Who will conceive with IVF?

When considering the chances of establishing a healthy ongoing pregnancy after in vitro fertilization (IVF), the cause of infertility plays a relatively minor role. In recent years, there has been a shift from determining the diagnosis to the individual prognosis for a given patient. A number of prognostic factors were identified, which enabled clinicians to appropriately counsel patients. Patient-determined factors are of crucial importance and some are amenable to intervention such as lifestyle and nutritional advice. However, the attention of clinicians remains on seeking adjuvant therapeutic interventions designed to improve the outcomes of IVF treatment. In this article, the patient-determined factors underlying the individual chance of conceiving and the more commonly prescribed empirical medical therapies prescribed to enhance outcomes are reviewed. It is concluded that greater attention to optimizing the health of the couple before starting IVF treatment may be more beneficial than adjuvant medical therapies during treatment.     

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Prospective comparison of hip fracture treatment: 856 cases followed for 4 months in The Netherlands and Sweden

In a prospective multicenter study 1115 hip fracture patients were registered in Rotterdam (The Netherlands), Sundsvall and Lund (Sweden). The patients had similar background parameters with a mean age of 78 years, about half of them living alone and just above 80 percent coming from independent living

For cervical fracture, hemiarthroplasty was the predominating treatment in Rotterdam (n 169), whereas osteosynthesis was used in Sundsvall (screws n 135) and Lund (hook-pins n 148). The mean (median) hospitalization time was 32 (20) days in Rotterdam, 16 (12) days in Sundsvall, and 17 (10) days in Lund. Discharge to independent living varied from 53 percent in Lund to 72 percent in Sundsvall. Functional outcome (walking ability and ADL capacity) was at 4 months similar in all groups, but at 2 weeks was lower in Rotterdam. Mortality at 2 weeks / 1 month 14 months was in Rotterdam 4/9/20, in Sundsvall 2/4/13, and in Lund 01311 0 percent.

Trochanteric fractures were treated by screwplate in Rotterdam (n 146) and Lund (n 78), and by Ender nails in Sundsvall (n 11 7). The mean (median) hospitalization time was in Rotterdam 39 (29) days, in Sundsvall 24 (1 5) days and in Lund 19 (11) days. Discharge to independent living varied from 41 percent in Lund to 57 percent in Sundsvall. Functional outcome was similar between the groups. Mortality at 2 weeks / 1 month 14 months was in Rotterdam 2/6/14, in Sundsvall 611 2/19 and in Lund 12/12/18 percent.

Thus, our study has shown that it is possible to perform a prospective multicenter study involving different European countries. The functional out- come after 4 months was very consistent between the centers studied, irrespective of choices made concerning operation method and rehabilitation routines. However, a difference in mortality within these first postoperative months was found, which seems attributable to the operation procedure.     

Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis.

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.     

A randomized clinical trial with a 0.6% amino acid/ 1.4% glycerol peritoneal dialysis solution.

BACKGROUND: Glucose is an accepted osmotic agent for peritoneal dialysis (PD) although it has several drawbacks. Some of these drawbacks have been addressed by the introduction of solutions with low glucose degradation products and physiological pH in dual-chambered bags. Despite this achievement, there is a need for alternative osmotic agents.This randomized clinical trial analyzes 3-month's clinical experience with a mixture of 0.6% amino acids and 1.4% glycerol. METHODS: The study was performed at the renal units of the University Hospitals Ghent, Belgium, and Utrecht, The Netherlands. Stable PD patients were randomized for either protocol A (test solution, n = 5) or protocol B (control regimen, n = 5). In both protocols, there was a run-in phase of 1 month with a dialysis regimen of 2 x 2 L 2.27% glucose solution (Dianeal; Baxter, Nivelles, Belgium), 1 x 2 L Extraneal (Baxter), and 1 x 2 L glucose solution (Dianeal). After this month-long run-in period, patients in group A received during 3 months 2 x 2 L amino acid/glycerol solution, 1 x 2 L Extraneal, and at least 1 x 2 L of a classic glucose solution. RESULTS: Glucose absorption decreased in the test group during the test phase (from 84.2 +/- 8.7 to 11.7 +/- 11.6 g/24 hours, p = 0.001). Dialysate levels of cancer antigen 125 (CA125) increased in the test group, from 17.5 +/- 11.0 to 32.4 +/- 4.6 units/L (p = 0.04), whereas, in the control group, the levels remained stable (15.5 +/- 8.7 and 14.9 +/- 9.8 units/L respectively, p = 0.4).There were no differences in serum urea, serum bicarbonate, serum osmolarity, serum albumin, or parameters related to skin-fold thickness or serum glycerol levels between control and test solutions. No differences were observed in obtained ultrafiltration after a 4-hour dwell with 2.27% glucose or the test solution, both measured at week 4 of the run-in period and week 12 of the test period. CONCLUSION: This study demonstrated that the use of a new 0.6% amino acid/1.4% glycerol-containing dialysis solution is safe and well tolerated. Glucose load was reduced significantly and dialysate CA125 levels improved significantly. Ultrafiltration was comparable with that of a 2.27% glucose solution. All these factors, in combination with the potential nutritional benefits, can contribute to a beneficial impact on the success of the PD technique. Further long-term studies in larger patient groups are warranted to explore the potential of this promising new solution.     

Prognosis of trochanteric pain in primary care

BACKGROUND: Trochanteric pain is the second most important diagnosis of hip problems presenting in primary care, but its incidence and prognosis in this context is largely unknown. AIM: To determine the 1- and 5-year prognoses of trochanteric pain and the predictive variables for consistent complaints. DESIGN OF THE STUDY: Retrospective cohort study. SETTING: One hundred and sixty-four patients (mean age = 55 years, 80% female) with incidental trochanteric pain in the years 1996 or 2000 were asked in 2001 for past and present symptoms of trochanteric pain. Therapeutic interventions, demographic factors and comorbidity were also investigated. METHOD: The databases of 39 GPs were screened in order to identify all incident cases with a suspicion of trochanteric pain in the years 1996 or 2000. These cases were sent a questionnaire. RESULTS: The incidence of trochanteric pain in primary care is 1.8 patients per 1000 per year. After 1 year at least 36% still suffered from trochanteric pain, and after 5 years this was 29%. Patients with osteoarthritis (OA) in the lower limbs had a 4.8-fold risk of persistent symptoms after 1 year, as compared to patients without OA. Patients who had received a corticosteroid injection had a 2.7-fold chance of recovery after 5 years, as compared with patients who had not received an injection. CONCLUSION: Trochanteric pain is shown to be a chronic disease in a substantial number of patients. The disorder is associated with much impairment when conducting daily activities.     

Avantage double mobility press--fit cup in total hip arthroplasty]

The Avantage double mobility press-fit cup was devised by Dr. Bousquet in the 70's to bring reasonable response to a problem of recurrent dislocation after total hip arthroplasty. The cup is attached to the femoral head by a bipolar polyethylene liner. The polyethylene liner moves freely inside a shiny--polished metal cup. The angular range of motion before impingement is increased by the mobility of the liner. The double connection (cup-liner, liner-head) reduces the stress on the metal cup and improve the stability of the prosthesis. The solution has proved to be efficient in reducing dislocation risk and maintains at the same time the appropriate range of motion. Between January 2004 and November 2005, 113 hip arthroplasties in 108 women with use of the double mobility cup were performed. The cemented version of the Avantage cup was inserted in 15 patients (mean age--76.9 years). Uncemented, HA coated implant was used in 98 patients (with mean age of 55 years). The mean follow-up was 20.4 months. No one patient was lost to follow-up. No postoperative dislocation was observed during follow-up. There was no unwanted leg lengthening greater than 1 cm. The Avantage cup may be indicated in any primary total hip arthroplasty especially in those with increased risk of postoperative dislocations. This cup enables a correct balance of the hip without a need of the unwanted lengthening of the leg.     

A family with visceral course of Niemann-Pick disease,macular halo syndrome and low sphingomyelin degradation rate

Summary We report a family with six patients suffering from a sphingomyelinase-deficient form of Niemann-Pick disease, all presenting with a visceral course of the disease. Retinal changes classified as macular halos in four members indicated neuronal storage and therefore an intermediate type of the disease. For further classification of the biochemical type, [choline-methyl-¹⁴C]sphingomyelin degradation studies were carried out in fibroblast cultures of all six members. The low degradation rates measured were similar to those usually found in the neuronopathic form (type A) of Niemann-Pick disease. This family illustrates the broad heterogeneity within the sphingomyelinase deficiency group of the Niemann-Pick disease. Apparently the finding of a low sphingomyelin degradation rate in fibroblast cultures does not necessarily imply a typical serious and lethal course of the disease.