Ideal Donor Research Articles

Methods of renal preservation

Various preservation techniques and solutions have been used for the preservation of kidneys before transplantation, with different methods falling in and out of favour over the decades. Debate has continued about whether machine perfusion or cold storage is the best method for preservation. There has been renewed interest in this area during the last decade because of the resurgence of the use of kidneys from non-heart-beating (NHB) donors. We present a general overview of the different available techniques, including a brief history of preservation, the mechanisms of renal injury, and how different types of preservation and preservation solutions ameliorate damage. We also review the available literature on outcomes after preservation with either machine preservation or cold storage on kidneys from heart-beating and NHB donors. Substantial evidence shows that machine preservation improves early kidney function after transplantation, especially those subjected to a degree of warm ischaemia or long preservation times. Nevertheless, cold storage remains the easiest and most economic method of preservation. The effect of preservation on long-term outcome is less clear, and more work is needed in this area. It may be that machine perfusion will find its niche as the preservation method of choice for suboptimal kidneys, whereas cold storage will be reserved for kidneys from the ideal donor.

Cell Therapy for Diabetes Using Piscine Islet Tissue

The islet tissue, called Brockmann bodies, in certain teleost fish is anatomically distinct from the pancreatic exocrine tissue and can be easily identified macroscopically. Expensive islet isolation procedures, such as required when procuring islet tissue from mammalian pancreases, are unnecessary. Tilapia islets transplanted into diabetic athymic nude mice will produce long-term normoglycemia and mammalian-like glucose tolerance profiles. Encapsulated tilapia islets function well after transplantation into euthymic recipients. Additionally, tilapia are potentially ideal xenogeneic donors because of markedly lower donor production costs, minimal islet procurement costs, and possibly decreased xenozoonotic potential relative to mammalian donors. Tilapia islets appear to be appropriately glucose responsive with high insulin output, can be cryopreserved, and are much more resistant to hypoxia than mammalian islets. Because tilapia and human insulin differ by 17 amino acids, we have cloned, sequenced, and modified the tilapia insulin gene by site-directed mutagenesis resulting in a tilapia insulin gene that codes for "humanized" insulin while still maintaining all of the tilapia regulatory (noncoding) sequences. We have now produced small numbers of founder transgenic tilapia with incorporation of our humanized tilapia insulin gene construct, and we have shown transmission and expression of the transgene in the beta cells and serum of their Fl offspring. Our ultimate goal is to achieve homologous recombination and to breed for homozygosity for the hybrid insulin gene. Subsequent generations of transgenic tilapia will undergo a program of genomic optimization selecting for growth, survival, and fecundity as well as stability of the transgene. Islets from the resulting transgenic fish, after extensive characterization, could be harvested, encapsulated, and then transplanted into diabetic patients.

Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation

Background: Currently the most important limitation in lung transplantation is donor availability. Although liberalization of donor criteria may aid in expanding the donor pool, the long-term effects of the use of “marginal” or “extended” donors remains unexplored. Methods: In this study, we included all patients who underwent lung transplantation from January 1996 to December 1999 at Loyola University Medical Center. We categorized patients as either receiving lungs from an “ideal” donor or an “extended” donor. Extended donors were defined as having any 1 of the following criteria: donor age > 55 years, tobacco history > 20 pack years, presence of infiltrate on chest x-ray, donor ventilator time > 5 days, or donor use of inhaled drugs (cocaine or marijuana). We then compared the 2 groups with regard to short-term (operating room [OR] complications, intensive care unit [ICU] complications) and long-term outcomes (1-year pulmonary function and survival). Results: Sixty-one (54%) patients received lungs from ideal donors and 52 (46%) patients received lungs from extended donors as defined above. We observed no significant differences between the 2 groups in OR complications (cardiopulmonary bypass, bleeding complications, life-threatening arrhythmias) or ICU complications (pneumonia, airway dehiscence, reoperation within 30 days related to transplantation). In addition, the 2 groups had similar median intubation times (21 hours in the ideal donor group and 20 hours in the extended donor group; p = n.s.), hospital length of stay (14 ± 12 days in the ideal donor group and 12 ± 8 days in the extended donor group; p = n.s.), and hospital survival (80% and 88% in the ideal and extended donor groups, respectively). One-year follow-up revealed similar pulmonary function (forced expiratory volume in 1 sec [FEV 1] = 2.4 liters and 2.4 liters in the recipients of bilateral ideal and extended donors, respectively, and FEV 1 = 1.9 liters and 1.5 liters in the recipients of single ideal and extended donors) and survival (72% and 79% in the ideal and extended donor groups, respectively; p = n.s.) between the 2 groups. Conclusions: Liberalization of donor criteria does not affect outcome in the first year after lung transplantation. By liberalizing donor criteria, we can expand the donor pool while assessing other possible mechanisms to increase donor availability.

Organ donor viral screening and its implications in transplantation; an overview

The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients a waiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient < 0.8 (RR = 1.3) (B), ischemia > 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg · min) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg · min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.

Reliability of island flaps raised after superficial and deep burn injury.

In select cases, to prevent any functional loss and to initiate early function during the early burn period, the reconstructive procedure of choice may be flap coverage. In these circumstances, when the ideal flap donor site is burned, the clinician may be hesitant to raise this flap because of questionable flap survival. The authors conducted this study to determine whether a superficially or deeply burned skin island flap would survive when elevated during the early postburn period. If these flaps are usable, they could expand the options available for burn wound coverage. They used a rat epigastric island flap model, and divided 50 study animals into two groups. In group 1 (N = 25), the right epigastric flap site was burned superficially and the left side was left uninjured. Island flaps were raised on both sides 4 days after the burn injury. The flaps were then sutured back into their original sites, and were evaluated 5 days after the surgery. In group 2 (N = 25), the right epigastric flap site was burned deeply and the left side was left uninjured. Island flaps were raised 4 days after the burn injury on both sides, as in group 1. The flaps were then sutured back into place and were evaluated 5 days after the surgery. All of the control flaps on the rats' left sides survived in both groups. In addition, all the superficially burned flaps survived in group 1 (100%), and 21 of the deeply burned flaps survived in group 2 (84%). There was no significant difference between superficially and deeply burned flaps with regard to survival, and the burned flaps were as successful as the unburned control flaps in both groups (p = 0.11). Skin island flaps elevated after superficial or deep burn injury are reliable in this animal model.

DOUBLE RENAL TRANSPLANTS FROM MARGINAL DONORS: 2-YEAR RESULTS

Marginal cadaveric renal transplant donors represent a potential source for expansion of the donor pool but these kidneys have generally demonstrated significantly poorer survival compared to those from conventional donors. A strategy to provide sufficient renal mass for adequate nephron dosing and subsequent improved survival is the use of both kidneys for a single recipient. We present our 2-year experience with double renal transplants from marginal donors. During an 8-year period 28 patients received double renal transplants (group 1) and 31 received a single transplant (group 2) from marginal donors. Donors were older than 55 years, or had diabetes mellitus, hypertension, greater than 15% glomerulosclerosis on biopsy, increasing creatinine or intrinsic renal parenchymal disease. Both groups were of similar age and the number of rejection episodes per year was similar but followup time differed (22.4+/-14.6 months for group 1 versus 43.7+/-20.5 for group 2). Male-to-female ratio, cold ischemia time, terminal creatinine and pre-transplant biopsy rates were similar for donors in both groups. Average donor age was younger in group 1 (48.9+/-15.8 versus 57.5+/-8.2 years, p = 0.01), and incidence of intrinsic renal disease and increasing donor creatinine was greater (12 versus 2, p = 0.002 and 4 versus 0, p = 0.04, respectively). Incidence of primary nonfunction (1 group 1 versus 5 group 2 patients) and delayed graft function (6 versus 7) was similar. The 1 and 2-year graft survival rates of 96% and 96%, respectively, for group 1 were significantly higher than those for group 2 (77% and 73%, p = 0.02). Our experience to date with double kidney transplants from marginal donors demonstrates acceptable 1 and 2-year survival rates significantly superior to the outcome using only 1 marginal kidney. This finding has important implications in the decision to use marginal donors in regard to cost-effectiveness and patient survival compared to the alternative of continued hemodialysis until an ideal donor organ becomes available.

The cosmetic split-thickness skin graft donor site.

Any split-thickness skin graft donor site is obvious to some degree because of pigment alterations and, at the worst, it can develop hypertrophic scarring. A predictably superior aesthetic result is possible if this site is converted to a full-thickness defect followed by primary closure, because a linear scar is the only residuum. Using a modified tumescent technique, the groin can also be readily used as a split-thickness donor site if a thin graft is preferred; it captures the attributes of an ideal donor site in which pain is diminished, healing rapid, and the scar inconspicuous, just as when it is used as a full-thickness skin graft donor site.

Lung transplantation: a decade of experience.

To review the 10-year clinical experience of a single institution's adult lung transplant program. Since July 1988, 450 lung transplants have been performed in 443 patients. Recipient diagnoses included emphysema in 229 patients, cystic fibrosis in 70 patients, pulmonary fibrosis in 48 patients, pulmonary hypertension in 49 patients, and miscellaneous end-stage lung diseases in 47 patients. Single-lung transplant was performed in 157 cases, bilateral sequential lung transplant in 283 cases, en bloc double-lung transplant in 8 cases, and heart-lung transplant in 2 cases. Graft lungs were obtained from local donors in 24% of cases and from distant donors in 76% of cases. Ideal donors were used in 74% of cases; in 26%, the donor was classified as marginal based on objective criteria. Four hundred six (91.6%) lung transplant recipients survived to hospital discharge. There were 37 hospital deaths from cardiac events (n = 8), primary graft failure (n = 8), sepsis (n = 6), anastomotic dehiscence (n = 6), and other causes (n = 9). A diagnosis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) was made in 191 patients (42.5%). BOS has not been improved by any specific therapy. Rates of freedom from BOS at 1, 3, and 5 years after the transplant are 82%, 42%, and 25%. One-, 3-, and 5-year actuarial survival rate for the entire group are 83%, 70%, and 54%. There is no statistical difference in survival according to diagnosis or type of lung transplant. Recipient waiting time was 116 days in the first 90 patients and 634 days in the most recent 90 patients. Lung transplantation offers patients with end-stage lung disease acceptable prospects for 5-year survival. Chronic rejection and long waiting lists for donor lungs continue to be major problems facing lung transplant programs. The use of marginal and distant donors is a successful strategy in improving donor availability.

Maximizing the utilization of donor organs offered for lung transplantation.

The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate. This study aims to assess the impact of utilization of marginal donors and aggressive donor management. A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome. Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support. Blood gases were repeated to assess the results of interventions. Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers. Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors). Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4). Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used. Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups. Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups. We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation.

Effect of concentration and degree of saturation of topical fluocinonide formulations on in vitro membrane transport and in vivo availability on human skin.

The thermodynamic activity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.

8-O-Sialylation of Neuraminic Acid

Synthesis of Neu5Acα(2−3)Galβ(1−4)Glc and Neu5Acα(2−8)Neu5Ac derivatives 12α and 14α, from lactose derivative 6 and 2,3-dehydro-Neu5Ac derivative 7, respectively, with anchimerically assisted Neu5Ac donor 3e, 3f, or 3g has been studied. Reaction of halogenose 3e, having a 3-phenoxythiocarbonyloxy moiety as the assisting group, afforded with 6 and 7 in the presence of equimolar amounts of AgOTf as promoter α-sialosides 11α and 13α which were readily deoxygenated to afford 12α and 14α, respectively. Reaction of phosphite 3f, having a 3-bromo substituent as the potentially anchimeric assisting group, furnished in the presence of catalytic amounts of TMSOTf with 6 as acceptor α-sialoside 15α and with 7 as acceptor β-sialoside 17β, which gave on debromination 12α and 14β, respectively. Reaction of readily available phosphite 3g, having a 3-thiobenzoyloxy group as the anchimeric assisting group, afforded with 6 and 7 in the presence of catalytic amounts of TMSOTf in very high yields α-linked sialosides 21α and 22α, which could be readily deoxygenated to afford 12α and 14α. Thus, 3g is an almost ideal sialyl donor for the high-yielding generation of α-glycosidic linkages also to low-reactive acceptors.

ARE TWO KIDNEYS BETTER THAN ONE? OUTCOME IN SINGLE (SNGL) VS EN BLOC (EB) AND DUAL (DU) KIDNEY TRANSPLANTS (TXP)

424 Because the functional mass from younger and elderly kidney donors is reduced, both kidneys from infants are used as an EB Txp and from aged donors as a DU Txp. We evaluated outcome in our recipients of SNGL (n=161) cadaveric kidney Txps vs EB (n=9) and DU (n=28) Txps from 1/95-12/97. We compared 15 donor (D) and 26 recipient (R) outcome variables including age (yrs), calculated admission creatinine clearance (AdCCr) in ml/min, average urine output (UO) in ml, delayed graft function (DGF), length of stay (LOS) in days, rejections (reject), serum creatinine (Cr) after Txp, graft (Gft) loss, and complications (Compl). We also compared outcome in SNGL vs DU and EB Txps as a group. Differences were significant at P<0.05; denoted by 1,2,3(ANOVA) or * (Chi square). TableIn summary, these data demonstrate that recipients of 2 kidneys from donors at the extremes of age have less DGF, fewer rejections, and similar short and intermediate outcomes compared to SNGL kidneys from ideal donors. Recipients of SNGL vs DU kidneys from donors ≥ 54 yrs of age have significantly higher serum Cr up to 1 yr after Txp. We conclude that recipients of two kidneys as an EB Txp or DU Txp provide excellent outcome which is comparable to SNGL kidneys.

WHO SHOULD BE TRANSPLANTED WITH KIDNEYS FROM IDEAL DONORS VERSUS MARGINAL DONORS?: A COST-EFFECTIVENESS ANALYSIS

683 As a result of the donor shortage, transplant centers have resorted to the expansion of donor acceptability criteria. The issue of how best to distribute kidneys from expanded and ideal donors remains unclear. The purpose of this study is to address this question using a 5 year decision analysis model. We reviewed our experience with 532 first cadaver kidney recipients transplanted between 01/84 and 01/96. The decision tree consists of a choice between 4 possible donor→recipient strategies: ideal→young (n=156), ideal→old (n=50), expanded→young (n=254) and expanded→old(n=72). Consideration of all possible permutations of patient and graft survival (5 year probabilities) yielded 20 possible outcomes in the decision tree. Criteria for an expanded donor were age >50 years, cold ischemic time> 24 h and death due to a cardiovascular event. Old recipient was defined as >50 years. The measures of outcome used in the model were utility, cost and cost/utility. Utilities which were obtained using the “Standard Reference Gamble” method were: death = 0, alive and dialysis-free = 1, alive and dialysis-dependent = 0.5 ±0.14. Baseline costs which were based on registry reports adjusted to 1996 dollars were: dialysis$45,205/year, transplant $108,983/first year, transplant follow-up >1 year$9,447/year. The expected values based on a 5 year model with death or graft failure at 3 years were calculated for each strategy:TableThe higher graft survival in older recipients is offset by the higher death rate in this group. At what point is the ideal→old strategy no longer effective because the rate of DWF is too high?. One-way sensitivity analysis was performed to address this question. High and low threshold survival rates were 0.81 and 0.58. i.e. 5 year patient survival in ideal→old needs to be at least 81% to make this strategy equal to ideal→young; a survival rate of less than 58% would make this strategy the least effective. In conclusion, the highest expected utility was achieved for ideal→young, whereas cost was lowest for ideal→old. A 5 year patient survival inferior to 81% would make the ideal→old strategy less cost-effective than ideal→young. Consideration of these donor and recipient issues are important in the assessment of the cost-effectiveness of kidney transplantation.

Renal transplantation: surgical aspects, complications and results

Despite the fact that kidney transplants have routinely been successfully performed for over 30 years there continues to be challenges for the transplant surgeon. These include a static donor pool, growing recipient list, declining number of ideal donors and greater reliance on marginal donors. Innovative methods to deal with these problems continue to be sought.

Coronary angioplasty and stenting following heart transplantation with older donors. Is this a rational approach?

The shortage of ideal donor hearts has led to an extension of the classical donor criteria of age. Higher incidence of focal coronary artery disease has been found in this older donor population requiring conventional angioplasty therapy. The authors present two patients with early coronary angiogram post transplantation, requiring angioplasty and stent in the lesions found.

Sisters of women with premature ovarian failure may not be ideal ovum donors: Sung L.; Bustillo M.; Mukherjee T.; Booth G.; Karstaedt A.; Copperman A.B. USA Fertil Steril 1997 67/5 (912–916)

Sisters of women with premature ovarian failure may not be ideal ovum donors: Sung L.; Bustillo M.; Mukherjee T.; Booth G.; Karstaedt A.; Copperman A.B. USA Fertil Steril 1997 67/5 (912–916)

HLA Typing for Transplantation of Stem Cells From Unrelated Donors

Transplantation of stem cells may cure some otherwise lethal malignant or genetic diseases. Close matching of HLA histocompatibility antigens is required. The ideal donor is a sibling with an identical HLA genotype as the patient, but 65% to 70% of patients can be helped only by an unrelated donor. The extreme polymorphism of HLA genes requires large registries of unrelated volunteers. HLA typing by traditional serologic methods identifies only gross mismatches, and laboratories may differ in some specificities assigned. Newly available DNA techniques can differentiate genes that result in the difference of only a single amino acid, and laboratories rarely disagree in their interpretations. DNA techniques require less time for identification of a compatible donor and result in improved rates of transplant success.

Factors influencing the outcome of donor marrow transplantation in adults from less than ideal donors: experience from two Australian centres.

This paper reports the results of 78 marrow transplants in two Australian hospitals between 1991 and 1996, using unrelated (n = 54) or mismatched related (n = 24) donors. Twenty-six patients received granulocyte-macrophage colony stimulating factor (GM-CSF) post-transplant as part of a phase II study. Fifty-four patients (74%) had advanced disease. To identify factors associated with a superior outcome post-transplant, to evaluate the effect of GM-CSF on engraftment and other transplant parameters, and to compare the overall results with those of published series. Review of patient records, a Medline search of the relevant literature and appropriate statistical analysis. The probability of overall survival and event-free survival (EFS) at three years was 35 +/- 6% and 22 +/- 6% respectively. Pre-transplant factors significantly associated with an inferior EFS were advanced disease, poorer performance status and age > 30 years. The EFS in patients with standard risk disease was 51 +/- 13% versus 10 +/- 5% in patients with advanced disease, p < 0.0001. Severe acute graft-versus-host disease was also associated with a poorer outcome. Neutrophil engraftment was faster in patients who received GM-CSF but there was no difference in any other transplant parameters. These results are consistent with reported series elsewhere and suggest that an extended family or unrelated donor transplant should generally be limited to patients with a good performance status and early phase but otherwise incurable haematological disease.

Sisters of women with premature ovarian failure may not be ideal ovum donors

Objectives: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. Design: Historical cohort study. Setting: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. Patient(s): Criteria for inclusion were oocyte recipients age ≤ 40 years, FSH >18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). Main Outcome Measure(s): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. Result(s): The ages of the donors to groups I and II were comparable (31.1 ± 16.7 versus 29.8 ± 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 ± 2.1 versus 8.6 ± 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E 2 on the day of hCG administration (2,356 ± 826 versus 1,847 ± 843 pg/mL; conversion factor to SI unit, 3.671), number of oocytes retrieved (25 ± 14 versus 22 ± 13), number of embryos transferred (4.4 ± 2.1 versus 4.0 ± 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). Conclusion(s): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.

FUNCTIONING FREE-MUSCLE TRANSPLANTATION FOR THE UPPER EXTREMITY

Functioning free-muscle transplantation (FFMT) is an advanced microneurovascular technique indicated in patients who have an injury with major functional muscle or muscle group loss or denervation and no locally available or ideal musculotendinous donor units. Over the 9-year period, from 1986 to 1994, 47 FFMTs were applied in patients who had severe hand and upper-extremity injuries (not including brachial plexus injury). Thirteen patients had 15 FFMTs to reconstruct muscle loss caused by severe Volkmann's ischemia. Seventeen patients had 21 FFMTs for reconstruction after severe crushing and traction injuries of the forearm or arm, with major muscle loss or major nerve injury. Nine patients, with 11 FFMTs, sustained major limb avulsion amputation for which replantation without nerve repair was done initially. FFMT was the only technique available to resolve the motor deficit and consequent deformity. Most patients achieved significant functional improvement.