Use of Perflubron Emulsion to Decrease Allogeneic Blood Transfusion in High-blood-loss Non-Cardiac Surgery: Results of a European Phase 3 Study

Background: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care.

Methods: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion.

Results: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53%vs. 43%, P < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit;P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss >= 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26%vs. 16% in the PFC and control groups, respectively;P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units;P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%;P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4%vs. controls, 2%) was not statistically significant.     

The Influence of Plasma Volume Expanders on Initial Haemostasis in the Rabbit Mesentery

An experimental study was undertaken to evaluate the effect of dose (1 and 2 g/kg b.w.) and molecular weight (40 000, 70 000, 110 000 and 500 000 daltons) of dextran on primary haemostatic plug formation in the rabbit mesenteric microcirculation. All experiments were made 3 h after the infusion of the different substances. Albumin and hydro-oxyethyl starch treatment was used for control plasma volume expansion and did not influence arteriolar and venular haemostasis as compared with saline. Dextran gave a prolonged haemostatic plug formation time with increasing dose and with increasing molecular weights. Clinically relevant doses of dextran 40 and 70 (1 g/kg b.w.) did not influence haemostatic plug formation time.     

Ultrastructure of Dental Enamel afflicted with Hypoplasia: An Atomic Force Microscopic Study

The ultrastructure of the human tooth enamel from a patient diagnosed with hypoplasia (HYP) was investigated using atomic force microscopy (AFM) and compared with the surface of normal human tooth enamel. Hypoplasia is a hereditary defect of dental enamel in which the enamel is deficient in either quality or quantity. AFM results presented for the HYP tooth enamel clearly demonstrate that the apatite crystal morphology in hypoplasia tooth enamel is perturbed in the diseased state which could result from a defective synthesis of the extracellular matrix proteins, e.g., amelogenin, by the ameloblasts. HYP enamel consisting of loosely packed, very small grains does not present a tendency for association, as in the case of the normal healthy tooth. Indeed, the enamel surface affected by HYP is porous and is made of much smaller grains. In some samples, the HYP part of enamel surface appeared in the form of a point-defect, which we believe may be associated with the early stages of the HYP deformation.     

An Electron Microscopic Study on the Process of Acid Demineralization of Cortical Bone

Demineralization has been shown to foster osteoinductive properties of cortical bone grafts, yet little is known about the process of demineralization and how to control it. The purpose of this study was to investigate the process of cortical bone demineralization by using scanning electron microscopy to evaluate how hydrochloric acid demineralizes cortical bone. Results showed that in the demineralization of diaphyseal cortical bone specimens using hydrochloric acid, a uniformly thick circumferential band of demineralized bone matrix surrounds an inner undecalcified bone core as the process of demineralization occurs. The interface between the demineralized and mineralized section of the bone specimens was extremely sharp. This interface between demineralized and undemineralized bone was noted to advance as a reaction front with increasing demineralization which resulted in continuous shrinkage of the inner cortical bone core. This study suggests that cortical bone demineralization can be best described using an advancing reaction front theory, and this explanation can be used for implementation of the concept of controlled demineralization. Received: 19 December 1996 / Accepted: 25 April 1997     

Preserving the Integrity of Oesophageal Stents with Laser Therapy and Argon Plasma Coagulation: An In Vitro Study

. Thermal lasers and argon plasma coagulation are widely used in the treatment of stent overgrowth in patients with advanced oesophageal malignancy. The aim of treatment is to achieve patency while avoiding damage to the prosthesis. This experimental study was designed to determine the power and duration of application that can be safely tolerated by four different types of oesophageal prostheses. Five stents were studied: wall stent; open metal mesh stent (uncovered Ultraflex); covered metal mesh stent (covered Ultraflex); Gianturco (Z-stent); Esophagocoil. Nd-YAG Laser, GaAlAs diode laser and argon plasma coagulation were applied in non-contact mode at gradually increasing power levels and duration and the effects were observed. The use of argon plasma coagulation on Esophagocoil stent seems safe in power settings of 100 W up to 10 s. The diode laser is intermediate in that Gianturco and Esophagocoil stents can withstand pulses of up to 50 W for about 2 s. The Nd-YAG laser is detrimental to most stents at power levels of 20 W. Only the Esophagocoil withstands Nd-YAG pulses of 60 W but only up to 1 s. Wallstent, open and membrane-covered mesh stents perform poorly in that they can only tolerate up to 1.5 s of power at 25 W with the Diode and 1.0 s of power at 20 W with Nd-YAG laser. The use of different thermal modalities on the five stents has indicated safe power limits and duration. Membrane-covered stents are always damaged by thermal laser application unless the membrane is truly transparent. Paper received 23 February 2000; accepted after revision 24 March 2000.     

Microscopic gonadoblastoma in dysgenetic gonad of an infant: An ultrastructural study

A microscopic gonadoblastoma found in the dysgenetic gonad of a six-month-old phenotypic female with a 46,XY genotype was studied with the electron microscope and compared with the cells from the testicular portion of the contralateral gonad. The germ cells within the tumor resembled the testicular germ cells and were not different from previously described germ cells in other gonadoblastomas of postpubertal patients. The sex cord cells of the present tumor were inactive and immature, but differed from the Sertoli cells of the patient's testis. The presence of hyalin globules and Call-Exner bodies in the epithelial tumor nests, coupled with the ultrastructural appearance of the sex cord cells is more consistent with them being immature granulosa rather than Sertoli cells. The immaturity of the sex cord cells in gonadoblastoma of this infant suggest that they are responsive to normal regulatory hormonal influences.     

Dermatofibrosarcoma Protuberans of the Forehead and Scalp with Involvement of the Outer Calvarial Plate: Multistaged Repair with the Use of Skin Expanders

BACKGROUND AND OBJECTIVE: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive and infiltrative tumor that requires Mohs' micrographic surgery or wide excision to treat. Adequate excision often leaves a cosmetic disfiguring defect, particularly if the tumor is located on the head and neck. Complex defects of the face present special problems, such as distortion, ectropion, and retraction of normal tissues. PATIENT AND METHODS: We present a case of an infiltrating DFSP of the forehead and scalp in a young woman. The tumor was removed, and the defect was reconstructed with multistaged repair, which included bone coverage, local and regional flaps, and the use of expanders. RESULTS: A multistaged repair was performed with good clinical outcome and satisfactory cosmetic results. CONCLUSION: Multistaged repair of the face is a viable alternative surgical approach to preserve facial contours and minimize distortion in the treatment of DFSP. This case illustrates the degree of complexity that the treatment of DFSP may involve.     

Intraoperative Varicocele Anatomy: A Microscopic Study of the Inguinal Versus Subinguinal Approach

PurposeThe groin approach to varicocelectomy is performed by an inguinal (aponeurosis of external oblique opened) or subinguinal (external oblique aponeurosis intact) technique. We describe the number and relationship of internal and external spermatic arteries, veins and lymphatics within the subinguinal portion of the spermatic cord in infertile men undergoing microscopic varicocelectomy and compare these findings to the microanatomy observed with the inguinal approach.Materials and MethodsA total of 48 consecutive patients underwent 84 microsurgical subinguinal varicocelectomies during which the detailed intraoperative microanatomy of the spermatic cord and gubernacula was recorded. These observations were compared with a previously reported group of 83 consecutive patients that underwent 115 inguinal varicocelectomies. Subinguinal microscopic findings were also evaluated relative to clinical varicocele grade.ResultsThe spermatic cord in the subinguinal dissection was characterized by a smaller number of large (greater than 5 mm) internal spermatic veins and a greater number of small (less than 2 mm) internal spermatic veins than the cord in the inguinal dissection (mean 0.4 vs 1.9 large veins and mean 7.9 vs 4.7 small veins, respectively). The subinguinal dissection was also characterized by a significantly greater percentage of external spermatic veins greater than 2 mm than that observed during inguinal dissection (93% vs 74%, respectively, p <0.05). Multiple spermatic arteries were identified in 75% of subinguinal dissections and in only 31% of inguinal dissections (p <0.03). Internal spermatic arteries were surrounded by a dense complex of adherent veins in 95% of cases using the subinguinal approach, whereas this finding was true in only 30% of cases with the inguinal approach (p <0.001). The clinical grade of a varicocele was significantly associated with the number of internal spermatic veins greater than 2 mm found intraoperatively (p <0.001) but not with the maximum internal spermatic vein diameter.ConclusionsAlthough the subinguinal approach to microsurgical varicocelectomy obviates the need to open the aponeurosis of the external oblique, it is associated with a greater number of internal spermatic veins and arteries compared with the inguinal approach. The primary branch point for the testicular artery occurs most commonly during its course through the inguinal canal. Internal spermatic arteries at the subinguinal level are more than 3 times as likely to be surrounded by a dense network of adherent veins than when they are identified at the inguinal level. Taken together, these data suggest that microscopic dissection is more difficult with a subinguinal incision.     

Breast Reconstruction with Implants,Tissue Expanders and AlloDerm: Predicting Volume and Maximizing the Skin Envelope in Skin Sparing Mastectomies

Abstract: AlloDerm has been used as a tissue supplement in conjunction with the pectoralis major muscle to provide full coverage over an implant in breast reconstruction. While this method of reconstruction has shown promising results there is little known on the relationship of AlloDerm size and potential immediate expansion volume. A retrospective chart review was completed evaluating all tissue expander or primary implant reconstructions using AlloDerm. Data recorded included: The type/size of implant/expander, dimensions of the AlloDerm used, initial fill volume, number of expansions and time period of expansion. Statistical analysis was completed with a linear regression model. AlloDerm was used on 49 patients (72 reconstructions). Thirty‐four patients (50 reconstructions) underwent reconstruction with a tissue expander and 15 patients (22 reconstructions) underwent a single stage reconstruction with a permanent implant. The tissue expander volume filled (cc) could be predicted by 5 × surface area of AlloDerm (cm²) ? 12 (R² = 0.62) and 80 × height of AlloDerm (cm) ? 15 (R² = 0.59). The tissue expanders could be filled to an average of 75% of total size and required three to four injections in the postoperative period to reach full expansion. Obviously, a requirement for maximal implant expansion is an appropriate skin sparing mastectomy. There is a mathematical relationship between fill volume and surface area as well as height of AlloDerm used in breast reconstruction. This analysis provides a guideline for immediate implant expansion to surgeons using AlloDerm in reconstructive breast surgery.     

Colloid cysts: experience with the management of 84 cases since the introduction of computed tomography

A retrospective review of colloid cysts diagnosed from 1974 to 1986 emphasizes the presenting symptoms of these lesions, their surgical management, and the contribution of modern imaging techniques to their diagnosis and therapy. In this 12-year period, 84 patients (45 men and 39 women) had a colloid cyst diagnosed. The patients' mean age was 46 years (range, 7-82 years). Surgery was performed in 55 patients, 7 of whom had undergone prior surgery elsewhere. The surgical approaches used were transfrontal-transventricular, transcallosal, computer-assisted stereotactic aspiration and resection by stereotactic craniotomy, and shunting of cerebrospinal fluid without removal of the lesion. There was no operative mortality, but complications occurred in 15 patients (27%). Preoperative imaging showed hydrocephalus in 93% of the patients: severe in 43%, moderate in 36%, and mild in 14%. In the surgically treated group, the most common presenting symptoms were headache, change in mental status, ataxia, nausea and vomiting, visual disturbance, emotional lability/inappropriate affect, depersonalization, and hypersomnolence. Twenty-four patients for whom surgery was not recommended are being followed up closely. Most of these patients had normal ventricles. The symptoms in this group included headache, anxiety/nervousness, ataxia, memory impairment, visual disturbance, and seizures. Five autopsy cases of patients with colloid cysts were available during this period and were reviewed. Direct removal of colloid cysts can be accomplished with low morbidity and mortality, avoiding the frequent revisions and complications related to shunt procedures. There is a subgroup of colloid cysts that can be operated upon electively or followed up closely with serial imaging studies.     

FK506 to Prevent Lung Injury After Hindlimb Ischemia and Reperfusion in a Rat Model: An Electron Microscopic Study

Purpose Hindlimb ischemia and reperfusion leads to lung injury in various animal models. We investigated the effectiveness of FK506, an immunosuppressive agent, which also modulates neutrophilic infiltration, in preventing lung injury after hindlimb ischemia and reperfusion in a rat model.Methods Twenty-seven male Sprague-Dawley rats were randomized to received FK506 at doses of 0.3mg/kg, 0.5mg/kg, or 1mg/kg body weight per day, or normal saline injections, as pretreatment, and there was also a sham group. On the 4th day, the animals were subjected to 2h of ischemia induced by a tourniquet, followed by reperfusion of the extremities for 2h. Lung tissue assays were performed for the lipid peroxidation product malondialdehyde (MDA) and total glutathione (GSH). Lung tissues were also examined histopathologically under light and electron microscopy.Results The MDA levels in the study groups were significantly lower than those in the control group (P < 0.05), but the total GSH levels did not differ significantly among the groups. Histopathologically, there were no significant differences among the groups given different doses of FK506, but there was a significant difference between the control group and all the treatment groups.Conclusion FK506 ameliorates the lung injury associated with ischemia and reperfusion of the lower limbs, and might have an inhibitory effect on the neutrophils that cause remote organ damage.     

An Evaluation of Plasma Antioxidant Levels and the Risk of Breast Cancer: A Pilot Case Control Study

Antioxidant micronutrients found in fruits and vegetables have been shown in numerous studies to be protective against cancer. There is limited information on the relationship between blood antioxidant micronutrient levels and cancer among ethnic minorities. We conducted a pilot case-control study to evaluate the potential for accrual to a study of the association of plasma levels of beta-carotene, retinol, lycopene, alpha-tocopherol, and gamma-tocopherol with breast cancer risk among African American and Caucasian women seen at a large university medical center in Detroit. Cases included women with newly diagnosed invasive breast cancer who had not yet had any cancer-related therapy and who were age-matched to controls within 5 years. Plasma levels of micronutrients were analyzed by high-pressure liquid chromatography. Compared to the expected accrual based on cancer registry data, only 26% (11/42) of African American women with breast cancer enrolled, while 100% (16/16) of Caucasian cases enrolled. Control women were quickly accrued with only a 6% refusal rate. Among African American women, there was a weak inverse association between plasma lycopene levels and breast cancer risk, with a mean level of 0.17 &mgr;mol/L (SD = 0.18) among cases, and 0.24 &mgr;mol/L (SD = 0.18) among controls (p = 0.09). There was a weak direct association between plasma retinol levels and breast cancer risk among African American women, with a mean retinol level of 2.37 &mgr;mol/L (SD = 0.73) among cases and 1.98 &mgr;mol/L (SD = 0.49) among controls (p = 0.132). The interaction effect of race and lycopene was statistically significant (p = 0.048). Among the lowest lycopene tertile, the risk of breast cancer among Caucasian women was 0.76 and the risk of breast cancer among African American women was 2.29, although these odds ratios were not statistically significant. Our recruitment efforts were largely successful among Caucasian cases and controls, and African American controls, but were unsuccessful among African American cases. The results suggest a possible relationship between plasma lycopene level and breast cancer among African American women, but these results should be confirmed by a larger, more definitive study.