Die Einstellung der Bev?lkerung zur klinischen Sektion

Background

The number of hospital autopsies has been declining for many years??in Germany as well as in other western countries. One possible reason for this could be the public??s negative view of autopsies.

Methods

Therefore, a representative survey was conducted to study the attitudes of the German population on postmortem examinations.

Results

In total, 84% of respondents generally accept hospital autopsies, while only 10% are in principle opposed to this practice. Many respondents (72%) would agree to the autopsy of their own dead body and 65% to the autopsy of relatives. Altogether, 9% of respondents had already been in a situation where a relative had died in a hospital and they were asked for permission to perform an autopsy. Of these 90, 56% agreed to and 44% refused autopsy.

Conclusion

The data suggest that the attitudes of the public are surprisingly positive and do not explain declining autopsy rates. Medical and institutional reasons must be considered instead as the possible cause of declining autopsy rates.     

Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda

Background

Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time.

Methods

If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time.

Results

Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy.

Conclusion

Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death.

     

Dream recall frequency and nightmare frequency in patients with sleep-disordered breathing

Question of the study

There are conflicting findings regarding dream recall frequency (DRF) in patients with sleep-disordered breathing: Various studies have reported less, equal, or higher DRF in comparison with healthy controls. Although more negatively toned dreams were found in these patients, nightmare frequency had not been found to be increased in a previous study. This study concerned whether DRF or nightmare frequency was altered in patients with sleep-disordered breathing without other comorbid diagnoses and whether disorder-related parameters, comorbidity, or drug intake was associated with DRF and nightmare frequency.

Patients and methods

The present study assessed home DRF and nightmare frequency via two rating scales in 1,706 patients with sleep-disordered breathing. These data were compared with those of healthy control samples from other studies.

Results

In comparison with the control group, a reduced DRF was found that was not associated with respiratory parameters or comorbidity. Similarly, nightmare frequency was reduced, and one might speculate whether these findings can be explained by cognitive dysfunction, which is often found in patients with sleep-disordered breathing. Use of antidepressants and psychiatric comorbidity were associated with heightened nightmare frequency.

Conclusions

Future studies should include current medication intake, measures of cognitive functioning, and sleep parameters in order to explain reduced DRF and reduced nightmare frequency in patients with sleep-disordered breathing.     

A comparative study of cranial, blunt trauma fractures as seen at medicolegal autopsy and by Computed Tomography

Background

Computed Tomography (CT) has become a widely used supplement to medico legal autopsies at several forensic institutes. Amongst other things, it has proven to be very valuable in visualising fractures of the cranium. Also CT scan data are being used to create head models for biomechanical trauma analysis by Finite Element Analysis. If CT scan data are to be used for creating individual head models for retrograde trauma analysis in the future we need to ascertain how well cranial fractures are captured by CT scan. The purpose of this study was to compare the diagnostic agreement between CT and autopsy regarding cranial fractures and especially the precision with which cranial fractures are recorded.

Methods

The autopsy fracture diagnosis was compared to the diagnosis of two CT readings (reconstructed with Multiplanar and Maximum Intensity Projection reconstructions) by registering the fractures on schematic drawings. The extent of the fractures was quantified by merging 3-dimensional datasets from both the autopsy as input by 3D digitizer tracing and CT scan.

Results

The results showed a good diagnostic agreement regarding fractures localised in the posterior fossa, while the fracture diagnosis in the medial and anterior fossa was difficult at the first CT scan reading. The fracture diagnosis improved during the second CT scan reading. Thus using two different CT reconstructions improved diagnosis in the medial fossa and at the impact points in the cranial vault. However, fracture diagnosis in the anterior and medial fossa and of hairline fractures in general still remained difficult.

Conclusion

The study showed that the forensically important fracture systems to a large extent were diagnosed on CT images using Multiplanar and Maximum Intensity Projection reconstructions. Difficulties remained in the minute diagnosis of hairline fractures. These inconsistencies need to be resolved in order to use CT scan data of victims for individual head modelling and trauma analysis.     

Examining the Use of ICD-9 Diagnosis Codes for Primary Immune Deficiency Diseases in New York State

Purpose

To use International Classification of Disease Codes (ICD-9) codes to investigate primary immune deficiency (PID) in New York State.

Methods

We investigated the diagnosis of Primary Immune Deficiency (PID) in New York State (NYS) using the Statewide Planning and Research Cooperative System (SPARCS) database, a comprehensive data reporting system that collects ICD-9 codes for each patient hospitalized in NYS.

Results

From 2000–2004 there were 13,539,358 hospitalizations for 4,777,295 patients; of these, 2,361 patients (0.05 %) were diagnosed with one or more of the ICD-9 codes for PID. Antibody defects were the most common diagnoses made. The PID population had significantly more Caucasians, and fewer African American or Hispanic subjects compared to the general population. Subjects with PID codes were younger, had longer hospitalizations, were less likely to have Medicare and more likely to have Medicaid or Blue Cross insurance. Most hospitalizations were due to respiratory and infectious diseases. Most patients resided in the most populous counties, Kings, New York and Queens, but the distribution of home zip codes was not proportional to county populations.

Conclusions

These data provide useful information on incidence and complications of selected PID diagnoses in one large state.     

CD4 count at presentation for HIV care in the United States and Canada: Are those over 50 years more likely to have a delayed presentation?

Background

A recent study reported a lower than expected specificity and positive predictive value of the rapid oral HIV test in the setting of routine emergency department (ED) screening. These results appeared inconsistent with the findings in another urban Emergency Department during the same time period.

Objective

To compare the specificity and positive predictive vale (PPV) of an oral rapid HIV test used in an ED screening program in Washington DC with that performed in the USHER clinical trial.

Design

Period cross-sectional analysis of rapid oral HIV testing conducted in an ongoing HIV screening program emergency department patients.

Setting

The George Washington University Emergency Department (Washington DC) from 7 February to 1 October 2007.

Patients

1,560 adults seen in the ED for non-HIV-related presenting complaints, who participated in the HIV screening program.

Intervention

Rapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered Western blot testing for confirmation.

Measurements

Specificity and positive predictive value for the program were determined. Findings were compared to those found in the USHER trial.

Results

Of 1,560 patients screened for HIV, 13 [0.8%, 95% CI 0.38% to 1.28%] had a reactive HIV screening test, and all were confirmed to be positive by Western Blot. The specificity was 100% (95% CI 99.6%-100%).

Limitation

Since non-reactive tests were not confirmed, the test sensitivity cannot be determined.

Conclusion

Review of our data conflict with findings from the USHER study surrounding false positive OraQuick HIV screening. Our data suggest that rapid HIV screening protocols implemented in EDs outside of the clinical trial paradigm perform effectively without an excess of false positive results. Compared with other screening tests, HIV rapid screening should remain an essential component of ED practice.     

Prevalence and Morbidity of Primary Immunodeficiency Diseases,United States 2001–2007

Purpose

Few studies have estimated population prevalence and morbidity of primary immunodeficiency diseases (PIDD). We used administrative healthcare databases to estimate the prevalence of PIDD diagnoses in the United States from 2001 to 2007.

Methods

MarketScan databases compile claims from commercial health insurance plans and Medicaid, recording individual diagnoses for outpatient encounters and hospital stays. We used a cross sectional survey to estimate prevalence of PIDD using related ICD-9 codes (279.0, 279.1, 279.2, 279.8, 279.9, 288.1 and 288.2). Persons with secondary immunodeficiency diagnoses were excluded from analysis.

Results

Between 2001 and 2007, prevalence of any PIDD diagnosis increased from 38.9 to 50.5 per 100,000 among privately insured and from 29.1 to 41.1 per 100,000 among publicly insured persons. B cell defects predominated. Prevalence was more than twice as high among Whites as among Blacks or Hispanics.

Conclusion

In this large database, we found a higher prevalence of diagnosed PIDD than has been reported previously from registries. Increased awareness may have contributed to the increasing prevalence.     

Rare saccular aneurysm in a medial type persistent trigeminal artery trunk and literature review

Purpose

We report an extremely rare case of saccular aneurysm in the left medial type persistent trigeminal artery (PTA) trunk and discuss its clinical importance.

Materials and methods

A 77-year-old woman who had symptom suggestive of vertebrobasilar insufficiency underwent cerebral magnetic resonance (MR) imaging and non-contrast three dimensional time-of-flight MR angiography (3D TOF MRA) using a 3 T scanner.

Results

3D TOF MRA images revealed a left medial type PTA originated from the left internal carotid artery C5 portion, through cavernous sinus and connected to the basilar artery with a saccular aneurysm in the mid portion of its trunk. The basilar artery (BA) under the union was hypoplastic. The bilateral posterior communicating arteries were absent.

Conclusion

To our knowledge, this is the first report of a medial type PTA associated with a saccular aneurysm in the PTA trunk. Being aware of this is crucial in clinical, because they can influence surgical and interventional procedures.     

Reduced Bone Density in Patients with Autosomal Dominant Hyper-IgE Syndrome

Background and Purpose

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare primary immunodeficiency disorder . It has been recognized as a multisystem disorder and is characterized by both immunologic and non-immunologic manifestations. Possible bone involvement in autosomal dominant HIES include fractures, scoliosis, cystic bone changes, and osteopenia. We sought to evaluate the changes in bone density in adolescents and young adults with AD-HIES, mostly with proven STAT3 mutation, followed in our institute.

Methods

We studied eight patients with AD-HIES who attended our immunology clinic. All patients underwent at least one bone mass dual-energy x-ray absorptiometry assessment (dual-energy x-ray absorptiometry scan).These findings were evaluated.

Results

The age of the patients at the time of their first bone density scan ranged between 10 and 24 years (mean 16.1?±?4.0 years); the duration of follow-up was 4–11 years (mean 5.8?±?3.5 years). Four patients had a history of fractures. Mean Z score in these patients was ?1.8?±?0.7. For three patients, Z score was below ?1. The other four patients had no history of fractures. Mean Z score in these patients was ?0.9?±?0.5. Only one patient in this group had a Z score below ?1. Bone density was below average in all patients; mean spinal Z score was ?1.6?±?0.4. Four patients were followed through the second decade, and all showed progressive deterioration in bone density. Three were treated with alendronate sodium, with improvement in the bone scan results.

Conclusions

Bone density decreases considerably over time in adolescents and young adults suffering from AD- HIES. Treatment with alendronate sodium may be effective in alleviating osteopenia.     

Serum vitronectin levels in patients with Beh?et’s disease

Background/aims

To determine serum vitronectin levels in Beh?et patients with and without ocular involvement, and to evaluate the relationship between vitronectin concentrations and clinical manifestations of Beh?et’s disease (BD).

Methods

Sixty-five patients with BD and 21 control subjects were included. All patients were queried for the clinical manifestations of BD. Serum vitronectin concentrations were determined by using in vitro enzyme immunoassay kits.

Results

Serum vitronectin levels between the patients and the control subjects were not different. There was no statistically significant difference between vitronectin levels in Beh?et patients with and without ocular involvement. No correlation was found between vitronectin concentrations and clinical manifestations.

Conclusion

This is the first study evaluating vitronectin levels in Beh?et patients. Further studies involving larger numbers of subjects would be useful to improve our understanding of the functions of vitronectin in BD.     

Morphometry,asymmetry and variations of cerebral sulci on superolateral surface of cerebrum in autopsy cases

Background

The cerebral sulci are known as main microanatomical borders that serve as a gateway and surgical passage to reach the ventricles or to the deeper lesions. It is a matter of curiosity that whether there is a convergence between the morphological asymmetry and the functional asymmetry, and also its significance in surgery. The aim of this study is make morphometric measurements and evaluate asymmetry of several sulci on the lateral aspects of the cerebrum in regard to main sulci and related reference key points.

Methods

A total of 100 cerebral hemispheres from 50 autopsy cadavers were examined. The lengths of several sulci on the superolateral aspect of the hemispheres and the distances between the sulci and nearby sulci and the reference key points were measured. Encountered variations were examined and photographed.

Results

Evaluation of the variations: superior frontal sulcus (SFS), inferior frontal sulcus, superior temporal sulcus (STS), precentral sulcus and postcentral sulcus were found to be discontinuous in 60, 46, 41, 84 and 70 % of the hemispheres, respectively. Evaluation of the asymmetry: the distances between SFS posterior end and longitudinal fissure, STS posterior end and lateral sulcus posterior end, as well as lengths of external occipital fissure (EOF), and discontinuous course of STS were significantly different between left and right hemispheres.

Conclusions

There is usually a morphological partial asymmetry between the right and left hemispheres for any individual. Also, some of our measurements were found to be compatible with the ones in the literature, while others were incompatible.     

Hereditary Autoinflammatory Syndromes: A Brazilian Multicenter Study

Objective

To evaluate the prevalence of genetic defects in clinically suspected autoinflammatory syndromes (AIS) in a Brazilian multicenter study.

Methods

The study included 102 patients with a clinical diagnosis of Cryopyrin Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD) and Pediatric Granulomatous Arthritis (PGA). One of the five AIS-related genes (NLRP3, TNFRSF1A, MEFV, MVK and NOD2) was evaluated in each patient by direct DNA sequencing, based on the most probable clinical suspect.

Results

Clinical diagnoses of the 102 patients were: CAPS (n?=?28), TRAPS (n?=?31), FMF (n?=?17), MKD (n?=?17) and PGA (n?=?9). Of them, 27/102 (26?%) had a confirmed genetic diagnosis: 6/28 (21?%) CAPS patients, 7/31 (23?%) TRAPS, 3/17 (18?%) FMF, 3/17 (18?%) MKD and 8/9 (89?%) PGA.

Conclusion

We have found that approximately one third of the Brazilian patients with a clinical suspicion of AIS have a confirmed genetic diagnosis.     

Spezialisierte histopathologische Zweitbegutachtung fortgeschrittener Ovarialkarzinome

Background

Retrospective studies have shown that a significant number of ovarian borderline tumors, ovarian metastases, and nonepithelial tumors were erroneously diagnosed as ovarian carcinomas. This may lead to unnecessary morbidity, suboptimal therapeutic modalities, and unintended bias in clinical trials. The aim of this study was to investigate the frequency and clinical significance of such diagnostic discrepancies.

Material and methods

Original histological slides from patients with ovarian carcinomas included in phase III chemotherapy trials of the Working Group on Gynecological Oncology (AGO) were reviewed by at least two specialized pathologists. Diagnostic discrepancies were classified as being either clinically relevant (major) or clinically not relevant (minor).

Results

A total of 454 out of 533 patients from the AGO OVAR11 (ICON7) trial gave consent to the second opinion on the pathology results. All of the 104 institutes of pathology responsible for the original diagnoses contributed to the study. The first diagnosis and the second opinion pathology review were identical in 295 out of 454 (65%) cases. In 128 cases (28.2%) a minor discrepancy was found and 31 cases (6.8%) were shown to have a major discrepancy.

Conclusion

The assumption of a significant number or erroneous diagnoses in chemotherapy trials of ovarian carcinomas was confirmed. A pathology review seems therefore desirable and may help to reduce unnecessary morbidity and optimize therapeutic strategies. Moreover, improvement of quality in therapy trials may become possible. In another study a new concept allowing a rapid pathology review before randomization of patients has now been successfully tested and it may well have potential to form the basis for modern networking consultation pathology.     

Terminal Deletion of 11q with Significant Late-Onset Combined Immune Deficiency

Purpose

We report a 45-year old female adult patient with terminal deletion of chromosome 11q resulting in clinical phenotype of late-onset combined immunodeficiency.

Methods

We describe the clinical phenotype and discuss the similarities between our patient and those with chromosome 22q11.2 deletion syndrome. Immunological evaluation included immunoglobulin levels, vaccine responses, number and function of T, NK and B cell subsets and comparative genomic hybridization test of blood and fibroblasts.

Results

The patient suffered from recurrent pneumococcal pneumonia and genital and cutaneous condylomas. She had a history of learning difficulties, dysmorphic features, autoimmune thyroiditis, chronic thrombocytopenia and severe asthma. We found Paris-Trousseau type thrombocytopenia, B-, T- and NK-lymphopenia, T cell oligoclonality and IgG hypogammaglobulinemia with inability to respond to pneumococcal polysaccharide, tetanus and diphtheria vaccines. A terminal deletion of chromosome 11q compatible with partial Jacobsen syndrome was found.

Conclusions

This confirms Jacobsen syndrome as a chromosome deletion syndrome able to cause combined immunodeficiency.     

Clinical Variability of Family Members with the C104R Mutation in Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI)

Purpose

Common Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. The C104R mutation in the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is the most frequent mutation identified in patients with CVID. We carried out a detailed immunological and molecular study in a family with a C104R mutation.

Methods

We have undertaken segregation analysis of a kindred with C104R mutations of the TACI gene. Detailed immunological and molecular investigations were carried out for this kindred and the clinical phenotype was compared to the genotype.

Results

Segregation analysis of our kindred showed that inheriting single or double copy of the C104R mutation does not consign an individual to CVID. All heterozygotes in the family were phenotypically different, ranging from asymptomatic to ill-health. A family member with a wild type TACI variant had CVID-related phenotype including IgA deficiency and type 1 diabetes. Interestingly, a family member with the homozygous C104R/C104R variant did not meet the criteria for CVID because he had excellent, albeit unsustained, vaccine responses to T cell dependent and T cell independent vaccine antigens despite profound hypogammaglobulinemia.

Conclusion

The C104R mutation does not correlate with the clinical phenotypes in this family.     

Clinical, Immunological, and Molecular Characterization of Hyper-IgM Syndrome Due to CD40 Deficiency in Eleven Patients

Purpose

Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare form of primary immunodeficiency with few reported cases. In this study, we further characterize the clinical, immunological, and molecular profiles of the disease in a cohort of 11 patients.

Methods

Molecular genetic analysis and a comprehensive clinical review of patients diagnosed with HIGM3 at our tertiary care center from 1994 to 2011 were undertaken.

Results

Eleven patients from seven families were enrolled. The patients had a median age of 9 years [ranging from 2 to 22 years old]. All 11 patients had recurrent chest infections at presentation. Pneumocystis jiroveci pneumonia was confirmed in three patients. Five patients had sclerosing cholangitis, and five patients had Cryptosporidium isolated from their stool. Six patients had nasal and sinus infections, and two of these patients had destructive nasal fungal infections. Eight patients had neutropenia. All of the patients had low IgG and normal or high IgM levels. IgA was undetectable in all but three patients. Two novel mutations were found: a splice site for intron 3 and a missense mutation located in the coding region of exon 3. Two patients underwent successful stem cell transplantation from a matched donor. Four patients are doing well on prophylaxis; two are very sick, one with protracted diarrhea and persistent Cryptosporidium and the other with neurological complications. Three patients died early in life as a result of severe sepsis.

Conclusions

To our knowledge, this report provides the largest cohort of patients with this disease with a very long follow-up period. Our cohort showed variable disease severity.     

Lifetime History of Depression, Type 2 Diabetes, and Endothelial Reactivity to Acute Stress in Postmenopausal Women

Background

Coronary heart disease is a major cause of mortality in women and persons with diabetes. Mental stress and major depressive disorder have both been associated with coronary heart disease. Endothelial functioning is a clinically meaningful manifestation of CHD that is detectable in its earliest stages.

Purpose

This study aims to determine whether acute stress and lifetime history of major depressive disorder are associated with functional and biochemical markers of endothelial function and whether this relationship varies by diabetes status.

Methods

Resting endothelial function was assessed for n?=?215 postmenopausal women with no known or suspected coronary artery disease participated. Of these, 108 had a positive lifetime major depressive disorder (L-MDD; assessed through structured clinical interview) and had been free of major depressive disorder for >6?months; 103 had type?2 diabetes. Endothelial reactivity to acute mental stress was assessed for n?=?114 of the participants. Endothelial function was assessed by flow-mediated dilation of the brachial artery (FMD) by total plasma nitrite, the cumulative molecule from nitric oxide (NO) generation, and by plasma endothelin-1 (ET-1).

Results

Participants with L-MDD had lower NO and lower FMD compared to never-depressed controls. Secondary analyses suggest that among participants with L-MDD, antidepressant medications are associated with higher NO. Participants with diabetes had higher NO but lower FMD than nondiabetic controls. Mental stress affected FMD in the entire sample. Diabetes moderated the effect of mental stress on NO and L-MDD moderated the effect of mental stress on ET-1.

Conclusions

History of depression, even in full remission, is associated with impaired endothelial functioning regardless of diabetes status. Acute mental alters FMD, NO, and ET-1 differentially among subgroups.     

Clinical Course in a Patient With Neutrophil-Specific Granule Deficiency and Rapid Detection of Neutrophil Granules as a Screening Test

Purpose

Neutrophil-specific granule deficiency (SGD) is a rare, congenital disorder characterized by atypical neutrophil structure and function that results in frequent and severe bacterial infections. However, the clinical course of patients with SGD have not been described in detail because of the scarcity of the disease. We present the clinical course of an adult patient with SGD and propose a method for making an early diagnosis of SGD.

Patient and Methods

A32-year-old Japanese woman with SGD had a small impetigo lesion on her face and experienced the rapid spread of a facial abscess to a pulmonary abscess via the blood stream. We also analyzed the expression of neutrophil granule proteins in our patient compared with a healthy control by flow cytometry.

Results

We confirmed defects of several neutrophil granule proteins in our patient by flow cytometry.

Conclusion

Severe bacterial infections sometimes occur and spread rapidly in SGD. Detection of neutrophil granules by flow cytometry is useful for a rapid diagnosis and a screening of SGD.     

Molekularbiologischer Erregernachweis aus FFPE-Proben bei zephaler Mykose

Background

Due to the lack of histopathological differentiation the unequivocal identification of fungal pathogens is rarely possible. In order to understand the pathogen spectrum causing cephalic mycosis the use of alternative methods is essential.

Material and methods

In a retrospective study 24 formalin-fixed, paraffin-embedded (FFPE) samples from patients with histologically confirmed cerebral or cephalic mycosis were analyzed with molecular biological methods.

Results

In two samples obtained during the patients’ lifetime human as well as fungal DNA was detected, making an unambiguous diagnosis possible. For tissue that had been fixed over a longer period, detection of human and fungal DNA was possible merely in 60% and 47?% of the samples, respectively. Most frequently diagnosed were aspergillosis (n?=?9), followed by mucormycosis (n?=?2) and imported blastomycosis (n?=?1).

Conclusions

Using biopsy material a DNA analysis seems promising although only with limited success using brain samples taken at autopsy which have been fixed over a longer period. For unambiguous retrospective diagnostics of pathogens when cephalic mycosis is suspected, the sample extraction for postmortem diagnostics should be performed prior to a long period of formalin fixation.     

Molecular epidemiology of DFNB1 deafness in France

Background

To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia.

Methods

Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia.

Results

There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were < 1.0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q.

Conclusions

Significant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied.