Proof of principle of a novel co-pulsating intra-ventricular membrane pump.

In this proof of principle study, we investigated the effectiveness and safety of hemodynamic support with the Intra-Ventricular Membrane Pump (IVMP). The IVMP was implanted into the apex of the left ventricle. Hemodynamic assessment was performed in six ex vivo beating porcine hearts (PhysioHeart platform). The cardiac output (CO), mean arterial pressure (MAP), coronary flow (CF) and pulse pressure (PP) were obtained before and during IVMP support and reported as means ± standard deviations. In two additional visualization experiments, the integrity of the mitral valve was assessed during IVMP support. We found a significant increase of the CO (+1.4 ± 0.2 L/min, P < .001), MAP (+13 ± 6 mm Hg, P = .008), CF (+0.23 ± 0.1 L/min, P = .004), and PP (+15 ± 4 mm Hg, P = .002) during IVMP support, when compared to baseline. No interference of the IVMP with mitral valve function was observed. An increase of premature ventricular complexes (PVC) was observed during support with the IVMP (mean PVC-burden 4.3% vs. 0.7% at baseline), negatively influencing hemodynamic parameters. The IVMP is able to significantly improve hemodynamic parameters in a co-pulsatile fashion, without hampering the function of the mitral valve. These findings provide a basis for future development of a catheter-based IVMP.

Nuclear chromatin characteristics of breast solid pattern ductal carcinoma in situ.

OBJECTIVE: To characterize nuclei from breast solid pattern ductal carcinoma in situ (DCIS) by their karyometric features and to search for the presence of statistically significantly different subsets of nuclei. STUDY DESIGN: One hundred nuclei from each of 6 normal, 13 solid DCIS, (9 low and intermediate grade and 4 high grade DCIS) histopathologic samples of breast tissue were digitally recorded. Karyometric features were computed and subjected to a nonsupervised learning algorithm (P-index) to identify significantly different subgroups. RESULTS: Nuclei in low grade lesions displayed a diploid/near diploid pattern, while the majority of intermediate grade lesions fell into a range beyond 5N. The high grade lesions showed substantial genomic instability and represented three statistically different subsets or phenotypes. CONCLUSION: There is a progression of nuclear abnormality from low grade to high grade DCIS. The nuclei from high grade DCIS form a heterogeneous set that represents three phenotypes. One of these phenotypes shows a nuclear chromatin pattern that more closely resembles poorly differentiated, infiltrating disease. The observation of such a phenotype may have prognostic implications.

Landscape characterization of peridomestic risk for Lyme disease using satellite imagery.

Remotely sensed characterizations of landscape composition were evaluated for Lyme disease exposure risk on 337 residential properties in two communities of suburban Westchester County, New York. Properties were categorized as no, low, or high risk based on seasonally adjusted densities of Ixodes scapularis nymphs, determined by drag sampling during June and July 1990. Spectral indices based on Landsat Thematic Mapper data provided relative measures of vegetation structure and moisture (wetness), as well as vegetation abundance (greenness). A geographic information system (GIS) was used to spatially quantify and relate the remotely sensed landscape variables to risk category. A comparison of the two communities showed that Chappaqua, which had more high-risk properties (P < 0.001), was significantly greener and wetter than Armonk (P < 0.001). Furthermore, within Chappaqua, high-risk properties were significantly greener and wetter than lower-risk properties in this community (P < 0.01). The high-risk properties appeared to contain a greater proportion of broadleaf trees, while lower-risk properties were interpreted as having a greater proportion of nonvegetative cover and/or open lawn. The ability to distinguish these fine scale differences among communities and individual properties illustrates the efficiency of a remote sensing/GIS-based approach for identifying peridomestic risk of Lyme disease over large geographic areas.

Diagnosis and therapy of subclinically infected prostheses.

We believe 5 to 7 percent of prosthetic devices are "subclinically" infected by Staphylococcus epidermidis. These infections are manifested by chronic pain, migration and late extrusion of the devices. To examine this problem, we cultured penile and mammary prostheses. For the experimental arm, we cultured painful penile and mammary prostheses that were being removed because of symptoms (pain). For patients in a control group, we cultured penile prostheses being replaced because of mechanical failure (no pain) and mammary tissue expanders that were temporarily installed. Actual parts of the device were cultured in Trypticase Soy Broth. There were 14 and 12 painful penile and mammary prostheses, 13 and ten, respectively, were cultured positive, for an infection rate of 88 percent. The primary organism identified was S. epidermidis. The nonpainful penile prostheses (zero of five and three of 22 mammary prostheses) grew S. epidermidis. The differences were highly significant (p < 0.001), suggesting that the painful prosthesis is infected. In an attempt to resolve the problem of the painful prosthesis, ten prosthesis were removed and exchanged for new devices. Patients received preoperative and postoperative antibiotics. All ten had positive cultures and nine of ten were successfully exchanged (no pain).

Subclinical infection of the silicone breast implant surface as a possible cause of capsular contracture.

In order to reexamine the possible association between bacterial presence and capsular contracture, 55 silicone devices (mammary implants or tissue expanders) were cultured at the time of their removal from 40 patients. Special culture techniques were used in an attempt to recover bacteria adhering to the smooth-surfaced implant and encased in glycocalyx biofilm. Bacteria were detected on 56% (15 of 27) of implants surrounded by contracted capsules and on 18% (5 of 28) of those without capsular contracture (p less than 0.05). Only three implants tested positive using routine plating techniques. The predominant isolate was Staphylococcus epidermidis. The concept that capsular contracture is associated with subclinical infection of silicone implants is supported by this study. With changes in the microbiological technique, bacterial recovery and growth occurs at a frequency greater than previously thought.

Reconstitution of the histologic characteristics of a giant congenital nevomelanocytic nevus employing the athymic mouse and a cultured skin substitute.

This study addresses the development of an animal model for human giant congenital nevomelanocytic nevi (GCNN). Skin grafts were made from 1) non-involved split-thickness skin from a 12-month-old GCNN patient, 2) nevus split-thickness skin from the same GCNN patient, 3) nevus full-thickness skin, and 4) cadaveric human split-thickness skin. For groups 1) and 2), human epidermal and dermal cells were enzymatically isolated and expanded in tissue culture. Composite grafts were made by placing the cultured dermal cells into a collagen-glycosaminoglycan (GAG) matrix, followed by placement of the epidermal cells onto the opposite, laminated side of the matrix. All grafts were placed onto full-thickness wounds of athymic mice and biopsies were obtained from 6 to 38 weeks later for light microscopy including S-100 immunoperoxidase staining, and electron microscopy. The GCNN cultured skin mice (group 2) developed black, raised skin in the healed wounds. None of the group 1 mice developed lesions, grossly or histologically. All of the nevus full-thickness mice retained the nevus grossly. Histopathologic examination at 38 weeks of the black, raised plaques of group 2 demonstrated a reconstituted dermis similar to group 3. Nevus cells were larger and more epithelioid in the upper dermis, as seen with true GCNN. These nevomelanocytes were not seen in the dermis at 24 weeks, suggesting that the nevus cells migrated from the epidermal component of the cultured graft to the dermis during this time frame (24-38 weeks). The melanocyte identity of these cells was confirmed with S-100 immunoperoxidase staining and electron microscopy. These findings are unique to this composite cultured graft system. The ability to culture specific types of melanocytes and place them int skin substitutes on athymic mice provides a basis for the study of GCNN and melanocyte biology in vivo.

Human antibody response following multiple injections of bovine collagen.

The enzyme-linked immunosorbent assay (ELISA) was selected to further characterize the human antibody response to Zyderm (ZCI). Our studies have involved both patients and volunteers. Five patients with delayed cutaneous hypersensitivity reactions to Zyderm were positive for anti-Zyderm antibody. Six of nine patients treated with Zyderm who never displayed cutaneous reactions did develop significant levels of anti-Zyderm serum antibody. Some of these patients progressively increased their antibody levels. None of the volunteers who received multiple skin-test doses (0.1 cc) of Zyderm developed significant levels of anti-Zyderm antibody. Polyvalent anti-Zyderm antibody titers among patients with positive ELISA absorbance ranged from 1:16 to greater than 1:128. All were positive for antibodies of the IgG subtype; half were positive for the IgA subtype. None was positive for IgM or IgE subtype. We did not observe cross-reactivity between patient anti-bovine collagen sera and commercially prepared antibodies to human anti-collagen types I, II, and III. Given the frequency of current Zyderm use, it seems evident that for most patients, biologic exposure to collagen does not pose a health hazard. Nevertheless, because of the scarcity of data pertaining to the long-term significance of humoral anti-Zyderm antibodies, physicians and patients should be aware that unanswered questions remain whenever clinical use of injectable collagen is recommended.

Cytotoxicity to cultured human keratinocytes of topical antimicrobial agents.

Cultured skin grafts administered clinically for closure of burn wounds may be contacted by topically applied antimicrobial agents. A study was performed to assess whether commonly used topical antimicrobial agents are toxic to cultured human keratinocytes (HK) in vitro. Serum-free MCDB 153 culture medium containing Neosporin G.U. irrigant (Neomycin, 40 micrograms/ml-polymyxin B sulfate, 200 units/ml) and a standard tissue culture antimicrobial agent of penicillin (10,000 units/ml)-streptomycin (10,000 micrograms/ml)-amphotericin B (25 micrograms/ml) had no effect on the keratinocyte growth rates when compared to standard MCDB 153 medium without antibiotics. Medium containing Sulfamylon (mafenide acetate, 0.85%), Polysporin (polymyxin B sulfate, 1 x 10(4) units/ml-bacitracin, 500 units/ml), gentamicin sulfate (0.1%), modified Dakins solution (25%), and acetic acid (0.25%) all showed statistically significant (P less than 0.01) decreases in keratinocyte growth rates. This data suggests that commonly applied antimicrobials may not be appropriate for cultured grafts in the concentrations that are used clinically.

Plastic surgery: treatment of burned hands.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in plastic surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in plastic surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Plastic Surgery of the California Medical Association and the summaries were prepared under its direction.

The scrotal myocutaneous flap.

The scrotum is a thermoregulatory, well-vascularized structure formed by skin and nonstriated muscle with unique elastic properties. This makes it an ideal source of tissue coverage for problem wounds in its vicinity. Two patients in which scrotal musculocutaneous flaps were used are reported: one, a paraplegic, with a recurrent ischioperineal decubitus ulcer, and another with an ulcer of the penis with exposed Dacron graft previously placed to treat Peyronie's disease. After reviewing the anatomy of the scrotum and the existent literature, we studied scrotal vascularity in a fresh specimen by transillumination. Based on our experience, we conclude that this flap is easy to perform, reliable, and very useful for wounds around the perineal region.

B-mode ultrasonic echo determination of depth of thermal injury.

A high-resolution high-frequency prototype B-mode ultrasonic scanning device was utilized to determine the depth of burn in a pilot study of five burned patients. Comparisons with clinical evaluations and histopathological studies of burn wound biopsies of the same burned areas failed to show any substantive improvement in predicting the depth of burn by ultrasonic scanning techniques. Current ultrasonic scanning is of no practical value to the burn surgeon for differentiating precisely between the depth of a deep dermal burn and a full skin thickness thermal injury.

Inhibition of wound contraction: comparison of full-thickness skin grafts, Biobrane, and aspartate membranes.

The mechanism by which open wounds contract is unknown. Although myofibroblasts are implicated in this natural process of wound healing, the evidence, however convincing, is only circumstantial. Control of wound contraction has been sought for many years, but only the application of full-thickness skin grafts is able to produce safe and effective clinical results. By comparing the synthetic skin substitute Biobrane and its component parts with full-thickness skin grafts in a rat wound model, we have demonstrated that dermis is not required for inhibition of wound contraction. We postulate that physical properties of skin and its synthetic analogues, including adherence to the wound surface, may be the signals to the open wound that effectively inhibit contraction. Whether myofibroblasts participate in this interaction remains unanswered.

Objective measurement of hypertrophic burn scar: a preliminary study of tonometry and ultrasonography.

Many people are burned each year and subsequently develop hypertrophic burn scars. An objective means for quantitatively measuring scar characteristics would be useful in monitoring resolution of the individual patient's scars as well as in evaluating different treatment protocols. Two methods for quantitative measurement of hypertrophic scars were evaluated in 4 patients at 8 scar sites over a 2-month period. A specially designed tonometer, the cicatrometer, assesses scar firmness and pliability. It is shown to provide a simple noninvasive means for objectively evaluating the progress of scar maturation and therapy. High-resolution ultrasonic scanning is shown to provide an objective, quantitative measurement of hypertrophic scar thickness, which can be compared between patients. This allows for the design of controlled trials comparing different treatment protocols.

Decrease in rate of wound contraction with the temporary skin substitute biobrane.

In burn patients normal wound healing contraction may lead to contracture deformity requiring secondary reconstruction. Full-thickness skin grafts are observed to inhibit both contraction and myofibroblasts by an unknown mechanism. The temporary synthetic skin substitute Biobrane has become an acceptable alternative to cadaver allografts for many burn and reconstruction wounds. We have postulated that this synthetic membrane might also share the ability to inhibit wound contraction. By comparing open and Biobrane closed wounds in 20 rats, we have demonstrated a significant (p less than 0.005) difference in wound size during the time that the Biobrane is adherent to the wound. Linear regression curves are used to express the rate of contraction and demonstrate a threefold decrease. Alternative mechanisms for this inhibition are postulated, including mechanical stenting versus direct inhibition of contractile myofibroblasts.

The early treatment and reconstruction of eyelid burns.

Eyelid burns occurred in 67% of the 210 patients with facial burns admitted to the San Diego Regional Burn Center between 1 December 1977 and 30 June 1982. Evaluation of 48 surviving patients with significant eyelid injury demonstrated the safety and effectiveness of early excision and grafting of eyelid burns. Tarsorrhaphies were found not to be useful in preventing ectropion and resulted in deformity of the lid margins. Our technique employing early excision and grafting and reconstruction of eyelid burns is illustrated.

Influence of a "discharge interview" on patient knowledge, compliance, and functional status after hospitalization.

Physicians commonly assume that they can educate hospitalized patients to follow prescribed treatment plans after discharge. In a prospective, controlled study, we assessed the effectiveness of a discharge interview given to each of 545 hospitalized patients assigned to one of four groups: a group in which the physicians caring for the patients received a 35-minute tutorial on how to conduct a discharge interview (n = 181), a group that received a 15-minute discharge interview from an investigator (n = 53), a group that received both interventions (n = 63), or a control group (n = 248). One month after discharge, all patients were telephoned, and a standardized questionnaire was administered. Results revealed that, 1 month after discharge, there were no significant differences among the four groups in knowledge of diagnosis, symptom status, activity level, medication knowledge and compliance, appointment keeping, and rates of rehospitalization. These results suggest that effective inpatient education may require more than a discharge interview.

Historical review of small and microvascular vessel surgery.

The history of small and microvessel surgery is reviewed to aid the beginning microvascular surgeon in gaining a perspective of the surgical techniques used on vessels less than 3 mm in diameter. Although microvascular surgery uses sophisticated microscopes, instruments, and sutures, the fundamental operative procedures are similar to those first worked out on larger vessels. The trial and error methods of past surgeons from many different disciplines have led to ever-expanding possibilities for treatment of sick and injured patients and to laboratory investigation of disease processes. We have tried to highlight the major steps in the development of vascular surgery leading up to our present core of microvascular techniques. We recognize that many of these will become obsolete tomorrow; however, in developing the new it is wise to avoid the mistakes of the past.