In situ laser measurement of oxygen concentration and flue gas temperature utilizing chemical reaction kinetics.

Combustion research requires detailed localized information on the dynamic combustion conditions to improve the accuracy of the simulations and, hence, improve the performance of the combustion processes. We have applied chemical reaction kinetics of potassium to measure the local temperature and O2 concentration in flue gas. An excess of free atomic potassium is created in the measurement volume by a photofragmenting precursor molecule such as potassium chloride or KOH which are widely released from solid fuels. The decay of the induced potassium concentration is followed with an absorption measurement using a narrow-linewidth diode laser. The temperature and O2 concentration are solved from the decay curve features using equations obtained from calibration measurements in a temperature range of 800°C-1000°C and in O2 concentrations of 0.1%-21%. The local flue gas temperature and O2 concentration were recorded in real time during devolatilization, char burning, and ash cooking phases of combustion in a single-particle reactor with a 5 Hz repetition rate. The method can be further extended to other target species and applications where the chemical dynamics can be disturbed with photofragmentation.

An Andean radiation: polyploidy in the tree genus Polylepis (Rosaceae, Sanguisorbeae).

The Andean tree genus Polylepis (Rosaceae) is notorious for the high morphological plasticity of its species and the difficulty in their circumscription. The evolutionary mechanisms that have driven diversification of the genus are still poorly understood, with factors as diverse as ecological specialisation, reticulate evolution, polyploidisation and apomixis being proposed to contribute. In the present study, chromosome counts, flow cytometry and stomata guard cell size measurements were employed to document for the first time the presence of polyploidy in the genus and to infer ploidy levels for most species. Inferred ploidy levels show a clear progression from diploidy in cloud forest species to polyploidy (tetra- to octoploidy) in the morphologically and ecologically specialised incana group, indicating that polyploidisation may have played a major role in speciation processes and the colonisation of novel habitats during the Andean uplift. At least two species of Polylepis comprise populations with varying degrees of ploidy. More extensive studies are needed to obtain a better understanding of the prevalence and effects of intraspecific polyploidy in the genus.

Performance of Surgical Stress Index during Sevoflurane-Fentanyl and Isoflurane-Fentanyl Anesthesia.

The performance of recently introduced Surgical Stress Index (SSI), based on heart rate and photoplethysmography, was estimated during sevoflurane-fentanyl and isoflurane-fentanyl anesthesia during surgical procedures. Forty ASA I-III patients were enrolled. Anesthesia was induced with fentanyl 2 mug kg(-1) and thiopentone 3-5 mg kg(-1). Tracheal intubation was performed 5 minutes after fentanyl bolus. Patients were randomly allocated to receive sevoflurane (n = 20) or isoflurane (n = 20) in 30% oxygen/air. State entropy was kept at 40-60, target being 50. During surgery, fentanyl boluses 1.5 mug kg(-1) were given at 30-40-minute intervals. SSI increased significantly after intubation. During surgery, the decrease of SSI after fentanyl boluses was similar in sevoflurane and isoflurane groups but SSI values were higher in sevoflurane than in isoflurane group. Tracheal intubation, skin incision, and surgical stimuli increased SSI from baseline, indicating that nociceptive stimuli increase SSI. Fentanyl boluses during surgery decreased SSI, indicating that increasing analgesia decreases SSI.

Diagnosis and treatment of menorrhagia.

One-third of all women experience heavy menstrual bleeding at some point in their life. In western countries, about 5% of women of reproductive age will seek help for menorrhagia annually. Half of all women who consult for hypermenorrhea have some uterine abnormality, most often fibroids (among patients under 40 years of age) and endometrial polyps (above 40 years of age). Appropriate treatment considerably improves the quality of life of these patients, and it is important to make a rigorous assessment of the patient to provide the best treatment options. This guideline provides instructions on how to examine and treat women of fertile age who have menorrhagia. The subject's own assessment of the amount of menstrual blood loss does not generally reflect the true amount. All patients should undergo a pelvic examination and, if the menstrual pattern has changed substantially or if anaemia is present, a vaginal sonography should be carried out as the most important supplemental examination. Vaginal sonography combined with an endometrial biopsy is a reliable method for diagnosing endometrial hyperplasia or carcinoma, but it is insufficient for diagnosing endometrial polyps and fibroids; these can be diagnosed more reliably by sonohysterography or hysteroscopy. Non-steroidal anti-inflammatory drugs and tranexamic acid reduce menstrual blood loss by 20-60%, and the effectiveness of a hormonal intrauterine system (IUS) is comparable with that of endometrial ablation or hysterectomy. Cyclic progestogens do not significantly reduce menstrual bleeding of women who ovulate. Treatment should be started with one of the drug therapies, i.e. the IUS, tranexamic acid, anti-inflammatory drugs, or oral contraceptive. Drug treatment should be used and evaluated before surgical interventions are considered. With an effective training and feedback system, it is possible to organise the diagnostics, medical treatment and follow-up of heavy menstrual bleeding in the primary health care setting or in outpatient clinics, which reduces the burden on specialist health care.

Etoricoxib pre-medication combined with intra-operative subacromial block for pain after arthroscopic acromioplasty.

BACKGROUND: Arthroscopic shoulder surgery under general anaesthesia is often associated with severe post-operative pain which may delay discharge and the start of rehabilitation. Etoricoxib is a new cyclo-oxygenase-2 inhibitor with a long duration of action and a lack of a deteriorating effect on platelet function. Therefore, the effect of pre-operative etoricoxib combined with local anaesthesia on post-operative pain and the discharge profile was studied in day-surgery patients undergoing arthroscopic shoulder surgery under general anaesthesia. METHODS: Thirty ASA I-II adult patients scheduled for arthroscopic shoulder surgery were enrolled in this randomized prospective study. Half of the patients received etoricoxib 120 mg orally (group E) and the other half received placebo tablet orally (group C) 1 h before surgery. All patients received 20 ml of bupivacaine 2.5 mg/ml solution with epinephrine at the start of surgery and 20 ml of bupivacaine 5.0 mg/ml solution with epinephrine at the end of surgery into the subacromial space. All patients received general anaesthesia with spontaneous breathing via a laryngeal mask. In the post-anaesthesia care unit, pain was assessed on a scale from 0 to 10 (visual analogue scale, VAS) and intravenous fentanyl 25 microg was administered as scheduled (VAS > or = 3). In the day-surgery unit and at home, the analgesic was a tablet containing paracetamol 500 mg + codeine 30 mg (VAS > or = 3), as needed. RESULTS: Patients in group E reported lower post-operative pain scores at 30, 60, 120 (P < 0.01) and 180 min (P < 0.05) after surgery, and longer time to first analgesic use (P < 0.05). Patients in group E required less fentanyl (P < 0.05) and were discharged more quickly (P < 0.05) than patients in group C. Patients in group E had a lower cumulative consumption of paracetamol + codeine tablets (P < 0.05) and lower pain scores (P < 0.05) during 7 days at home than patients in group C. Adverse events were rare in both groups. CONCLUSION: In patients having arthroscopic shoulder surgery under general anaesthesia combined with intra-operative subacromial regional analgesia, etoricoxib 120 mg reduced immediate and late post-operative pain, and facilitated early post-operative discharge.

Analgesia and discharge following preincisional ilioinguinal and iliohypogastric nerve block combined with general or spinal anaesthesia for inguinal herniorrhaphy.

BACKGROUND: Preincisional ilioinguinal and iliohypogastric nerve block (IINB) reduces postoperative analgesics after inguinal herniorrhaphy. The effect of an IINB on postoperative pain and discharge profile was therefore studied in day-surgery patients undergoing inguinal herniorrhaphy with general or spinal anaesthesia. METHODS: Seventy ASA I-II adult patients scheduled for inguinal herniorrhaphy received an IINB before the surgical incision with 15 ml of 0.5% bupivacaine. In a randomized fashion half of them received general anaesthesia with spontaneous breathing via a laryngeal mask (GA-group) and the other half received spinal anaesthesia with 5 mg of bupivacaine diluted with sterile water to 2.5-ml volume (SPIN-group). In the postanaesthesia care unit (PACU), pain was assessed on a scale from 0 to 10 (VAS) and ketorolac 30 mg i.v. (VAS < 5), or fentanyl 0.05 mg i.v. (VAS > or = 5) was administered as scheduled. In the day surgery unit and at home the analgesic was a tablet of ibuprofen 200 mg + codeine 30 mg (VAS > or = 3). RESULTS: Patients in the SPIN-group reported lower postoperative pain scores at 30, 60 min (P < 0.0001) and 120 min (P < 0.05) after surgery, and longer time to first analgesic use (P < 0.0001). Patients in the GA-group had a shorter time to discharge without voiding (P < 0.001) and with voiding (P < 0.05). After discharge, there were no significant differences between the groups regarding pain scores at rest and at walking, or the doses of analgesic. Adverse events were rare in both groups. CONCLUSION: Only a relatively short immediate analgesic benefit could be demonstrated by a combination of IINB with spinal anaesthesia compared with IINB combined with general anaesthesia. The use of general anaesthesia facilitated an earlier postoperative discharge than spinal anaesthesia.

Comparison between intra-articular bupivacaine with epinephrine and epinephrine alone on short-term and long-term pain after knee arthroscopic surgery under general anesthesia in day-surgery patients.

BACKGROUND: : Postarthroscopy analgesia has been provided with intra-articular bupivacaine, but reported results are conflicting regarding efficacy and the duration of analgesia. The immediate and long-term effects of intra-articular bupivacaine with epinephrine after arthroscopic knee surgery were therefore studied in a day surgery setting. METHODS: : 120 ASA I-II patients scheduled for arthroscopic knee surgery were given general anesthesia with spontaneous breathing via a laryngeal mask. In a randomized and blinded fashion half of them received, at the end of surgery, intra-articularly 20 mL 0.5% bupivacaine with epinephrine (B + E-group) and the other half 20 mL saline with epinephrine (S + E-group). All patients received ketoprofen 100 mg i.v. during surgery and another 100 mg 2-3 h postoperatively. The patients were observed for about 4.5 h in the day surgery unit before discharge. RESULTS: : The results showed that in comparison with the S + E-group, significantly fewer patients in the B + E-group needed analgesics (P < 0.0001) and the amount required was also significantly less postoperatively, before discharge (about 4.5 h postoperatively) (P < 0.0001). The latency to the need for the first postoperative analgesic was shorter in the S + E-group patients (P < 0.0001). At home, during seven days after discharge, the need for analgesic (oral ketoprofen 100 mg) was greater in the B + E-group (P < 0.05), especially only during the second postoperative day, but the visual analoque pain scale (VAPS) scores were low with no differences between the groups. No complication occurred. CONCLUSION: : It is concluded that a good postoperative pain control of intra-articular bupivacaine with epinephrine was found only in the immediate postoperative period (i.e. before discharge) in a day-surgery arthroscopic knee surgery patients.

Progestin-releasing intrauterine systems.

The levonorgestrel-releasing intrauterine system (LNG IUS) is an effective method for contraception. It has a strong antiproliferative action on the endometrium. The endometrium is transformed under the influence of local levonorgestrel and becomes unresponsive to ovarian estrogens. This process is associated with progressive reduction of menstrual blood loss and menstrual duration. Scanty and irregular bleeding and/or spotting is usual during the first 3 to 4 months. The reduction of menstrual blood loss continues and after the first 9 months many women have no bleeding at all. However, they have normal ovarian function. The absence of bleeding is a result of the local antiproliferative action of the LNG IUS on the endometrium, which is also responsible for many health benefits during the use of this method. As with oral contraceptives, the risk of pelvic inflammatory disease is reduced, because of reduced menstrual blood loss, endometrial suppression, and thickening of the cervical mucus. There are some steroidal side effects: mood changes, oily skin, and acne. Weight increase is similar to that associated with copper intrauterine devices: 500 g per year over 5 years. Users should be told that the LNG IUS does not prevent sexually transmitted infection, and therefore women at risk should also use condoms for their protection.

Therapeutic use of the LNG IUS, and counseling.

The intrauterine release of levonorgestrel (LNG) alters the function of the endometrium. This phenomenon offers special health benefits for users and a manner of local intrauterine therapy. In this review we discuss use of LNG-releasing intrauterine system (LNG IUS) in treatment and prevention of anemia and in the therapy of menorrhagia and dysmenorrhea. The antiproliferative effect of the LNG IUS on the endometrium offers targeted therapy against the proliferative action of estrogen on the endometrium during hormone replacement therapy. The LNG IUS as an alternative to sterilization is also discussed. There are also promising therapeutic fields such as use of the LNG IUS in the treatment of endometriosis and in the protection of endometrium exposed to tamoxifen during breast cancer treatment. Special attention is paid to counseling because successful use of the LNG IUS requires good training of the providers and extensive counseling of users.

Effect of preincisional ilioinguinal and iliohypogastric nerve block on postoperative analgesic requirement in day-surgery patients undergoing herniorrhaphy under spinal anaesthesia.

BACKGROUND: By choosing spinal anaesthesia instead of general anaesthesia, and by infiltrating the wound area with local anaesthetic the need for postoperative analgesics may be reduced. An ilioinguinal and iliohypogastric nerve block (IINB) in inguinal herniorrhaphy was, therefore, studied in a day surgery setting in combination with a spinal block. METHODS: One hundred ASA I-II adult patients scheduled for inguinal herniorrhaphy were given spinal anaesthesia with hyperbaric 0.5% bupivacaine. In a randomized and blinded fashion half of them received an IINB 5 min before the surgical incision with 10 ml of 0.5% bupivacaine (B-IINB) and the other half with saline (S-IINB). All patients received ketoprofen 100 mg i.v. during surgery and another 100 mg 2-3 h postoperatively. The patients were observed for about 6 h in the day surgery unit before discharge. RESULTS: The results showed that in comparison with the S-IINB group, significantly fewer patients in the B-IINB group needed analgesics (P<0.01) and the amount required was also significantly less postoperatively, before discharge (about 6 h postoperatively) (P<0.05). The latency to the need for the first postoperative analgesic was shorter in the S-IINB patients (P<0.01). At home the VAS scores and the need for analgesics (oral ketoprofen 100 mg) were low with no differences between the groups. No complications occurred. CONCLUSION: It is concluded that no long-term analgesia could be demonstrated by a preincisional IINB performed during spinal anaesthesia in day-surgery inguinal herniorrhaphy patients. Thus, reduced analgesic requirement was seen only for about 6 h postoperatively.

Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women.

OBJECTIVE: The aim of this study was to assess whether oral delivery and transdermal delivery of sequential combined hormone replacement therapy have similar effects on systemic blood pressure, as measured by 24-hour automated ambulatory recordings. STUDY DESIGN: Eighty-two healthy postmenopausal women, of whom 73 completed the study, were randomly assigned to start hormone replacement therapy with either orally (n = 38) or transdermally (n = 35) administered medication. Ambulatory blood pressure was recorded for a 24-hour period before the start of hormone replacement therapy and again 2 and 6 months later. Analysis of variance was used for data analysis. RESULTS: Hormone replacement therapy by both oral and transdermal routes was associated with slight but nonsignificant drops in mean 24-hour systolic and diastolic ambulatory blood pressure. Daytime systolic ambulatory blood pressure (mean +/- SE) fell significantly (P <.05) and similarly at 2 months in the oral (3.8 +/- 0.2 mm Hg) and transdermal (4.0 +/- 0.3 mm Hg) treatment groups. The daytime ambulatory blood pressure remained significantly lower than baseline at 6 months in the oral treatment group (-3.6 +/- 0.3 mm Hg), whereas the fall at 6 months in the transdermal group (-3.1 +/- 0.3 mm Hg) was not significant. Mean daytime diastolic ambulatory blood pressure was reduced in both the oral (-1.8 +/- 0.8 mm Hg) and transdermal (-3.5 +/- 0.7 mm Hg; P <.05) treatment groups at 2 months but not at 6 months. Nighttime ambulatory blood pressures in both groups remained unaffected by hormone replacement therapy. CONCLUSION: Sequential combined hormone replacement therapy delivered by both oral and transdermal routes caused significant falls in the daytime ambulatory blood pressure of normotensive postmenopausal women at 2 months of treatment. This fall persisted as long as 6 months of treatment in the oral treatment group but not in the transdermal treatment group.

In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells.

The human gene POLG encodes the catalytic subunit of mitochondrial DNA polymerase, but its precise roles in mtDNA metabolism in vivo have not hitherto been documented. By expressing POLG fusion proteins in cultured human cells, we show that the enzyme is targeted to mitochondria, where the Myc epitope-tagged POLG is catalytically active as a DNA polymerase. Long-term culture of cells expressing wild-type POLG-myc revealed no alterations in mitochondrial function. Expression of POLG-myc mutants created dominant phenotypes demonstrating important roles for the protein in mtDNA maintenance and integrity. The D198A amino acid replacement abolished detectable 3'-5' (proofreading) exonuclease activity and led to the accumulation of a significant load (1:1700) of mtDNA point mutations during 3 months of continuous culture. Further culture resulted in the selection of cells with an inactivated mutator polymerase, and a reduced mutation load in mtDNA. Transient expression of POLG-myc variants D890N or D1135A inhibited endogenous mitochondrial DNA polymerase activity and caused mtDNA depletion. Deletion of the POLG CAG repeat did not affect enzymatic properties, but modestly up-regulated expression. These findings demonstrate that POLG exonuclease and polymerase functions are essential for faithful mtDNA maintenance in vivo, and indicate the importance of key residues for these activities.

Clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy: a randomized controlled study.

BACKGROUND: To evaluate clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy. METHODS: Fifty women scheduled for abdominal hysterectomy were randomized to undergo either laparoscopic (n = 25) or abdominal (n = 25) hysterectomy. Surgical characteristics, hospital stay, convalescence and complications were analyzed. Blood samples for assay of markers of tissue trauma (interleukin-6, C-reactive protein, tumor-associated trypsin inhibitor and tumor-associated antigen CA 125) were taken preoperatively, on the first, second and seventh postoperative day and at the follow-up visit four weeks after surgery. RESULTS: In uncomplicated hysterectomies (n = 18) the operating time (85.3 min versus 57.5 min, p < 0.00001) was longer for laparoscopic group but the hospital stay (2.1 days versus 3.4 days, p < 0.00001) and sick leave (21.4 days versus 38.5 days, p < 0.00001) were shorter in the laparoscopic group. Postoperative increases in all markers were significant in both groups. The interleukin-6 concentration was highest on the first postoperative day in both groups, that of C-reactive protein on the second postoperative day in both groups, tumor-associated trypsin inhibitor on the seventh postoperative day in the laparoscopic group and on the second postoperative day in the abdominal group and tumor-associated antigen CA 125 on the seventh postoperative day in both groups. Both interleukin-6 and C-reactive protein levels were lower in the laparoscopic group on the first (p = 0.01 and p = 0.03, respectively) and on the second postoperative day (p = 0.02 and p < 0.001, respectively) compared with the abdominal group. No differences were seen in tumor-associated trypsin inhibitor and tumor-associated antigen CA 125 levels between the groups. CONCLUSION: Laparoscopic hysterectomy should replace abdominal hysterectomy whenever possible because of a more favorable clinical outcome and less tissue trauma.

Expression of the gene for mitoribosomal protein S12 is controlled in human cells at the levels of transcription, RNA splicing, and translation.

The human gene RPMS12 encodes a protein similar to bacterial ribosomal protein S12 and is proposed to represent the human mitochondrial orthologue. RPMS12 reporter gene expression in cultured human cells supports the idea that the gene product is mitochondrial and is localized to the inner membrane. Human cells contain at least four structurally distinct RPMS12 mRNAs that differ in their 5'-untranslated region (5'-UTR) as a result of alternate splicing and of 5' end heterogeneity. All of them encode the same polypeptide. The full 5'-UTR contains two types of sequence element implicated elsewhere in translational regulation as follows: a short upstream open reading frame and an oligopyrimidine tract similar to that found at the 5' end of mRNAs encoding other growth-regulated proteins, including those of cytosolic ribosomes. The fully spliced (short) mRNA is the predominant form in all cell types studied and is translationally down-regulated in cultured cells in response to serum starvation, even though it lacks both of the putative translational regulatory elements. By contrast, other splice variants containing one or both of these elements are not translationally regulated by growth status but are translated poorly in both growing and non-growing cells. Reporter analysis identified a 26-nucleotide tract of the 5'-UTR of the short mRNA that is essential for translational down-regulation in growth-inhibited cells. Such experiments also confirmed that the 5'-UTR of the longer mRNA variants contains negative regulatory elements for translation. Tissue representation of RPMS12 mRNA is highly variable, following a typical mitochondrial pattern, but the relative levels of the different splice variants are similar in different tissues. These findings indicate a complex, multilevel regulation of RPMS12 gene expression in response to signals mediating growth, tissue specialization, and probably metabolic needs.

Modelling in Escherichia coli of mutations in mitoribosomal protein S12: novel mutant phenotypes of rpsL.

The rpsL gene of Escherichia coli encodes the highly conserved rps12 protein of the ribosomal accuracy centre. We have used the E. coli gene to model the phenotypic effects of specific substitutions found in the mitochondrial gene for rps12. Variants created by in vitro mutagenesis were tested in two different plasmid vector systems, in both streptomycin-sensitive and streptomycin-resistant hosts. A substitution with respect to eubacterial rps12 (K87-->Q), found in all metazoan and fungal mitochondrial orthologues thus far studied, is associated with low-level resistance to streptomycin and a modest (15%) drop in translational elongation rate, but without significant effects on translational accuracy. An amino-acid replacement at a highly conserved leucine residue (L56-->H), associated with the phenotype of sensitivity to mechanical vibration and hemizygous female lethality in Drosophila, creates a functionally inactive but structurally stable protein that is not assembled into ribosomes. The presence in the cell of the mutant, but not wild-type, rpsL greatly downregulates the level of a prominent polypeptide of approximately 50 kDa. These results indicate novel structure-function relationships in rps12 genes affecting translational function, ribosome assembly and drug sensitivity, and indicate a novel regulatory pathway that may influence ribosome biogenesis.

Oral contraceptives and thrombosis. From risk estimates to health impact.

OBJECTIVE: The scientific debate on oral contraceptives (OCs) and thrombotic diseases continues unabated. The aim of this survey was to evaluate available scientific data on OCs and thrombotic diseases and to make tentative prescription recommendations of OCs to women with and without various thrombotic risk factors. CONSENSUS: In women 15-29 years old, venous thromboembolism is about twice as common as arterial complications. In women between 30 and 44 years, the number of arterial complications exceeds venous diseases by about 50%. The mortality from arterial diseases is 3.5 times higher than the number of deaths from venous diseases in women below 30 years, and 8.5 times higher in women 30-44 years old. A significant disability is more frequent in women suffering and surviving an arterial complication than in women with venous thromboembolism. Although many important scientific issues still have to be addressed, the available scientific data suggests a differential influence of OCs with second and third generation progestagens on the risk of venous and arterial diseases. OCs with second generation progestagens seem to confer a smaller increase in the risk of venous diseases and a higher increase in risk of arterial complications, compared with OCs containing third generation progestagens. The possible difference on the venous side seems to be smaller than primarily anticipated. RESULTS: Young women without any known risk factor for thrombotic diseases may use any low-dose OC. If OCs are prescribed to women with known risk factors for arterial thrombotic disease; e.g. smoking, diabetes, controlled hypertension, migraine without aura, family disposition of acute myocardial infarction (AMI) or thrombotic stroke, a low-dose pill with a third generation progestagen may have an advantage. If OCs are considered for women with risk factors for venous disease such as severe obesity, varicose veins, family history of VTE or with factor V Leiden mutation, a low-dose combined pill with a second generation progestagen may be preferable. In women above 30 years, OCs with third generation progestagens generally seem to confer less overall thrombotic morbidity, mortality and disability than OCs with second generation progestagens. These women should reconsider, however, the indication of combined OCs in the presence of significant risk factors of thrombotic diseases.

PIP: This article discusses available scientific data on oral contraceptives (OCs) and thrombotic diseases and provides tentative prescription recommendations of OCs to women, with and without various thrombotic risk factors. Several studies concerning OCs and venous thromboembolism (VTE), including the original studies serving as scientific databases, were presented. VTE was twice as common as arterial complications in women 15-29 years old, while arterial complications were 50% higher than VTE in women between 30 and 44 years of age. The mortality of arterial disease was 3.5 times higher than the number of deaths from venous disease in women below 30 years, and 8.5 times higher in women aged 30-44 years. The available scientific data suggests a differential influence of OCs with second and third generation progestagens on the risk of venous and arterial diseases. From this consensus, a low-dose OC was prescribed for young women without any known risk factor for thrombotic diseases. Women with a known risk factor for arterial thrombotic disease, a low-dose pill with a third generation progestogen, may have an advantage while a low-dose pill combined with a second generation progestogen was preferable for women with risk factors for venous disease. In women above 30 years, OCs with third generation progestagens generally seem to confer less overall thrombotic morbidity, mortality, and disability than OCs with second generation progestagens. These women should reconsider, however, the indication of combined OCs in the presence of significant risk factors of thrombotic diseases.

Randomized comparison of oral and transdermal hormone replacement on carotid and uterine artery resistance to blood flow.

OBJECTIVE: To compare the long-term effects of oral and transdermal hormone replacement therapy (HRT) on carotid and uterine vascular impedance. METHODS: Sixty-three postmenopausal women were randomized to 1 year's treatment with oral or transdermal sequential combined HRT. Carotid and uterine artery pulsatility indices (PIs) were assessed by color Doppler at baseline, and after 2, 6, and 12 months of treatment. Fifty-eight women completed the trial, 27 in the oral and 31 in the transdermal group. In a subgroup of 30 women, we also performed Doppler measurements in the estrogen-progestin combined phase. The study had 90% power to detect a difference between treatment groups of 0.05 in the carotid artery and of 0.25 in uterine artery PI at the 5% significance level. RESULTS: The carotid PI decreased significantly (P < .001) and similarly during both regimens. This drop was already clearly detectable during the second month, from 0.97 (0.95, 1.01) (mean and 95% confidence intervals [CII) to 0.94 (0.91, 0.97) in the oral and from 0.98 (0.94, 1.00) to 0.92 (0.89, 0.95) in the transdermal group, but it continued up to 12 months (0.85 [0.82, 0.88], 13% of baseline values in the oral group and 0.84 [0.81, 0.871, 14% in the transdermal group). In the uterine arteries, the drop in PI was steeper and greater and reached its maximum at 6 months (39% and 40%, respectively). Drops in carotid and uterine PI correlated positively with baseline PI values, but were not affected by patient age, time from menopause, previous HRT and smoking. Addition of norethisterone acetate did not counteract drops in carotid and uterine PI in either group. CONCLUSION: Oral and transdermal sequential HRT are similarly effective at 1 year in reducing impedance to flow in carotid and uterine circulation. This long-term vascular effect might explain how HRT protects women from cardiovascular disease.

Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy.

OBJECTIVE: To study whether levothyroxine (LT4) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. DESIGN AND METHODS: Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH)2-D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age- and sex-matched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT4 (a mean daily dose of 215 microg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. RESULTS: When on T4 therapy, patients had significantly higher mean levels of ALP (+21%, P < 0.05), OC (+35%, P < 0.01), PICP (+10%, P < 0.05), PINP (+46%, P < 0.001), ICTP (+21%, P < 0.05), and HOP (+37%, P < 0.001) compared with controls. After stopping treatment, OC (-42%, P < 0.001), PINP (-7%, P < 0.05), and ICTP (-54%, P < 0.001) decreased, whereas PICP (+24%, P < 0.001) and 1,25(OH)2D (+29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. CONCLUSIONS: Patients with differentiated TC have high bone turnover when on LT4 suppressive therapy, After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.

The long-term effects of oral and transdermal postmenopausal hormone replacement therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane.

OBJECTIVE: Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin- and thromboxane A2, all of which may be factors in the protective effect of HRT against cardiovascular disorders. DESIGN: Prospective, randomized study. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Fifty-two healthy postmenopausal female nonsmokers (n = 42) or smokers (n = 10) who had climacteric symptoms. INTERVENTION(S): The women received either oral HRT (2 mg of estradiol on days 1-12, 2 mg of estradiol plus 1 mg of norethisterone acetate on days 13-22, and 1 mg of estradiol on days 23-28; n = 21) or transdermal HRT (50 microg/d of estradiol on days 1-28 followed by 250 microg/d of norethisterone acetate on days 14-28; n = 21) for 1 year. Ten female smokers received transdermal HRT for 1 year. MAIN OUTCOME MEASURE(S): Plasma levels of nitrate as an index of nitric oxide production, endothelin-1, and urinary output of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha) and that of the thromboxane A2 metabolite (2,3-dinorthromboxane B2) were measured before and during the combined phases of the 2nd, 6th, and 12th treatment months. RESULT(S): Both regimens increased plasma estradiol levels and alleviated vasomotor symptoms. Neither regimen caused significant changes in nitrate, endothelin-1, prostacyclin, or thromboxane A2 in nonsmoking women. Female smokers had significantly higher levels of endothelin-1, which were significantly reduced by transdermal HRT at 6 months of treatment. CONCLUSION(S): Nitric oxide, endothelin-1, prostacyclin, and thromboxane A2 are not of primary importance in the protective effect of sequential oral HRT against cardiovascular disorders in otherwise healthy nonsmoking postmenopausal women. In this regard, transdermal HRT appears comparable to oral HRT. Postmenopausal female smokers have high levels of endothelin-1 that are reduced by transdermal HRT.

Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties.

The levonorgestrel-releasing intrauterine device LNg IUD is a new contraceptive method that combines the advantages of both hormonal and intrauterine contraception. It gives users non-contraceptive health benefits and can also be used as an effective therapy for menorrhagia. The local release of LNg within the endometrial cavity results in strong suppression of endometrial growth as the endometrium becomes insensitive to ovarian estradiol. The endometrial suppression is the reason for a significant reduction of menstrual blood loss or amenorrhea, and for the disappearance of dysmenorrhea. The bleeding pattern during the use of the LNg IUD is characterized by reduction of the blood loss and in the number of bleeding days per cycle. During the first two to three months of use, however, irregular spotting is common. The removal of the device results in a quick return of menstrual bleeding and fertility. The failure rate of copper-releasing IUDs, as with other methods of fertility regulation, is higher in young women and decreases with age. The LNg IUD, on the other hand, has the same low pregnancy rate in every age group of the users. The LNg IUD also gives protection against ectopic pregnancy and pelvic inflammatory disease and, by reducing menstrual blood loss, increases the body iron stores. The LNg IUD can be used to effectively treat menorrhagia. This has been demonstrated in studies with quantitative determination of menstrual blood loss. During the first year of use, the LNg IUD reduced menstrual blood loss by 90% from pretreatment levels. Comparative clinical trials with the LNg IUD cover more than 10,000 women-years of follow-up during use over five to seven years. The Pearl pregnancy rate in studies has been 0.0-0.2 per 100 women-years. The overall ectopic Pearl pregnancy rate is 0.02 per 100 woman-years. The LNg IUD is marketed in Denmark, Finland, Norway, Sweden and in the United Kingdom.

PIP: The levonorgestrel-releasing intrauterine device (LNg IUD) is a new contraceptive method which combines the advantages of both hormonal and intrauterine contraception. It confers noncontraceptive health benefits and can also be used as an effective therapy for menorrhagia. The new device is currently being marketed in Denmark, Finland, Norway, Sweden, and the UK. Comparative clinical trials with the LNg IUD cover more than 10,000 women-years of follow-up during use over 5-7 years. The Pearl pregnancy rate has been 0.0-0.2 per 100 women-years and the overall ectopic Pearl pregnancy rate is 0.02 per 100 woman-years. The local release of LNg in the endometrial cavity results in the strong suppression of endometrial growth as the endometrium becomes insensitive to ovarian estradiol. The endometrial suppression is the reason for a significant reduction of menstrual blood loss or amenorrhea, and for the disappearance of dysmenorrhea. Use of the LNg IUD results in the reduction of blood loss and in the number of bleeding days per cycle. Irregular spotting is, however, common during the first two-three months of use. The reduction in menstrual blood loss results in an increased storage of iron in the body. Menstrual bleeding and fertility are quickly restored following removal of the device. Finally, unlike copper-releasing IUDs, the failure rate of the LNg IUD is not dependent upon the user's age, and it protects against ectopic pregnancy and pelvic inflammatory disease.