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OBJECTIVES@#To investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC).@*METHODS@#Using an enzyme-linked immunosorbent assay (ELISA), we measured the expression of FABP4 in plasma of 50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls. The content of the visceral fat area (VFA) as seen with abdominal computed tomography (CT) scanning was measured by ImageJ software. The expression levels of FABP4, E-cadherin, and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.@*RESULTS@#The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group (22.46 vs. 9.82 ng/mL; @*CONCLUSIONS@#High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients. FABP4 protein was highly expressed in CRC tissues and associated with TNM stage, differentiation, and lymph node metastasis of CRC. The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression, suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition (EMT).
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Objective To evaluate the bone repair capacity ofpolylactic acid-polyglycolic acid copolymer (PLGA)/collagen type Ⅰ (CoI) microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats.Methods Prepared PLGA microspheres.The microspheres were coated with Col.BMSCs of the third passage were cultured with PLGA/CoI microspheres.Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models.The osteoporotic rats were randomly divided into 5 groups,including SHAM group,PBS group,Cell group,MS group and Cell+ MS group.There were 8 rats in each group.Different material was injected into the intertrochanteric bone defect site which was made with electric drill.Four rats of each group were sacrificed at 1 month and 3 months post-operation.The fenora were taken to measure the intertrochanteric bone mineral density (BMD) with DEXA and evaluate trabecular stucture with Micro CT.Results After 7 days of coculture,BMSCs seeded on PLGA/CoI microspheres had nice adherance and proliferation.There was no difference of BMC and BMD among all groups at 1 month post-operation.Tb.Th of Cell+MS group was higher than that of PBS group and MS group at 1 month post-operation.％Tb.Ar of Cell+MS group was higher than that of Cell group and MS group at 1 month post-operation.Tb.Sp of Cell+MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation.After 3 months of operation,the BMC of Cell+MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference.BMD and Tb.Th of Cell+MS group was higher than those of other groups.％Tb.Ar of Cell+MS group was higher than that of SHAM group and PBS group.Tb.Sp of Cell+MS group had a tendence to reduce compared with other groups but showed no statistical difference.Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs.The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.
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Objective To evaluate the results and complications of hip arthroplasty performed as a salvage procedure after the failed treatment of intertrochanteric hip fractures in elderly patients. Methods Between 2004 and 2009,10 patients were treated with hip arthroplasty after the failed treatment of intertrochanteric fracture.There were six females and four males,at mean age of 75.7 years ( range,68-84 years).The initial treatment of fractures included dynamic hip screw (DHS) fixation in three cases,dynamic condyle screw (DCS) fixation in one,proximal femur fixation with reconstruction interlocking nail in three and conservative treatment without internal fixation in three.The failed procedures included avascular necrosis in four cases,cephalic implant cutting in three,nonunion in two and malunion associated with osteoarthritis in one.Joint hip replacement was performed except for pre-operative infection.Harris score at follow-up was recorded and prosthesis position was evaluated by imaging. Results Six patients were treated with total hip arthroplasty with a cemented cup (three patients) and an uncemented cup ( three patients) and four with a bipolar hemiarthroplasty.A long-stem implant was used in 5 of the 10 hips.The average duration of follow-up was 4.6 years (2-7 years).The mean duration of surgery was 128 minutes and mean blood loss was 764 ml.The mean Harris hip score increased from 37 preoperatively to 85 postoperatively.The functional results were satisfactory.One 84-year-old patient with the implant intact died 2 years postoperatively from a brain hemorrhage. Conclusions Hip arthroplasty is an effective salvage procedure after the failed treatment of intertrochanteric fractures in elderly patient.Most patients have better pain relief and functional improvements in spite of technical difficulties than primary arthroplasty.In the meantime,attention should be paid to patients with poor bone quality,bone loss,or articular cartilage damage.
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Objective To investigate the role of hybrid bone grafting using autograft and freezedried allograft bone in restoration of acetabular bone defect,as well as to evaluate the clinical results of this grafting technique combined with acetabular scaffold in dealing with massive acetabular deficiency.Methods Between April 1999 to December 2007,18 patients (19 hips) underwent acetabular revision by using a mixture of autograft and allogenic freeze-dried cancellous bone particles plus acetabular scaffold.There were 8males and 10 females,aged from 33 to 76 years (average,64.7 years).The acetabular defects were caused by aseptic loosening of primary total hip arthroplasty in 17 patients and osteoarthritis secondary to osteotomy in 1 case of acetabular dysplasia.There were 5 cases of Paprosky Ⅱ B defect,2 Paprosky Ⅱ C defect,6 Paprosky ⅢA defect and 6 Paprosky ⅢB defect.Results All patients were followed up for 3.6 to 12.3 years (average,6.5 years).Harris hip score improved from preoperative 38.7±9.6 to 87.6±7.8 at final follow-up.According to X-rays,bone incorporation evidenced by trabecular bridging of the host-donor interface was found at 3to 6 months postoperatively,and effective bone incorporation was achieved in all cases one year postoperatively.Polyethylene wear occurred in one case.Acetabular component loosening was not found at final follow up.Conclusion Impacted bone grafting using a mixture of autograft and freeze-dried allograft bone can efficiently restore acetabular bone defect.Adding autograft bone to freeze-dried allograft bone is a highly effective way of achieving graft incorporation.Hybrid bone grafting technique with acetabulum scaffold is an attractive option for the treatment of extensive acetabular deficiency.
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Objective To summarize the perioperative characters of femoral neck fractures in patients aged at over 80 years by analyzing the surgical treatment procedures. Methods A retrospective study was done on data of patients with femoral neck fractures treated surgically from June 2000 and June 2008. There were 25 males and 36 females, at average age of 83.4 years (80-94 years). Of all, there were 53 patients with fresh fractures including six with type Garden Ⅰ or Ⅱ fractures and 47 with type Garden Ⅲ or Ⅳ fractures, eight with old fractures ( all type Garden Ⅳ). Fifty-one patients (84%) were accompanied with preexisted internal medical or neurological diseases. Six patients with type Garden Ⅰ or Ⅱ fractures were treated with cannulated screw fixation (CSF). Among 55 patients with type Garden Ⅲ or Ⅳ fractures inclu-ding 47 fresh fractures and 8 old ones, 53 patients were treated by hip hemiarthroplasty (HHA) but the other two by cemented total hip arthroplasty (THA) because of preexisting hip osteoarthritis. Results The average operation duration and blood loss were 51 minutes and 50 ml in CSF group, 81 minutes and 180 ml in HHA group, 105 minutes and 350 ml in THA group. Fifteen patients (25%) had postoperative com-plications, mostly hypotension, cardiac insufficiency and atrial fibrillation, accounting for 12%. Postoperative hemoglobin was decreased by 11.9%, 17.1% and 18. 1% on average respectively in CSF group, HHA group and THA group, and postoperative albumin decreased by 10.8%, 18. 1% and 20.2% on average respectively in CSF group, HHA group and THA group. There were 17 patients (28%) with hemoglobin below 100 g/L and four (7%) with albumin below 30 g/L after operation. Conclusions The patients aged ≥80 years with femoral neck fractures are usually accompanied with preexisted internal medical or neurological diseases and have high risk in operation. Adequate preoperative preparation and active prevention and treatment of perioperative complications are important for successful operation and good postoperative results.
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BACKGROUND: The main pathological change of intervertebral disc herniation is that nucleus pulposus protrudes from ruptured annulus fibrosus, thus we can hypothesize that it is possible to prevent disc herniation prior to its protrusion by coagulating it as a whole.OBJECTIVE: To observe the coagulation effects of intervertebral disc nucleus pulposus by alum solution.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed between September 2002 and April 2003 at Department of Animal Experiment, Peking University First Hospital, Beijing China.MATERIALS: Twenty-six healthy adult hybrid dogs, 9 for in vitro experiment and 17 for in vivo experiment, weighing 16-21kg, with no restrictions on male and female, were obtained from Department of Animal Experiment, Peking University First Hospital, Beijing, China.METHODS: Twenty canine in vitro intervertebral discs obtained from 5 dogs were randomly divided into 4 groups, with 5 discs in each group, and were put into 2.5%, 5%, 10% alum solutions and 0.9% physiological saline, respectively. Effects of disc coagulation were observed after immersing for 1 day and 10 days, respectively. Another 16 in vitro intervertebral discs obtained from 4 dogs, composed of L2/3, L3/4, L4/5, L5/6, were also injected with the above 4 experimental solutions, 0.15ml, respectively. Sixty-eight in vivo intervertebral discs were obtained from 17 dogs and divided into 4 groups: blank control group, physiological saline group, 10% alum solution+one puncture point group, and 10% alum solution+two puncture points group, 17 discs in each group. Harvesting time: 3 days, 2 weeks, 1 month and 3 months postoperation.MAIN OUTCOME MEASURES: Effects of alum solutions on the coagulation of the intervertebral discs and related histological changes were observed and an alum solution of suitable concentration was preliminarily selected. General observation, light microscopic observation and scanning electron microscopic observation were made of the nucleus pulposuses.RESULTS: In the in vitro and in vivo experiments, it was found that physiological saline did not produce the effect of coagulation on the nucleus pulposus, while immersion in the alum solution induced nucleus pulposus coagulation in the in vitro intervertebral discs. Also, as the concentration of the alum solution increased, the volume of the coagulated nucleus pulposus gradually decreased. After alum solution was injected into the in vitro intervertebral discs, no nucleus pulposus coagulation appeared. When the 10% alum solution was injected into the in vivo intervertebral discs, nucleus pulposus coagulation occurred, with the strongest coagulation effect reached at 1 month postoperation. This was manifested in the agglutination reaction centered around the puncture point. When there were 2 puncture points, 2 coagulated lumps might appear. There was an increase in the mesenchymal component of the coagulated nucleus pulposus. Histochemical and scanning electron microscopic examinations confirmed the proliferation of large numbers of collagen fibers in the mesenchyme.CONCLUSION: Alum can promote nucleus pulposus to coagulate around the injection point. This may be related to the increase of collagens and the fibrosis resulting from stimulation of the nucleus pulposus by alum solution.
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Objective To evaluate the application of SOLIS in the surgery on anterior intervertebral fusion for the treatment of traumatic cervical disc protrnsion. Methods 53 traumatic single segment cervical disc protrusion were divided into three groups randomly. The A group (SOLIS) :n=18, SOLIS filled with autocancellous bone were implanted between the cervical vertebrae. The B group(Syncage) :n =16, as the first group Syncage filled with auto-cancellous bone were implanted. The C group:n=19,anterior cervical decompression and fusion with bone autograft and internal fixation with ACPS. The operations of the surgery on anterior cervical decompression in three groups were the same. Recovery of nerve function was observed by JOA score and the fusion state, stability and changes of interver-tebra height of fusion segment were evaluated by X ray. Results The average duration of the follow-up was 16.5 months in 53 cases. Bony fusion could be found 3～9months after operation in all cases. In all A (SOLIS) group cases,the movement of the implanted $OLIS Cage were not found. The heights of the cervical intervertebral spaces and the physiological curvature were restored without loss in the duration of follow-up. The average JOA was(10.4±2.4) be-fore operation and(14.9±2.0)after operation. There was highly significant variation between the former and the latter (P<0.01). In the B (Syncage)group,5 cases had cage subsidence, therefore the height of intervertebra and the phys-iological curvature were lost. The average JOA was (10.6±2.5) before operation and (13.2±2.3) after operation.There was significant variation between the former and the latter(P<0.05). In the C group the third group, the move-ment of the fixed titanium plate were not found in the duration of follow-up in 18 cases. The titanium plate fixation was loose in 1 case. The average JOA was(10.5±2.4) bofore operation and(15.1±1.9) after operation. There was high-ly significant variation between the former and the latter(P<0.01). After operation,there was significant difference in the JOA score between the A group and the B group,between the C group and the B group(P<0.05) ,and there was no difference between the A group and the C group(P>0.05). Conclusion Treatment of single segment prolapse of the cervical intervertebral disc with SOLIS cage has some advantages such as higher fusion rate, higher recovery rate of nerve function and low rate of loss of intervertebra] height.
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[Objective]To refine operative indications of rotating hinge prostheses and report the medium term results of these implants,and to analyze the reasons for postoperative complications.[Method]From 1999 to 2007,42 Endo-Model(Link) rotating hinge prostheses were used in 34 patients.The cases were all gonarthrosis with severe genu varus,genu valgus or flexion contracture.Bone defect or instability was found in these cases before operation.The mean follow-up was 6.4 years(2.3-10.4 years).[Result]One case of deep infection,and one periprosthetic fracture were noted.And 3 cases of patella subluxation or tilt were detected by postoperative X-ray.All patients had excellent pain relief and restoration of walking capability.The average HSS score improved from 40.5 points to 89 points after surgery.[Conclusion]Besides being used in revision surgery,rotating hinge prostheses are indicated in primary arthroplasties for patients with severe ligament laxity,substantial deformity or bone losses.With appropriate indication selection and accurate operative skill,satisfactory medium term result can be obtained.
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[Objective] To investigate the radiographic changes of patella after total knee arthroplasty(TKA)with non-resurfaced patellar.[Methods]Fifty-one patients(64 knees)underwent TKA with patellar non-resurfaced.Average age was 68.5 years(range,57~78 years).Average follow-up was 4.8 years(range,2.5~8 years).The radiographic changes of patella,patellar tilt,and patellar lateral shift were evaluated.The functional results of patellofemoral joint were analyzed.[Results]The patellar tilt and lateral shift were improved obviously after surgery.Most patella tracking lied in the middle and there were no obvious degeneration with the time passing.Osteophytes formation and deterioration of patellar tracking were the most common abnormal radiographic changes.There were no obvious relationship between symptoms of patellofemoral joint and patellar degeneration.[Conclusion]Patellar tracking can be improved immediately after non-resurfaced total knee arthroplasty in osteoarthritis patients.There will not be obvious patellar degenerative changes with time passing.
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[Objective] To evaluate clinical effect of total hip arthroplasty(THA)with a short-neck and straight stem in patients with osteoarthritis secondary to developmental dysplastic hip with high dislocation.[Methods]From June 2002 to October 2007,total hip arthroplasties with a short-neck and straight stem were performed for 11 patients(12 hips)with osteoarthritis secondary to developmental dysplastic hip with high dislocation.All were females with an average age of 51 years(range from 41 to 68 years).The operations were performed through a posterolateral approach.All the acetabular cups were reconstructed at the original anatomic location,and structural autogenous bone-grafting was performed if the cup was not covered enough by host bone.Short-neck and straight femoral stems were used with cement fixation.During operation,the soft tissue around hip was released extensively.[Results]After surgery,the center of the hip had an average distal translation of 4.5cm(range from 3.8 to 4.8 cm)and the limb length had an average increase of 3.9cm(range from 3.6 to 4.3 cm).All the patients were followed up for a mean time of 36 months(range from 10 to 66 months).All structural autografts united and none of acetabular and femoral components showed loosening.No radiolucent line was observed at the bone-cement and at the implant-cement interface around femoral stem.No patient had sciatic or femoral nerve palsy.The mean Harris score increased from preoperative 41.8 points to postoperative 86.2 points.[Conclusion]THA with a short-neck and straight stem for treatment of osteoarthritis secondary to developmental dysplastic hip with high dislocation avoids femoral shortening osteotomy and greater trochanter osteotomy when the center of hip had a distal translation less than 5cm in preoperative plan,and this choice provides satisfactory results at early-term follow-up.
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[Objective] To evaluate the efficacy and safety of drainage blood autotransfusion after total knee or hip arthroplasty.[Methods]Drainage blood in the first 6 hours postoperation was collected and reinfused using the ContavacTM CBCⅡ system in 30 patients taken total knee or hip arthroplasty.The efficacy was evaluated basing on the amount of the allogenic transfusion,the decreasing of the hemoglobin level and the morphology of the red blood cells in the drainage blood.The safety was evaluated basing on whether the patients had autotransfusion complications including fever,hemolytic reaction,coagulation disorders,pulmonary embolism and systemic infection.[Results]The volumes of total blood drainage,autotransfusion and allogenic transfusion were(946?433)ml,(622?313)ml and(233?348)ml,respectively.The average hemoglobin level of drainage blood was 99.67g/L and no apparente haemolysis happened.However,the hemoglobin level significantly decreased after operation in the peripheral blood.Only one rheumatoid arthritis patient had an abnormal fever during autotransfusion process,no other complication was observed.[Conclusion]Drainage blood in the first 6 hours postoperation is valid blood content.Drainage blood autotransfusion is an effective and safe way to slow down the hemoglobin reduction and reduce allogenic blood transfusion in patients being treated with total knee or hip arthroplasty.
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[Objective]To analyze the failure mechanisms in patients undergoing revision surgery in different time after index total hip arthroplasty(THA).[Method]The clinical records and radiographs of 78 revision hip surgeries between June 1995 and June 2005 loere reviewed.Forty-two cases were total hip arthroplasty and 36 were hemiarthroplasty.Thirty-six patients had revision surgery within 5 years and 42 more than 5 years.[Result]The causes of early revision THA included infection(16 cases),aseptic loosening,acetabular erosion,and mechanical failure.In the late revision THA,aseptic loosening was the most common reason,and the next common reason were acetabular wear and osteolysis around a well-fixed implant.[Conclusion]Infection is a common reason for the early revision.Aseptic loosening is the major cause for the late revision total hip arthroplasty.
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[Objective]To investigate the effect of coagulation of intervertebral disc nucleus pulposus(IDNP) by alum.[Method]In vitro,20 canine intervertebral discs(I D) were divided into 4 groups,and immersed into 2.5%,5%,10% alum solution and normal saline respectively.Another 16 I D also randomized into 4 groups and were injected into I D with corresponding solution.In vivo,6 canine ID were grouped into 4:A.blank control;B.one injection of alum;C.two points injection of alum;D.injection of N.S.Experimental dogs were sacrificed and disc samples were taken at 3 days,2 wks,and 1 month post-injection.Gross observation,histological exam by microscopy and scan electron microscopy(SEM) and histochemical test were performed.[Result]NS did not coagulate the IDNP in vivo and in vitro,while in vivo,coagulation was seen around the injection points,two points with two coagulation blocks,and grew with time culminating on one month after injection,but there was no coagulation appeared after alum injection.In vitro,histological study showed aboundant collagenous fibers gathered in coagulation lock representing manifold function of mesenchyme.[Conclusion]The alum can make the IDNP to be coagulated in vivo,the mechanism of coagulation is the collagenous fiber proliferation and fibrosis due to manifold function of mesenchyme.
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Objective To study the causes and symptoms about locking knee of unclear causes and analyze the thrapeutic effects of arthroscopy. Methods Arthroscopy was performed for 47 cases who suffered from locking knee of unclear causes.The main focuses observed were synovial shelf(16 cases),synovial hyperplasia(15 cases),synovial cyst(3 cases),Hoffa disease(4 cases)and patellofemoral malalignment(9 cases).These synovial focuses were resected by arthroscopic shaving.For Hoffa disease,arthroscopic partial resection of the infrapatellar fat pad was done.For patellofemoral malalignment,the procedures consisted of a standard lateral retinacular release and distal realignment of the patella. Results All patients were followed up for 2 months to 3 years on (an average of 1 year).The locking of knee disappeared for all cases and painless of knee for 46 cases.The functional recoveries of Knee joint were mostly excellent. Conclusions The main causes consisted of synovial shelf?hyperplasia?cyst,Hoffa disease and patellofemoral malalignment for locking knee of unclear causes.Arthroscopy is not only an important diagnostic method,but also a significant procedure of treatment and the therapeutic effects are satisfactory.
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Objective To investigate the immunologic reactions around prosthesis and the relationship between immunologic reactions and aseptic loosening. Methods Nine specimens of bone- implant interface membranes obtained during revision of loosened total joint replacements were examined in order to investigate the evidence of hypersensitivity. T lymphocytes and it's subgroup (CD 3, CD 4, CD 8),macrophages (CD 68),IL－ 2 receptor (CD 25) and HLA－ DR antigens were demonstrated by immunohistochemistry on tissue sections. The relationship between the changes of T lymphocytes and inflammatory reactions was also evaluated. Results Histological examinations showed granuloma with a plenty of macrophages and foreign body giant cells in all sections of interface membranes. The number of T lymphocytes increased in five of nine cases, and three of them expressed IL－ 2 receptor. The distribution of T lymphocytes and subpopulations was similar in all cases. The increase of T lymphocytes and IL－ 2 receptor expression showed positive correlation with an increase of macrophages and inflammation reactions. Conclusion Hypersensitivity to the prosthetic materials can exist after total joint replacement. Hypersensitivity may be one of the reasons of prosthetic aseptic loosening.
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Objective To investigate the methods of diagnosis and treatment for delayed infection after hip arthroplasty. Methods From March 1998 to April 2004, 11 patients with delayed infection after hip arthroplasty were analyzed retrospectively. There were 4 males and 7 females with average of 66 years, ranging from 49 to 81 years. The interval between infection and primary hip arthroplasty varied from 9 to 96 months(mean 25.5 months). Pain is the most common symptom in all patients with an infected hip arthroplasty. Abnormal ESR was observed in 9 cases. The increase of CRP was found in 8 patients, and fistula occurred in 5 patients. Radiography findings, such as loosening, osteolysis, and endosteal scalloping, are present on 10 patients. One-stage exchange arthroplasty was performed in 8 patients, among whom 7 prostheses with antibiotic-impregnated cement and one with plain cement for fixation were chosen. Two-stage exchange arthroplasty was performed in 3 patients. After thorough irrigation and debridement of the infected joint and the removal of the femoral and acetabular components, a temporary spacer with irrigation device and antibiotic-loaded beads or a bulb were inserted between the first and second stage. The interval was a minimum of 4 weeks. During the delayed reconstruction, the final prostheses were fixed with antibiotic-loaded cement after the infection was eliminated. Results All 11 patients were followed up for a period of 8 to 72 months. Fracture of femoral shaft happened during the debridement in one patient. None of recurrent infection was found during the average 29.3 months follow-up. Conclusion No test is 100 percent specific; therefore, the diagnosis of infection relies on the patients' history, and the physical examination findings, and the lab test combined with results of imaging study, etiology as well as pathology. The key to success is that the treatment must be tailored to the patients' status.
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Objective To elucidate the characteristics and treatment options of the primary joint arthroplasty in patients who had a previous history of the joint infection. Methods Eight total joint arthro-plasties in patients who had previous infection of the joint, were analyzed retrospectively from 1992 to 2001. The diagnosis of joint infection was pyogenic infection in six cases, and tuberculous infection in two cases. Total hip arthroplasty was performed in six cases, the average age of which was 38.1 years (24 to 51 years), and the average quiescent period of infection was 22 years ranging from 6 to 30 years. In these six cases, the average age of infection was 16 years (6 to 31 years); the quiescent period of all five pyogenic infections was more than 20 years, and the quiescent period of other one with tuberculous infection was six years. Total knee arthroplasty was performed in two cases. Results The count of WBC, ESR and CRP were examined routinely with normal values before surgery. While, there were no evidences of infection through intraopertive exploration, and bacterial culture of joint fluids and synovial tissue. The duration of follow-up was 2 to 11 years. The affected limbs had significant shortened deformity of 2 to 6 cm before surgery in hip infections. The hip joints had mal-development and flexion-contracture deformity. All of the patients had no active in-fection before arthroplasty. 5 patients with a quiescent period of pyogenic infection of more than 20 years had no recurrence of infection after total hip arthroplasty. One patient with a quiescent period of 6 months had recurrence of the infection after total knee arthroplasty. There were no recurrence of infection in 2 pa-tients who had tuberculous infection. The results were good except aseptic loosening in one total hip arthro-plasty. Conclusion The total joint replacement for patients with previous joint infection is more difficult in performing in one-stage and on younger patients. The good results can be achieved only on condition that the active infection healed completely, and the patients must keep a definite long period of quiescent time after infection.