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Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe.

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.

Aged↗

Childhood body mass index and later cancer risk: a 50-year follow-up of the Boyd Orr study.

Associations between childhood BMI and adult cancer risk were investigated in a historical cohort study based on the Carnegie ("Boyd Orr") Survey of Diet and Health in Pre-War Britain (1937-9). In 14 centres in England and Scotland, children had their height and weight measured. We included 2,347 individuals aged between 2 and 14 years 9 months at the time of measurement, who were traced through the National Health Service Central Register. Relative cancer risk (registration or death) was estimated in relation to age- and sex-specific BMI SD scores. We studied associations with (i) all cancers, (ii) cancer groups stratified according to their relationship to smoking and (iii) certain site-specific cancers. In the 50 years of follow-up, 188 men and 192 women developed cancer. There was a 9% increase (95% CI -3 to 22%) in risk of cancer in adulthood per SD increase in BMI measured in childhood. There was no evidence of confounding by childhood or adulthood socioeconomic position, other anthropometric variables, childhood energy intake or birth order. There was a 30% increase (95% CI 10-54%) in risk of smoking-related cancers per SD increase in childhood BMI. There was no relationship between BMI and cancers not related to smoking. Associations for all cancers and non-smoking-related cancers tended to be stronger in children who were measured at an older (>8 years) rather than a younger (< or =8 years) age. We conclude that childhood BMI is related to increased risk of cancer in later life, particularly smoking-related cancers.

Adolescent↗

Reduced incidence of cervical cancer in mothers of sons with allergic rhinoconjunctivitis, asthma or eczema.

Because infection with human papillomavirus is a necessary cause of cervical cancer, it is likely that host immunological factors involved in defense against such infections are important for susceptibility to this cancer. By examining associations between allergy in sons and cervical cancer in their mothers, we aimed to test for genetic components involved in both allergy and cervical cancer development. Women born in Sweden between 1932 and 1960 with at least 1 son with medical records from military conscription examination were included in the study (N = 717,963). Among these women there were 41,910 in situ and 3,618 invasive cases of cervical cancer. Hazard ratios of in situ and invasive cervical cancer were estimated as functions of allergic rhinoconjunctivitis, asthma and eczema diagnoses in sons. Adjustment was made for the possible confounders: age, year of birth, education, socio-economic index, geography, number of conscripted sons and total number of offspring. The risk of in situ and invasive cervical cancer was lower for women having sons diagnosed with hypersensitivity (allergic rhinoconjunctivitis, asthma or eczema). Fully adjusted hazard ratios for women with 1 hypersensitive son were for in situ 0.86 (95% CI 0.84-0.88) and for invasive cervical cancer 0.82 (95% CI 0.74-0.91). The protective effects were similar between the 3 allergic diagnoses and increased with number of sons with a diagnosis. There was no significant association between non-cervical cancer in mothers and allergy in sons. These results strengthen the hypothesis that inherited immunological factors are important in determining risk of cervical cancer, probably by affecting mechanisms for viral persistence.

Adolescent↗

Susceptibility of abortion patients to infection: Correlation to cervical flora.

Cervical bacterial microflora was studied with a semiquantitative method in 29 women both before and after the termination of their pregnancy. The main findings were high prevalence of anaerobic bacteria (in 72%-79% of the specimens) consisting predominantly of Bacteroides species and anaerobic Gram-positive cocci, and low prevalence of aerobic bacteria (in 24%-38% of the specimens). Among the other microbes studied, the prevalence of Chlamydia excretors was high (24%), probably reflecting a promiscuous study population. Seventeen percent of the women developed febrile postabortion endometritis or salpingits. However, the cervical culture results predicted neither the patient prone to infection nor her response to antimicrobial treatment, suggesting the need for more data concerning the virulence properties of the bacteria, together with isolation of the organism from an infected site.

Abortion, Spontaneous↗

Postirradiation vaginal occlusion: nonoperative management.

The effects of irradiation therapy on the surrounding pelvic structures are well known. Most women develop some degree of vaginal stenosis following irradiation for cervical cancer. Although complete vaginal occlusion is less common, it seriously affects the patient's self-image. The author treated five patients who had complete vaginal occlusion following irradiation for stage II uterine cervical carcinoma. By means of a regimen of digital pressure and an estrogenic cream, for an average of six weeks, the function of the vagina was restored.

Dilatation↗

The tricho system: hypertrichosis, radiation, and cancer.

Five women in their 6th to 8th decades were treated for facial hypertrichosis in Erie, Pennsylvania, 30 to 40 years ago. The epilations were performed with an X-ray device called "Tricho System," which was manufactured, sold, and proclaimed safe by its physician-inventor. The beauty shop operator who administered these treatments may or may not have received "instruction" by the company in the operation of the equipment. At varying intervals, each of the 5 women developed radiodermatitis and basal cell and/or squamous cell carcinoma at the sites of epilation. All presented to the plastic surgical service at the Hamot Medical Center in Erie, Pennsylvania. Two underwent massive radical resective surgery, 2 required extensive excision and resurfacing, and 1 refused resective surgery although she had had a previous surgical attempt 17 years earlier. Case histories are presented in detail. This series is representative of the epidemic nature of Tricho-System-induced disease.

Aged↗

Intrauterine infection and prematurity.

Intrauterine infection is a major cause of premature labor with and without intact membranes. Intrauterine infection is present in approximately 25% of all preterm births and the earlier the gestational age at delivery, the higher the frequency of intra-amniotic infection. Microorganisms may also gain access to the fetus before delivery. A fetal inflammatory response syndrome elicited in response to microbial products is associated with the impending onset of preterm labor and also with multi-systemic organ involvement in the human fetus and a higher rate of perinatal morbidity. The most common microorganisms involved in intrauterine infections are Ureaplasma urealyticum, Fusobacterium species and Mycoplasma hominis. The role of Chlamydia trachomatis and viruses in preterm labor remain to be determined. Use of molecular microbiology techniques to diagnose intrauterine infection may uncover the role of fastidious microorganisms that have not yet been discovered. Antibiotic administration to patients with asymptomatic bacteriuria is associated with a significant reduction in the rate of preterm birth. However, such benefit has not been demonstrated for patients with bacterial vaginosis, or women who carry Streptococcus agalactia, Ureaplasma urealyticum or Trichomonas vaginalis. Antibiotic administration to patients with preterm premature rupture of membranes is associated with prolongation of pregnancy and a reduction in the rate of clinical chorioamnionitis and neonatal sepsis. The benefit has not been demonstrated in patients with preterm labor and intact membranes. Major efforts are required to determine why some women develop an ascending intrauterine infection and others do not and also what interventions may reduce the deleterious effect of systemic fetal inflammation.

Amniotic Fluid↗

Early-stage cervical adenocarcinoma treated by surgical intent: the role of para-aortic lymph node dissection.

OBJECTIVE: Previous reports suggest that cervical adenocarcinomas have a unique pattern of spread and are more apt to metastasize to para-aortic lymph nodes. The purpose of this study was to further define the node of para-aortic lymph node dissection in early-stage cervical adenocarcinoma treated by surgical intent. METHODS: Institutional review board approval was obtained to perform a computerized search of the data of all women diagnosed with cervical adenocarcinoma between 1982 and 2000. Hospital charts were retrospectively reviewed. Follow-up was obtained from the tumor registry, medical records, and correspondence with health care providers. RESULTS: Three hundred (87%) of 345 early-stage (FIGO IA(1)-IIA) cervical adenocarcinoma patients were primarily treated by surgical intent. Two hundred seventy-six underwent pelvic and para-aortic node dissection (n = 69) or pelvic node dissection only (n = 207); 24 had no lymph node dissection. The median number of lymph nodes removed was 13 pelvic (range, 1-58) and 3 para-aortic (range, 1-17). Three (4%) of 69 patients had para-aortic nodal metastases. Each had either grossly evident para-aortic adenopathy (n = 2) or an adnexal metastasis. Thirty-six of 40 women developing recurrent disease had at least some component of pelvic recurrence; 4 had only extrapelvic disease. Three patients undergoing para-aortic node dissection developed an isolated extrapelvic recurrence despite originally negative para-aortic nodes (n = 2) or treatment by extended-field radiation for para-aortic metastases. One woman undergoing only pelvic node dissection had an isolated extrapelvic recurrence despite originally negative nodes. CONCLUSIONS: Early-stage cervical adenocarcinoma primarily treated by surgical intent has a very low risk of para-aortic metastases. These were detected only when there was gross evidence of nodal or adnexal disease.

Adenocarcinoma↗

Reversible bone marrow aplasia induced by naproxen.

We report a case of reversible bone marrow aplasia related to the use of naproxen. A 71-year-old women developed severe pancytopenia after she had been treated with naproxen for more than 8 weeks. Bone marrow examination showed marked hypocellularity compatible with aplastic anemia. Full recovery of the pancytopenia and bone marrow was observed when naproxen was discontinued. Absence of exposure to other drugs and lack of underlying disorders known to cause bone marrow aplasia makes this case unique.

Aged↗

[Incidence of hepatotoxic side effects during antituberculous therapy (INH, RMP, EMB) in relation to the acetylator phenotype (author's transl)].

In 95 patients with active tuberculosis, we investigated in a prospective study the influence of the acetylator phenotype on the hepatotoxic side effects of the antituberculous regimen isoniazid (INH) 10 mg/kg, rifampicin (RMP) 10 mg/kg, and ethambutol (EMB) 25 mg/kg. Besides a much higher incidence of isoniazid hepatitis (SGOT, SGPT greater than 200 U/l) in 12.6% of patients treated--as compared to the incidence reported in large chemoprophylaxis trials with isoniazid monotherapy in the range of 0.5%-1% (IUAT 1969, U.S.P.H.S. 1971)--we observed a significant, higher risk of isoniazid-induced hepatotoxicity in slow acetylators (p less than 0.01): in 26 of 56 slow acetylators (= 46.4%), but only in 4 of 30 rapid acetylators (=13.3%) were transaminases in the serum elevated greater than 50 U/l. The 12 patients with the most severe hepatotoxic side effects (SGOT, SGPT greater than 200 U/l) were all slow acetylators. Women developed severe hepatic injury more often than men (p less than 0.05). In cases with isoniazid hepatitis, triple therapy was either stopped or reduced to a combination RMP, EMB. In cases with less severe liver injury, triple therapy was continued. In all patients transaminases normalized within 2-4 weeks. On return to full triple therapy, none of the patients developed new elevation of transaminases. The constant occurrence of isoniazid hepatitis during the 2nd-4th week (19 +/- 7 days) as well as the normalization without any new hepatotoxic reaction suggest that there may be an interaction between RMP and isoniazid metabolism limited to the early phase of chemotherapy.

Acetylation↗

Early pregnancy termination: an improved technique for 'menstrual regulation' with ultrasound assistance.

We performed aspiration of early pregnancy on 100 women requesting termination, using a low caliber angled catheter under sonographic guidance, without analgesia or anesthesia. The sonographic inclusion criteria for the study were: (1) mean gestational sac diameter less than 30 mm, or (2) crown rump length less than 10 mm when an embryo was visualized. The uterine content was successfully evacuated in all cases and none needed an additional curettage. Two women developed mild endometritis which responded to antibiotic therapy. This refinement of this 'menstrual regulation' technique seems to be safer when compared with the reported results of the original technique.

Abortion, Induced↗

Intrathecal catheter insertion during labour reduces the risk of post-dural puncture headache.

PURPOSE: To describe the anaesthetic management and report the incidence of PDPH in three parturients who had experienced accidental dural puncture during labour and the subsequent deliberate intrathecal insertion of an epidural catheter. CLINICAL FEATURES: Inadvertent dural puncture with a 16-gauge Tuohy needle occurred during the first stage of labour at 3-4 cm cervical dilatation in all three women. The 20-gauge epidural catheter was immediately inserted into the subarachnoid space after accidental dural penetration. Intermittent intrathecal injections of lidocaine or bupivacaine with fentanyl were administered to provide analgesia during labour and delivery. Two of the women had spontaneous vaginal deliveries, whereas Caesarean section was performed in one case due to acute fetal distress during the second stage of labour. The intrathecal catheter was left in-situ for 13-19 hr after delivery and the women were questioned daily for symptoms of PDPH. None of the three women developed PDPH after dural puncture and intrathecal catheterisation with the epidural catheter. CONCLUSION: Immediate intrathecal insertion of the epidural catheter after accidental dural puncture during labour proved to be an effective prophylactic technique to prevent PDPH in these three parturients.

Adult↗

[Localized Sweet syndrome].

A 73-year-old women developed an inflammatory tumor on her right cheek within 3 weeks. The lesion measured more than 7 cm in diameter, contained a central crateriform depression and was studded with several sterile pustules. Histology showed a dense dermal infiltration of neutrophils, but no leukocytoclasia or destruction of dermal tissue. There was no associated leukocytosis or fever, but the patient suffered from recurrent chronic bronchitis. Because the acute inflammation was progressive under treatment with antibiotics, high-dose corticosteroids were given systemically. The tumor regressed quickly and resolved without scarring. Although this localized Sweet's syndrome is unusual, it fulfills several major and minor criteria of Sweet's syndrome and thus represents a rare form of this disease.

Aged↗

[Finger tip necroses after dihydroergotamine medication in limited systemic scleroderma].

A 78 year old women developed acute fingertip necrosis just a few days after starting dihydroergotamine. The lesions healed in 3 weeks after the medication was stopped. The patient had suffered from Raynaud syndrome for 5 years and limited systemic sclerosis was diagnosed during the necrotic episode. Advanced age and microangiopathies are contraindications to the use of ergot-containing preparations.

Aged↗

Three clinical variants of gastroesophageal reflux disease form two distinct gene expression signatures.

It has been proposed recently that gastroesophageal reflux disease (GERD) patients may be categorized into three distinct groups exhibiting non-erosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Measurement of relative gene expression levels was undertaken to identify distinct molecular subclasses in different variants of gastroesophageal disease. The measurements were made with Affymetrix U133A 2.0 GeneChips and RNA isolated from mucosal samples of normal squamous esophageal epithelium from 24, 28, and 26 patients with NERD, ERD and BE, respectively. Statistical testing of microarray data showed that gene expression profiles are discriminative for BE and NERD, but not for combinations of BE and ERD or NERD and ERD. In addition, women developing NERD exhibited transcriptional patterns that differed from those of men with BE. In clustering analyses, we did not observe correlations between sex and assignment of gene expression profile of ERD patients to either the NERD or the BE group. Although the biological significance of the identified genes remains uncertain, we hypothesize that GERD is a monophyletic disease that develops with the onset of gastroesophageal reflux and represents two main molecular classes, which may result in different progressions to inflammatory process within esophageal epithelium modulated by sexual dimorphism. While normal epithelium samples from NERD and BE patients are molecularly homogeneous, esophageal mucosa from ERD patients is molecularly similar to either NERD or BE. These findings may be useful for defining molecular markers which could predict potential progression to Barrett's metaplasia among patients with reflux disease.

Adult↗

[Dupuytren contracture in North Germany. Epidemiological study of 500 cases].

Dupuytren's disease is the "classical" hand illness of the north: it affects people of Celtic or Viking descent throughout the whole of northern Europe, whereas it is an unknown disease in the Mediterranean region. Dupuytren's contracture appears to be an extremity-related disease. Owing to the unclear etiology and a lack of up-to-date demographic data for northern Germany this study aims--together with the literature--to elucidate the role of associated illnesses in an attempt to discover pathogenic explanations. 566 patients suffering from Dupuytren's disease in the area around Hanover were analysed with respect to epidemiological features and their Tubiana contracture stage. 91.2% were of pure northern German stock, 12.5% had a family predisposition. The male-to-female ratio was 7:1. Men were afflicted on average at the age of 56 years. Intellectuals were scored 3.17, while manual workers scored 4.21. There were pre-existing ipsilateral lesions in 15% of cases. 55.1% had bilateral contracture. Ectopic penile and plantar fibrosis or knuckle pads were found in 6.7% of cases. The distribution of stages I-IV decreased by 2.4% from 59.1% among the 1,808 afflicted finger rays. With a score of 3.7-3.72, drinkers and smokers presented significantly more severe contractures, while the 8.2% of diabetics displayed a milder form. Among the epileptics--all of whom were affected bilaterally--the Tubiana stage of 3.71 exceeded the median manual score of 3.63 for the group as a whole. Thus Dupuytren's disease is a general but not an exclusively extremity-related sickness. The androtropy is pathognomic. Women develop the disease one decade later than men. In old age the male-to-female ratio equalizes. Drinkers, smokers and heavy manual workers present a more severe affliction, while diabetics suffer from a significantly less severe form. Although the ulnar type dominates, the radial type accounts for 14.4% of cases. 1.9 million Germans are chronically ill because of Dupuytren's disease. Despite a trauma history, Dupuytren's disease is not recognized as an occupational disease.

Adult↗

Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria.

AIMS/HYPOTHESIS: The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30-299 mg/g). METHODS: Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE(4 years)) and by computing the change in urinary albumin excretion during the study (Delta UAE). RESULTS: At baseline, the duration of diabetes averaged 13.3 years (range = 4.0-23.8 years) and the mean glomerular filtration rate was 159 ml x min(-1) x 1.73 m(-2) (range = 98 - 239 ml x min(-1) x 1.73 m(-2)). Median urinary albumin excretion was 67 mg/g (range = 25-136 mg/g) and it increased to 625 mg/g (range = 9-13471 mg/g) after 4 years; 10 subjects (63 %; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio >/= 300 mg/g). Neither mean arterial pressure nor HbA(1 c) changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE(4 years), r = -0.49, p = 0.05; DeltaUAE, r = -0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression (UAE(4 years), r = 0.11, p = 0.67; DeltaUAE, r = 0.09, p = 0.73) and mesangial volume fraction had only a modest effect (UAE(4 years,) r = 0.42, p = 0.11; DeltaUAE, r = 0.48, p = 0.06). CONCLUSION/INTERPRETATION: Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important part in the development and progression of diabetic renal disease. [Diabetologia (1999) 42: 1341-1344]

Adult↗

Lethal hemorrhage caused by aortoenteric fistula following endovascular stent implantation.

A 55-year-old women developed an aortointestinal fistula between the bifurcation of the aorta and the distal ileum following implantation of multiple endovascular stents into both common iliac arteries for treatment of aortoiliac occlusive disease. Ten months before the acute onset of the gastrointestinal hemorrhage two balloon-expandable steel stents had been implanted into both common iliac arteries. Due to restenosis and recurrent intermittent claudication, three balloon-expandable covered stents were implanted 4 months later on reintervention. The patient presented with abdominal pain and melena, and fell into hemorrhagic shock with signs of upper gastrointestinal bleeding. After transfer to our hospital, she again developed hemorrhagic shock with massive upper and lower gastrointestinal bleeding and died during emergency laparotomy. The development of aortoenteric fistulas following endovascular surgery/stent implantation is very rare and has to be considered in cases of acute gastrointestinal hemorrhage.

Angiography↗