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Biomedical subjects

G Lindmark

Publications and source records attributed to G Lindmark.

At least 37 records · Page 2Linked to original sources

[Quality registry for better treatment of rectal cancer established. Economical support is required to use the benefits of the information].

The treatment of rectal cancer has changed significantly during the last 30 years. With improved surgical technique and the introduction of preoperative radiotherapy sphincter preserving surgery is now predominant and the rate of local recurrence has been reduced substantially. However, new therapy concepts may also introduce an increased risk of complications. A register to monitor quality control in rectal cancer treatment in Sweden was established in 1995. It covers over 95 per cent of the patients with rectal cancer reported to the Swedish National Cancer Registry. Collection of data and validation are done by six regional oncology centres under supervision of surgeons appointed by the hospitals involved. The results are then collated to a nationwide quality register, enabling regions to compare themselves with other regions, and hospitals with other hospitals.

Cost-Benefit Analysis↗

Maternal smoking affects fetal growth more in the male fetus.

This study investigated the association between maternal cigarette smoking and fetal growth, evaluated by longitudinal ultrasound examinations and by neonatal anthropometric measurements. The investigation was carried out in a healthy population of affluent Scandinavian women, parity 1 and 2, who were selected consecutively and prospectively, and with term, normal pregnancies. Three hundred and six non-smoking, 242 light-smoking and 308 heavy-smoking mothers and their newborns were examined. Ultrasound measurements were performed in pregnancy weeks 17, 25, 33 and 37. Biparietal diameter (BPD), mean abdominal diameter (MAD) and femur length were recorded. The negative effect on fetal growth from maternal smoking was found to affect the male fetus proportionally more than the female. Boys born to heavy-smoking mothers had a weight reduction of 8.2% and a lower fat accretion (as measured by subscapular skinfold) of 12%, whereas girls had a weight and fat reduction of 4.8% and 2% respectively. In boys (but not girls) born to smokers, head circumference was significantly smaller, also reflected by significantly smaller mean BPD measurements recorded from pregnancy week 18 onwards. The MAD measurements became successively more negatively affected in the second half of pregnancy in both males and females. A greater intrauterine growth velocity and a different hormonal milieu are suggested as possible explanations of the greater male susceptibility.

Adult↗

Introduction of the Misgav Ladach caesarean section at an African tertiary centre: a randomised controlled trial.

OBJECTIVE: To determine whether the Misgav Ladach caesarean section technique can offer benefits compared with conventional caesarean section technique in the prevailing conditions of a busy African tertiary centre. DESIGN: A randomised controlled trial. SETTING: A tertiary African obstetric unit with 18,000 deliveries annually. PARTICIPANTS: Three hundred and thirty-nine women undergoing caesarean section. METHODS: Eight residents and registrars were instructed in the Misgav Ladach technique for caesarean section during one week, after which the study commenced. The course participants instructed their colleagues; in total, 16 doctors participated. Women requiring caesarean section were randomised to Misgav Ladach or to the conventional lower midline incision procedure, excluding those with a previous scar. RESULTS: During 11 weeks 339 randomised procedures (328 of which were emergency procedures) were carried out. Mean operating time was 25 x 3 minutes for Misgav Ladach and 32 x 6 minutes for the lower midline incision procedure (95% CI -8 x 3; -6 x 3). Mean blood loss was 354 mL and 447 mL (-133; -53), and the number of sutures 3 x 1 and 6 x 1 (-3 x 1; -2 x 9), respectively. No significant difference was found in Apgar scores. Mobilisation was earlier with the Misgav Ladach procedure. No difference was found in overall post-operative infection rates i.e. wound infection or febrile illness, but the combination of wound infection and fever was more common in the Misgav Ladach group. CONCLUSION: The Misgav Ladach caesarean section confers benefits such as reduced blood loss, conservation of time and suture material, and rapid mobilisation, but more studies are needed to explore modifications aimed at reducing post-operative infections in settings with limited resources.

Adolescent↗

The effect of smoking on glucose homeostasis and fetal growth in pregnant women.

OBJECTIVE: To examine the relationship between maternal blood glucose levels, cigarette smoking in pregnancy and fetal growth. DESIGN: A prospective study of healthy parous women from early pregnancy and their infants. SETTING: Three Scandinavian university hospitals covering all deliveries from well defined geographical areas. SUBJECTS: Study groups of non-smoking (150), light smoking (131) and heavily smoking mothers (218), para 1 and 2 and with > 37 weeks of gestational length. MAIN OUTCOME MEASURES: Oral glucose tolerance test performed in pregnancy week 37, glycated hemoglobin measured the 3rd day post partum and neonatal anthropometric parameters including skinfold measurements. RESULTS: Among heavily smoking mothers 12.4% displayed a 2-hour glucose value in the range of gestational diabetes (> 8.5 mmol/l) compared to 9.2% among light smokers and 6.0% among nonsmokers (p < 0.05). Heavily smoking mothers also had significantly (p < 0.05) higher glycated hemoglobin compared to nonsmokers, 5.01 v.s. 4.86. These changes in glucose parameters in smokers were not associated with higher birthweights. CONCLUSIONS: Smoking in pregnancy affects parameters of glucose homeostasis in the direction of gestational diabetes. The retarding effect of smoking on fetal growth abolished any expected growth stimulation from the higher blood glucose levels seen in the smokers.

Adult↗

A community based study of HIV in women in rural Gutu District, Zimbabwe 1992 to 1993.

OBJECTIVE: To estimate the prevalence of HIV-1 infection and its relation to socio-economic and obstetric history factors. DESIGN: A cross sectional study. SETTING: 12 randomly selected villages in rural Gutu District, Zimbabwe. SUBJECTS: All women of fertile age (15 to 44 years) in the selected villages were invited to participate. In total 1,213 women were interviewed and examined. On average 75% and 81% of those eligible in 1992 and 1993 respectively participated (range for villages 57 to 87%). MAIN OUTCOME MEASURES: HIV sero-positivity. RESULTS: HIV prevalence was high, 21.9%. Single women below 20 years had the lowest prevalence (7.6%), while the highest (30.0%) was found in married women aged 20 to 29 years. Using a case-referent approach, women divorced, widowed or separated had twice as high a risk of being HIV positive as single women (Odds Ratio (OR) = 2.03; 95% confidence interval (CI) 1.40 to 2.93). There was a huge difference in the prevalence of HIV between villages, from 8.4 to 32.8%, thus the risk of having HIV in the two villages with the highest prevalence was more than five times higher (OR = 5.21 and 5.31 respectively) than in the village with the lowest. The multivariate logistic regression confirmed the findings of an increased risk for women aged 20 to 39 years as compared with women 15 to 19 years, and for women that were divorced, widowed or separated as compared with single. It also confirmed that the huge difference in the prevalence found between wards was statistically significant. CONCLUSION: Women contract HIV early in marriage. Young men's risk behaviour needs to be addressed and women must be aware of their risks before marriage.

Adolescent↗

Symptoms and findings related to HIV in women in rural Gutu District, Zimbabwe, 1992 to 1993.

OBJECTIVE: To relate self-reported morbidity and clinical findings to HIV-status in rural women in Zimbabwe. DESIGN: A cross sectional study. SETTING: 12 randomly selected villages in rural Gutu District, Zimbabwe. SUBJECTS: In 1992 to 1993 all women of fertile age (15 to 44 years) in the selected villages were interviewed and examined (n = 1,213). Retrospectively, HIV status was assessed anonymously from frozen blood samples. MAIN OUTCOME MEASURES: Self-reported morbidity, body mass index (BMI), arm circumference, palpable lymphnodes, prevalence of syphilis, haemoglobin, HIV status. RESULTS: Overall HIV prevalence was 22%. Mean haemoglobin (Hb) was significantly lower (p < 0.005) and anaemia was significantly more common (p < 0.001) among HIV positive women. Syphilis prevalence was 2.2%, a positive syphilis test increased the risk of being HIV positive three-fold. Persistent cough was significantly more common in HIV positives (OR = 3.0, 95% CI 1.4-6.2). Palpable lymphnodes was the most common clinical finding and generalised lymph adenopathy had a positive predictive value of 67% for HIV. Self-reported morbidity was low and no increased pregnancy loss was reported related to HIV. CONCLUSION: The low morbidity found in 1992 to 1993, in spite of the high prevalence, indicates a fairly short duration of the HIV infection and would also have contributed to the late awareness of the problem.

Adolescent↗

Immunohistochemically detected thymidylate synthase in colorectal cancer: an independent prognostic factor of survival.

Intratumoral thymidylate synthase (TS) expression and M(r) 53,000 phosphoprotein (p53) overexpression were studied immunohistochemically in sections from stored paraffin-embedded primary colorectal cancers in 70 patients who had undergone surgery during the years 1987-1990. These cancers were classified according to Dukes' stage A-D, using monoclonal antibodies TS 106 and DO-7. In patients with Dukes' stage A-C tumors, univariate analyses showed that there was a significant correlation (P = 0.048) between disease-free survival and TS expression and between TS expression and time to death with colorectal cancer (P = 0.038). In patients with Dukes' stage A-D tumors, overall survival was correlated to TS expression (P = 0.015), Dukes' stage (P < 0.001), and level of tumor differentiation (P = 0.044) but not to p53 overexpression. Patients with low intratumoral TS expression survived significantly longer than patients with high expression. Cox multivariate analysis showed that Dukes' stage (P < 0.001) and TS expression (P = 0.043) could independently serve as prognostic factors for time to death with colorectal cancer in patients with Dukes' stage A-D tumors.

Adult↗

Maternal morbidity and mortality associated with multiple gestations.

OBJECTIVE: To test the hypothesis that women with multiple gestations are at increased risk of adverse maternal outcomes. METHODS: We studied the association between multiple gestation and frequency of adverse maternal outcomes in 885,338 pregnancies recorded in the Perinatal Information System database of the Latin American Center for Perinatology and Human Development, Montevideo, Uruguay, between 1985 and 1997. Relative risks (RRs) were adjusted for 14 potential confounding factors through multiple logistic regression models. RESULTS: There were 15,484 multiple gestations. Among parous women, multiple gestation was associated with a twofold increase in risk of death compared with singleton gestations [adjusted RR 2.1; 95% confidence interval (CI) 1.1, 3.9]. Compared with singleton gestations, women with multiple gestations had adjusted RRs of 3.0 (95% CI, 2.9, 3.3) for eclampsia, 2.2 (95% CI, 1. 9, 2.5) for preeclampsia, and 2.0 (95% CI, 1.9, 2.0) for postpartum hemorrhage. Likewise, there was significant association between multiple gestation and increased incidence of preterm labor, anemia, urinary tract infection, puerperal endometritis, and cesarean delivery. The incidences of premature rupture of membranes, third-trimester bleeding, and gestational diabetes mellitus were not statistically different for singleton and multiple gestations. CONCLUSION: Multiple gestation increases the risk of significant maternal morbidity and mortality.

Adult↗

Enzymatic mutation detection in the P53 gene.

BACKGROUND: The enzymatic mutation detection (EMD) assay uses the bacteriophage resolvase T4 endonuclease VII, which cleaves preformed heteroduplex molecules at mismatch sites, forming two shorter fragments that can be resolved by gel electrophoresis. The method can be used to detect single and multiple base changes, as well as insertions and deletions. METHODS: The sensitivity, specificity, and positional accuracy of mutation detection by EMD with the PASSPORT(TM) Mutation Scanning Kit were assessed in a blind fashion for three analytical platforms (radioactive detection and automated laser sequencers ALFexpress and ABI PRISM 377). PCR products of 703 bp covering codons 188-393 of the P53 gene were prepared from colorectal tumor samples and analyzed by EMD; the results were compared to data from cDNA sequencing. A 1362-bp PCR product prepared from IL4r gene was used to test detection of multiple base changes in long PCR products. RESULTS: The sensitivity for detection of mutations using EMD exceeded 90%, and the specificity exceeded 80% on all analysis platforms. The method localized 90% of mutations to within two codons and four codons for automated laser sequencers and detection by radioactivity, respectively. The method detected at least five mismatches in heteroduplexes >1 kb. CONCLUSIONS: The EMD system facilitates efficient detection of genetic variation in fragments exceeding 1 kb irrespective of location and type. The technology is particularly well suited to the detection of mutations in genes frequently mutated at unpredictable locations.

Colorectal Neoplasms↗

Risk assessment at the end of pregnancy is a poor predictor for complications at delivery.

OBJECTIVE: To evaluate the usefulness of prenatal risk assessment for prediction of need for obstetric interventions. DESIGN: Area based retrospective study. SETTING: Västerås Central Hospital, Sweden, with all antenatal care units in the area. SUBJECTS: All women delivered at the only delivery ward in the area, after attending antenatal care at the affiliated ANC-units in 1990 (n = 2008) and 1992 (n = 1874). MAIN OUTCOME MEASURES: Obstetric interventions at delivery. RESULTS: During the two years 81% and 83% of the study population delivered an infant in vertex presentation at term but 15% and 17% without risk factors or complications at the end of pregnancy had complications during delivery. The relative risk for interventions when risk factors were present was 2.2 and with spontaneous onset of labor 1.3/1.4. Low risk primiparae had unforeseen complications in 25% and multiparae in 10%. Relative risk for multiparae with risk factors and spontaneous labor was 2.2/1.8 and for primiparae 1.4/1.6. CONCLUSIONS: Individual prediction of obstetric emergencies has low accuracy, which should be included in the information to women as well as in discussions with health pianners.

Apgar Score↗

Missense mutations in hMLH1 associated with colorectal cancer.

One of the most prevalent hereditary syndromes associated with colorectal cancer is hereditary nonpolyposis colorectal cancer (HNPCC). The inherited gene defects in HNPCC have been shown to reside in DNA mismatch repair genes, mostly hMSH2 or hMLH1. Most HNPCC patients are heterozygous with regard to the relevant mismatch repair gene; they have one normal and one mutated allele, and mismatch repair in normal somatic cells is functional. Cancer predisposition in HNPCC is believed to be associated with the loss of the wild-type allele in somatic cells, resulting in defective DNA mismatch repair. This gives rise to DNA microsatellite instability (MSI), an increased somatic mutation rate, and eventually, to the accumulation of mutations in genes involved in colorectal carcinogenesis. In support of this theory, colorectal tumors in HNPCC patients and in mice deficient for hMSH2 or hMLH1 show MSI. Here, we describe two missense mutations in hMLH1 exon 16 associated with colorectal cancer. Interestingly, the tumors do not show MSI. This raises some potentially important issues. First, even microsatellite-negative colorectal tumors can be associated with germline mutations and these will be missed if an MSI test is used to select patients for mutation screening. Second, the lack of MSI in these cases suggests that the mechanism involved in carcinogenesis could be different from that generally hypothesized.

Adaptor Proteins, Signal Transducing↗

Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor.

Hereditary non-polyposis colorectal cancer (HNPCC) is linked to an inherited defect in the DNA mismatch repair system. DNA from HNPCC tumours shows microsatellite instability (MSI). It has been reported that HNPCC patients have a better prognosis than patients with sporadic colorectal cancer. We examined whether the presence of MSI in a series of unselected colorectal tumours carries prognostic information. In a series of 181 unselected colorectal tumours, 22 tumours (12%) showed MSI. Survival analysis at 5-10 years follow-up showed no statistically significant difference in prognosis between MSI-positive and -negative tumours. Our results suggest that the MSI phenotype as such is not an independent prognostic factor.

Aged↗

The complexity of pregnancy anemia in Dar-es-Salaam.

OBJECTIVES: To investigate the main causes of anemia in pregnancy in Dar-es-Salaam and identify appropriate investigations at all levels of care. MATERIALS: All pregnant women booking for antenatal care at 2 clinics (n = 2,235) were screened for anemia. Investigations for etiology of anemia were done in all anemic women (Hb <10.5 g/dl) (n = 361). METHODS: Blood cell counts, microscopy of blood films, S-ferritin, C-reactive protein, HIV, stool parasite and bone marrow analysis were performed. RESULTS: Iron deficiency dominated in 86% and malaria in 1/3 of anemia cases. Since 42% had indication of ongoing inflammation, S-ferritin was less useful as indicator of iron deficiency but blood film microscopy identified most cases.

Acquired Immunodeficiency Syndrome↗

Prognostic value of p53 genetic changes in colorectal cancer.

PURPOSE: To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND METHODS: The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments. RESULTS: Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival. CONCLUSION: Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression.

Aged↗

Effectiveness of primary level antenatal care in decreasing anemia at term in Tanzania.

BACKGROUND: In Tanzania the prevalence of anemia in pregnancy is high inspite of a high antenatal attendance and an established national policy of routine hematinic supplementation and malaria chemosuppression to all pregnant women, free of cost in all antenatal clinics. OBJECTIVES: To assess the effectiveness of reinforcing existing antenatal clinic routines for prevention and treatment of anemia in pregnancy, combined with individual and community health education. METHODS: A prospective controlled intervention study in two antenatal clinics at primary level. At booking (median 24 weeks), 1045 women were screened for anemia and followed-up to late pregnancy (gestational age > or =34 weeks). In addition to hematinic and malaria prophylaxis, extra interventions at the study clinic included retraining of staff, group and individual counselling of women and community health education in the area. RESULTS: There was a significant overall increase in median Hb from 10.1 g/dl at booking to 10.6 g/dl in late pregnancy, and prevalence of anemia (Hb < or =10.5 g/dl) was reduced from 60% at booking to 47%, at both clinics, with 57% reduction in the proportion with severe anemia (Hb <7.0 g/dl). Severely anemic women increased their median Hb by 3.2 g/dl during antenatal care. No additional effect was observed from an individual and community information program. CONCLUSION: Ensuring an adequate supply of drugs seems to be the most important activity to achieve safe hemoglobin levels in pregnant women, but even an active antenatal program has a limited effect when anemia is highly prevalent and booking is late.

Adult↗

Colorectal cancer with and without microsatellite instability involves different genes.

There is evidence supporting a multistep genetic model for colorectal tumorigenesis. In familial adenomatosis polyposis (FAP), the inherited defect is a mutation in the APC gene. The vast majority of all sporadic colorectal cancers also show mutations in the APC gene, and the tumorigenesis in sporadic colorectal cancer and FAP is assumed to involve the same genes. Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germline mutations in DNA mismatch repair genes and, as a result of defective mismatch repair, microsatellite instability (MSI) is frequently seen. Tumorigenesis in HNPCC was first thought to involve mutations in the same genes as in FAP and sporadic colorectal cancer. Recently, however, an alternative pathway to development of colorectal cancer has been suggested in colorectal tumors with MSI, compared to those tumors without the MSI phenotype. We used a consecutive series of 191 sporadic colorectal cancers to find out if there were any differences between the two groups of tumors regarding the prevalence of mutations in the APC, KRAS, TP53, and TGFbetaR2 genes. As expected, 86% (19/22) of MSI-positive tumors showed a mutation in TGFbetaR2, while only one of 164 (0.6%) MSI-negative tumors did. A highly statistically significant negative association was found between MSI and alterations in APC and TP53. The MSI-positive tumors were screened for mutations in exon 3 of beta-catenin, which has been suggested to substitute for the APC mutation in the genesis of colorectal cancer, without finding mutations in any of the 22 MSI-positive tumors. The number of mutations found in KRAS was lower in MSI-positive than in MSI-negative tumors but the difference was not statistically significant. Our results strongly support the idea that carcinogenesis in MSI-positive and MSI-negative colorectal cancer develops through different pathways.

Adenomatous Polyposis Coli↗

The usefulness of initial risk assessment as a predictor of pregnancy complications and premature delivery.

BACKGROUND: Risk assessment is an essential component of all programs for surveillance of pregnancy. The objective of the study is to assess the usefulness of initial risk status as predictor for pregnancy complications and premature delivery. METHODS: A retrospective, area-based study including all women giving birth at Västerås Central Hospital, Sweden in 1990 (2,008) and 1992 (1,874). Data was collected before and after the introduction of a reduced routine surveillance program. The study populations were classified in a low-risk group and three risk groups according to presence of risk factors at booking (initial risk factors), development of pregnancy complications (later risk factors) or a combination of both. Relative risk for premature delivery and predictive value of initial risk factors for pregnancy complications were analyzed. RESULTS: The relative risk for premature delivery was significantly increased in all three risk categories both years except for the group with only initial risk factors in 1990. Risk factors were present at booking in 27% (1990) and 26% (1992). Pregnancy complications developed in 35% and 28%, respectively. The positive predictive value of initial risk factors for pregnancy complications was 40% and 33%, adding little useful information. CONCLUSION: The relative risk for premature delivery was correlated to obstetric risk but was moderately increased with initial risk factors only. The initial risk status is a poor predictor of pregnancy complications and cannot alone be used for individual planning of surveillance during pregnancy. Even for low risk women routine programs must be structured to secure adequate identification of current complications.

Female↗

Mutation analyses of KRAS exon 1 comparing three different techniques: temporal temperature gradient electrophoresis, constant denaturant capillary electrophoresis and allele specific polymerase chain reaction.

Mutations in the KRAS gene is a key event in the carcinogenesis of many human cancers and may serve as a diagnostic marker and a target for therapeutic intervention. In this study we have applied three different techniques for mutation detection of KRAS exon 1 mutations: Allele specific polymerase chain reaction (AS-PCR), temporal temperature gradient electrophoresis (TTGE) and constant denaturant capillary electrophoresis (CDCE). Samples from 191 sporadic colon carcinomas were analyzed. AS-PCR were performed with oligonucleotides specific for know mutations in codon 12 and 13 of the KRAS gene. In TTGE analyses, linear ramping of the temperature were performed during electrophoresis in a constant denaturant gel. CDCE analyses were performed using fluorescin labeled PCR-products. Separation was achieved under constant denaturing conditions using high temperature in a gel-filled capillary followed by laser detection. A mutated KRAS gene was found in 42/191 (22.0%) of the samples using AS-PCR, in 62/191 (32.5%) using TTGE and in 66/191 (34.6%) of the samples using CDCE. In the TTGE and CDCE analyses the sequence of the mutant were determined by comparing the electrophoretic pattern to that of known mutations or by mixing the sample with known mutations prior to reanalysis. In a titration experiment mixing mutant and wild-type alleles prior to PCR, the sensitivity for mutation detection was shown to be 10(-2) for TTGE and under optimized conditions 10(-3) for CDCE.

Alleles↗