Primary Grafting Research Articles

TRANSHEPATIC METABOLISM OF TNF-α, IL-6, AND ENDOTOXIN IN THE EARLY HEPATIC REPERFUSION PERIOD AFTER HUMAN LIVER TRANSPLANTATION

Several studies have shown that the postoperative course of cytokines such as TNF-α or IL-6 is predictive of rejection and infection after human orthotopic liver transplantation (OLT). The aim of this prospective clinical trial was to evaluate the impact of transhepatic metabolism of endotoxin (ET), tumor necrosis-factor-alpha (TNF-α), and interleukin-6 (IL-6) after hepatic ischemia/reperfusion on the postoperative graft function. In 13 consecutive elective adult OLT patients with primary grafts, we determined concentrations of ET, TNF-α, and IL-6 in the radial artery, portal vein, and right hepatic vein at 1, 4, 7, 10, and 13 min after reperfusion. Of the 13 patients, four had ET levels below the detection limit (<10 ng/L), and one patient had extremely high ET concentrations (151 ng/L in the hepatic vein). In the remaining patients the mean ET levels were 26pm14,26pm15, and 24pm14 ng/L in the portal vein, hepatic vein, and in the radial artery, respectively. These values indicate that in patients with a moderately elevated ET level, no transhepatic concentration differences of ET exist. However, in the patient with severe endotoxemia, the liver was apparently an ET-producing organ (HV-P: 29pm13 ng/L). TNF-α levels were not measurable in four patients, and varied between 15 and 72 pg/ml (portal vein) in the remaining patients. The transhepatic concentration differences (HV-P and HV-A, respectively) of patients with PNF or dysfunction were higher than in those with "good" or "excellent" graft function (HV-P: 160pm122 pg/ml vs. 7.3pm9.7 pg/ml; P<0.01 and HV-A: 137pm101 pg/ml vs. 3.9pm12 pg/ml; P<0.01, respectively). Arterial IL-6 levels were below 88 pg/ml (mean value: 31pm20 pg/ml) at the beginning of the operation, and increased considerably in three patients during the anhepatic phase and after reperfusion. No clinical correlation was found with the transhepatic concentration differences of IL-6. We conclude that in OLT patients without infection no transhepatic ET exchange was documented. However, a stimulated hepatic TNF-α release seems to be predictive of the beginning of liver dysfunction.

Teflon prosthesis in orbital floor fracture

Primary bone grafting is the recommended treatment for orbital floor fractures with bone defects, but this technique has a greater operative morbidity than the simpler use of the Teflon prosthesis. This study evaluates the use of the Teflon prosthesis. In 9 years, 110 patients with 115 orbital floor fractures were treated with Teflon prostheses. Of those, 90 patients had only orbital floor or orbito-zygomatic fractures and 20 had panfacial fractures. The mean operative time was 87 mins. Seventy-seven patients had good results. Complications included diplopia, ectropion, enophthalmia and palpable prosthesis. Seven prostheses required removal between three and 11 months postoperatively. No prosthesis became infected. Orbital floor reconstruction with a Teflon prosthesis is a relatively simple and short procedure associated with a low morbidity, giving good results except in cases of severe floor defects.

Facial Growth and Development in Unilateral Cleft Lip and Palate during the Period of Puberty: Comparison of the Development after Periosteoplasty and after Primary Bone Grafting

X-ray cephalometry was used in studies of facial growth and development carried out in 32 males with complete unilateral cleft lip and palate. They underwent primary periosteoplasty and were examined at the ages of 10 and 15 years. The results were compared with the development of the face in a longitudinal study of 20 males with the same type of cleft who were operated with a primary bone graft. The series with periosteoplasty showed a more marked proclination of the upper dentoalveolar component with the restoration of a positive overjet, as compared to a persistent anterior crossbite in the males with bone grafts. The lower jaw showed a larger protrusion, while individuals with bone grafts were characterized at the ages of 10 and 15 years by a larger posterior rotation of the mandible. The growth of the maxilla did not differ between series. In both series, there was a marked reduction in the growth of maxillary depth and of upper lip height, while the highest growth rate showed parameters of nasal prominence. An increasing mandibular protrusion and maxillary retrusion resulted in an impairment of sagittal jaw relations and in the flattening of the face, both of which occurred in almost all patients. The rotation of the lower jaw was not correlated with either the convexity of the face, sagittal jaw relations, or an overjet. The independence of developmental changes of selected characteristics at their initial state documented the impossibility of predicting the development of the face on the basis of a single x-ray examination at a given stage of development. Fixed appliances promoted a more marked proclination of upper incisors and the alveolar process than removable appliances, but they exerted no direct action on the other facial parameters studied.

Primary (Early) Alveolar Bone Grafting

Early primary bone grafting is successful when performed as a separate operative procedure after lip repair and before palate closure. It must be done in conjunction with neonatal orthopedics. The graft is placed only after the alveolar segments have molded and grown to a butt joint. Minimal soft-tissue dissection of the alveolus and maxilla are performed. The graft stabilizes arch form, allows for tooth migration and eruption through its site, and decreases anterior and posterior crossbite. There is no facial growth attenuation, and a good foundation for further soft-tissue growth is provided.

An assessment of the duration of cephapirin-induced coagulation abnormalities as measured by thromboelastography

Cephalosporin antibiotics are used prophylactically in cardiothoracic surgery to prevent postoperative infection. In 30 patients undergoing primary elective coronary artery bypass grafting, the whole blood coagulation system was prospectively evaluated before, and 10 and 30 minutes after administration of 1 g of cephapirin (Cefadyl, Bristol Laboratory, Evansville, IN). All patients had normal preoperative coagulation studies and had not received anticoagulant or antiplatelet therapy within 7 days of surgery. At 10 minutes after cephapirin administration, 23 of 30 patients had a significant change in all phases of whole blood coagulation as monitored by thromboelastography (TEG). Thirty minutes after cephapirin administration there was no statistical difference compared with the baseline TEG. It is concluded that cephapirin can cause a significant but transient change in the viscoelastic properties of blood. Coagulation parameters of the TEG should be measured prior to cephapirin administration to prevent errors in establishing baseline values prior to cardiopulmonary bypass.

Femorocrural grafting and regrafting: Does polytetrafluoroethylene have a role?

Between 1980 and 1988, 263 patients received 307 femorocrural bypass grafts. 180 were primary infrainguinal grafts, 106 secondary, 18 tertiary and three quaternary. Rest pain or tissue loss was the indication in 96% of cases. Outflow vessels were the tibioperoneal trunk (n = 34), posterior tibial artery (n = 115), peroneal artery (n = 89) and anterior tibial artery (n = 69). 88 primary vein grafts were completed. 201 polytetrafluoroethylene (PTFE) grafts were inserted (92 primary and 109 subsequent reconstructions). There were no direct PTFE to crural vessel anastomoses. A Miller cuff was used in the majority (n = 175). The three year primary patency for primary vein grafts (36%) was similar to primary PTFE grafts (29%), but significantly higher than subsequent PTFE grafts (20%) (p = 0.03). Three year foot salvage for primary vein grafts (65%) was similar to primary PTFE (64%), but significantly better than subsequent PTFE (42%) (p = 0.02). The results support both redo femorocrural grafting for critical ischaemia, as judged by foot salvage rates, and the use of PTFE with a distal vein cuff in primary and subsequent femorocrural reconstruction if autologous vein is not available.

Improved results of living-related liver transplantation with routine application in a pediatric program.

Living related liver transplantation (LRT) was introduced as a response to the shortage of donor organs that has existed for small children. Results were promising in the initial experience, with a one-year patient survival of 80% and a graft survival of 75%. Since the completion of the protocol, LRT has been considered routinely in the management of children in our center. We present here our experience with 45 consecutive transplants in which LRT accounts for 40% of grafts with an overall patient survival of 90%. Between 4/91 and 4/92, 45 OLT were performed in 41 children. Median age was 2.7 years (3 months to 13 years) and weight was 10.4 kg (3.5-60 kg). Thirty-five were primary grafts, 10 were retransplants. One patient received 2 grafts in the orthotopic auxiliary position. Cholestatic disorders including biliary atresia accounted for 60%, metabolic diseases for 15%. Grafts were obtained from cadaver donors in 27/45 (60%) cases; reduction was required in 12/27 (44%). LRT was performed in 18 cases. Fifty-two percent of recipients of cadaver grafts were UNOS status 4, while 16% of LRT recipients met these criteria. Actual patient survival for cadaver grafts is 21/24 (88%) and graft survival is 20/27 (74%). Patient survival in 18 LRT was 94%. Two grafts were lost to arterial thrombosis for a graft survival of 83%. All donors have been discharged and are well. One patient, a teenager with fulminant hepatitis, was successfully transplanted with a left lobe from his father. This experience demonstrates the programmatic flexibility accorded by use of LRT. Since 40% of grafts were LRT, more livers were available for urgent use for patients who did not have a donor available, as reflected in the 73% incidence of cadaver recipients on status 3 or 4. Therefore, patients are more likely to receive a transplant at the optimal time. We are now prepared to offer LRT for fulminant hepatic failure since the benefit of graft availability appears to outweigh concerns about coerced donation. The successful treatment of a teenaged patient may herald extension of LRT to adults. We conclude that the use of LRT should be expanded.

THE IMMUNOPHARMACOLOGY OF IMMUNOSUPPRESSION BY 15-DEOXYSPERGUALIN

We have used two murine bioassays, a nonprimarily vascularized heart transplant model and a host-versus-graft (HvG) popliteal lymph node (PLN) hyperplasia assay, to study the novel immunosuppressant, 15-deoxyspergualin (DSG). Using these methods, we investigated DSG's immunosuppressive potency, efficacy, and mechanisms of action. Dose-response studies showed that prolongation of heart allograft survival by DSG was dose dependent with an ED50 +/- SD of 1.45 +/- 0.39 mg/kg/day and that DSG was nearly seven times more potent than cyclosporine. Low maintenance doses of 0.25 or 1.0 mg/kg/day of DSG that followed an initial 14-day course of 5.0 mg/kg/day DSG enabled heart allografts to survive for more than 200 days without recipient weight loss or other signs of overt toxicity. When used as treatment for ongoing acute rejection, DSG prolonged graft survival. Although a 30-day course of 5.0 mg/kg/day of DSG caused significant but reversible body-weight loss, no overt, gross, or histopathologic evidence of significant tissue toxicity was observed in mice treated with 5.0 mg/kg/day DSG for 13 consecutive days. Frequent, intermittent administration of DSG was more immunosuppressive than less frequently administered high doses of DSG, but continuous infusion did not augment drug efficacy or reduce its toxicity. Isobologram analysis of graft survival in recipients treated with both DSG and CsA showed that this drug combination produced synergistic immunosuppression. In contrast to DSG's efficacy when administered posttransplant, the survival of grafts in recipients that were treated with DSG for 30 days posttransplant was only minimally prolonged. When recipients were sensitized by primary grafts, administration of DSG only during the period of sensitization or only immediately after implantation of secondary grafts failed to prevent accelerated rejection. If, however, graft recipients were treated with DSG both before and after implantation of secondary grafts, accelerated graft rejection was prevented. DSG induced partial alloantigen-specific unresponsiveness, since in DSG-treated C3H recipients of primary BALB/c grafts, secondary BALB/c grafts survived longer than third-party C57BL/6 secondary grafts. A dose of DSG that prolonged graft survival maximally did not suppress the in vivo lymphoproliferative response to alloantigen in the PLN assay. In contrast, doses of CsA that prolonged graft survival minimally suppressed the HVG response significantly. Thus, these studies showed that DSG was a more potent and effective immunosuppressant than CsA, and that DSG treatment prolonged graft survival substantially without apparent toxicity. Furthermore, unlike CsA, a dose of DSG that prolonged heart allograft survival did not suppress alloantigen-stimulated lymphoproliferation in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Long Term Results Following Immediate Reconstruction of Orbital Fractures: A Critical Morphometric Analysis

M Dawar, OM Antonyshyn. Long term results following immediate reconstruction of orbital fractures: A critical morphometric analysis. Can J Plast Surg 1993; 1(1):24-29. The purpose of this study is to review the long term morphological results following primary reconstruction and bone grafting of orbital fractures. All patients presenting to the Victoria General Hospital in Halifax, Nova Scotia between July 1988 and December 1990 with orbital fractures of sufficient severity to require immediate reconstruction were included in the study. The series consists of 39 fractured orbits in 29 patients. In all patients, a standardized data sheet was used in recording patient demographics, and clinical and intraoperative findings. The surgical management of orbital fractures and in particular the redraping of periorbital soft tissues was performed according to a standard protocol. Long term morphometric assessment was performed between 11 and 38 months postoperatively, with a mean follow-up of 27 months. A McCoy facial trisquare and Hertel exophthalmometer were used in the anthropometric evaluation of ocular globe position and position of the periorbital soft tissue landmarks. Postoperative assessment of globe position revealed a 5% incidence of enophthalmos and an 11 % incidence of hyperophthalmia. Minor asymmetries in globe position measuring less than 2 mm were noted in a further 61 % of patients. Ectropion was documented in 8% of patients, but an asymmetry in the height of the palpebral fissure was noted in a further 34% of patients. In terms of canthal relations, lateral canthal dystopia was the most commonly observed deformity, with vertical dystopia occurring in 18% of patients and transverse dystopia in 33% of patients. The observed sequelae and complications of orbital fractures are discussed and possible causative factors identified.

Comparison of angioscopy and angiography for monitoring infrainguinal bypass vein grafts: Results of a prospective randomized trial

This study was designed to determine whether, in primary infrainguinal bypass grafts in which only saphenous vein is used as the graft conduit, routine monitoring with intraoperative angioscopy can improve early graft patency as compared with standard monitoring with intraoperative completion angiography; and to delineate the advantages and disadvantages of these two modalities and their respective roles for the routine monitoring of the infrainguinal bypass graft. A total of 293 patients undergoing primary saphenous vein infrainguinal bypass grafting were prospectively randomized and monitored with either completion angioscopy or completion angiography. Clinical parameters, indications for operation, graft anatomy, and configuration were evenly matched in both groups. Forty-three bypasses were excluded from the study after randomization, including 12 veins randomized to angiogram, deemed inferior, and prepared with angioscopy. In the 250 bypass grafts (angioscopy 128, angiography 122) there were 39 interventions (conduit, 29; anastomosis, 8; distal artery, 2), 32 with angioscopy and 7 with angiography (p < 0.0001). Twelve (4.8%) of the 250 grafts failed in less than 30 days, four (3.1%) of 128 in the angioscopy group and eight (6.6%) of 122 in the angiography group (p = 0.11 by one-sided hypothesis test). Although no statistical improvement in the proportions of failures in primary saphenous vein bypass grafts routinely monitored with completion angioscopy rather than the standard completion angiogram was demonstrated, the study delineates a trend that favors completion angioscopy for routine vein graft monitoring and demonstrates the advantages of angioscopy in preparing the optimal vein conduit.

Primary and Secondary Nasal Bone Grafting After Major Facial Trauma

Primary and Secondary Nasal Bone Grafting After Major Facial Trauma

Primary pressure grafts in early reconstruction of deep facial burns

The face is an area of great cosmetic importance where the repair of deep burns is particularly delicate, as both appearance and function must be taken into account. In order to improve the aesthetic prognosis of full skin thickness facial burns, a primary pressure graft technique was used in eight patients. Early excision was carried out during postburn day 3 and after good-quality granulation tissue was obtained around day 10, a full skin thickness graft was applied. Pressure was applied to the graft and maintained for 10 days. The grafts took successfully in all patients with very satisfactory cosmetic results. This is an original technique as it replaces burned tissue at a very early stage with tissue which is normal in thickness and quality.

Skin Care Of The Healed Burned Patient

Many complications beset the skin formed over burn wounds, whether by primary re-epithelialization or grafting techniques, and these can evolve over days to decades. Mechanisms by which re-epithelializations, reattachment, and remodeling may result in skin prone to blistering, dryness, itching, contact dermititis, photosensitivity, and hypertrophic changes relatively early in the course of healing are considered, and therapeutic approaches are discussed. Late development of benign and malignant lesions calls for long-term surveillance of the healed skin of burned patients.

Craniofacial Development in Children with Unilateral Clefts of the Lip, Alveolus, and Palate Treated According to Four Different Regimes

Lateral skull radiographs of 85 patients with unilateral clefts of the lip, alveolus and palate treated according to four different regimes were compared longitudinally, at three different ages, regarding mandibular and vertical facial development. It was found that there were no lasting differences in mandibular morphology resulting from regimes including primary or early secondary bone grafting. The non grafted group, however, showed increased mandibular length and anterior height. The jaw angle was increased and there was a more favourable sagittal jaw relationship. Regimes that included primary bone grafting were associated with reduced upper anterior facial height, which resulted in less harmonious facial proportions compared with treatment regimes including early secondary bone grafting done during the mixed dentition, or no bone grafting at all. Vertical development was greatest where bone grafting was excluded.

Distal Anastomotic Hyperplasia in Superficial Femoral-Popliteal Vein Femoropopliteal Bypass Grafts

The incidence of distal anastomotic hyperplasia (DAH) in superficial femoral- popliteal veins (SF-PVs) used as femoropopliteal bypass (FPB) grafts was inves tigated, with particular reference to the form of distal anastomotic construction. Seventy-seven SF-PV grafts that met specific angiographic follow-up criteria quali fied as "studied" grafts. DAH was identified in 13 (17%). Cobra head anastomoses, 2 cm or less in length, were used in 21 grafts and yielded 6 in stances of DAH (29%). When 8 sharply tapered 3 cm (swordfish) anastomoses were constructed, 3 grafts (37.5%) developed DAH. With 3 cm moderately ta pered (fishmouth) anastomoses in 48 grafts, DAH was seen 4 times (8%). Be cause the distal 1 cm of the swordfish configuration was very narrow, the swordfish and cobra head constructions were functionally equivalent and were grouped together as "short" anastomoses. The difference in the incidence of DAH with long and short anastomoses, 8% vs 31%, was statistically significant (p = .016). In the 48 "studied" grafts with fishmouth anastomoses, the occurrence of all 4 DAHs among the 15 female diabetic limbs was also significant (p = .019). Constructing 3 cm moderately tapered anastomoses significantly reduced the incidence of DAH, the leading cause of graft failure, in SF-PV FPB grafts. The achievement of primary and assisted patency rates of 84% and 91% at both three and five years in the 93 SF-PVs placed as primary FPB grafts since October, 1982, was largely due to the reduction in DAH that resulted from anastomotic modification.

The Domed Dermis-Fat Graft Orbital Implant

Dermis-fat grafts have been widely used in the reconstruction of the anophthalmic socket, both primarily after enucleation and secondarily after extrusion or migration of an existing implant. The dermis-fat graft is an effective means of replacing orbital volume and affording motility of the ocular prosthesis with both low morbidity and a satisfactory cosmetic result. We present a modification to the dermis-fat graft technique. Our modification creates a domed shape to the anterior surface of the graft that simulates the curvature of the eye. The dome-shaped graft creates deeper fornices than a standard flat-surfaced dermis-fat graft. It also allows better contact between the prosthesis and the dermis as the graft moves. The prosthesis can be thinner centrally and lighter than a prosthesis fabricated for a socket with a standard dermis-fat graft or spherical implant. This results in better motility of the prosthesis while also replacing orbital volume. There is no additional morbidity associated with this technique. We have used this procedure successfully in 18 patients; 10 were primary grafts and eight secondary grafts. Motility of the prosthesis was satisfactory in all cases. There was no abnormal graft shrinkage. All grafts maintained their domed shape. Follow-up ranged from 6 to 21 months.

LIVER TRANSPLANTATION IN PATIENTS OVER SIXTY YEARS OF AGO

LIVER TRANSPLANTATION IN PATIENTS OVER SIXTY YEARS OF AGO

CYCLOSPORINE-INDUCED TOLERANCE TO INTRATESTICULAR ISLET XENOGRAFTS

Survival of highly immunogenic hamster islet xenografts can be achieved in rats if the graft is transplanted into the abdominal testis. Permanent survival requires the administration of cyclosporine during the first thirty days after grafting. The majority of grafts will survive indefinitely beyond this point if the grafted animals receive a once-weekly maintenance dose of CsA until day 100, when CsA is no longer necessary. Hamster islet xenografts transplanted under the kidney capsule or into the portal vein are rejected, regardless of CsA treatment. Animals maintaining long-term primary intratesticular xenografts accept secondary contralateral testicular xenografts. CsA is not required. Primary grafts are also resistant to the adoptive transfer of lymphocytes from rat donors primed to hamster xenoantigens. Secondary hepatic and renal islet xenograft survival is also extended--some hepatic grafts long-term. Therefore, the combination of CsA and the privileged status of the abdominal testis leads not only to the acceptance of primary intratesticular islet xenografts but also to partial immunological unresponsiveness of subsequent grafts in other sites.

A comparative experimental study on primary and secondary nerve grafting following inferior alveolar nerve injury

The damaged inferior alveolar nerve of rabbit was repaired with autogenous ipsilateral greater auricular nerve grafting primarily and secondarily, and electrophysiological, ultrastructural, microvascular and histochemical investigations were performed in this study. The results indicated that the experimental effects of group 1 out of 3 groups (group 1 with immediate grafting, group 2 with grafting after 4 weeks, and group 3 with grafting after 8 weeks) were the best and those of group 2 were second only to group 1 with no obvious difference between these two groups (P greater than 0.05). However, the results of group 3 were not good enough, and there was significant difference from the other two groups (P less than 0.05). Therefore, we were led to conclude that the injury should be repaired at once or within 4 weeks after inferior alveolar nerve was damaged, or within 2 or 3 months thereafter, to improve the function of the injured nerve as greatly as possible.

FOLLOW-UP OF CYCLOSPORINE-TREATED PEDIATRIC RENAL ALLOGRAFT RECIPIENTS AFTER CESSATION OF PREDNISONE

We attempted cessation of prednisone therapy in 16 pediatric renal allograft recipients who were between the ages of 3 1/2 and 16 years at the time of transplantation. Fourteen had primary grafts and 2 had second grafts. Nine had cadaver and 7 had living-related donor grafts. At the time of cessation of prednisone, cyclosporine was the only other immunosuppressive therapy for 15 of the patients and 1 patient was receiving CsA and azathioprine. All the patients had stable serum creatinines at the time prednisone was stopped, between 7 months and 5 years posttransplantation. Seven patients have had no episodes of rejection, continuing to receive CsA as their only immunosuppressive therapy and have stable renal function between 16 months and 3 1/2 years (mean: 2 years) after stopping prednisone. Stopping the small maintenance dose of prednisone resulted in improved growth in patients whose epiphyses were not fused. They improved their weight:height ratios and lost their cushingoid appearance. Serum cholesterol levels declined significantly. Patients who required antihypertensive drugs to control their blood pressure while receiving prednisone required fewer or no drugs when off prednisone. Nine patients had acute rejection episodes and were put back on maintenance prednisone following a 3-day steroid pulse. All these patients had a prompt improvement in renal function following the steroid pulse. However, only 3 stabilized function at preprotocol baseline Scr. Four currently have functioning grafts with Scr greater than the preprotocol Scr. Two patients have returned to dialysis. Although stopping steroids is a worthy goal in pediatric renal allograft recipients, we cannot recommend this strategy as routine management because of the 56% rate of acute rejection episodes in the patients who had prednisone withdrawn.