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Biomedical subjects

G Lindmark

Publications and source records attributed to G Lindmark.

At least 19 recordsLinked to original sources

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR.

Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT-PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A-D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

Aged↗

Dilemmas and paradoxes in providing and changing antenatal care: a study of nurses and midwives in rural Zimbabwe.

This paper describes the experiences of caregivers in a rural district in Zimbabwe, in caring for pregnant women within a context of changing antenatal care routines. Data were generated using individual interviews with 18 nurses and midwives. The caregivers experienced their working situation as stressful and frustrating due to high staff turnover, inconsistent policies, parallel programmes and limited resources, including time. They also faced difficulties when implementing some of the proposed changes. Furthermore, the caregivers had to deal with the pressure and resistance from the pregnant women, whose reasoning and rationale for using care appeared different from those of the health professionals. In light of the above, we stress the necessity for reflecting on and including the experiences and perspectives of caregivers and the users of care, as well as their contexts and realities, when implementing change.

Evidence-Based Medicine↗

Effectiveness of referral system for antenatal and intra-partum problems in Gutu district, Zimbabwe.

We conducted a population-based cohort study to determine the prevalence of antenatal and intra-partum referrals, compliance with advice and perinatal outcomes in referred pregnant women in Gutu district, Zimbabwe. The cohort was composed of 10,572 women who received antenatal care in 23 rural health centres (RHC) in Gutu district between January 1995 and June 1998. Pregnancy records of women with antenatal or intra-partum referral were analysed for indication, compliance and perinatal outcomes. Using women who had no antenatal referral or those who complied as referents, the association of referral with perinatal outcome was expressed as relative risk (RR) with 95% confidence intervals (CI). A total of 30% of women (3,094/10,572) had an antenatal referral. Among women attending RHC in labour, 13% (694/5,338) were referred intra-partum. Nulliparous and women younger than 20 years were more likely to be referred. Nurse - midwives' compliance with referral recommendations was low as 59% women with historical risk factors and 52% with raised blood pressure (>140/90 mmHg) were not referred. Women complied with referral advice except when indication was high parity. Women with antenatal referral were more likely to have hospital delivery, 70% vs 18% (p < 0.001). A total of 13% (993/7,478) of women referred themselves for hospital delivery. The risk of perinatal death was elevated among intra-partum referrals (RR 3.4; 95% CI 1.7 - 6.8), self-referrals (RR 2.6; 95% CI 1.5 - 4.5) and also among women with historical risk factors who were not referred (RR 4.8; 95% CI 2.5 - 9.2). We concluded that although there was a functional referral system in Gutu district its efficiency was reduced by failure of health personnel to comply with referral recommendations. Women took appropriate action for most referral indications.

Adolescent↗

Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer.

Biallelic germline mutations in the base excision repair gene MYH have been shown to predispose to a proportion of multiple colorectal adenomas and cancer. To evaluate the contribution of MYH mutations to non- FAP, non-HNPCC familial colorectal cancer, 84 unrelated Swedish individuals affected with colorectal cancer from such families were screened for germline mutations in the coding sequence of the gene. None of the cases was found to carry any pathogenic sequence change. We then determined the prevalence of the two most common pathogenic MYH mutations found in Caucasians, Y165C and G382D, in 450 Swedish sporadic colorectal cancer cases and 480 Swedish healthy controls. The frequency of both variants in Swedish cases and controls was similar to those previously reported. In addition, we found that previously unknown sequence variations at the position of amino acid 423 (R423Q, R423P, and R423R) appear to occur more frequently in cases than in controls (p = 0.02), a finding that warrants future studies.

Amino Acid Substitution↗

Does maternity care improve pregnancy outcomes in women with previous complications? A study from Zimbabwe.

To determine the utilization of maternal health care services and pregnancy outcomes for women with a history of complications in previous pregnancy, we analysed the pregnancy records of multiparous women (parity > or =1) who booked and completed follow-up in Gutu district, Zimbabwe between January 1995 and June 1998. Women with previous uncomplicated pregnancies (n = 6140) were classified as low risk, whereas those with complications of previous pregnancy (n = 1077) were classified high risk. At enrolment, there was no difference in maternal age and parity between low- and high-risk women. A higher proportion of high-risk women had more than five antenatal visits (32% versus 21%; P<0.001) and gave birth in hospital (47% versus 18%; P<0.001). The risk of antenatal (relative risk [RR] 1.57; 95% confidence interval [CI] 1.32-1.88), labour/delivery (RR 1.98; 95% CI 1.75-2.25) and neonatal (RR 1.83; 95% CI 1.44-2.34) complications was elevated in high-risk women. There was increased risk for perinatal death in high-risk women, but this did not reach statistical significance (RR 1.56; 95% CI 0.98-2.49). The recurrence ratio for most complications was low and the sensitivity of historical risk markers in predicting women likely to develop further complicated pregnancies was only 23%. Most women with previous pregnancy complications can safely give birth in the rural health centre. We concluded that high-risk women had an elevated risk of complications in the index pregnancy and that better utilization of maternal health care, especially for delivery, reduced adverse perinatal outcomes.

Adult↗

Classification of perinatal death in a developing country.

OBJECTIVES: To evaluate and compare the three most commonly used perinatal death classification systems: (1) the Nordic-Baltic; (2) the Aberdeen; and (3) the Wigglesworth, and assess their applicability in a developing country (Sudan) with a high perinatal mortality rate, and their justification for practical use in quality assurance and audit activities. METHODS: At Omdurman Maternity Hospital (OMH), Khartoum, Sudan, 166 perinatal deaths were prospectively assessed during a 3-month period (May-August 2000) with a total of 2260 births. Narratives of 166 perinatal deaths were prepared for the purpose of audit. A panel of two Danish and one Sudanese obstetrician categorized the cases according to: (1) the Nordic-Baltic; (2) the Aberdeen; and (3) the Wigglesworth classification. RESULTS: By all three classifications a similar fraction of cases (approx. 85%) were allocated to one category only, and in 15% of cases the assessors were in doubt into which of two categories the cases should be allocated. The necessary information is often not available, giving at least 40% classified as 'unknown' in the Aberdeen classification, whereas the Wigglesworth classification results in an even larger group of unspecified asphyxia. CONCLUSION: Classification of perinatal deaths in developing countries is associated with problems regarding application, validity and usefulness. The Nordic-Baltic classification seems to be most suitable for appropriate stratification using routinely recorded variables and providing categories associated with specific levels of care.

Cause of Death↗

Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors.

BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction. MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification). RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68. CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

Adenocarcinoma↗

Labor induction with vaginal misoprostol and extra-amniotic prostaglandin F2alpha gel.

OBJECTIVE: To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostaglandin F2alpha (PGF2alpha) gel for induction of labor. METHOD: A randomized controlled trial, with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg, was conducted in Harare Maternity Hospital. A total of 152 women were admitted for induction of labor with a term singleton, pregnancy and cephalic presentation were recruited. The main outcome was duration of induction. RESULTS: There were no differences in the characteristics of women in the two groups at recruitment. In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin (OR=0.36; 95% C.I. 0.17-0.73) and delivery by cesarean section for failure to progress (OR=0.11; 95% C.I. 0.00-0.88). The risk for duration of induction to vaginal delivery exceeding 12, 18 or 24 h was reduced by 18%, 38% and 68%, respectively, but only the risk for duration >24 h was significantly reduced (OR=0.32; 95%C.I. 0.11-0.91). The mean duration of induction was shorter in the misoprostol group, 15.2 vs. 23.6 h (P=0.02). There were no differences in fetal outcome. CONCLUSION: Misoprostol 50 microg was associated with less use of oxytocin in labor, a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel.

Administration, Intravaginal↗

Usefulness of risk scoring at booking for antenatal care in predicting adverse pregnancy outcome in a rural African setting.

Antenatal care (ANC) attempts to screen and provide surveillance and treatment to individuals according to the level of need. We assessed the value of antenatal risk allocation made at the first visit in identifying women who will experience pregnancy complications in a rural area in Zimbabwe. As part of an ANC trial women were allocated into low- and high-risk categories based on medical, demographic and obstetric history. All highrisk women were recommended hospital delivery. This evaluation is based on 5223 women who received traditional care from nurse-midwives in 12 rural health centres, of whom 2890 (55%) were classified as high risk by the traditional risk markers, including 1618 nulliparous women. Complications occurred in 924 (17.7%) women 577 (62.4%) of whom had risk markers identified at booking. Twenty per cent (577/2890) of women classified as high risk developed complications. There was a high recurrence of complications, such as hypertensive disorders, operative delivery and preterm delivery. Nulliparity was a risk for low birth weight, operative delivery and hypertensive disorders, whereas grandmultiparity (> or =6) was a risk for hypertension in pregnancy. Young age (< or =16 years) was)a risk factor for low birth weight and perinatal death. Age above 35 years was not an independent risk factor. The traditional risk allocation system, with a likelihood ratio of 1.16, was not effective in identifying women at risk of pregnancy complications and resulted in too large a risk group for referral.

Adolescent↗

No benefit, but increased harm from high dose (100 microg) misoprostol for induction of labour: a randomised trial of high vs. low (50 microg) dose misoprostol.

Misoprostrol, a synthetic analogue of prostaglandin E(1), has been used for cervical preparation. Its ideal dose, route and frequency of administration are still under investigation. We conducted a randomised controlled trial, in a tertiary hospital in a developing country, to compare misoprostol 50 microg (low) and 100 microg (high) for effectiveness and safety in induction of labour at term. Women admitted for induction of labour with a singleton live fetus in cephalic presentation after 37 weeks' gestation were recruited. A misoprostol tablet was inserted in the posterior vaginal fornix at 8-hour intervals. Main outcomes were duration of induction, maternal and fetal complications. The mean duration of induction was 15.4 (SD 10.6) and 14.2 (SD 13.6) h in the low- and high-groups respectively (P = 0.095). There was no difference in need for augmentation with oxytocin (OR 0.82; 95% Cl 0.36-1.86) or operative delivery (OR 1.29; 95% CI 0.26-6.84). There were two uterine ruptures and four intrapartum stillbirths in the high misoprostol group. There was no difference in postpartum haemorrhage, 9.5% vs. 7.9% (P = 1.00) and admissions to the neonatal unit 18.8% vs. 17.0% (P = 0.980) in the 1ow- and high-groups) respectively. Misoprostol 50 microg was as effective as the 100 microg dose for induction of labour whereas the higher dose had an increased risk of serious complications.

Adolescent↗

Iron status and iron deficiency anaemia in adolescents in a Tanzanian suburban area.

OBJECTIVES: To assess the extent and degree of anaemia in adolescents in a Tanzanian suburban area, to estimate the contribution of iron deficiency, using serum (S)-ferritin and soluble transferrin receptor (sTfR) as markers of iron deficiency. MATERIALS: Consecutive primigravidae at booking for antenatal care (n = 76), primary school boys (n = 101) and postmenarchal girls (n = 130) age >or=12 years were investigated. METHODS: Weight and height were measured; venous blood was drawn for haematological analyses, malaria screening, S-ferritin, sTfR, and C-reactive protein. Stool specimens were analysed for intestinal parasites. RESULTS: Anaemia (Hb <105 g/l) was highly prevalent in adolescent primigravidae (75.5%). Adolescent girls were more anaemic (Hb <120 g/l) than boys (14.5 vs. 7.9%). Iron deficiency and hookworm infestation were predominant in both groups of adolescents, however, malaria contributed more to anaemia in the primigravidae. Nearly 40% of the anaemic primigravidae had indication of infection, and S-ferritin was less useful as a marker of iron deficiency in this group. sTfR identified iron deficiency in both pregnant and non-pregnant adolescents.

Adolescent↗

Anaemia in women of reproductive age in Dar-es-Salaam, Tanzania.

BACKGROUND: Anaemia is among the greatest health problems in reproductive age women in developing countries. OBJECTIVES: To estimate the prevalence of anaemia among non-pregnant parous women, and to investigate the main underlying cause for the anaemia. SETTING: A sub-urban Maternal and Child Health Clinic (MCH) in Dar es Salaam. DESIGN: Cross-sectional. METHODS: Consecutive parous non-pregnant women who had brought their children for vaccination and/or had come for family planning to Mbagala MCH clinic were invited to participate in the study. Obstetric and social history was recorded, and their height and weight were checked. Haemoglobin was measured using HemoCue hemoglobinometer. Anaemic women were further investigated to determine the cause of anaemia by haematological and biochemical tests. RESULTS: Five hundred and four parous non-pregnant women were screened, 49% were anaemic (Hb <12 g/dl) and 1.6% severely anaemic (Hb <7 g/dl). Anaemia was not related to socio-demographic and obstetric history characteristics, but decreased significantly with increasing Body Mass Index (BMI) (p=0.042). The prevalence of anaemia was significantly lower in women using hormonal contraceptives, compared to non-users (36% vs 54%) (p=0.04). Eighty-seven percent of the anaemic women were iron deficient and 8.7% had elevated serum C-reactive protein indicating undiagnosed infections. CONCLUSION: Nutritional deficiencies in women have to be corrected before and between pregnancies and all contacts women have with the health system should be utilised for anaemia control interventions, in addition to long-term community approaches. To improve maternal health calls for a broader agenda and a change of approach in the MCH-clinics.

Adolescent↗

COL11A1 in FAP polyps and in sporadic colorectal tumors.

BACKGROUND: We previously reported that the alpha-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of beta-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/beta-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/beta-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer.

Adenomatous Polyposis Coli↗

Symptoms across pregnancy in relation to psychosocial and biomedical factors.

BACKGROUND: There is current interest in symptoms during pregnancy, but yet little is known about their prevalence and how often they are experienced across pregnancy. The reasons why some women experience more symptoms or experience them more often than others has received limited research attention. OBJECTIVE: To document the prevalence and frequency of 27 pregnancy symptoms and to systematically investigate, cross-sectionally and prospectively, the effect of psychosocial factors on the prevalence and frequency of these symptoms, while controlling for biomedical factors. METHODS: Four hundred and seventy-six nulliparous Scandinavian women who attended routine prenatal care in Uppsala county, Sweden, were studied six times during pregnancy (gestational weeks 10, 12, 20, 28, 32, and 36). RESULTS: The prevalence of symptoms was high, but only a smaller portion of these symptoms were experienced frequently. Psychological stress particularly contributed to the prevalence and frequency of concurrent symptoms and predicted symptoms up to 16 weeks later, independent of medical risk, smoking, and weight gain. CONCLUSIONS: Prevalence rates may be inflated, because many symptoms were experienced only 'occasionally' during each of the 4-week periods we sampled. By examining how frequently symptoms were experienced, we gained an indication of which symptoms are more likely to be bothersome or intrude upon daily activities. Psychosocial variables accounted for individual differences in symptom reports after taking biomedical factors into account. Attention to psychosocial variables in future studies will aid in our understanding of the etiology of pregnancy symptoms.

Adaptation, Psychological↗

Perinatal deaths and insufficient antenatal care in Latvia.

OBJECTIVE: A national audit on perinatal deaths was performed to assess the quality of antenatal care, and to suggest measures for improved antenatal care. MATERIAL AND METHODS: Medical records of all the perinatal deaths in Latvia in the years 1995-1996 have been studied. Non-attenders and attenders of antenatal care were characterized by socio-economic and medical variables: maternal age, parity, history of perinatal outcome, health status and behavioral hazards during the index pregnancy, length of gestation and birth weight. The Nordic-Baltic perinatal death classification was used. RESULTS: In 85 of 442 cases (19%) of perinatal deaths women had not taken advantage of antenatal care provided for them. Non-attenders were more likely to be smokers (p<0.001) and alcohol abusers (p<0.005), above 35 years of age (p<0.005), and had higher parity (p<0.001). Non-attenders more often had systemic diseases and pregnancy complications. Neonatal complications, such as congenital syphilis (p<0.05) and other infections (p<0.05), were more common among non-attenders. There was no difference in rates of preterm birth and low birth weight between attenders and non-attenders. CONCLUSIONS: One fifth of mothers with perinatal death did not attend ANC, and in some women who attended ANC, lack of intervention was related to the perinatal death.

Adult↗

Tanzanian midwives' views on becoming a good resource and support person for postpartum women.

OBJECTIVES: to explore midwives' views in relation to the provision of systematic postpartum care. DESIGN: qualitative focus group study using grounded theory approach. SETTING: Dar es Salaam, Tanzania. PARTICIPANTS: 49 nurse/midwives in five focus group discussions, each having 9-11 participants. FINDINGS: eight categories were identified: 'reflecting', 'getting ready', 'defining abilities', 'networking', 'integrating', 'balancing', 'dealing with reality', and 'caring'. The identified core category that integrated and encapsulated all other categories was 'becoming a good resource and support person for postpartum woman'. The mediating factors found to have potential for influencing how a midwife can function in order to become a good resource and support person were: a) the structure and approach in maternal and child health services, b) midwives' knowledge, attitude and skills, c) informal sources of knowledge to parents, and d) cultural beliefs and practices. CONCLUSION: the findings of this study provide an understanding of the way midwives feel and think about the provision of postpartum care. The findings demonstrate that midwives need support in their efforts to achieve what they consider necessary for postpartum care. Interventions for educating and supporting midwives should be targeted at enabling them to deal with all the factors that influence their role and help them to identify and use better strategies to provide quality care.

Anecdotes as Topic↗

A germline E-cadherin mutation in a family with gastric and colon cancer.

Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.

Adult↗

Serum anti-p53 in relation to mutations across the entire translated p53 gene in colorectal carcinomas.

Previous reports have claimed that antibodies to mutated p53 protein indicate poor outcome in malignant disease. The mechanism behind this highly specific process is unclear, although it has been claimed that certain DNA alterations are prone to induction of immune response, since wild-type p53 is almost never immunogenic. The aim of the present analysis was to evaluate whether the presence of anti-p53 was statistically significantly related to any certain DNA alterations in the entirely expressed p53 gene in primary tumors of colorectal cancer. P53 serum antibodies were determined by an enzyme linked immunosorbant assay (ELISA). P53 antibodies were detected in serum of 24 of 88 patients (27%). Twenty-two of 24 (92%) sero-positive patients had mutations in their p53 gene while only 22 of 64 (34%) sero-negative patients had p53 mutations (p<0.01). Mutations were mainly missense with a trend to significantly higher frequency of deletions in sero-negative patients compared to sero-positive subjects (8/25, 32% and 2/22, 9% respectively, p<0.08). Mutations in sero-positive patients were mainly located in exon 5 and 7 and within conserved regions (17 of 22 mutations). In sero-negative patients missense mutations were usually located in exon 5, 7 and 8 being also most frequently located within conserved regions. Most of the p53 deletions in sero-negative patients were however located outside conserved regions (seven of eight deletions). There was no statistical difference between sero-positive and negative patients concerning the spectrum of mutations along the expressed gene. Our study demonstrates that p53 antibodies are usually related to p53 gene mutations but a mutational event is not sufficient to elicit self-immunization. Cellular protein binding to p53 or individual differences of major histocompatibility complex based presentation of p53 protein sequences by immune cells is therefore the most likely explanation between sero-negative and sero-positive patients.

Adult↗