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Biomedical subjects

I Persson

Publications and source records attributed to I Persson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Genetic polymorphism of cytochrome P450. Functional consequences and possible relationship to disease and alcohol toxicity.

The hepatic cytochrome P450 system participates in the oxidative metabolism of numerous endogenous and exogenous compounds. In total several hundred different P450s have been cloned, but it appears that in humans only about 5-10 isoforms account for the major part of drug metabolism. Some of these are polymorphically distributed in the population. Cytochrome P450 2D6 catalyzes the oxidation of over 25 clinically important drugs, eg neuroleptics, antidepressants and lipophilic beta-blockers. Seven % of Caucasians and 1% of Orientals are defective in this enzyme and clearance of drugs metabolized by the enzyme may be substantially decreased in these individuals, with potentially increased risks for side effects caused by the drug treatment. Some individuals are ultrarapid metabolizers and do not achieve therapeutic drug levels at ordinary doses. The molecular genetic basis of these polymorphisms are presented. Methods for genotyping, which can be of predictive value for a more efficient drug therapy, are discussed. Ethanol-inducible cytochrome P450 2E1 (CYP2E1) oxidizes ethanol and acetaldehyde, in addition to over 80 toxicologically important xenobiotics. Furthermore, this isozyme produces reactive oxy radicals which are implicated in the aetiology of alcoholic liver disease. The gene is polymorphic and a mutation in a putative binding site for HNF1, described to affect gene expression, is more rare among subjects with lung cancer as compared to healthy controls. Further studies might give an answer as to whether any of the polymorphic CYP2E1 alleles is associated with the sensitivity to obtain alcoholic liver disease.

Animals↗
PubMed1994

Risk factors for fractures of the distal forearm: a population-based case-control study.

To evaluate the risk factors for early osteoporosis in consecutive patients with fracture of the distal forearm, a population-based case-control study was carried out using postal questionnaires supplemented by interviews when necessary. All men and women between the ages of 40 and 80 years who were resident in the County of Uppsala (population 265,000) and who sustained a fracture of the distal forearm during a defined 12-month period were initially included. Of 427 cases, 385 (90.2%) replied. Those with previous fragility fractures were excluded, leaving 367 patients in the study (mean age 61.9 +/- 10.6 years): 302 women (mean age 62.8 +/- 10.1 years) and 65 men (mean age 57.5 +/- 11.8 years). For each patient an age- and sex-matched control without previous fragility fractures was selected from the population register. The questionnaire concerned heredity, diseases and medications, general health, tobacco smoking and physical activity. Reproductive variables and postmenopausal hormone replacement therapy were analyzed extensively. In neither sex were any significant, consistent differences found with regard to chronic diseases, medications, physical activity or smoking. In females heredity for fractures (odds ratio, OR = 1.46) was associated with an increased risk. Nulliparous women had an increased risk of forearm fractures (OR = 1.72) while late menopause (OR = 0.95) and postmenopausal oestrogen therapy > 2 years (OR = 0.44) appeared to be protective. It is concluded that lifestyle factors did not discriminate between fracture patients and controls in this strict population-based investigation, suggesting that in affluent Western societies, with their high fracture rate, most individuals have an osteoporosis-prone way of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Reduced risk of breast and endometrial cancer among women with hip fractures (Sweden).

To test the hypothesis that osteoporosis, which results partly from long-term estrogen deficiency, is associated with a lowered risk of breast and endometrial cancer, a population-based cohort study was performed in Sweden. Some 18,000 women were followed through record-linkages after a first hip fracture, on average for almost six years, to ascertain the incidence of breast and endometrial cancer. Expected numbers were derived from the general population. Overall, 253 cases of breast cancer were observed cf 300 expected (standardized incidence ratio [SIR] = 0.84; 95 percent confidence interval [CI] = 0.74-0.95). Forty-eight cases of endometrial cancer were found cf 55 expected (SIR = 0.87, CI = 0.54-1.16). There was no clearcut pattern of breast cancer risk by age at diagnosis of hip fracture, follow-up time, or calendar period. Our results are consistent with the a priori hypothesis that long-term estrogen deficiency is associated with a reduced risk of developing breast cancer as well as endometrial cancer.

Aged↗
PubMed1994

The role of obesity and weight fluctuations in the etiology of renal cell cancer: a population-based case-control study.

The causes of renal cell cancer (RCC) are poorly understood. Besides smoking, obesity remains the only risk factor that is fairly well established. The association between obesity and RCC appears stronger and more consistent in women than in men. We investigated the question of whether this apparent sex difference could be explained by repeated weight changes (weight cycling), less physical exercise, or pharmacological treatment of obesity in women. Structured face-to-face interviews were carried out with 379 (70% of all eligible) incident cases of RCC and 353 (72% of eligible) controls. The relationships between RCC and adult height, weight, and body mass index (BMI), defined as weight/height, were analyzed. Odds ratios (ORs) were estimated through logistic regression. No association was found between adult height and RCC. In men, weight and BMI appeared at most to be weakly related to risk of RCC. In women, higher adult weight and BMI (usual, highest, and lowest) and also high BMI at ages 30, 40, and 50 years were consistently associated with a significantly increased risk of RCC. Women with an usual adult BMI in the top 5% had a nearly 3-fold increased risk of RCC [OR, 2.67; 95% confidence interval (CI), 1.02-7.01]. Compared with individuals with no weight-loss periods, 2 or more such periods implied an OR of 0.96 (95% CI, 0.32-2.90) in men and 3.87 (95% CI, 1.20-12.45) in women. Physical activity at work reduced the risk of RCC in men but not women. Regular use of diet pills containing amphetamine was associated with an increased risk of RCC (OR, 4.06; 95% CI, 1.35-12.22).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden.

BACKGROUND: The protective effect of postmenopausal estrogen replacement therapy on coronary heart disease has been shown in several studies. However, the effect on stroke is more controversial, and data on estrogen-progestin combinations are sparse. METHODS: A total of 23,088 women living in the Uppsala (Sweden) Health Care Region were identified from pharmacy records as having been prescribed noncontraceptive estrogens during 1977 through 1980. They were followed up from 1977 to 1983 for admissions to the hospital because of a first stroke (International Classification of Diseases, Eighth Revision, codes 430 through 438 and 344). The mean observation time was 5.8 years. The expected number was based on person-years in the cohort and incidence rates in the population of the region. RESULTS: Overall, 361 cases of first stroke were observed in the cohort, as compared with 403.2 expected (relative risk [RR], 0.90; 95% confidence limits, 0.81, 0.99). The RR for acute stroke (International Classification of Diseases, Eighth Revision, codes 431 through 436) was 0.85 (0.75, 0.97). In women younger than 60 years at entry who were prescribed estradiol compounds (1 to 2 mg) or conjugated equine estrogens (0.625 to 1.25 mg), the risk of any stroke was reduced by almost 30% (RR, 0.72; 0.58, 0.88) and the risk of acute stroke was reduced by 40% (RR, 0.61; 0.46, 0.79). Women prescribed a combined estradiol-levonorgestrel brand also had a lowered risk of stroke (RR, 0.61; 0.40, 0.88). Weak compounds (mainly estriol) showed no stroke-protective effect, nor was there any relationship between hormone replacement and risk of subarachnoid hemorrhage. CONCLUSION: Hormone replacement therapy with potent estrogens alone or cyclically combined with progestins can, particularly when started shortly after menopause, reduce the risk of stroke.

Cerebrovascular Disorders↗
PubMed1993

Genetic polymorphism of cytochrome P4502E1 in a Swedish population. Relationship to incidence of lung cancer.

Genetic polymorphism of CYP2E1 was investigated among 195 Swedish patients with lung cancer and 206 controls. Three different polymorphic sites were found, all in introns, using RFLP and the restriction enzymes DraI, RsaI and TaqI. The frequencies of the rare alleles were 0.08-0.18 and much lower than previously described among Japanese. No significant difference in distribution of the polymorphic alleles between controls and lung cancer patients was evident, in contrast to results of a previous Japanese study. However, examination of a polymorphic site in the 5'-flanking region, within a putative binding motif for the hepatic transcription factor HNF-1, revealed a significantly less frequent distribution of the mutated allele (c2) among the lung cancer patients as compared to controls. It is concluded that major interethnic differences exist in the genetic polymorphism of CYP2E1 and that people carrying the c2 allele might be at lower risk for developing lung cancer.

Base Sequence↗
PubMed1993

Hormone replacement therapy and breast cancer mortality in Swedish women: results after adjustment for 'healthy drug-user' effect.

No change of breast cancer mortality has been reported previously after long-term hormone replacement therapy. A conceivable explanation for the apparent discrepancy between incidence and mortality may be selection bias due to lower prevalence of breast cancer in women who receive replacement hormones, compared with nonexposed women. We used a new approach to correct for bias due to this 'healthy drug-user effect,' by adjusting the external, population-based, mortality rates for such cases prevalent during the recruitment period of our cohort. In this cohort of some 23,000 Swedish women, who were prescribed various hormone replacement regimens, breast cancer mortality was analyzed after follow-up to 12 years. External analyses revealed overall standardized mortality ratios for breast cancer rising from 0.71 to 0.81, but not significantly different from unity, after adjustment procedures. In multivariate regression models, excluding prevalent cases in the cohort, women prescribed estradiol, conjugated estrogens, or an estrogen-progestin combination were not at a higher risk relative to those given other and weak estrogens, relative risks being 0.81 and 0.68, respectively. On the basis of the present analytical approach, we conclude that breast cancer mortality does not appear to be changed overall or in subgroups, despite increased incidence.

Aged↗
PubMed1993

Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up.

OBJECTIVE: To determine the long-term risk of hip fracture following fracture of the distal forearm. DESIGN: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. FRACTURE COHORT: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period, 1968-1972, in all 1,126 women and 212 men. CONTROL COHORT: An equal number of population-based, age- and sex-matched control persons selected from a population register. MEASUREMENTS: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. RESULTS: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. CONCLUSIONS: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.

Adult↗
PubMed1993

In vitro activity of the new quinolone BAY y 3118 against anaerobic bacteria.

The in vitro activity of BAY y 3118 against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides spp. and fusobacteria was determined by an agar dilution method. This activity was compared with that of ciprofloxacin, ofloxacin, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. BAY y 3118, imipenem, clindamycin and metronidazole were the most active agents tested. The in vitro activity of BAY y 3118 against anaerobic bacteria was superior to that of ciprofloxacin and ofloxacin.

Anti-Bacterial Agents↗
PubMed1993

In vitro activity of DMG-Mino and DMG-DM Dot, two new glycylcyclines, against anaerobic bacteria.

The in vitro activity of DMG-Mino and DMG-DM Dot against 350 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides species and fusobacteria was determined by the agar dilution method. Their activity was compared with that of minocycline, doxycycline, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. DMG-Mino and DMG-DM Dot and imipenem were the most active agents tested. DMG-Mino and DMG-DM Dot had in vitro activity superior to that of minocycline and doxycycline.

Anti-Bacterial Agents↗
PubMed1993

Cholecystectomy and colorectal cancer.

BACKGROUND: An increased risk of large bowel cancer, especially of the right colon, following cholecystectomy has been reported in some studies but contradicted in others. The aim of this study was to settle this question by creating a cohort of cholecystectomy patients that was large enough and with a sufficient follow-up time to detect even weak associations. METHODS: A population-based cohort consisting of 62,615 patients who underwent cholecystectomy was followed up for the occurrence of colorectal cancer up to 23 years. RESULTS: There were 633 colorectal cancers versus 637.9 expected (standardized incidence ratio [SIR] = 0.99; 95% confidence interval [CI] = 0.92-1.07). Analyses of an extensive number of subgroups including sex, age at operation, duration of follow-up, underlying diagnosis, type of operation, and different cancer sites did not show any association. However, for cancer of the right colon among women, the risk was increased (SIR = 1.24; 95% CI = 1.03-1.48) most prominent 15 years or more after operation (SIR = 1.54; 95% CI = 1.03-2.22). CONCLUSIONS: Overall, there is no excess risk of colorectal cancer following cholecystectomy, but consistent with some earlier reports, we observed an increased risk among women for right-sided colon cancer 15 years or more after operation.

Adult↗
PubMed1993

Trends in breast cancer incidence in Sweden 1958-1988 by time period and birth cohort.

Statistics from the Swedish National Cancer Registry based on all 110,658 cases of invasive breast cancer during the 31-year period 1958-1988 were analysed. Age-specific incidence rates increased over successive calendar periods. The average annual increase in the age-standardised incidence rate was 1.3%, with the greatest percentage changes among the youngest age groups. During the latter half of the study period, the rates of increase tended to diminish in the youngest age groups and even reversed significantly among women from 75 years of age. In analyses using age-period-cohort models, the best fit of the cancer incidence data was found for the full model which simultaneously considered the effects of age, period and cohort. Cohort effects were found to be more important than period effects, in terms of model fit. These effects emerged as a seemingly consistent, and in a logarithmic scale, fairly linear increase in the relative risk of breast cancer incidence with a 3-fold elevation in women born in the 1950's relative to those born in the 1880's. It is concluded that the rising breast cancer incidence in Sweden is explained chiefly by birth cohort effects, which indicate persistent secular changes in largely unknown risk factors associated with life style. We could not in the present data see any clear evidence for an adverse effect of contraceptive or replacement sex steroids on breast cancer incidence.

Adult↗
PubMed1993

The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN: A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. MEASUREMENTS: Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk factor for hip fractures in women.

Aged↗
PubMed1993

Maintained bone density at advanced ages after long term treatment with low dose oestradiol implants.

OBJECTIVE: To investigate whether the bone preserving effect of low dose oestrogen replacement therapy (20 mg oestradiol implanted subcutaneously every six months) persists during continuous long term treatment through advanced ages. DESIGN: Cross sectional clinical study of postmenopausal women treated with oestradiol implants as compared with nonusers matched for age. SETTING: Outpatient research unit at a university hospital. SUBJECTS: Thirty-five women with a mean age of 67 years (range 47-83 years) at the time of investigation who, after a prior hysterectomy, had been treated with oestradiol implants for climacteric symptoms for a mean period of 16 years (range 5.5-31 years). The results were compared with those in women matched for age and without any diseases or medications known to affect the bone metabolism. MAIN OUTCOME MEASURES: Bone mineral densities (BMD) in the distal forearm, vertebrae and hip analysed by study group, age and duration of treatment. RESULTS: Implant users had a median serum oestradiol concentration in the luteal range, 313 (range 126-1711) pmol/l, and premenopausal levels of follicle stimulating hormone (FSH). All women except one who were given the standard dose at the standard intervals had serum oestradiol levels below 650 pmol/l. Compared with nonusers, women treated with oestradiol implants had 20 to 25% higher BMD at all measurement sites: distal radius (P < 0.0001), lumbar vertebrae (P < 0.0002) and femoral neck (P < 0.0001). These differences also remained after adjustment for potential confounders (height, age at menarche, parity, smoking habits, physical exercise and education) (P < or = 0.01 at all sites). In a multiple regression analysis the negative effect of advancing age was more than compensated by the positive effect of increasing treatment duration with a higher BMD at all measurement sites in women with a longer as compared with shorter, duration of treatment; the regression coefficients were significant (P < 0.05) in the spine and hip measurements. CONCLUSIONS: Continuous long term treatment with low dose oestradiol implants yielding physiological levels of serum oestradiol preserves both compact and cancellous bone and the effect seems to persist into advanced ages without any inevitable age related bone loss.

Aged↗
PubMed1993

Scleroderma and malignancy: an epidemiological study.

OBJECTIVES: Although case reports and some patient series suggest an increased risk of cancer among patients with scleroderma, there are no population based studies to support this association. A population based follow up study was therefore carried out of 233 patients with scleroderma from the six-county Uppsala health care region of Sweden for the time period 1955-84. METHODS: Using the inpatient registry for the Uppsala health care region, all patients with scleroderma were identified. Their unique identification codes were then used to perform a record linkage with the National Cancer Registry. Expected cancer rates were determined using the age and gender specific rates for the Uppsala health care region. RESULTS: The standardised incidence ratio (SIR) for all cancers among these patients was significantly increased (SIR = 2.4; 95% CI = 1.5 to 3.6). The SIRs for lung cancer (SIR = 7.8; 95% CI = 2.5 to 18.2) and non-Hodgkin's lymphoma (SIR = 9.6; 95% CI = 1.1 to 34.5) were also significantly increased. Excluding patients who were diagnosed with cancer within a year of their scleroderma diagnosis resulted in similar findings, though the SIR for non-Hodgkin's lymphoma was no longer statistically significant. CONCLUSIONS: Larger population based investigations of cancer risk among patients with scleroderma are needed to confirm these initial findings and to evaluate in greater detail possible cancer risk among these patients.

Aged↗
PubMed1992

Alcoholism and liver cirrhosis in the etiology of primary liver cancer.

The aim of this study was to determine the risk of developing primary liver cancer in patients with a diagnosis of alcoholism, liver cirrhosis, or both. Three population-based, mutually exclusive cohorts were defined on the basis of hospital discharge diagnosis between 1965 and 1983. Complete follow-up through 1984--excluding the first year of follow-up--showed that among 8,517 patients with a diagnosis of alcoholism, 13 cancers occurred, vs. 4.2 expected (standardized incidence ratio (SIR) = 3.1; 95% confidence interval (CI) = 1.6 to 5.3); among 3,589 patients with liver cirrhosis, 59 cancers occurred, vs. 1.7 expected (SIR = 35.1; 95% CI = 26.7 to 45.3), and among 836 patients with both diagnoses, 11 cancers occurred, vs. 0.3 expected (SIR = 34.3; 95% CI = 17.1 to 61.3). Thus, alcoholism alone entailed a moderately increased risk and alcoholism with liver cirrhosis did not increase the high relative risk for liver cancer more than cirrhosis alone. We conclude that alcohol intake may be a liver carcinogen only by being causally involved in the development of cirrhosis; and further, that the risk of developing liver cancer following cirrhosis in this population is similar to or higher than that after chronic hepatitis-B-virus infection in other Western countries.

Aged↗