Molecular studies of achondroplasia

Background:

Achondroplasia (ACH) is the most frequent form of short-limbed dwarfism, caused by mutations in the FGFR3 gene. It follows an autosomal dominant inheritance, though most cases are sporadic. The molecular techniques are the only available methods to confirm the diagnosis of a skeletal dysplasia. Clinical and radiological features are only suggestive and not confirmatory. The present study was conducted to find out how often the clinical diagnosis of achondroplasia is verified on molecular studies.

Materials and Methods:

From 1998 through 2007, we carried out molecular analysis for the two common mutations in the FGFR3 gene in 130 cases clinically suspected to have ACH.

Results:

A diagnostic mutation was identified in 53 (40.8%) cases. The common mutation (1138G>A) was present in 50 (94.7%) of the positive cases, while the rare 1138 G>C substitution was found in three (5.3%).

Conclusion:

This study shows that confirmation of clinical diagnosis of ACH by molecular genetic testing is essential to distinguish it from other skeletal dysplasias, to plan therapeutic options, and to offer genetic counseling. Management (medical and surgical) in patients confirmed to have ACH, is briefly discussed.     

Fine-needle aspiration biopsy for the primary diagnosis of lymphoproliferative disorders involving the spleen: one institution's experience and review of the literature

We report the fine-needle aspiration (FNA) biopsy findings for the primary diagnosis of lymphoproliferative disorders involving the spleen. We analyzed six cases of primary diagnosed lymphoma involving the spleen and out of these cases, identified one case of primary splenic lymphoma. We explore the potential pitfalls and difficulties encountered in making a primary diagnosis of lymphoma involving the spleen and how the preparation of the specimen for flow cytometric studies and/or cell block for immunohistochemical analysis can greatly aid in making a definitive diagnosis. To the best of our knowledge, this is the first report of T-cell rich B-cell subtype of diffuse large B-cell lymphoma and only the second report of primary splenic lymphoma of the spleen diagnosed by FNA biopsy. An extensive review and analysis of the literature involving FNA biopsy of the spleen is also discussed.     

Pulmonary metastasis of giant cell tumor of the bone diagnosed by fine-needle aspiration biopsy

Giant cell tumor is a benign but locally aggressive tumor that primarily affects the epiphyses of long bones of young adults. Pulmonary metastases in giant cell tumor are rare (about 1-9%). Here, we report a case of metastatic pulmonary giant cell tumor in a patient who had a previous history of giant cell tumor of the distal femur with multiple recurrences. The diagnosis of pulmonary metastasis was achieved by cytologic evaluation with concurrent immunohistochemical studies in material obtained by fine-needle aspiration biopsy. The aspirate smears contained clustered and dispersed mononuclear and osteoclast-like giant cells that had bland nuclei with inconspicuous nucleoli. All multinucleated cells showed immunoreactivity to KP-1 antibody, a histiocytic marker (not lineage specific) and only a subset of mononuclear cells (30%) stained with this marker. Twenty percent of the mononuclear cells also displayed increased Ki-67 and p53 protein expression. The pulmonary metastasis was similar morphologically and immunophenotypically to the recurrent giant cell tumor of the bone.     

Association Between Acute Medical Exacerbations and Consuming or Producing Web-Based Health Information: Analysis From Pew Survey Data

Background

The Internet is an increasingly important resource for individuals who seek information from both health professionals and peers. While the demographic and health characteristics of persons who use health information technology has been well described, less is known about the relationship between these health characteristics and level of engagement with health information technology. Even less is known about whether persons who produce Web-based health information differ in health status from persons who consume such content.

Objective

We explored the health characteristics of persons who engage with the Internet for the purposes of consuming or producing Web-based health information, and specifically, whether healthier versus sicker persons engage with health information technology in different ways.

Methods

We analyzed data from the 2012 Pew Health survey, a landline and cell phone survey of 3104 adults in the United States. Using multiple logistic regression with sampling weights, we examined the association between sociodemographic and health characteristics and the consumption or production of Web-based health information. Sociodemographic variables included age, sex, race, and education. Health characteristics included self-reported health status, presence of chronic condition(s), and having an acute medical exacerbation. Acute medical exacerbations were defined as an emergency department visit, hospitalization, or other serious medical emergency in the last 12 months.

Results

The majority of the sample reported good or excellent health (79.7%), although 50.3% reported having at least one chronic condition. About a fifth (20.2%) of the sample experienced an acute medical exacerbation in the past year. Education was the sociodemographic characteristic most strongly associated with consuming Web-based health information. The strongest health-related predictors of consuming Web-based health information were an acute medical exacerbation (OR 2.39, P<.001) and having a chronic condition (OR 1.54, P=.007). Having an acute medical exacerbation was the only predictor of producing Web-based health information (OR 1.97, P=.003). All participants, regardless of health status, were most interested in Web-based health information regarding diseases or medical problems. However, persons with acute medical exacerbations were more likely to seek Web-based health information regarding medical tests, procedures, and drugs compared to persons without acute medical exacerbations.

Conclusions

Producers of Web-based health information differ from consumers of this information in important health characteristics that could skew the content of peer-generated Web-based health information and overrepresent the experiences of persons with acute medical exacerbations. Providers may have a role to play in directing patients towards high-quality, easy-to-understand online information, especially information regarding treatments and procedures.     

Development and validation of a normal-phase HPTLC method for the simultaneous analysis of lamivudine, stavudine and nevirapine in fixed-dose combination tablets

This paper presents the development and validation of an improved method for the simultaneous analysis of lamivudine (LVD), stavudine (STV) and nevirapine (NVP) using high-performance thin-layer chromatography (HPTLC) with densitometric detection. Separation was performed on silica gel 60F(254) plates. The mobile phase is comprised of ethylacetate, methanol, toluene and concentrated ammonia (38.7:19.4:38.7:3.2, v:v:v:v). Detection wavelength was 254 nm. The R(f) values were 0.24±0.03, 0.38±0.04 and 0.69±0.04 (n=8) for LVD, STV and NVP, respectively. An F-test indicated that calibration graphs were adequately linear at the evaluated concentration ranges. The pooled %RSD for repeatability of the percentage amount recovered for LVD, STV and NVP were found to be 0.62, 0.54, and 0.79, and the pooled %RSD for time-different intermediate precision were 1.66, 1.27 and 1.21. The percentage recoveries for the trueness were 99.2%±1.5 for LVD, 98.6%±1.5 for STV and 99.3%±1.7 for NVP (n=3). Most factors evaluated in the robustness test were found to have an insignificant effect on the selected responses at 95% confidence level. This method was successfully used to analyze fixed-dose tablets samples of LVD, STV and NVP.     

A provider participatory implementation model for HIV testing in an ED

Background

The Centers for Disease Control and Prevention recommends routine HIV screening for adults.

Objectives

Community-based participatory research incorporates subjects in the design and conduct of research. We included nurses and physicians in the implementation of HIV rapid test use in the emergency department (ED). We explored the process, facilitators, and barriers.

Methods

We identified clinical champions and trained staff. Physicians obtained consent and ordered HIV testing; nurses performed rapid testing. Testing rates were tracked by electronic medical record. We conducted regular meetings between staff and researchers. Semistructured qualitative interviews with providers were conducted at 3 months.

Results

By week 15, we administered 121 tests. After the eligibility protocol evolved to incorporate ED nursing concerns regarding staffing limitations from a random sampling model to one focused on testing during nonpeak hours, the weekly number of tests increased. Eighteen percent of providers favored nontargeted HIV screening, 27% favored the current model of testing at nonpeak hours, 32% supported diagnostic testing, and 18% favored no testing or “other.” Barriers include written consent, electronic documentation, time constraints, and belief that screening is not a core ED duty. Facilitators include ease of test administration, belief that ED patients are at higher risk, and flexibility to tailor screening efforts according to patient volume.

Conclusions

The ED-based HIV testing is feasible within a Veterans Hospital Administration setting. Involvement of nursing in a community-based participatory research implementation model may facilitate staff acceptance of nontargeted HIV screening and be a mechanism to initiate administration of clinical preventive services to ED patients with limited primary care contact.     

A Self-Observation Study of Headache Symptoms in Children

SYNOPSIS
The purpose of the present study was to examine symptom configurations experienced by children with problem headache and to determine whether headache symptoms in children can be analyzed along a continuum of severity. Forty-seven children between the ages of 8 and 17 years monitored their headache activity on a daily basis for a 3-week period. The self-observation data indicated that children did not show a tendency to experience their headache symptoms in terms of distinct muscle contraction and migraine symptom clusters. On the contrary, both categories of symptoms were observed to increase in frequency with increasingly problematic headaches. The presence of both muscle contraction and migraine symptoms increased in a linear fashion with the number of daily headache hours reported by the children during the self-observation period. The measure of headache hours also correlated significantly with the total number of head pain locations and symptoms reported by the children. A regression analysis revealed that the symptom of nausea with the addition of the symptoms of dull and aching pain, bilateral forehead pain, feelings of tightness and pressure, and light sensitivity accounted for 77% of the variance associated with the severity measure of headache hours. Further support for viewing headaches in children in terms of severity came from an analysis of the time of onset of headache activity characteristic of the different children in the sample. Children with more severe headache activity experienced their attacks at an earlier time of day than children with less severe headache activity. Overall, the self-observation data provided additional support for the severity model and supported the utility of extending the model to the study of headache disorders in children.