Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis.

BACKGROUND: Understanding the true prevalence of lymphangioleiomyomatosis (LAM) is important in estimating disease burden and targeting specific interventions. As with all rare diseases, obtaining reliable epidemiological data is difficult and requires innovative approaches. AIM: To determine the prevalence and incidence of LAM using data from patient organizations in seven countries, and to use the extent to which the prevalence of LAM varies regionally and nationally to determine whether prevalence estimates are related to health-care provision. METHODS: Numbers of women with LAM were obtained from patient groups and national databases from seven countries (n = 1001). Prevalence was calculated for regions within countries using female population figures from census data. Incidence estimates were calculated for the USA, UK and Switzerland. Regional variation in prevalence and changes in incidence over time were analysed using Poisson regression and linear regression. RESULTS: Prevalence of LAM in the seven countries ranged from 3.4 to 7.8/million women with significant variation, both between countries and between states in the USA. This variation did not relate to the number of pulmonary specialists in the region nor the percentage of population with health insurance, but suggests a large number of patients remain undiagnosed. The incidence of LAM from 2004 to 2008 ranged from 0.23 to 0.31/million women/per year in the USA, UK and Switzerland. CONCLUSION: Using this method, we have found that the prevalence of LAM is higher than that previously recorded and that many patients with LAM are undiagnosed.

Emerging clinical picture of lymphangioleiomyomatosis.

OBJECTIVE: To provide a comprehensive update of the clinical picture of lymphangioleiomyomatosis (LAM) using two large patient registries. METHODS: A cross sectional questionnaire survey which included questions on 14 LAM symptoms, pneumothorax, tuberous sclerosis complex (TSC), date of diagnosis, and pulmonary function tests (PFTs). RESULTS: The response rate was 70.5% (n = 328). The mean age at the time of the survey was 46.7 years. The mean age at diagnosis was 42.7 years for women diagnosed 1 year before the survey and 35.8 years for women diagnosed 10 years previously. The main symptoms were dyspnoea (74%), fatigue (72%), cough (47%) and chest pain (44%); younger patients (<40 years) were less likely to report dyspnoea (p = 0.02). Patients with TSC (n = 51) were less likely to report dyspnoea (p = 0.05) and 76.5% reported angiomyolipoma (p < 0.0001) compared with patients with sporadic LAM. Patients with pneumothorax (63.0%) were less likely to report dyspnoea or fatigue (p < or = 0.05) than patients without pneumothorax. PFT results showed that low forced expiratory volume in 1 second and carbon monoxide transfer factor were highly associated with dyspnoea (p < 0.0001), but not with fatigue or history of pneumothorax. CONCLUSION: Previously considered a condition of women of childbearing age, more older women (50% without pneumothorax) are now being diagnosed with LAM. LAM should be considered in women over 40 with unexplained dyspnoea. LAM patients with pneumothorax have less fatigue and less dyspnoea than those without pneumothorax. Fatigue has been overlooked as a symptom of LAM and appears across the spectrum of pulmonary function.

A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery.

BACKGROUND: The incidence of blood transfusion in coronary artery bypass graft (CABG) surgery remains high. Preoperative identification of those at high risk for requiring blood will allow for the cost-effective use of some blood conservation modalities. Multivariable analysis techniques were used in this study to develop a prediction rule for such a purpose. STUDY DESIGN AND METHODS: Data were prospectively collected for all patients undergoing elective first-time CABG surgery from January 1997 to September 1998 at a tertiary-care teaching hospital (n = 1007). The prediction rule was developed on the first two-thirds of the sample by using logistic regression methods to examine the relationship of patient demographics, comorbidities, and preoperative Hb with perioperative blood transfusion. The remaining one-third of the sample was used to validate the rule. RESULTS: The transfusion rate was 29.4 percent. The prediction rule included preoperative Hb (g/dL, OR 0.928, p<0.0001), weight (kg, OR 0.938, p<0.0001), age (years, OR 1.037, p<0.01), and sex (male/female, OR 0.493, p<0.01); receiver operating characteristic = 0.86. When externally validated, the rule had a sensitivity of 82.1 percent and a specificity of 63.6 percent (at a selected probability cutoff). CONCLUSION: A simple and valid prediction rule is developed for predicting the risk of blood transfusion in patients undergoing first-time elective CABG surgery.

Asymmetry: molecular, biologic, embryopathic, and clinical perspectives.

This overview of asymmetry addresses the following topics: chiral molecules; asymmetric signaling molecules, including N-cadherin, Shh, Fgf8, lefty1, lefty2, nodal, Pitx2, activin betaB, activin receptor IIA, and cSnR; situs abnormalities; asymmetric cell division; laterality in humans and animals; behavioral asymmetry in humans and animals; asymmetric embryopathies, including Tessier-type "clefts"; hemiasymmetries such as hemihyperplasia, hemihypoplasia, and hemiatrophy; asymmetric vascular syndromes, including Klippel-Trenaunay and Sturge-Weber syndromes; plagiocephaly of the synostotic and deformational types; somatic mosaicism, including a discussion of McCune-Albright syndrome, fibrous dysplasia, GNAS1 mutations, and Proteus syndrome.

Association of perforation of the appendix with female tubal infertility.

Although perforation of the appendix is considered a risk factor for female tubal infertility, the epidemiologic evidence supporting this relation is inconsistent. Risk factors for tubal infertility were compared for 121 women with documented primary tubal infertility attending in vitro fertilization clinics in Toronto, Canada, from July to December 1998 and 490 controls who were pregnant during the same time period. Self-administered questionnaires and review of medical records were used to assess exposures. The authors found that neither history of acute appendicitis nor perforation of the appendix was a statistically significant risk factor for tubal infertility. The crude odds ratio for perforated appendicitis was 3.4 (95% confidence interval (CI): 0.9, 12.9), and the adjusted odds ratio was 1.4 (95% CI: 0.3, 6.2). In addition to increased age and annual income, cigarette smoking (odds ratio (OR) = 2.0, 95% CI: 1.2, 3.2), history of endometriosis (OR = 6.0, 95% CI: 2.8,12.8), and history of pelvic inflammatory disease (OR = 6.0, 95% CI: 2.8, 12.8) were significantly associated with tubal infertility in multivariate analysis. These data do not provide substantial evidence that perforation of the appendix is an important risk factor for female tubal infertility.

Weaver syndrome with neuroblastoma and cardiovascular anomalies.

We report on an infant with Weaver syndrome, neoplasia and cardiovascular anomalies. Stage 4S neuroblastoma underwent spontaneous resolution. Three neoplasms have been reported in Weaver syndrome: another stage 4S neuroblastoma [Muhonen and Menezes, 1990: J Pediatr 116:596-599], an ovarian endodermal sinus tumor [Derry et al., 1999: J Med Genet 36:725-728], and a sacrococcygeal teratoma [Kelly et al., 2000: Am J Med Genet 95:492-495]. No case was associated with cardiovascular anomalies. Our patient had VSD and PDA, and although several other patients with Weaver syndrome have had cardiovascular anomalies, they were shown not to have neoplasia.

Osteomyelitis in the diabetic patient: diagnosis and treatment. Part 2: Medical, surgical, and alternative treatments.

In the diabetic population, wound and foot infections are often mixed, containing from three to six organisms. This creates a significant problem regarding antibiotic protocols. Many of these episodes result in contiguous bone infections with subsequent erosive changes, sequestra, and involucrum. A multidisciplinary approach to treatment is often required. Studies have shown that a protocol of 6 weeks of intravenous antibiotics may be appropriate to treat osteomyelitis; however, this is controversial and often not curative. Osteomyelitis is a surgical disease; a subtle balance between medical and surgical therapy is necessary if a potentially curative outcome is to be achieved. The duration of antibiotic therapy may be shortened considerably after surgical intervention. In cases of infection mitigated by severe peripheral vascular disease, end-stage renal disease, diabetes, or other medical problems where surgery is not an option, long-term antibiotics may be used as suppressive therapy along with adjunctive local treatments. The following is the second article of a two-part series. The first paper discussed the diagnosis and microbiology of contiguous osteomyelitis in the diabetic foot. This article outlines the various medical, antibiotic, and surgical options available to the clinician. Adjunctive and alternative therapies also are discussed.

Merging the old skeletal biology with the new. I. Intramembranous ossification, endochondral ossification, ectopic bone, secondary cartilage, and pathologic considerations.

Skeletogenesis and chondrogenesis result from a sequence of events involving epithelial-mesenchymal interaction, condensation, and differentiation. Types of bone and cartilage formation include: (1) intramembranous ossification, (2) endochondral ossification, (3) combined endochondral and intramembranous ossification, (4) heterotopic bone and cartilage formation, and (5) secondary cartilage formation. Pathologic conditions with bone and cartilage include: (1) benign and malignant tumors and (2) reactive osseous and cartilaginous metaplasia.

Merging the old skeletal biology with the new. II. Molecular aspects of bone formation and bone growth.

Molecular aspects of bone formation and bone growth are discussed together with selected genetic disorders of the involved genes. Topics covered include: collagenopathies and osteogenesis imperfecta; core binding factor transcription factors and cleidocranial dysplasia; bone morphogenetic proteins and fibrodysplasia ossificans progressiva; transforming growth factor beta, suture closure, and craniosynostosis; Indian hedgehog, parathyroid hormone-related protein together with its receptor, and Jansen metaphyseal chondrodysplasia.

Predicting difficult intubation: a multivariable analysis.

PURPOSE: To develop a clinically useful and valid model for predicting difficult laryngoscopic tracheal intubation in patients with seemingly normal airways by adhering to the principles of multivariable model development. METHODS: This was an observational study performed at a tertiary-care teaching hospital. Preoperatively, 444 randomly selected patients requiring tracheal intubation for elective surgery were assessed. In addition, 27 patients in whom tracheal intubation was difficult, but were not assessed preoperatively, were assessed postoperatively. One assessor, blinded to the intubation information, collected the predictor variables. A reliable definition for difficult intubation was used and all attempts were made to eliminate sources of bias. Multivariable modeling was performed using logistic regression and the model was validated using the bootstrapping technique. RESULTS: Of the 461 patients included in the analysis, 38 were classified as difficult to intubate. Multivariable analysis identified three airway tests that were highly significant for predicting difficult tracheal intubation. These were: 1) "mouth opening", 2) "chin protrusion", and 3) "atlanto-occipital extension". Using these tests, a validated, highly reliable and predictive model is produced to determine the probability of difficult intubation for patients. At a selected probability cut-off value, the model is 86.8% sensitive and 96.0% specific. CONCLUSION: A simple and accurate multivariable model, consisting of three airway tests, is produced for predicting difficult laryngoscopic tracheal intubation. Additional studies will be required to determine the accuracy and feasibility of this model when applied to a large sample of new patients by multiple anesthesiologists.

Multiple meningiomas, craniofacial hyperostosis and retinal abnormalities in Proteus syndrome.

Because clinical evidence suggests that Proteus syndrome may be caused by a somatic mutation during early development, resulting in mosaicism, the possible types of abnormalities and their clinical distributions are highly variable. Here, we report on an unusual patient with Proteus syndrome. Manifestations included multiple meningiomas, polymicrogyria, and periventricular heterotopias. Both eyes had epibulbar cystic lesions. The retina showed diffuse disorganization with nodular gliosis, retinal pigmentary abnormalities, chronic papilledema, and optic atrophy. Other abnormalities included progressive cranial, mandibular, maxillary, and auditory canal hyperostoses, epidermal nevi, and mental deficiency. The limbs were proportionate, and the hands and feet were normal.

Ocular manifestations in Proteus syndrome.

We report on the ocular manifestations of a Proteus syndrome patient. Several of the manifestations are due to severe maldevelopment and malfunction of the neuroretina including strabismus, nystagmus, high myopia, and retinal pigmentary abnormalities. In reviewing the literature, strabismus and epibulbar tumors were recorded most commonly. Some articles about presumed Proteus syndrome are spurious; these have not been included here. Also, because of anecdotal and nonsystematic study of the eye and because of the ascertainment bias inherent in literature reports, numbers of cases of each ocular manifestation have not been tabulated.

Fronto-ocular syndrome: newly recognized trigonocephaly syndrome.

We describe an apparently unique disorder, Fronto-Ocular syndrome, present in a mother and her two daughters, and comprising trigonocephaly due to coronal and metopic craniosynostosis, ocular hypotelorism, ocular proptosis and ptosis, epicanthal folds, hypoplastic supraorbital ridges, elevated nasal bridge, thin philtrum, high-arched palate and a narrow bifrontal region. Both daughters have glabellar capillary hemangiomas, a congenital heart defect and mild developmental disabilities. Review of the literature failed to disclose any syndrome with similar findings. It is likely that this disorder represents an autosomal dominant condition, that arose as a new mutation in the mother. Mutational analysis of fibroblast growth factor receptor (FGFR) 1 and FGFR2 failed to identify the molecular basis of the disorder.