The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study

A cohort of 485 couples starting their first in-vitro fertilization(IVF) attempt between January, 1989 and February, 1991 inclusive,were followed until June 1, 1992. A total of 1086 treatmentcycles were initiated (mean 2.2, range 1–6). Of these,235 (21.8%) cycles were cancelled, giving a total of 851 embryoreplacements (mean 1.7, range 1–5). After IVF treatment,189 women have either delivered or have an ongoing pregnancyin the second or third trimester. This gives a baby take-homerate of 17.4% per started cycle and 22.2% per embryo replacement.For 91 (18.6%) of the couples, the treatment was abandoned priorto completion of the three scheduled IVF attempts and 57 (11.7%)of these had no completed IVF cycles. In the group of coupleswith reduced sperm quality, the delivery rate was significantlylower than that of the other groups. A total of 193 women hadembryos cryopreserved in at least one IVF cycle; 124 of thesewomen started a frozen embryo replacement cycle and 88 had atleast one cycle with replacement of frozen/thawed embryos, resultingin 25 deliveries/ongoing pregnancies. Due to the Norwegian lawon assisted procreation 65 (33.7%) of the women have had theirfrozen embryos thawed and discarded after 12 months of storage.The cryopreservation programme, with the limitations of theNorwegian law, gives a 5.2% increase in the baby take-home ratefor women entering the IVF programme, an increase of 13.2% inthe number of ongoing pregnancies/deliveries and an 11.6% increasein number of children/viable fetuses. A total of 214 women havedelivered or have ongoing pregnancies in the second or thirdtrimester. This represents 44.1% of the 485 women accepted forIVF treatment, irrespective of whether they were treated ornot, and 50.0% of those couples who completed at least one IVFcycle.     

Evidence for the existence of two forms of α2A-adrenoceptors in the rat

Summary The _2A-adrenoceptors in rat spleen, kidney, spinal cord and cerebral cortex were studied using [³H]-RX821002 radioligand binding. In the spleen, spinal cord and cerebral cortex, the ligand bound to saturable sites with a K _d of about 1 nmol/l and capacities of 134, 240 and 290 fmol/mg protein, respectively. Computer modelling competition curves for 39 drugs, including those for _2A-, _2B- or _2C-adrenoceptor selective drugs, indicated that the sites labelled by [³H]-RX821002 in the spleen consisted of a single population of _2A-adrenoceptors. However, the competition curves for guanoxabenz were definitely biphasic and resolved into two site fits, indicating that guanoxabenz was binding to both high affinity (K _d = 35 nmol/1) and low affinity (K _d = 8900 nmol/1) _2A-adrenoceptor sites in the proportions 57% and 43%, respectively. The K _d ^Sfor a number of ₂-adrenoceptor subtype selective drugs, measured in competition with [³H]-RX821002 in cerebral cortex and spinal cord, were highly correlated with those obtained in the spleen indicating their _2A-adrenoceptor nature. However, by contrast to the results with the spleen, the guanoxabenz competition curves for the spinal cord and cerebral cortex were monophasic and resolved only into one site fits, the K _d of guanoxabenz being about 4000 nmol/l for both tissues. Drug K _d ^Sfor kidney _2A-adrenoceptors were also determined using [³H]-RX821002. For nearly all drugs tested, the K _d ^Swere highly correlated with those found for the _2A-adrenoceptors in the other rat tissues. However, for guanoxabenz, the data indicated that it competed with [³H]-RX821002 at a single _2A-adrenoceptor site with a K _d of 39 nmol/1. When the rat _2A-adrenoceptor gene RG20 was transiently expressed in COS-7 cells and its ligand binding properties probed using [³H]-RX821002, the drug K _d ^Sobtained were also highly correlated with those found for the _2A-adrenoceptors in the spleen, cerebral cortex, spinal cord and kidney of the rat. For the RG20 encoded receptor, the guanoxabenz competition curves were steep and monophasic and modelled best into one site fits, with the Kd of guanoxabenz being 5200 nmol/1.It is suggested that guanoxabenz can differentiate between two forms of _2A-adrenoceptors in the rat: _2A1 and _2A2. The _2A1-form is present in the spleen and kidney where it shows a high apparent affinity for guanoxabenz. The _2A2-form shows a low apparent affinity for guanoxabenz and is present in the spleen, cerebal cortex and spinal cord. The _2A2-form of the rat ₂-adrenoceptor appears to be encoded by the RG20 gene. The _2A, and _2A2-adrenoceptor forms do not represent high and low affinity receptor forms for agonists because assays included EDTA, Gpp(NH)p and Na⁺, which eliminated the high affinity receptors for agonists.     

The disappearance of multiresistant Staphylococcus aureus in Denmark: changes in strains of the 83A complex between 1969 and 1989.

During the 1960s multiresistant strains of Staphylococcus aureus were problematic in Denmark and other countries. An analysis of the phage types and antibiotic resistance patterns of S. aureus strains collected from approximately 20,000 Danish patients per year has given us a general picture of the evolution of S. aureus in Denmark during the last 30 years. Multiresistant S. aureus (i.e., strains resistant to penicillin, streptomycin, and tetracycline and often to methicillin and erythromycin as well) belonged mostly to the 83A complex, a relatively homogeneous subset of group III strains that can be further divided into six subtypes. The disappearance of multiresistant strains in Denmark began with a decline in the frequency of isolation of the most resistant subtypes, which was followed by a gradual decrease in the resistance of all 83A subtypes; thus strains of the 83A complex ultimately became no more resistant than other strains. As the proportion of strains of S. aureus accounted for by the 83A complex declined from 24% in 1969 to 6% by the late 1980s, this complex was replaced by strains of type 95, the 94,96 complex, and group II, all of which only rarely show resistance to multiple agents.     

A dietary and behavioural programme for the treatment of obesity. A 4-year clinical trial and a long-term posttreatment follow-up

OBJECTIVES: To evaluate weight loss maintenance after 4 years of nonpharmacological, nonsurgical obesity treatment, including a very low calorie diet (VLCD), diet and behavioural support. Furthermore, to assess weight development amongst completers and noncompleters beyond the active 4-year treatment period. DESIGN: Clinical trial. SETTING: Two Swedish county hospitals. SUBJECTS: A total of 113 patients were randomized to a 2-year treatment programme with or without an initial VLCD period. The 87 patients who completed the 2-year programme were offered the chance to continue a support programme for another 2 years. A total of 55 patients completed the entire 4-year programme. INTERVENTIONS: All the patients took part in a comprehensive support programme, including a hypocaloric diet and behavioural support, either as single treatment (non-VLCD group) or following the VLCD period (VLCD group). RESULTS: Significant 4-year weight losses were found in both groups, 7.6 +/- 12.2 kg (VLCD group) and 6.3 +/- 8.5 kg (non-VLCD group), (P < 0.01, n.s. between groups). The completers (n = 55) had maintained a weight loss of 3.3 +/- 10.7 kg (P < 0.05) 8 years after randomization. After 6 years, the noncompleters (n = 58) had gained 3.2 +/- 9.7 kg compared with baseline (P < 0.05). The difference in weight change between completers and non-completers was highly significant (P < 0.01). CONCLUSIONS: Highly significant weight losses can be maintained after a 4-year comprehensive treatment programme, including a hypocaloric diet and behavioural support. An initial VLCD period did not significantly affect the long-term weight loss. The posttreatment long-term weight loss was larger amongst completers than amongst patients who did not complete the treatment.     

High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation

OBJECTIVES: To evaluate the results of treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO), minimal sedation, and pressure supported ventilation. DESIGN AND SETTING: Observational study in a tertiary referral center, Intensive Care Unit, Astrid Lindgren Children's Hospital at Karolinska Hospital, Stockholm, Sweden. SUBJECTS AND METHODS: Seventeen adult patients with ARDS were treated with venovenous or venoarterial ECMO after failure of conventional therapy. The Murray score of pulmonary injury averaged 3.5 (3.0-4.0) and the mean PaO2/FIO2 ratio was 46 (31-65). A standard ECMO circuit with nonheparinized surfaces was used. The patients were minimally sedated and received pressure-supported ventilation. High inspiratory pressures were avoided and arterial saturation as low as 70% was accepted on venovenous bypass. RESULTS: In one patient a stable bypass could not be established. Among the remaining 16 patients 13 survived (total survival rate 76%) after 3-52 days (mean 15) on bypass. Major surgical procedures were performed in several patients. The cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. CONCLUSION: A high survival rate can be obtained in adult patients with severe ARDS using ECMO and pressure-supported ventilation with minimal sedation. Surgical complications are amenable to surgical treatment during ECMO. Bleeding problems can generally be controlled but require immediate and aggressive approach. It is difficult or impossible to decide when a lung disease is irreversible, and prolonged ECMO treatment may be successful even in the absence of any detectable lung function.     

Neurological signs are common in patients with urodynamically verified "idiopathic" bladder overactivity

Overactive bladder dysfunction is an expression of defective neuromuscular control of the lower urinary tract. The causes and the way to classify this problem are currently under debate. In some patients the overactive bladder is one sign of a neurological disorder, in so called "idiopathic detrusor instability" the cause is less obvious. That an overactive bladder has a neurogenic cause is a reasonable hypothesis. We made a detailed neurological investigation in 45 patients with idiopathic overactive bladder. Cerebrospinal fluid (CSF) was examined and blood tests for vitamin B(12)and folic acid deficiency were checked, too. In 37 of the 45 patients (82%) pathological signs were observed in the neurological tests. The most common finding was central or peripheral paresis of the legs appearing in 24 patients (53%). Of the 45 patients, eight received a neurological diagnosis, definite or possible MS or dorsal column sensation neuropathy. The results of this study give an indication of the importance of the neurological examination and suggest that neuropathy might not be uncommon in patients with so-called idiopathic detrusor instability. This also invites to reconsideration of the current classification. It is possible that a new classification based on a functional view could provide a better fundament in the search of etiologic and pathogenetic factors and also guide in the selection of the treatment most optimal for the individual patient.     

Ultrasound contrast agents and their use in urogenital radiology: status and prospects

The analysis of bone structure in vivo is an important goal in osteoporosis, because the determination of bone mineral density alone is insufficient to predict whether an individual patient will eventually suffer an osteoporotic fracture or not. An additional structural analysis may significantly improve the statistical assessment of fracture risk. In this study we present a method to generate realistic although enlarged 3D phantoms of trabecular bone. These phantoms are useful in characterizing the potential of in vivo imaging procedures for the analysis of bone structure and to verify textural or structural analysis methods applied to these images. Our phantoms are based on a real trabecular bone specimen that was converted to a plastic model using the technique of stereolithography. The trabecular network is modeled by hydroxyapatite. Limitations of the stereolithographic process prevent the generation of exact 1:1 replicas of the real bone. A histomorphometric analysis of μCT scans of the phantoms showed that an excellent replication of the bone structure could be achieved in phantoms enlarged by a factor of 2.5 with "trabecular" hydroxyapatite concentrations up to 400 mg/cm³. In order to demonstrate the usefulness of our phantoms, we investigated one of them with various thin-slice CT protocols using clinical single- and multi-slice spiral CT scanners. The enlargement of the phantoms limits their use on high spatial resolution CT scanners (resolution >20 lp/cm). The limited hydroxyapatite concentration requires enhanced exposure rates for the phantoms scans to offset the larger impact of noise due to the lower contrast in the phantoms. Electronic Publication     

Psychiatric manifestations of autoimmune disorders

Opinion statement Psychiatric symptoms are common to many autoimmune disorders. Patients often will have mood disorders, anxiety, cognitive deficits, delirium, and psychosis. These symptoms may reflect the direct or indirect effect of the autoimmune disorder on the central nervous system, may be related to medications used to treat the disorder, or may be a direct psychologic impact from suffering with the autoimmune disorder. Accurately recognizing the psychiatric component and generating a differential diagnosis is a complex task for the treating physician. Treatment of the psychiatric component to the disorder often will include addressing steroid induced side effects, psychotropic medications, psychotherapy, patient and family education, and a strong physician-patient relationship.