshops in Stockholm between 1994 and 1997. The aim of this study was to assess the impact of the project on the practice of rectal cancer surgery in Stockholm and to analyse whether surgeon case volume and participation in the workshops influenced patient outcome. METHODS: All 652 patients who had an abdominal resection for rectal cancer in Stockholm between 1995 and 1997 were included. Outcome was compared in patients operated on by teams that included high-volume surgeons (more than 12 operations per year) with teams that included low-volume surgeons (12 operations or fewer per year), as well as between teams that including workshop participants and non-participants. RESULTS: Forty-six surgeons operated on the 652 patients. Five high-volume surgeons operated on 48 per cent of the patients. In these, outcome was significantly better than in patients treated by low-volume surgeons (local recurrence rate 4 versus 10 per cent (P = 0.02); rate of rectal cancer death 11 versus 18 per cent (P = 0.007)). Twenty-six surgeons were workshop participants and performed 93 per cent of the operations. Radiotherapy, TME and sphincter-preserving surgery were more common among patients treated by workshop participants. CONCLUSION: The TME project has had an impact on rectal cancer surgical practice in Stockholm. Variability in patient outcome was mainly related to case volume, with better results obtained in patients treated by high-volume surgeons.

Adult↗

PubMed2002

A randomized controlled trial of shared care versus routine care for patients receiving oral anticoagulant therapy.

OBJECTIVES: To evaluate the effect of a shared care programme (SCP), defined as a scheme based on shared responsibility, enhanced information exchange, continues medical education and explicit clinical guidelines, between general practitioners (GPs) and a hospital outpatient clinic (HOC), on oral anticoagulant therapy (OAT). DESIGN: The study was a 2-year prospective, randomized, controlled trial, preceded by a 1-year period of observation. SETTING: The HOC, GPs, and OAT patients in the admission area of Aarhus University Hospital, Aarhus County, Denmark, covering 310 300 inhabitants. SUBJECTS: A total of 207 GPs, including their enlisted patients on OAT, were invited, and 61.4% accepted participation. They were randomized into an intervention group [group-INT: 64 GPs and 453 patients (170 patients on OAT throughout the study period, i.e. full follow-up)], and a control group [group-CON: 63 GPs and 422 patients (173 with full follow-up)]. The remaining 80 GPs served as a nonresponder group (group-NON) of 485 patients (184 with full follow-up). MAIN OUTCOME MEASURE: Therapeutic control of OAT in terms of time spent by the patients within the therapeutic interval (TI) of an international normalized ratio (INR) between 2.0 and 3.5. RESULTS: The groups did not differ significantly with regard to age, sex, OAT indication, anticoagulant drug used, or the therapeutic control at baseline. In a comparison based on intention-to-treat principles, the therapeutic control increased statistical significance amongst patients with full follow-up in group-INT compared with group-CON (median time within TI: group INT = 86.6% vs. 80.5%, P = 0.007). CONCLUSION: An SCP of anticoagulant management is effective in reducing patient time outside the therapeutic INR interval in OAT patients randomly assigned to an SCP, as compared with a control group.

Administration, Oral↗

PubMed2001

Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients.

BACKGROUND: Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo. METHODS: The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography. RESULTS: In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04). CONCLUSION: Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.

Double-Blind Method↗

PubMed2001

The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study.

BACKGROUND: The Stockholm II trial is a population-based prospective randomized trial on preoperative radiotherapy in rectal carcinoma. METHODS: Eligibility criteria were age younger than 80 years and biopsy-proven adenocarcinoma of the rectum judged resectable for cure with an abdominal procedure. Between 1987 and 1993, 557 patients were included. Patients were randomized to preoperative radiotherapy (RT+) followed by surgery within a week (n = 272) or surgery alone (RT-; n = 285). Radiotherapy was given with 25 grays in 1 week to the rectum and pararectal tissues. Curative resection was performed in 481 patients (86%). Median follow-up was 8.8 years. RESULTS: Among patients who underwent curative surgery, the incidence of pelvic recurrence was 12% (RT+) and 25% (RT-), respectively (P < 0.001). The overall survival rate in irradiated patients who underwent curative surgery was improved (46%) versus (39%; P < 0.03). For all included patients, the difference was 39% (RT+) compared with 36% (RT-; P = 0.2). Within 6 months of surgery, 13 of 272 (5%) of the irradiated patients died of intercurrent disease versus 4 of 285 (1%) of the nonirradiated (P = 0.02). Cardiovascular death was the main cause of intercurrent death and occurred in 35 of 272 (13%) of the irradiated patients compared with 20 of 285 (7%) among the nonirradiated (P = 0.07). CONCLUSIONS: Preoperative short-term radiotherapy reduces the risk of pelvic recurrence and can improve survival after curative surgery for rectal carcinoma. An increased risk of intercurrent death may reduce the benefit especially in elderly patients.

Adenocarcinoma↗

PubMed2001

Effect of pravastatin on plasma markers of inflammation and peripheral endothelial function in male heart transplant recipients.

Statins appear to have several biologic effects beyond those of lipid metabolism, and we hypothesized that immunomodulating effects of statins are important for the beneficial effects of these medications after heart transplantation. Our findings suggest that pravastatin treatment reduces plasma markers of inflammation and improves peripheral endothelial function in heart transplant recipients, possibly contributing to the observed clinical benefits of statin treatment in these patients.

Cell Adhesion Molecules↗

PubMed2001

Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects.

PURPOSE: An elevated plasma homocysteine concentration is an independent risk factor for cardiovascular diseases. In this study, we tested the hypothesis that hyperhomocysteinemia induces endothelial dysfunction mediated, at least in part, through nitric oxide-dependent mechanisms and that folic acid supplementation improves endothelial function in hyperhomocysteinemic subjects. SUBJECTS AND METHODS: Endothelial function was evaluated in healthy controls and hyperhomocysteinemic subjects by measuring plasma levels of the nitric oxide-derived end products nitrite and nitrate and by assessing vasodilatory responses in the skin microcirculation and forearm vasculature. In the subjects with hyperhomocysteinemia, these measurements were repeated after 6 weeks and 12 months of folic acid supplementation. RESULTS: Compared with healthy controls, hyperhomocysteinemic subjects had significantly lower median plasma levels of nitric oxide-derived end products (12.1 microM [range 4.4 to 41.8] versus 24.6 microM [13.6 to 53.2]; P <0.001), a significantly lower endothelium-dependent vasodilatory response to acetylcholine (P <0.01), hyperemic response in the microcirculation (P <0.01), and total forearm blood flow during reactive hyperemia (P = 0.01). There was no significant difference in the endothelium-independent response. Folic acid treatment for 12 months increased the plasma level of nitric oxide-derived end products by 121% (95% confidence interval [CI], 72% to 170%), the vasodilatory response to acetylcholine by 124% (95% CI, 36% to 212%), and the ischemia-mediated hyperemic responses in the microcirculation by 60% (95% CI, 25% to 96%) and in the forearm vasculature by 47% (95% CI, 21% to 73%). CONCLUSIONS: Homocysteine appears to induce its atherogenic effect, at least in part, by depressing endothelial function, possibly through nitric oxide-dependent mechanisms. This effect can be reversed by folic acid supplementation.

Adult↗

PubMed2001

Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer.

BACKGROUND: Preoperative radiotherapy improves local control and survival in rectal cancer, but may also increase postoperative morbidity and mortality rates. Establishing selection criteria for preoperative radiotherapy is crucial. The tumour level above the anus may be one such criterion. The effect of preoperative radiotherapy in relation to the distance between the tumour and the anus was therefore assessed. METHODS: In 457 patients operated for cure included in the Stockholm II Trial the local recurrence rate in irradiated and non-irradiated patients was analysed in relation to the tumour location (low, mid or upper rectum). RESULTS: Radiotherapy reduced the local recurrence rate from 30 to 20 per cent in low rectal cancer, from 25 to 11 per cent in mid rectal cancer and from 21 to 5 per cent for tumours in the upper rectum. CONCLUSION: With conventional surgical techniques preoperative radiotherapy plays an important role in rectal cancer irrespective of the location of the tumour. To irradiate only patients with tumours in the lower rectum and to omit this treatment for patients with tumours in the mid and upper rectum cannot be recommended. Whether this statement is valid with standardized total mesorectal excision (TME) surgery is not known. Until this knowledge is available the current indications for preoperative radiotherapy should probably also be used with TME surgery.

Adenocarcinoma↗

PubMed2001

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.

Blood Pressure↗

PubMed2000

Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins.

The Pax6 genes encode evolutionary conserved transcription factors that act high up in the regulatory hierarchy controlling development of central organs such as the eyes and the central nervous system. These proteins contain two DNA-binding domains. The N-terminal paired domain is separated from a paired-type homeodomain by a linker region, and a transactivation domain is located C-terminal to the homeodomain. Vertebrate Pax6 genes express a paired-less isoform of Pax6 (Pax6DeltaPD) from an internal start codon in the coding region between the paired domain and homeodomain. We now provide evidence for an interaction between the full-length isoform and Pax6DeltaPD, which enhances the transactivation activity of Pax6 from paired domain-binding sites. The paired-like homeodomain protein Rax behaved similarly to Pax6DeltaPD. Both Pax6DeltaPD and Rax bound to the homeodomain of Pax6 in vitro in the absence of specific DNA binding. Coimmunoprecipitation experiments following cotransfection confirmed the existence of complexes between Pax6 and Pax6DeltaPD, Pax6 and Rax, and Pax6DeltaPD and Rax in vivo. Interestingly, the C-terminal subdomain of the paired domain and the homeodomain can interact with each other. The paired domain can also interact with itself. Surprisingly, GST pull-down assays revealed that the homeodomains of such diverse proteins as Chx10, Six3, Lhx2, En-1, Prep1, Prox1, and HoxB1 could all bind to Pax6, and several of these enhanced Pax6-mediated transactivation upon coexpression. Since many homeodomain proteins are coexpressed with Pax6 in several tissues during development, our results indicate the existence of novel regulatory interactions that may be important for fine tuning of gene regulation.

Base Sequence↗

PubMed2000

[Improved therapeutic results in rectal cancer. Preoperative radiotherapy and continuing education of the surgeons is efficient].

The aim of the Stockholm Colorectal Cancer Study Group is to improve treatment results in colorectal cancer. Between 1980 and 1993 the group conducted two randomised trials on preoperative radiotherapy in rectal cancer including 1406 patients. In both trials radiotherapy significantly reduced local recurrence and improved cancer specific survival. To further improve treatment results, four workshops have been held to introduce the "TME concept" to surgeons in Stockholm. The workshops included live surgical demonstrations and histopathology sessions. When patients included in the Stockholm trials (1980-1993) were compared to patients included in the "TME project" (1995-1996) the rate of abdominoperineal procedures was reduced from 60 to 27 per cent. Within two years of follow up the local recurrence rate was reduced from 15 to 6 per cent and cancer related deaths from 16 to 9 per cent. It is concluded that surgical teaching initiatives may have a significant impact on cancer outcomes.

Clinical Competence↗

PubMed2000

Effect of a surgical training programme on outcome of rectal cancer in the County of Stockholm. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer Research Project.

BACKGROUND: The Stockholm I and II randomised trials demonstrated the value of preoperative radiotherapy in preventing local recurrence in rectal cancer. This, study investigated the potential for further improvement by introduction of the concept of total mesorectal excision (TME) to surgeons in Stockholm, Sweden. METHODS: Workshops started in 1994 and included 11 television-based demonstrations and two histopathology sessions. The study population consisted of all patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995-96 (TME project; n=447). Outcomes at 2 years were compared with those from the Stockholm I (n=790) and II (n=542) trials as historical controls. FINDINGS: For patients with curative abdominal resections, there were no differences between the Stockholm I (n=686), Stockholm II (n=481), and TME project (n=381) groups in 30-day mortality (30 [4%], six [1%], and 12 [3%]), anastomotic leakage (27 [10%], 18 [9%], and 23 [9%]), or all complications (204 [30%], 169 [35%], and 134 [35%]). This similarity was achieved despite a decrease in the proportion of abdominoperineal procedures from 55-60% to 27%. Local recurrence occurred in significantly fewer of the TME group than of the Stockholm I and II groups (21 [6%] vs 103 [15%] and 66 [14%], p<0.001) as did cancer-related death (35 [9%] vs 104 [15%] and 77 [16%], p<0.002). INTERPRETATION: A surgical teaching initiative had a major effect on cancer outcomes. The proportion of abdominoperineal procedures and the local recurrence rate decreased by more than 50% and there is already evidence of a decline in rectal-cancer mortality.

Adult↗

PubMed2000

Use of competition kinetics with fast reactions of grignard reagents

Competition kinetics are useful for estimation of the reactivities of Grignard reagents if the reaction rates do not differ widely and if exact rates are not needed. If the rate of mixing is slower than the rate of reaction, the ratios between the rates of fast and slow reagents are found to be too small. This is concluded from experiments in which results obtained by competition kinetics are compared with results obtained directly by flow stream procedures. A clearer picture of the reactivity ratios is obtained when the highly reactive reagent is highly diluted with its competitor. A fast reagent may account for almost all the product even when present as only 1 part in 100 parts of the competing agent. In this way allylmagnesium bromide is estimated to react with acetone, benzophenone, benzaldehyde, and diethylacetaldehyde ca. 1.5 x 10(5) times faster than does butylmagnesium bromide. The rates found for the four substrates do not differ significantly, and it seems possible that there is a ceiling over the rate of reaction of this reagent, for example, caused by diffusion control. This may explain that competition kinetics using allylmagnesium bromide have failed to show kinetic isotope effects or effects of polar substituents with isotopically or otherwise substituted benzophenones. A recently reported alpha-deuterium secondary kinetic isotope effect for the reaction of benzaldehyde with allylmagnesium bromide was observed at -78 degrees C, but was absent at room temperature. It is suggested that the reaction of benzophenone and benzaldehyde with allylmagnesium bromide has a radical-concerted mechanism since no radical-type products are produced and since no color from an intermediate ketyl is observed even at -78 degrees C.

Journal Article↗

PubMed2000

Local recurrence of rectal cancer: MR imaging before and after oral superparamagnetic particles vs contrast-enhanced computed tomography.

The aim of this study was to compare three imaging strategies for the diagnosis of local recurrence of rectal cancer: (a) MR imaging; (b) MR imaging after administration of enteral superparamagnetic particles (Ferristene); and (c) contrast-enhanced CT. Seventeen patients with previous surgery for rectal cancer were examined, 12 patients with local tumour recurrence in the pelvis and 5 patients with postoperative changes. Pelvic multi-coil MR imaging before and after oral administration of superparamagnetic contrast medium [Abdoscan (Ferristene USAN), Nycomed-Amersham, Lidingö, Sweden] as well as abdominal and pelvic CT was performed in all patients. The examinations were independently evaluated by three different radiologists. The general effect of the oral MR contrast medium, the delineation of normal and pathological structures as well as confidence in the diagnosis were registered on a visual analog scale (VAS). The diagnosis according to MR before and after oral contrast medium, and CT, was compared, in 16 patients, with the final diagnosis which was verified by biopsy (n = 3), surgery (n = 6), clinical follow-up (n = 4) and by follow-up with MR or CT (n = 3). No significant improvement in MR image quality was found after enteral contrast medium. The post-contrast MR diagnosis was not changed in any of the patients. The diagnosis on MR correlated with the final diagnosis in 12 of 16 patients (sensitivity 91%, accuracy 62%) and the diagnosis on CT in 11 of 16 patients (sensitivity 82 %, accuracy 56 %). The radiologists' "confidence" in the diagnosis and the degree of accordance with the final diagnosis did not score higher on MR after than before oral contrast administration; however, the accordance with the final diagnosis scored better on MR than on CT. No advantages of orally administered superparamagnetic contrast medium were observed in the examined patient group. Magnetic resonance is preferable to CT in diagnosing local tumour recurrence.

Administration, Oral↗

PubMed2000

Rectal tumour staging: MR imaging using pelvic phased-array and endorectal coils vs endoscopic ultrasonography.

The aim of this study was to compare MR imaging and endoscopic ultrasonography (EUS) for the local staging of rectal tumours. Forty-nine patients were examined on a 1.5-T MR unit using either a pelvic phased-array coil (n = 37) alone or combined with an endorectal coil (n = 12). Sagittal and axial sequences with T2-weighted fast spin-echo and axial T1-weighted spin-echo techniques were employed. The EUS technique was performed using a flexible endosonoscope. The results were compared with findings at histopathological sectioning of the specimen. The T-stage on MR correlated with histopathology in 32 of 49 patients and on EUS in 29 of 49 patients. The N-stage on MR correlated with histopathology in 22 of 49 patients and on EUS in 26 of 49 patients. Tumour penetration of the rectal wall was predicted by MR with 86 % sensitivity and 65 % specificity, and by EUS with 89% sensitivity and 33% specificity. Preoperative radiotherapy was administered to 40 of the patients after the examinations which may explain some of the overstaging by MR and EUS. Three patients with surgically and histopathologically confirmed invasion of neighbouring organs in the pelvis were detected preoperatively on MR but none on EUS. Tumour penetration of the rectal wall and local lymph node metastases cannot accurately be predicted with MR or EUS. Magnetic resonance, however, seems to be more useful for preoperative identification of clinically occult advanced disease.

Aged↗

PubMed2000

Peripheral endothelial dysfunction in heart transplant recipients: possible role of proinflammatory cytokines.

Endothelium-dependent vasodilation in the peripheral circulation may be impaired in heart transplant recipients (HTx rec). Conflicting results have been obtained and the mechanisms involved have not been examined. In the present study, we examined whether long-time survivors of heart transplantation (Tx) show signs of endothelial dysfunction in the peripheral microcirculation, and further investigated the possible role of endothelium-related markers and proinflammatory cytokines in this process. The vasodilatory responses to acetylcholine (Ach) (endothelium-dependent) and sodium nitroprusside (SNP) (endothelium-independent) were evaluated by skin laser-Doppler perfusion measurements in 63 clinically stable HTx rec 6 yr (range 1-13 yr) after Tx, and compared with 20 healthy controls. Ten HTx rec were also followed prospectively with three repeated measurements during the first year after Tx. Plasma von Willebrand factor, big-endothelin (b-ET), and proinflammatory cytokines were measured by enzyme immunoassays. Vascular responses to both Ach and SNP were significantly attenuated in the HTx rec compared with controls. In longitudinal testing, there was a significant reduction in endothelium-dependent vasodilation, but not independent vasodilation from 1 to 12 months after Tx. Plasma levels of vWF and b-ET, as well as levels of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta, were all markedly increased in HTx rec. HTx rec responses to Ach were negatively correlated to TNF-alpha levels in plasma (r = -0.39, p < 0.01). Moreover, there was also a significant positive correlation between plasma b-ET and TNF-alpha (r = 0.34, p < 0.01). In the long-term follow-up of HTx rec, endothelial dysfunction is demonstrated by both regulation of blood flow in the skin microcirculation and by raised markers of endothelial activation in plasma. This endothelial dysfunction may be related to enhanced levels of proinflammatory cytokines in these patients.

Acetylcholine↗

PubMed2000

Added value of CEA scintigraphy in the detection of recurrence of rectal carcinoma.

PURPOSE: To explore the diagnostic value of immunoscintigraphy compared to CT and/or MR imaging in the diagnosis of local recurrence (LR) of rectal cancer. MATERIAL AND METHODS: Forty-six patients suspected of having LR of rectal cancer were retrospectively studied. Carcinoembryonic antigen (CEA) scintigraphy findings were compared to CT and/or MR in all patients, and with data from surgery and morphology (31 patients), biopsy (7 cases) and follow-up (8 patients). RESULTS: CEA scintigraphy was not complementary to CT and/or MR in the detection of LR. Two false-positive and 14 false-negative diagnoses of LR occurred with CEA scintigraphy. Distant metastases including metastatic lymph nodes were found by this method in only 7 of 27 patients with proven metastases. CT/MR were able to demonstrate these metastases in 21 of 27 patients. CONCLUSION: Accuracy and sensitivity of CEA scintigraphy in the detection of LR and distant metastases is lower than that of CT and/or MR. However, CEA scintigraphy seems to have a high specificity and could therefore be used in patients with a strong clinical suspicion of LR but negative CT/MR investigations. Available diagnostic methods have limitations in differentiating between benign, post-treatment changes and LR of rectal cancer and in staging of malignant disease.

Adult↗

PubMed2000

Perinatal deaths in the Faroe Islands during 1986-95.

OBJECTIVE: To examine causes of perinatal mortality in the Faroe Islands, where it has been increased compared to other Nordic societies. METHOD: Cases were classified according to a fetal/obstetric, a fetal/neonatal, and a fetal/obstetric/neonatal classification (classifications C1, C2, and C3, respectively). SETTING: The Faroe Islands 1986-1995; as reference materials were used a) the preceding decade in the Faroes and b) a parallel period in Denmark. SUBJECTS: We examined all available information regarding each case from hospital records, midwife records, birth certificates, death certificates and autopsy records. RESULTS: The perinatal mortality was 10.3 per 1,000 total births (83/8,096) compared with 13.7 (102/7,458) in the preceding decade; the fall could be attributed to fewer cases with preeclampsia, antepartum bleedings (C1) and antepartum asphyxia (C2) and the number fell despite an increased occurrence of cases attributed to congenital malformations. Perinatal mortality in Denmark was 8.3 (4,574/550,971), where rates were lower of cases with congenital malformations and fetoplacental dysfunction, but where the rate was higher of cases related to preterm birth (C3). CONCLUSIONS: Although the perinatal mortality rate still is higher in the Faroes than Denmark, the rate had fallen in the Faroes from 1976-85 to 1986-1995. The fall was mainly due to fewer cases attributable to antepartum asphyxia, preeclampsia, antepartum bleedings, and hyaline membrane disease, a pattern compatible with a more efficient perinatal service in the Faroes in the latter period.

Birth Certificates↗

PubMed1999

Possible role of proinflammatory cytokines in heart allograft coronary artery disease.

Transplant coronary artery disease (Tx-CAD) is the main determinant of long-term prognosis after heart transplantation. Immunologic processes may play a central role in the development of Tx-CAD, but the pathogenesis has not been fully clarified. We examined plasma levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins (IL)-1beta and IL-6, and the CC-chemokine macrophage chemoattractant protein-1 (MCP-1) in 62 cardiac allograft recipients undergoing yearly heart catherization with coronary angiography for evaluation of graft disease. In this cross-sectional study, we found significantly increased levels of IL-1beta, IL-6, TNF-alpha, and MCP-1 compared with healthy controls even several years (median 7 years) after transplantation in periods with no intercurrent illness. Although no significant differences were found in plasma levels of IL-1beta and TNF-alpha between patients with (n = 25) and without (n = 37) Tx-CAD, the Tx-CAD group had significantly increased levels of IL-6 and MCP-1 compared with both controls and transplant recipients without Tx-CAD. Increased IL-6 levels compared with controls were found only in patients with Tx-CAD. Finally, while there was no significant relation between Tx-CAD and altered lipid status, the combination of high plasma concentrations of IL-6 or MCP-1 and high low-density lipoprotein cholesterol was strongly associated with increased occurrence of Tx-CAD. These findings indicate that cardiac allograft recipients have a persistent immune activation long term after transplantation. This activation, as particularly reflected in increased MCP-1 and IL-6 levels, may be related to the development of Tx-CAD.

Adult↗