Comparing human and mouse salivary glands: A practice guide for salivary researchers.

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.

Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice.

Autoresuscitation (AR) is a highly conserved response among mammals, which allows survival from transient extreme hypoxia. During hypoxia, bradycardia, and hypoxic gasping develop after a brief period of hyperactivity. Normally, AR occurs if oxygen is restored during the gasping period where an initial heart rate increase is rapidly followed resumption or eupneic breathing. Humans and other mammals can survive multiple immediately repeated AR. A defective AR capacity has been implicated in Sudden Infant Death Syndrome. We had reported earlier that inbred strains of mice such as BALB/cJ could survive a characteristic number of immediately repeated AR trials, but that SWR/J mice failed to AR from a single hypoxic episode. We now report that strains closely related to SWR/J, FVB/N and SJL/J exhibit partial resuscitation defects relative to BALB/cJ or other mouse strains, establishing a genetic basis for variation in AR failure. The AR trial phenotype of BALB/cJ x SWR/J intercross F(1) and F(2) mice was consistent with BALB/cJ dominance and a discrete number of loci. Genome-wide mapping conducted with 60 intercross F(2) animals linked two loci to the number of AR trials survived, including one sex-specific locus with male expression, consistent with the observed 50% male bias for Sudden Infant Death Syndrome in humans. A locus carried on SWR/J chromosome 10 seems to be particularly important in AR failure and was confirmed in a partial consomic line. These results establish a genetic basis for AR failure phenotype in mice, with relevance to Sudden Infant Death Syndrome.

An unusual sinonasal tumor: soft tissue perineurioma.

Soft tissue perineuriomas are an unusual type of peripheral nerve sheath tumors distinct from schwannomas and neurofibromas, with interesting histologic findings. They are not well characterized on radiographic examination. We report this case of a patient with sinonasal perineurioma to help define the imaging and pathologic features of this rare head and neck tumor.

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage. Other technical factors include vasospasm, lack of adequate contrast volume or exposure time, a venous bleeding source, and a large surface bleeding area. We report the use of multidetector computed tomography (MDCT), or CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT may offer a very sensitive means to evaluate the source of acute LGIB, while avoiding some of the morbidity and intense resource use of contrast angiography, and may provide unique morphologic information regarding the type of pathology. Screening with the more rapid and available MDCT, followed by either directed therapeutic angiography or surgical management, may represent a reasonable algorithm for the early evaluation and management of acute LGIB in which an active bleeding source is strongly suspected.

Hyperplasia of mantle/marginal zone B cells with clear cytoplasm in peripheral lymph nodes. A clinicopathologic study of 35 cases.

We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.

Accuracy of administrative and trauma registry databases.

OBJECTIVE: Accurate data are needed to evaluate clinical outcomes, therapeutic modalities, and quality of care in trauma. Administrative data, usually used for billing, and trauma registries, have been used to perform these functions. This study compares data for trauma patients from administrative and trauma registry databases at a Level I trauma center. METHODS: Data from patients injured in 1998 were obtained from both the trauma registry and administrative database. These International Classification of Diseases, Ninth Revision, Clinical Modification codes signify an admitting diagnosis of trauma. Patients from each database were "matched" by admission date, medical record number, age, and name. The two matched data sets were compared for accuracy in recording data. Chi-square analysis was used to compare groups. RESULTS: There were 2,702 patients found in both databases. One hundred eighteen patients with significant trauma were recorded in the trauma registry, but not in the administrative database. Comparison of recorded data for "matched" patients is as follows. The underreporting of mechanism of injury, diagnoses, diagnostic interventions, surgical procedures, and complications was rampant throughout the administrative database. Statistical significance was seen in the comparison between the trauma registry and the administrative database with motor vehicle collisions (458 vs. 391), abdominal injuries (346 vs. 293), orthopedic injuries (1,243 vs. 1,101), and thoracic injuries (486 vs. 397). Diagnostic interventions such as diagnostic peritoneal lavage, head computed tomographic scans, and abdominal computed tomographic scans were all grossly underrecorded, with only 40%, 12%, and 9% captured by the administrative database, respectively. Analysis of surgical procedures revealed these same trends, with statistical significance seen in abdominal and orthopedic procedures. Complications such as acute respiratory distress syndrome and deep venous thrombosis showed statistically significant differences. Mortality was underreported in the administrative database, with 14 deaths omitted. CONCLUSION: This study shows that administrative data have copious omissions of specific injuries, diagnostic and therapeutic interventions, as well as complications. The trauma registry recorded more of the diagnoses, diagnostics, procedures, and outcomes in the care of trauma patients. Trauma registries may be more useful than administrative databases in assessing quality of care and diagnostic and therapeutic interventions.

Retrohepatic vena cava and juxtahepatic venous injuries.

The daunting mortality encountered with retrohepatic vena cava and juxtahepatic venous trauma is testimony to the difficulties inherent in their management. For a successful outcome, the operating surgeon must be able to rapidly identify the nature of the injury and tailor the choice of procedure accordingly. Atriocaval shunting, balloon shunting, sequential vascular clamping, and perihepatic packing are all methods of treatment with which the surgeon must be familiar. In this review, we present a case of this injury caused by a gunshot wound. This serves as a useful starting point for a discussion of the techniques available for addressing this injury.

Alteration in Kupffer cell function after mild hemorrhagic shock.

Functional changes in Kupffer cells occur after profound hemorrhagic shock. This study was performed to demonstrate if Kupffer cell changes also occur after mild hemorrhagic shock. Sprague-Dawley rats were bled to a systolic blood pressure of 60 to 70 mmHg and resuscitated with Lactated Ringers solution (twice the shed blood volume) after 30 min. Resuscitation produced immediate recovery of blood pressure and allowed long-term recovery of the animals. Sham animals received anesthesia and monitoring only. Thirty minutes after resuscitation, Kupffer cells were isolated by centrifugal elutriation and cultured for 48 h. In Kupffer cells isolated from shocked animals, phorbol ester-stimulated superoxide production increased 7-fold and lipopolysaccharide- (LPS) stimulated prostaglandin E2 (PGE2) production increased 4-fold. Tumor necrosis factor-alpha (TNFalpha) production, on the other hand, was decreased by 50%. A non-significant trend toward increased phagocytosis was also observed, whereas LPS-stimulated nitric oxide production was unchanged. In conclusion, mild hemorrhagic shock produced increases in superoxide and PGE2 production, and decreases in TNFalpha production by Kupffer cells, changes that may be appropriate to defend against the infectious challenges that often follows trauma and hemorrhage.

Accuracy of administrative data in trauma: splenic injuries as an example.

BACKGROUND: Accurate data are needed to evaluate clinical outcomes, therapeutic modalities, and quality of care in trauma. Administrative data, usually used for billing, have been used to evaluate performance and assess therapy in other medical specialties. This study was performed to determine whether administrative databases are accurate in the recording of information about trauma patients with splenic injuries. METHODS: Patients who had blunt splenic injuries were identified using a state trauma registry. The medical records of those patients were reviewed. The data collected by chart review were compared with data in the statewide administrative database of patients who had splenic injuries at the same four Level I and II trauma centers in the same 5-year period. Age, sex, admission date, and hospital were matched to assure comparison of the identical cohort. chi2 analysis was used to compare dichotomous data and Student's t test continuous data. RESULTS: The administrative database identified 641 and the trauma registry identified 529 patients with a diagnosis of splenic injury. A total of 401 patients were found in both databases. Of these, 120 (22.7%) patients were not recorded in the administrative database. Injury Severity Score was underreported by the administrative database (25.74 +/- 14.7 vs. 19.52 +/- 11, p < 0.0001). The administrative database underreported orthopedic, chest, and head injuries (317 vs. 215, 325 vs. 228, and 234 vs. 155, respectively; all p < 0.0001). Use of abdominal computed tomographic scan and diagnostic peritoneal lavage were also underreported (260 vs. 56 and 104 vs.17, both p < 0.0001). The number of operations on the spleen and number of orthopedic procedures were underreported (259 vs. 225, p < 0.014 and 147 vs. 94, p < 0.0001). Complications were markedly underreported by the administrative database (200 vs. 47, p < 0.0001) CONCLUSION: This study shows that administrative data lack accuracy in the recording of associated injuries, injury severity, diagnostics, procedures, and outcomes data in patients with splenic injuries. Whether these data should be used to evaluate treatment modalities or quality of care in trauma is questionable.

Occupation-related burn injuries.

Unlike household burn injuries, the characteristics of burn injuries in the workplace have not been well described. In an effort to understand the causes and effects of occupation-related burn injuries and to aid in prevention, we sought to describe work-related burn injuries by frequency, burn type, age of the patients, body parts burned, and occupation of the patients. This was a statewide, cross-sectional study of all burns that occurred in the workplace during 1994. Data on fatal injuries were obtained from the National Census of Fatal Occupational Injuries. Survey data from the North Carolina Department of Labor were used for nonfatal injuries. Burns caused 34 deaths (15.3%) and 1720 injuries in the workplace in 1994. Of the nonfatal injuries, 1363 (79.2%) were caused by exposure to caustic substances or hot objects or substances. The head and upper extremities were the most frequently injured body parts (936 injuries; 57.6%). The average age of those burned was 30.7 years; most of the patients ranged from 25 to 35 years old. High-risk occupations included vehicle and equipment cleaners, food service personnel, and millwrights (11.3%, 5.3%, and 5.2% of burn injuries, respectively). Unlike the flame burns that occur in homes, exposure to caustics and hot objects and substances caused the majority of on-the-job burn injuries. Protective gear for the head and upper extremities may prevent a significant number of burns. Education and prevention programs may best be directed at workers with high-risk occupations and workers in the 25- to 35-year age range.

Use of an unmanned police car to reduce traffic speed.

OBJECTIVE: Motor vehicle collisions are the most common mechanism of traumatic death. Speeding is often implicated as a causal factor in motor vehicle crashes. One potential intervention, to prevent speeding, is the placement of a roadside unmanned police car. This study sought to answer the following questions: is speeding reduced by this intervention, does this intervention lose effectiveness over time, and when the car is removed, do motorists resume speeding? METHODS: A radarless speed detector was placed on a roadway that had a history of speed-related collisions. Baseline speeds were recorded for 12 days. Thereafter, an unmanned police cruiser was parked near the road, and speeds were recorded for 10 days. The police car was removed, and data collection continued 1 more week. The difference between the proportion of motorists exceeding 45-mph in the baseline period and the decoy intervention period was tested by using a chi2 test. RESULTS: During the baseline surveillance, 72.0% of vehicles (186,578 of 259,074 motorists) had speeds greater than 45 mph. After placement of the unmanned police car, 41.0% of motorists (92,272 of 225,026 motorists) exceeded 45 mph (p < .0001). Over the 10-day study period, when the decoy police car was in place, the percentage of motorists exceeding 45 mph gradually increased from 27.2% to 47.4%. Upon removal of the police car, speeding returned approximately to baseline, with 67.5% of motorists (120,640 of 178,752 motorists) exceeding 45-mph. CONCLUSION: Parking an unmanned police car beside a road was associated with a large reduction in speeding over a 10-day period. Removal of the unmanned police car resulted in a return to preintervention speeding.

Acinetobacter calcoaceticus pneumonia and the formation of pneumatoceles.

Pneumatoceles are cystic lesions of the lungs often seen in children with staphylococcal pneumonia and positive-pressure ventilation. Acinetobacter calcoaceticus is an aerobic, short immobile gram-negative rod, or coccobacillus, which is an omnipresent saprophyte. The variant anitratus is the most clinically significant pathogen in this family, usually presenting as a lower respiratory tract infection. Acinetobacter has been demonstrated to be one of the most common organisms found in the ICU. We present three critically ill surgery patients with Acinetobacter pneumonia, high inspiratory pressures, and the subsequent development of pneumatoceles. One of these patients died from a ruptured pneumatocele, resulting in tension pneumothorax. Treatment of pneumatoceles should center on appropriate intravenous antimicrobial therapy. This should be culture directed but is most often accomplished with Imipenem. Percutaneous, computed tomographic-guided catheter placement or direct tube thoracostomy decompression of the pneumatocele may prevent subsequent rupture and potentially lethal tension pneumothorax.

Accuracy of administrative data in trauma.

BACKGROUND: Accurate data are needed to evaluate outcomes, therapeutics, and quality of care. This study assesses the accuracy of administrative databases in recording information about trauma patients. METHODS: Patients with thoracic aorta injury were identified with a state trauma registry, and the medical records were reviewed. Data collected were compared to administrative data on patients with thoracic aorta injuries, at the same hospitals in the same time period. RESULTS: Fifteen patients (16.3%) with thoracic aorta injury were not recorded in the administrative database, and 23 patients (18.7%) were misdiagnosed. Ninety-one patients were found in both data sources. The administrative database significantly (P < .05) underrecorded abdominal injuries (50 vs 35), orthopedic injuries (117 vs 75), and chest injuries (77 vs 48). The number of aortograms (78 vs 8), type of operative procedures (use of graft; 70 vs 30), use of bypass (35 vs 16), and complications (77 vs 33) were underreported (P < .05). The Injury Severity Score was underestimated by the administrative database (38.65 +/- 12.41 vs 25.66 +/- 9.53; P < .05). CONCLUSIONS: Administrative data lack accuracy in the recording of associated injury, injury severity, diagnostic, and procedural data. Whether these data should be used to evaluate treatment or quality of care in trauma is questionable.

Host priming, not target antigen type, decides rejection rate in mice primed with MHC II "knockout" cultured keratinocytes.

BACKGROUND: Lack of skin for autograft continues to be problematic in patients with large burns. Allograft and xenograft have been used, but are prone to rapid rejection. Use of cultured keratinocytes (CK) and major histocompatibility complex (MHC) II "knockout" grafts leads to prolonged graft survival compared to allograft. Whether this prolongation is secondary to decreased priming efficacy or target recognition is unknown. Whether a combination of these techniques would generate a less immunogenic allograft remains to be determined. METHODS: CBA mice (n = 100) were flank-grafted with full thickness C57BL/6 (B6 FT), B6 cultured keratinocytes (B6 CK), B6 major histocompatibility complex II "knockout" full thickness (KO II FT), B6 major histocompatibility complex II "knockout" cultured keratinocytes (KO II CK), or a full thickness autograft (Auto). Three weeks after priming flank grafting, B6, MHC I (KO I), and KO II full thickness tail grafts were placed on each mouse. Tail graft rejection was assessed daily by an observer blinded to flank and tail-graft type. A 4-point grading system for graft color, hair loss, and texture was used. RESULTS: Animals primed with KO II CK flank grafts had increased survival of tail grafts over B6 FT flank grafted controls (12.3 +/- 1.05 vs 10.1 +/- 1.00, P < 0.05). Within flank graft groups, however, B6, KO I, and KO II tail graft survival was similar. CONCLUSIONS: KO II CK allografts decrease host priming compared to normal B6 FT allograft. MHC deletion (KO I or KO II) does not protect a target graft from rejection in a primed host. CK and KO techniques may offer a less immunogenic allograft and a readily available source of wound coverage in patients with extensive burns.

Immunogenicity of cultured keratinocyte allografts deficient in major histocompatibility complex antigens.

BACKGROUND: Full-thickness (FT) and cultured keratinocyte (CK) allografts have been used as temporary skin replacements in patients with massive burns, but these grafts are ultimately rejected after restoration of host immunocompetence. Genetic engineering has permitted the creation of knockout (KO) mice deficient in class I or class II major histocompatibility antigens. This study examines the immunogenicity of such grafts to determine if these genetically modified keratinocytes could be used for permanent wound coverage. METHODS: Host sensitization to alloantigen was assessed by second-set rejection. CBA mice (n = 111) were primed with flank grafts consisting of FT and CK allografts from normal C57BL/6 donors, FT and CK class I KO allografts, FT and CK class II KO allografts, and CK autografts. Three weeks later, hosts were challenged with normal tail allografts and observed for second-set rejection. Median graft survival was analyzed by chi2 and Wilcoxon rank tests. In the second experiment, cytotoxic T lymphocytes (CTLs) were harvested from CBA mice (n = 28) 3 weeks after flank grafting. CTL effectors were tested on radiolabeled targets at various ratios in a 51Cr release assay. Dilution curves of CTL activity were compared by analysis of variance. RESULTS: Hosts primed with CK or FT allografts demonstrated accelerated rejection of second-set tail grafts compared with hosts covered with CBA autografts. CK knockout grafts were less immunogenic than FT knockout skin; class II KO allografts were considerably less immunogenic than class I KO allografts. CTL activity against the knockout CK allografts was negligible compared with that of hosts primed with normal allografts or FT knockout allografts. CONCLUSION: Although full-thickness knockout skin retains substantial immunogenicity, cultured keratinocytes deficient in class II antigens fail to prime for accelerated second-set rejection and do not elicit a CTL response in the graft recipient. This lack of immunogenicity may permit the indefinite survival of allogeneic knockout keratinocytes in patients requiring massive wound excision and coverage.

The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury.

INTRODUCTION: Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. METHODS: Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, animals were anesthetized and received either a 0, 20, or 40% burn. Spleens were harvested 3, 7, 10, and 14 days after burn injury (n = 96), cocultured with B6 stimulator splenocytes, and assessed for CTL response to radiolabeled allogeneic targets in a 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for CD4, CD8, and CD25 antigens. In experiment 3, splenocytes from 0 and 40% burned animals on Postburn Days 3 and 14, were cocultured with B6 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-gamma (IFN-gamma) using ELISA: RESULTS: The CTL response for 20 and 40% burned animals decreased 3 days postburn (-11.9 and -30.1%, P < 0.05), returned to baseline in 7-10 days, and was increased by 14 days postburn (15.8 and 22.6%, P < 0.05). The T-helper lymphocyte population (CD4) from 40% burn animals was significantly decreased on Postburn Days 3 and 14 (10.12 +/- 0.45% vs 11.78 +/- 0.29% and 10.19 +/- 0.24% vs 14.21 +/- 0.97%, respectively, P < 0.05). The CTL effector (CD8) splenocyte population was significantly higher in the burned animals on Postburn Day 14 (4.55% vs 3.71%, P < 0.05). On Postburn Day 3, average IL-5 production was higher in the burned animals (1.80 pg/ml vs 0.59 pg/ml, respectively, P < 0.05). The burn group, on Postburn Days 3 and 14, showed a decrease in mean IL-2 production (212.81 pg/ml vs 263.6 pg/ml and 342.7 pg/ml vs 421.4 pg/ml, respectively, P < 0.05). Mean IFN-gamma production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/ml and 218.16 pg/ml vs 263.42 pg/ml, P < 0.05). CONCLUSIONS: Burn injury impairs the effector limb of the CTL response as a function of burn size in the immediate postburn period. CTL activity returns to baseline within 7-10 days postburn and has a rebound increase by Day 14. Early CTL suppression, after burn injury, may be due to a decrease in the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-gamma production and increased IL-5 production.

Management and outcome of splenic injury: the results of a five-year statewide population-based study.

Although splenectomy was the preferred method of treating the injured spleen in the past, the methods of splenorrhaphy and nonoperative management have appeared to gain in popularity. The purpose of this study was to determine whether the management of splenic injuries has changed over the course of time and if there has been any differences in the morbidity and mortality associated with different methods of treatment. We retrospectively examined the discharge records from 2627 patients with splenic injuries from the North Carolina Discharge Database. There were 2258 adults and 369 pediatric patients for evaluation. The rate of nonoperative therapy increased from 33.9 per cent to 46.3 per cent over the 5 years of the study, whereas the rate of splenectomy decreased from 52.9 per cent to 43.4 per cent over the same time period. Splenorrhaphy was used in approximately 10 per cent of the injuries over the course of the entire study period. Adults treated nonoperatively required late operation 6.0 per cent (49/811) of the time. The pediatric late operation rate for nonoperative management was 0.4 per cent(1/231). Reoperation after splenorrhaphy was 2.9 per cent (7/240) for adult patients and 4.3 per cent (2/47) for pediatric patients. The majority of adults (57.2%) with an Injury Severity Score (ISS) < or = 15 were able to be cared for via nonoperative methods, whereas the majority of adults (66.4%) with an ISS > 15 required splenectomy. The majority of pediatric patients were able to be cared for in a nonoperative fashion in both the ISS < or = 15 (83.4%) and ISS > 15 (45.5%).