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Biomedical subjects

D J Terris

Publications and source records attributed to D J Terris.

At least 37 records · Page 2Linked to original sources

Autologous and heterologous blood transfusion in head and neck cancer surgery.

OBJECTIVE: To determine if the use of autologous blood ameliorates the increased risk for cancer recurrence that has been associated with perioperative blood transfusion. DESIGN: Retrospective medical record review. SETTING: Tertiary care hospital. PATIENTS: One hundred sixty-five consecutive patients with stages II to IV squamous cell carcinoma of the head and neck treated surgically at a university hospital from January 1, 1989, through December 31, 1994. MAIN OUTCOME MEASURES: We evaluated the impact of perioperative autologous and heterologous blood transfusion and 10 other variables on recurrence. Univariate and multivariate analyses were used. RESULTS: Heterologous blood recipients had a 59% recurrence rate, whereas those who had received autologous blood or no transfusion had recurrence rates of 33% and 35%, respectively. The following 4 variables had a statistically significant association with recurrence by multivariate analysis: previous treatment of current malignancy (P<.001); receipt of heterologous blood (P = .04); positive margin (P = .04); and nodal disease (P = .04). The receipt of heterologous blood was associated with a 40% increased risk for recurrence. CONCLUSION: Autologous blood products should be used during head and neck cancer surgery if possible when transfusion is necessary.

Blood Transfusion, Autologous↗

Tissue oxygen distribution in head and neck cancer patients.

BACKGROUND: The importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been known. METHODS: We evaluated the tissue oxygenation status with a polarographic needle electrode system in 37 patients with malignancies of the head and neck and correlated the pO2 of 25 patients with treatment outcome. RESULTS: Sixteen tumors contained areas of severe hypoxia, defined by pO2 values below 2.5 mm Hg. Tumor oxygenation parameters were not correlated with hemoglobin, age, and history of tobacco use. There were no subcutaneous PO2 values below 10 mm Hg (ie, no areas of moderate or severe hypoxia), whereas this degree of hypoxia was commonly found in the tumors. Though not statistically significant, hypoxic tumors showed trends for poorer treatment outcome. CONCLUSION: Our data demonstrate a great interindividual variability in the oxygenation of head and neck cancers and appears unassociated with clinical parameters. The method is capable of identifying patients with poorly oxygenated tumors, thereby providing important information for selecting patients who might need customized therapy designed to kill hypoxic tumor cells. Hypoxic tumors show a consistent trend for poor treatment outcome.

Adult↗

Postoperative irradiation of minor salivary gland malignancies of the head and neck.

OBJECTIVES: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors. MATERIALS AND METHODS: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years). RESULTS: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted. CONCLUSIONS: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

Adenocarcinoma↗

Functional recovery following nerve injury and repair by silicon tubulization: comparison of laminin-fibronectin, dialyzed plasma, collagen gel, and phosphate buffered solution.

PURPOSE: This study was designed to investigate the potential for enhancement of peripheral nerve regeneration by the manipulation of the neural microenvironment with laminin-fibronectin solution (LF), dialyzed plasma (DP), collagen gel (CG), or phosphate buffered saline (PBS) in a silicon tubulization repair model. METHOD: A rat sciatic nerve model of injury and repair was used to study the effects of exogenous matrix precursors (contained in LF or DP), CG or PBS on nerve regeneration. A total of 50 Sprague-Dawley rats underwent left sciatic nerve transection and repair by silicon tubulization. The silicon tubules were either left empty (E), or filled with solutions of LF, DP, CG, or PBS. Nerve function was assessed preoperatively and then postoperatively, every 10 days for 90 days using sciatic functional indexes (SFI). On postoperative day 90, the sciatic nerves were harvested for histologic analysis and the posterior compartment muscles of each animal were harvested and weighed. Molecular analysis for two proteins associated with neural regeneration was performed on the nerve segments. RESULTS: All five animal groups demonstrated equivalent functional recovery. Comparison of the rate of recovery and mean maximal recovery between each group revealed no statistically significant differences, with P-values ranging from 0.30 to 0.95. Posterior compartment muscle masses were similar in all groups except for LF, whose animals had muscle masses 8-9% lower than CG, PBS, or E (P < 0.05). CONCLUSION: Alteration of the regenerating neural microenvironment with exogenous matrix precursors (LF, DP), CG or PBS failed to improve sciatic functional recovery after nerve transection and silicon tubulization in this model. From this study, we conclude that LF, DP, CG, and PBS do not enhance the rate or degree of recovery of peripheral nerve function across a narrow gap when nerves are repaired by silicon tubulization.

Animals↗

DNA damage measured by the comet assay in head and neck cancer patients treated with tirapazamine.

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Animals↗

Uses and limitations of FDG positron emission tomography in patients with head and neck cancer.

OBJECTIVE: Numerous authors have reported the potential usefulness of positron emission tomography (PET). These studies have had conflicting results, at least partly owing to limited sample sizes. The objective of this study is to define not only the uses, but also the limitations of PET in patients with head and neck cancer. STUDY DESIGN: Nonrandomized, retrospective analysis of PET at an academic institution. METHODS: The authors performed 146 PET scans on 133 patients with head and neck cancer. Eighteen patients (19 PET scans) with thyroid disorders were excluded. A minimum 1 year of follow-up was available in 84 patients, who were separated into groups based on whether the PET was used to detect unknown primary cancers (n = 20), stage neck nodal and distant metastases (n = 8), monitor response to nonsurgical therapy (n = 22), or detect recurrent or residual cancers (n = 34). The results of PET were compared with results from computed tomography (CT) and magnetic resonance imaging (MRI) performed in the same patients. RESULTS: Of the unknown primary cancers, PET correctly identified 7 of 20 primary sites, giving a sensitivity of 35%. When combined with CT or MRI, the sensitivity increased to 40%. When used for detection of metastatic disease, PET demonstrated five of five nodal metastases (100%) and two of four distant metastases (50%). In evaluating the response to nonsurgical therapy, PET had a sensitivity of 50% and a specificity of 83% for detecting tumor at the primary site and a sensitivity of 86% and a specificity of 73% for detecting nodal disease. When used for evaluation of recurrent/residual disease, PET identified seven of seven cases of local recurrences/residual disease and had a specificity of 85%. PET also detected seven of seven cases of nodal disease and had a specificity of 89%. CONCLUSIONS: For staging purposes, PET is limited by its lack of anatomic detail. However, PET compares favorably with CT and MRI in detecting recurrent/residual cancers. PET imaging complements the more traditional imaging modalities (CT or MRI), especially for an unknown primary cancer.

Carcinoma, Squamous Cell↗

Cosmetic enhancement associated with surgery for obstructive sleep apnea.

OBJECTIVE: To document the capacity of surgery for obstructive sleep apnea (OSA) to incorporate techniques that incidentally improve the cosmetic features of the patients. STUDY DESIGN: Retrospective analysis of surgical outcomes at an academic practice. METHODS: Moderate to severe OSA usually requires multilevel pharyngeal surgery, including tongue base surgery. The surgical procedures, including hyoid myotomy and mandibular osteotomy with tongue advancement, afford the opportunity to address cosmetic deficits, such as microgenia and excessive submental skin and fat. Outcomes achieved using these procedures over a 4-year period were analyzed. RESULTS: Of 428 consecutive patients presenting for evaluation of sleep-related breathing disorders, 212 were deemed surgical candidates. Ninety-seven of these had office-based procedures for snoring, upper airway resistance syndrome, or mild OSA. The remaining 115 had formal surgical procedures done, and 68 of these had multilevel pharyngeal surgery. Of these, 12 had defined cosmetic deficiencies that were addressed at the time of the sleep apnea surgery. There were 7 men and 5 women, with a mean age of 48.2 years. The group was moderately obese (mean BMI = 31.8) and had moderate to severe OSA (mean RDI = 37.0, mean LSAT = 78%). Cosmetic deficits identified included turkey gobbler deformity (n = 8), microgenia (n = 6), excessive submental fat (n = 2), and nasal deformity (n = 1); several patients had more than one addressable problem. All patients achieved an improved postoperative appearance. Representative photographs are presented. CONCLUSIONS: A surgical approach to the management of sleep apnea affords an opportunity to also address cosmetic deficiencies, including excessive submental skin and fat, microgenia, and nasal deformities.

Cosmetic Techniques↗

Peripheral nerve regeneration in CNTF knockout mice.

OBJECTIVES: To determine the role of ciliary neurotrophic factor (CNTF) in the regeneration of the mouse sciatic nerve following injury by studying the CNTF knockout mouse in a blinded, randomized and controlled evaluation. STUDY DESIGN: Fifty-eight wild-type and 57 CNTF knockout mice were randomly assigned to one of four treatment groups: sham surgery (sciatic nerve exposure), sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair using 10-0 monofilament suture. Walking track analysis was performed before and after surgery at weekly intervals for 7 weeks, using a previously described formula. At the completion of walking track analysis, morphometric histological analysis of axon number and axon diameter in the distal sciatic nerves was performed. RESULTS: The wild-type and knockout mice that underwent only sham surgery had no change in their walking tracks during the study interval (P = .30 on postoperative day 49). The wild-type mice that underwent sciatic nerve crush showed complete functional recovery (P = .66 on postoperative day 28), but the CNTF knockout mice whose sciatic nerves were crushed did not fully recover (P = .05 on postoperative day 49). The CNTF knockout and wild-type mice showed similar levels of recovery after transection without repair (P = .78), and the rate of contracture formation was not significantly different (P = .40). The CNTF knockout and wild-type mice showed similar levels of recovery after epineurial repair (P>.31), however the rate of severe contractures was greater in the CNTF knockout mice (6 of 13) than in the wild-type mice (2 of 12) (P = .11). CONCLUSION: The absence of CNTF impairs the ability of mice to recover from a sciatic nerve crush injury. There is also a trend toward a greater rate of contracture formation after sciatic nerve transection and epineurial suture repair when CNTF is unavailable. These findings suggest that CNTF is important for recovery of neuronal function following crush and transection nerve injuries.

Animals↗

Repair with collagen tubules linked with brain-derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model.

OBJECTIVE: To determine if brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) can be successfully delivered to transected and repaired peripheral nerves by cross-linking the factors to collagen tubules (CTs). METHODS: Forty-eight Sprague-Dawley rats underwent left sciatic nerve transection and repair. In the control group, CTs were implanted with no neurotrophic ligand (n=13). There were 3 experimental groups: CT with BDNF covalently linked to the collagen matrix (CT/BDNF; n=12), CT with CNTF covalently linked (CT/CNTF; n=12), and CT with both BDNF and CNTF covalently linked (CT/BDNF/CNTF; n=11). Functional outcome of neural regeneration was assessed every 10 days using walking track analysis, which was submitted to a sciatic functional index. Nerve morphometry, electrophysiologic studies, and molecular analysis for neural proteins were performed at the completion of the study at postoperative day 90. RESULTS: Animals in all 3 experimental groups achieved significantly superior maximal functional recovery, larger nerve cross-sectional areas, and a greater number of axons when compared with the control CT group (P<.001, P<.05, and P<.05, respectively). The animals in the CT/BDNF/CNTF group displayed the best functional recovery and had the largest axon diameters, greatest amplitude, and the fastest nerve conduction velocities. Molecular analysis revealed significant differences in the expression of neurofilament, neural cell adhesion molecule, myelin-associated glycoprotein, and myelin basic protein. CONCLUSIONS: We present the first evidence that CNTF covalently linked to CTs can improve functional recovery compared with CTs alone. We also support the previous finding that BDNF covalently linked to CTs significantly increases the functional recovery of transected and repaired nerves. Finally, we found that cotreatment produced the best functional recovery in our model.

Animals↗

Functional recovery of transected nerves treated with systemic BDNF and CNTF.

The purpose of this study was to investigate the effect of systemic co-injections of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringer's solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive.

Animals↗

Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse.

The sciatic functional index previously described in rats has proven to be a reliable index of functional recovery following sciatic nerve injury and repair. A similar functional assay of sciatic, peroneal, and posterior tibial nerve lesions was developed in a mouse model. Forty-eight C57/BL6 mice were randomly divided into 4 groups: sham surgery, sciatic nerve transection, peroneal nerve transection, and posterior tibial nerve transection. Preoperative and postoperative (48 hours) walking tracks were obtained. The pawprints were analyzed in a blinded fashion for measurements of print length (PL), toe spread (TS), intermediate toe spread (IT), and the orthogonal distance from the toe of one paw to the hind pad of the opposite paw (TOF). Multiple linear regression analysis was performed using these measurements to determine their significance and appropriate weighted contribution to the index formula for each nerve lesion. For the sciatic functional index, changes in the PL (P = 0.0092) and TS (P = 0.0008) were significant, resulting in an R2 value of 0.88. For the peroneal functional index, only TS (P < 0.0001) was significant with R2 = 0.83. For the posterior tibial index, only PL (P < 0.0001) was significant with R2 = 0.89. Formulas for a sciatic, peroneal, and posterior tibial functional index were created based on the coefficients derived from the multiple linear regression analysis. The indices that were developed will allow investigators to assess functional recovery following specific nerve lesions in mice.

Animals↗

Feasibility study of lactate imaging of head and neck tumors.

A proton spectroscopic imaging sequence was used to investigate the feasibility of lactate imaging in head and neck tumors. The sequence employs a two-shot lactate editing method with inversion recovery for additional lipid suppression, and a restricted field of view to suppress motion artifacts. Variations in acquisition parameters and two different receive coils were investigated on twelve patients. Elevated lactate was detected in three patients, no lactate was observed in seven patients, and two studies were inconclusive because of severe motion or inhomogeneity artifacts. Best results were obtained with an anterior/posterior neck coil at a 288 ms echo time (TE).

Adult↗

In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5 T using PRESS excitation with applications to the study of brain and head and neck tumors.

Two T2-independent J-difference lactate editing schemes for the PRESS magnetic resonance spectroscopy localization sequence are introduced. The techniques, which allow for simultaneous acquisition of the lactate doublet (1.3 ppm) and edited singlets upfield of and including choline (3.2 ppm), exploit the dependence of the in-phase intensity of the methyl doublet upon the time interval separating two inversion (BASING) pulses applied to its coupling partner after initial excitation. Editing method 1, which allows for echo times TE = n/J (n = 1, 2, 3, . . . . ), alters the BASING carrier frequency for each of two cycles so that, for one cycle, the quartet is inverted, whereas, for the other cycle, the quartet is unaffected. Method 2, which also provides water suppression, allows for editing for TE > 1/J by alternating, between cycles, the time interval separating the inversion pulses. Experimental results were obtained at 1.5 T using a Shinnar Le-Roux-designed maximum phase inversion pulse with a filter transition bandwidth of 55 Hz. Spectra were acquired from phantoms and in vivo from the human brain and neck. In a neck muscle study, the lipid suppression factor, achieved partly through the use of a novel phase regularization algorithm, was measured to be over 10(3). Spectra acquired from a primary brain and a metastatic neck tumor demonstrated the presence of lactate and choline signals consistent with abnormal spectral patterns. The advantages and limitations of the methods are analyzed theoretically and experimentally, and significance of the results is discussed.

Aspartic Acid↗

Management of the clinically positive neck in organ preservation for advanced head and neck cancer.

BACKGROUND: To investigate clinicopathologic predictive criteria for the optimal management of neck metastases in patients with advanced head and neck cancers treated with combined chemoradiotherapy. METHODS: Prospective study, 48 patients. Mean length follow-up, 23 months. RESULTS: Neck stage predicted neck response to chemoradiotherapy; N3 necks showed more partial responses (P = 0.04), and N1 necks showed more complete responses (P = 0.12). Primary tumor site strongly predicted the pathologic response found on neck dissection in patients with a clinical partial response (cPR) following chemoradiotherapy. There was no difference in survival between patients with a clinical complete response (cCR) after chemoradiotherapy, and patients with a pathologic complete response (pCR) after neck dissection (P = 0.20); however, when grouped together, these patients survived longer than did patients with a pPR at neck dissection (P = 0.06). CONCLUSIONS: Clinical response to induction chemotherapy is a poor predictor of ultimate neck control. Induction chemotherapy followed by chemoradiotherapy, and planned neck dissection for patients with persistent cervical lymphadenopathy, provides good regional control.

Adult↗

Conservation of resources: indications for intensive care monitoring after upper airway surgery on patients with obstructive sleep apnea.

Although significant complications can result after upper airway surgery for obstructive sleep apnea (OSA), there is a lack of consensus regarding the most appropriate level of monitoring in the perioperative period. A retrospective analysis was performed on the operative records of 109 adult patients who underwent 125 surgical procedures from January 1, 1991, to May 31, 1996, with particular emphasis on complications that would have mandated intensive care monitoring and management. Airway complications occurred in one patient (0.8%), who became obstructed immediately after surgery; he responded to naloxone and suctioning. Five other patients (4%) suffered oxygen desaturation to levels below 90% (none fell below 80%, and in only one case was it below the lowest preoperative oxygen saturation level). Cardiac complications, primarily significant hypertension, were the most common adverse events. Four (3.2%) bleeding complications were encountered; all occurred after discharge from the hospital. Routine postoperative intensive care monitoring for all adult patients undergoing upper airway surgery for OSA is unnecessary. Although high-risk patients cannot always be identified preoperatively, significant complications generally emerge within 2 hours after surgery. Therefore a decision regarding the level of postoperative monitoring needed may be made with confidence during the period of time that the patient is in the recovery room.

Adult↗

Cephalometric parameters after multilevel pharyngeal surgery for patients with obstructive sleep apnea.

Cephalometric studies have shown narrowing in the upper airway at multiple levels in patients with obstructive sleep apnea. Uvulopalatopharyngoplasty (UPPP), mandibular osteotomy with genioglossus advancement, and hyoid myotomy with advancement address narrowing in the retropalatal and retrolingual regions. In an effort to relate postoperative clinical changes to anatomic changes, cephalometric studies were performed on 44 patients who underwent multilevel pharyngeal surgery (UPPP, genioglossus advancement, hyoid myotomy with advancement). Both pre- and postoperative radiographs were available for 23 of these patients. The posterior airway space (P = .09), minimal posterior airway space (P = .04), posterior uvular space (P = .06), mandibular plane-to-hyoid distance (MP-H) (P = .06) and central incisor-to-tongue base distance (P = .02) all improved after surgery. None of the measurements of the posterior airway were significantly different between responders and nonresponders. The degree of collapse of the palate on modified Müller maneuver was highly correlated with the severity of sleep apnea as measured by the respiratory disturbance index; the collapse of the lateral pharyngeal walls was moderately correlated; and collapse of the base of tongue was not correlated. Cephalometric radiographs may reflect the anatomic changes that result from upper airway surgery for sleep apnea, but these changes are not useful for assessing surgical efficacy. The modified Müller maneuver, however, may represent a more predictive evaluation.

Adult↗

A longitudinal, functional study of peripheral nerve recovery in the mouse.

OBJECTIVES: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. STUDY DESIGN: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. RESULTS: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). CONCLUSIONS: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.

Animals↗