Genetic factors influencing the risk of multiple myeloma bone disease.

A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for ~6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio=1.38, P=4.09 × 10(-9)) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.

Significance of minimal or no intraperitoneal fluid visible on CT scan associated with blunt liver and splenic injuries: a multicenter analysis.

BACKGROUND: The use of ultrasound (U/S) for the evaluation of patients with blunt abdominal trauma is gaining increasing acceptance. Patients who would have undergone computed tomographic (CT) scan may now be evaluated solely with U/S. Solid organ injuries with minimal or no free fluid may be missed by surgeon sonographers. OBJECTIVE: The purpose of this study was to describe the incidence and clinical importance of liver and splenic injuries with minimal or no free intraperitoneal fluid visible on CT scan. We hypothesized that these solid organ injuries occur infrequently and are of minor clinical significance. METHODS: Patient records and CT scans were reviewed for the presence of and outcome associated with blunt liver and splenic injuries with minimal (<250 mL) or no free fluid detected by an attending radiologist. Data were collected from six major trauma centers during a 4-year period before the introduction of U/S and included demographics, grade of injury (American Association for the Surgery of Trauma scale), need for operative intervention, and outcome. RESULTS: A total of 938 patients with liver and splenic injuries were identified. In this group, 11% of liver injuries and 12% of splenic injuries had no free fluid visible on CT scan and could be missed by diagnostic peritoneal lavage or U/S. Of the 938 patients, 267 (28%) met the inclusion criteria; 161 had injury to the spleen and 125 had injury to the liver. In the 267 patients studied, 97% of the injuries were managed nonoperatively. However, 8 patients (3%) required operative intervention for bleeding. Compared with the liver, the spleen was significantly more likely to bleed (p = 0.01), but the grade of splenic injury was not related to the risk for hemorrhage (p = 0.051). CONCLUSION: Data from this study suggest that injuries to the liver or spleen with minimal or no intraperitoneal fluid visible on CT scan occur more frequently than predicted but usually are of minimal clinical significance. However, patients with splenic injuries may be missed by abdominal U/S. We found a 5% associated risk of bleeding. Therefore, abdominal U/S should not be used as the sole diagnostic modality in all stable patients at risk for blunt abdominal injury.

All-terrain vehicle injuries in children: industry-regulated failure.

Although the sale of all-terrain vehicles (ATVs) to children under 16 years of age was prohibited in 1988, they continue to represent half of the ATV-associated injuries. We conducted a retrospective review of ATV injuries admitted to our institution from 1988 to 1998. We identified 76 patients over the last 10 years, with 50 patients admitted in the last 4 years. Children <16 years of age account for 50 per cent of all ATV-injured patients. Only eight per cent of these children wore helmets. We conclude that despite industry regulation, nearly half of ATV injuries continue to involve children under 16 years of age. The consent decree restricting access of children <16 years of age to ATVs has been ineffective and expired in April 1998. Significant morbidity and mortality continues to occur in children <16 years of age who operate these vehicles. Reform is needed, such as legislation that would mandate the sale of safety equipment on ATV purchase, as well as provide for ATV safety education.

Use of the laryngeal mask airway in air transport when intubation fails.

BACKGROUND: A prospective, nonrandomized cohort study was conducted to determine the effectiveness of the laryngeal mask airway (LMA) for management of the difficult airway in patients requiring air transport. METHODS: The LMA was inserted in those patients who could not be successfully intubated. Data were collected to evaluate the effectiveness of the LMA and to document any complications attributed to its use. RESULTS: Inclusion criteria were met in 17 of the 25 patients receiving an LMA. The device was inserted successfully in 16 of 17 of the patients (94%). In-flight oxygen saturation ranged from 97 to 100%, and end-tidal carbon dioxide ranged from 24 to 35 mm Hg. At arrival, initial arterial blood gas values indicated adequate oxygenation in all patients and adequate ventilation in 15 of 16 patients (94%). There was no evidence of complications. CONCLUSION: Our patient data show that when conventional methods have failed, the LMA can be safely, rapidly, and effectively used for temporary airway control.

Ultrasound: impact on diagnostic peritoneal lavage, abdominal computed tomography, and resident training.

Our objective was to determine the impact of abdominal ultrasound (US) on 1) the use of diagnostic peritoneal lavage (DPL) and abdominal computed tomography (ACT) for diagnosing blunt abdominal trauma (BAT) and on 2) surgical resident training. The study design was a retrospective chart review. Patients sustaining BAT who had ACT or DPL done during the 1-year period before the introduction of US (pre-US) were compared with those from a 1-year period beginning 6 months after US (post-US). Data collected included diagnostic modality, demographic data, mortality, associated injuries, length of stay, mechanism of injury, and number of exploratory laparotomies. Of 128 patients in the pre-US group, 35 patients (27%; P < 0.001) underwent DPL, 0 patients (0%; P < 0.001) received US, and 92 patients (72%) received ACT, with positive results for 31 patients (34%). Exploratory laparotomy was performed on 35 patients (27%) in the pre-US group. Of 140 patients in the post-US group, 8 patients (6%; P < 0.001) underwent DPL, 120 patients (85%; P < 0.001) received US, and 108 patients (77%) received ACT, with positive results for 44 patients (42%). Exploratory laparotomy was performed on 22 patients (15%; P < 0.001) in the post-US group. Resident experience with DPL before and after the introduction of US and availability of US for graduated residents was documented. Chi-square and Fisher's exact test were used for statistical analysis. Resident experience changed from 22 to 3 DPLs per year in the pre- and post-US groups, respectively. Ten per cent of graduating residents had US available for use after leaving this institution. US replaced DPL and resulted in slightly more positive ACT scans in assessing BAT at our institution. Paradoxically, only 10 per cent of graduating residents had US available after leaving this institution. Until the use of US for diagnosing BAT has widespread use in the community, we must question our adequacy of resident preparation for diagnosing BAT.

Early detection of hemoperitoneum by ultrasound examination of the right upper quadrant: a multicenter study.

BACKGROUND: The focused assessment for the sonographic examination of the trauma patient (FAST) is a rapid diagnostic test that sequentially surveys for hemopericardium and then the right upper quadrant (RUQ), left upper quadrant (LUQ), and pelvis for hemoperitoneum in patients with potential truncal injuries. The sequence of the abdominal part of the examination, however, has yet to be validated. The objectives of this multicenter study were as follows: (1) to determine where hemoperitoneum is most frequently identified on positive FAST examinations; and (2) to determine if a relationship exists between that areas and the organs injured. METHODS: Ultrasound registries from four Level I trauma centers identified patients who had true-positive FAST examinations. Demographic data, areas positive on the FAST, and organs injured were recorded; injuries were classified as multiple, single solid organ (liver or spleen), isolated hollow viscus, or retroperitoneal. Relationships between positive locations on the FAST examinations and the associations of organs injured to areas positive were assessed using McNamara's chi2 test; a p value < 0.05 was considered statistically significant. RESULTS: The RUQ was the most common site where hemoperitoneum was detected, and this was statistically significant compared with either the LUQ or the pelvis. Also, statistically significant correlations (p < 0.001) were observed between positive RUQ areas on the FAST and multiple injuries, single solid organ (liver or spleen) injury, and retroperitoneal injuries. CONCLUSION: Blood is most often found on the FAST in the RUQ area in patients with multiple intraperitoneal injuries or isolated injury to the liver, spleen, or retroperitoneum, but not when there is injury to a hollow viscus.

Overexpression of nerve growth factor in skin increases sensory neuron size and modulates Trk receptor expression.

Sensory neuron development and differentiation is dependent on a family of growth factors known as neurotrophins. Neurotrophins modulate neuron development via trk tyrosine kinase receptor proteins trkA, trkB and trkC. To determine how elevated levels of a target-derived neurotrophin might affect neuronal differentiation, we analysed trk expression in the trigeminal ganglion of transgenic mice that overexpressed nerve growth factor (NGF) in the skin. Increased levels of NGF caused a five-fold increase in neurons expressing trkA mRNA and a two-fold increase in neurons expressing trkC. In control mice, cell size distributions of neuronal subpopulations expressing each trk mRNA showed the three subpopulations distributed over a narrow, overlapping range. In contrast, cell size distribution in NGF-transgenic mice was significantly divergent due in large part to hypertrophy of trkA neurons and, to a lesser extent, trkC neurons. In addition, we examined neurons that bound the isolectin B4 from Bandeiraea simplicifolia (BS-IB4) because most of these neurons do not express any trk receptor in the adult. There was a significant increase in the size of BS-IB4-positive neurons in transgenic mice; however, there was no increase in their number. These studies indicate that an increased level of target-derived NGF affects the development of sensory neurons that in the adult express trkA or trkC, as well as neurons that do not express trk receptors.

Utility of the routine chest X-ray after "over-wire" venous catheter changes.

The Seldinger technique is commonly used to change central venous access catheters in the Intensive Care Unit. These catheters are routinely being changed to prevent septic complications. Some of these changes are performed by an "over-wire" technique. To assess the utility of postprocedural chest X-rays on critically ill patients after an over-wire catheter change, we followed 68 patients after they had 80 catheter changes. This study assesses catheter position by use of a postprocedural X-ray. During the study, we found no misplaced catheters and minimum symptomatology in 80 patients. The trauma/critical care fellows performing the procedures rated them as easy in 97.5 percent of the changes. The conclusion of the study is that, if the catheter change is technically easy and the patient has no symptoms, a postprocedural X-ray is not necessary.

Expression of an epidermal keratin protein in liver of transgenic mice causes structural and functional abnormalities.

To examine the role of keratin intermediate filament proteins in cell structure and function, transgenic mice were isolated that express a modified form of the human K14 keratin protein in liver hepatocytes. A modified K14 cDNA (K14.P) sequence was linked downstream of the mouse transthyretin (TTR) gene promoter and enhancer elements to achieve targeted expression in hepatocytes. Hepatocytes expressing high levels of the transgene were found to have abnormal keratin filament networks as detected by indirect immunofluorescence using an antibody specific for the transgene product. Light and electron microscopic level histological analysis of isolated liver tissue showed in many cases degenerative changes that included inflammatory infiltration, ballooning degeneration, an increase in fat containing vacuoles, and glycogen accumulation. These changes were most evident in older mice over four months of age. No indication of typical Mallory body structures were identified at either the light or electron microscopic level. To evaluate secretory function in transgenic livers, bile acid secretion rates were measured in isolated perfused liver and found to be approximately twofold lower than aged-matched controls. These findings indicate that expression of an abnormal keratin in liver epithelial cells in the in vivo setting can alter the structure and function of a tissue and suggest a role of the keratin network in cellular secretion.

The prevalence of boredom proneness and depression among profoundly deaf residential school adolescents.

We investigated boredom proneness and depression among 50 profoundly deaf residential school adolescents using the Boredom Proneness (BP) scale and a version of the Beck Depression Inventory (BDI) that has been modified for use with deaf subjects. Consistent with previous research, the deaf students had a significantly higher incidence of depression than the hearing students. In addition, the deaf students were found to be significantly more boredom prone than the hearing subjects. The results suggest that deafness not only increases a person's vulnerability to mild levels of depression, but also tends to augment one's tendency toward experiencing boredom. Implications for educational settings and areas for future research are discussed.

Pelvic fractures at a community hospital.

One hundred twenty-eight pelvic fractures were reviewed. Of the 128 patients with pelvic fractures, there were seven deaths. Pelvic fractures associated with the greatest blood loss and complications were those which occurred in crush-type injuries secondary to automobile accidents or other heavy impact injuries. Unless fractures were of a crush-type with massive fractures, the amount of blood loss correlated more closely with the history of injury than it did with the x-ray appearance of pelvic fracture. A single patient in this series had greater than 45 units blood loss and exhibited many of the basic problems encountered when dealing with patients with major pelvic fractures. The case of this patient is reviewed in detail, including component therapy for massive blood loss. The prophylactic use of caval filtration or an umbrella device might be warranted in patients with massive pelvic fractures.

Protein blotting in uniform or gradient electric fields.

Experimental data and computer mapping were used to analyze electric fields generated by a variety of electrode arrays in protein blotting apparatus. Asymmetric electrode arrays were found to generate nonuniform fields that effected uneven transfers of 125I-labeled albumin from gels to nitrocellulose membranes. Symmetric arrays with multiple (four), independent wire electrodes, supplied individually with electric current, generated the most uniform fields and effected the most even transfers of the test protein. With multiple independent electrodes, gradient electric fields can be generated in which differences in electrophoretic elution between large and small proteins can be eliminated. Transfer apparatus with either uniform or gradient electric fields are expected to improve qualitative results and make possible quantitation of protein blotting.