Tissue expansion in a patient with extensive nevus comedonicus.

Nevus comedonicus is a rare developmental abnormality of the pilosebaceous apparatus that presents as an aggregation of dilated follicular orifices filled with pigmented keratinous material. Occurrence of extensive or giant lesions is even more rare. Indications for treatment include recurrent infections and cosmetic reasons. Therapeutic approaches include topical keratolytic agents, manual extraction of comedones, dermabrasion, and excision of smaller lesions. Increasing clinical experience with tissue expansion has suggested that it might be used effectively in the definitive treatment of an extensive nevus comedonicus previously considered too large to excise without the use of a skin graft, despite the potential risk of infection within the lesion during the course of expansion. We report the first patient with giant nevus comedonicus to be treated using tissue expansion. This patient demonstrates that prompt treatment of cellulitis and abscesses within the lesion will keep this process isolated from the adjacent expanders and will not compromise a planned excision and reconstruction.


Penicillamine-induced pseudoxanthoma elasticum-like skin changes requiring rhytidectomy.

A 42-year-old woman with pronounced skin laxity of her neck underwent a rhytidectomy and was found to have pseudoxanthoma elasticum-like changes of her skin. Her medical history was significant for Wilson's disease, requiring that she take penicillamine for 26 years. In patients on long-term penicillamine therapy, 20% to 33% will develop a dermatopathy. The drug has been used to alter scar formation in various surgical conditions. Penicillamine is known to alter cross-linking of elastin and collagen fibers. A review of the literature reveals other penicillamine-related dermatopathies that may present to the surgeon.


Utility of the inferior gluteal vessels in free flap coverage of sacral wounds.

An improved technique for gaining access to the inferior gluteal vessels is presented. This method allows rapid isolation of these vessels, preservation of greater pedicle length, and improved access for the performance of microsurgery. The innervation and function of the gluteus maximus is also preserved. We believe the use of this technique makes the inferior gluteal vessels the receptor vessels of choice for microsurgical procedures in the sacral area. An illustrative patient is presented in whom these vessels were used for a combined serratus anterior-latissimus dorsi free muscle flap for sacral wound coverage.


Nonorthopedic use of the fracture table.

Use of the fracture table for patient positioning instead of the standard operating room table is advantageous in many nonorthopedic surgical situations. Benefits include circumferential accessibility of bilateral lower extremities, permitting two or more surgical teams to work simultaneously on different anatomical sites. Burns and multiple acute and chronic leg wounds are particularly suitable for this technique.


The transverse gracilis musculocutaneous flap.

Through detailed anatomical study and latex injection of 24 cadaver legs, the blood supply to the skin overlying the gracilis muscle was examined. The proximal pedicle entered the gracilis muscle 10 +/- 2 cm below the pubic tubercle. The dissections identified both septocutaneous and musculocutaneous perforators from the proximal gracilis pedicle. These branches had a pronounced tendency to travel in a transverse direction, supplying the cutaneous territory over the adductor longus and sartorius anteriorly and extending for > 5 cm beyond the posterior margin of the gracilis muscle. This information led to a "new" transverse design of the gracilis musculocutaneous flap, such that the vascular perforators are invariably included in the cutaneous portion of the flap. In contrast, the traditional design, because of skin mobility, may allow elevation outside the skin territory of the muscle perforators.


The occipital artery flap for transfer of hair-bearing tissue.

The posterior scalp is investigated as the donor site for the transfer of hair-bearing tissue based on the occipital artery. The dissection of fresh cadavers was performed and the occipital artery was noted to have three major branches including a vertical, transverse, and descending branch. The vessel connection across the midline allowed transfer of the posterior scalp to the desired recipient site. This vessel provides the possibility of transfer of large areas of hair-bearing tissue to a single stage. The variability of flap design is described as well as the technical considerations for a successful transfer.


The composite lateral arm free flap: vascular relationship to triceps tendon and muscle.

We studied the vascular relationship of the lateral arm flap to triceps tendon and muscle in 16 dissected cadaver arms. We designed composite lateral arm free flaps containing fasciocutaneous components, triceps muscle, and/or triceps tendon. Vascular communication between the lateral arm fascia and triceps tendon was negligible. In contrast, a mean of 3.6 vessels passed through triceps muscle from the posterior radial collateral artery to the harvested triceps tendon; in each dissection at least 1 vessel entered the proximal 5 cm and 1 vessel entered the distal 5 cm of harvested tendon. Methylene blue injections confirmed that perfusion of the triceps tendon was through triceps muscle and not through lateral arm fascia. We used the composite lateral arm free flap in 6 patients, 3 with triceps muscle and 3 with triceps tendon. Baltimore Therapeutic Evaluation testing in those patients where triceps tendon was harvested showed no deficit in elbow extension. Complete coverage of composite defects was achieved with a single surgical procedure in all patients.


Characteristics of prosthetic mesh and autogenous fascia in abdominal wall reconstruction after prolonged implantation.

This study evaluated two types of prosthetic mesh and autogenous fascia in long-term abdominal wall reconstruction for rats. Marlex mesh, Gore-Tex patch, and autogenous fascia were implanted and left in place for 1 year. Materials were removed and evaluated using tensile strength of the material, tensile strength of the suture line, and adhesions. No change in the tensile strength of any of the materials were found at 1 year follow-up. Tensile strengths were significantly greater for Gore-Tex patch and Marlex mesh than the autogenous fascia. The Marlex mesh, however, had a weak and a strong tensile strength direction. These were significantly different (p < 0.05). Suture line tensile strength was greater for autogenous fascia and Marlex mesh than it was for the Gore-Tex patch, which was significantly weaker (p < 0.05). The greatest number of adhesions were seen in the Marlex mesh group. No significant difference was present in adhesions between Gore-Tex patch and autogenous fascia. In summary, autogenous fascia showed virtually no adhesions and good suture line strength. While it was the weakest of the three materials examined, the strength was still within the normal range and adequate for abdominal wall reconstruction.


Coverage of widely separate defects of the lower extremity: application of cluster analysis.

A patient with lower extremity reconstruction is presented with a radial forearm free flap designed using the cluster analysis method of cutaneous perforators. The cutaneous vascular anatomy of fasciocutaneous flaps is discussed as well as the application of the mathematical model of analysis of the vascular territories within specific flaps to assist in "custom" flap design. The ultimate goal of this technique is the creation of flaps that provide a more precise and anatomical reconstruction of the proposed defect.


The medial arm flap.

The reports of transfer of the medial arm flap have been inconsistent, and confusion remains about its anatomy and use. In 40 fresh cadaver arms, the vascular supply to the medial side of the arm was studied after latex injection. The superior ulnar collateral artery was present in 39 of 40 dissections and was the most consistent prominent blood supply to this area. In 57.5% of dissections, direct cutaneous arteries > 1.0 mm were present, and in 47.5%, multiple muscular cutaneous arteries > 1.0 mm were present. Although the blood supply to the medial arm flap is multiple, at least one pedicle > 1.0 mm can be found in all dissections. To date, 10 consecutive medial arm flaps were used to cover upper and lower extremity defects without any flap loss. With knowledge of the anatomical variations, the medial arm flap is a plausible reconstructive option.


The versatile metacarpal and reverse metacarpal artery flaps in hand surgery.

Vascular anatomy of dorsal metacarpal arteries was investigated in fresh cadaver dissections and by injection of methylene blue. Origin and termination of the vessels were studied, as well as their connection to the palmar vasculature. Vascular territories and elevation of flaps based on these vessels are also discussed. The second dorsal metacarpal artery was found to be the most consistent. This vessel has a large distal connection to the palmar vessels which allows both proximal and reverse elevation. Representative cases and surgical technique are described.


Psychological adjustment following work-related hand injury: 18-month follow-up.

Severe, work-related hand injuries are often accompanied by a significant number of psychological symptoms that are frequently associated with posttraumatic stress disorders. These symptoms occur in the following four domains of psychological functioning: cognitive, affective, physiological, and behavioral. This study examined the incidence of a variety of symptoms occurring with work-injured patients. Interviews were conducted at 1 week, 3 months, 6 months, 12 months, and 18 months after injury. Symptom frequencies were recorded. The results indicate that many of these symptoms were persistent 18 months later and continued to be significantly debilitating. The results support the need for psychological intervention after severe, work-related hand injuries.


Creating a hyperbaric oxygen treatment unit in a major medical center: a personal experience.

Hyperbaric oxygen therapy has regained the interest of physicians and surgeons, including plastic surgeons, after some years of disinterest and suspicion on the part of many. Under the leadership of the Undersea and Hyperbaric Medical Society, the rationale for hyperbaric oxygen treatment has been subjected to rigorous review. Interest in hyperbaric oxygen therapy on the part of plastic surgeons is largely related to its adjunctive use in the management of compromised tissue. When the decision is made to install a hyperbaric unit in a hospital, the next most critical decisions will be the choice of a medical director who has whole-hearted enthusiasm for the project, the choice of a monoplace or multiplace chamber, a suitable site for the unit, ancillary equipment to support the unit, and staffing that is appropriate to the uses conceived for the unit. Pitfalls and problems are described.


Comprehensive correction of the craniofacial deformity in achondroplastic dwarfism.

The treatment of this patient serves to demonstrate a craniofacial team approach to a unique and moderately severe problem. By the modification and careful combination of standard techniques, i.e., frontofacial advancement, and Le Fort I and vertical mandibular osteotomy, a good correction has been obtained. Analysis of the problem clearly indicated the need for moving multiple components of the facial skeleton into new positions to provide correction. The upper and lower midface required simultaneous movements in exactly opposite directions to normalize the skeletal deformity. To address the excess forehead height and projection, a modification of the usual frontofacial advancement was necessary. Rotation of the frontofacial segment forward inferiorly allowed correction of the orbital deficiency while also allowing shortening of the vertical forehead dimension. This is a deviation from the straight linear advancement usually dissected. Simultaneous retroposition and rotation of the maxilla allowed correction of the plane of occlusion while lengthening the midface. The unique combination and application of standard techniques of craniofacial surgery in this patient allowed a very good result.


Tire explosion injuries to the upper extremity.

Several articles have been published that bring attention to the destructive potential of tire explosions. Although the severity of tire explosion injuries to the head and neck region is well established, only one previous article has reported injuries to the upper extremity. Fourteen patients with upper extremity tire explosion injuries have been treated by us from 1980 to 1988. Each injury was caused by single-piece wheel assemblies, as opposed to multipiece wheel assemblies, which have traditionally been associated with the injury. Three representative patient reports are discussed. Prevention of this injury can be achieved by increased public awareness, formal industrial safety training, tire servicing with dedicated equipment including restraining devices or barriers, complete evaluation of wheel/tire serviceability before tire mounting, separation of servicing of single and multipiece wheels, and complete tire deflation before servicing.


Self-inflicted midline facial gunshot wounds: the case for a combined craniofacial and microvascular team approach.

Self-inflicted gunshot wounds to the face are extremely complex and difficult to manage. In the past, these patients have been treated by debridement, hemostasis, and soft tissue closure with reconstruction deferred to a later time. This approach consigned the patient to significant facial contracture and scarring, which is impossible to adequately correct secondarily. As a result of this traditional approach, patients had substantial disfigurement as well as dysfunction. At the Medical College of Wisconsin, we have begun an aggressive multispecialty team approach in which the maximum possible reconstruction is performed acutely. This has resulted in superior aesthetic and functional results, and in a substantially lower number of hospitalizations, surgical procedures, and hospital days. This approach includes the spectrum of current plastic surgical techniques including the craniofacial approach using open reduction with accurate miniplate reconstruction and acute bone grafting as well as soft tissue reconstruction and replacement using composite multiple-stacked free tissue transfer. We believe the overall approach provides a superior result and we will continue a program of aggressive and acute intervention.


Toxic shock syndrome following latissimus dorsi musculocutaneous flap breast reconstruction.

Acute toxic shock syndrome (TSS) not related to menstruation has comprised an increasing proportion of cases reported to the Center for Disease Control in recent years. We report a patient with TSS resulting from a postoperative donor site infection after bilateral breast reconstruction with latissimus dorsi musculocutaneous flaps. The diagnosis, management, and outcome of TSS are reviewed. The plastic surgeon should be aware of TSS as a potential postoperative complication of routine procedures in plastic surgery.


Expanded midline forehead flap for coverage of nonnasal facial defects.

A 13-month-old infant with a giant hairy nevus of the superior portion of the right cheek, which measured 3.5 x 5.5 cm, was treated by excision and coverage using expanded midline forehead flap. This approach stands in contrast both to the standard technique of excision and full-thickness grafting for large facial defects as well as to the use of the midline forehead flap for nonnasal reconstruction. Although this approach did necessitate the placement of a midline forehead scar, the overall result was sufficiently superior to justify its use. The child has good, stable, soft coverage with no contour or landmark distortion. The child is presented in an 18-month follow-up with photographic documentation.


Penile replantation after self-inflicted amputation.

In 4 men with self-inflicted penile amputation, replantation was successful using microsurgical technique. Postoperative complications were minimal. In 1 man who had amputated his penis and then amputated his scrotum and testicles, a small skin graft was necessary to close a portion of the defect. A mild urethral stricture that developed in this man responded to dilation. Return of sensation was excellent. Normal erections were reported by all men. Microsurgical replantation is the treatment of choice for this injury and is superior to other techniques of penile reattachment, which have a high incidence of distal necrosis, fistula and stricture formation, as well as incomplete or absent sensation and compromised erectile function. Of concern in this group of men is the high incidence of previous or subsequent penile mutilation. Two of the 4 men have a history of recurrent self-mutilation. The follow-up in this series is longer than previously reported and the overall psychiatric pathology appears to be quite severe and persistent.


Transfer of an inferior rectus abdominis myocutaneous flap following enterostomy.

A rectus abdominis myocutaneous flap was successfully transferred in a patient in whom a mucous fistula had previously been brought through the midportion of the muscle. The flap was used to close a large defect in a paraplegic. Previous enterostomy is not a contraindication to the use of this flap. Preoperative arteriography to confirm the presence of a patent deep inferior epigastric artery is recommended prior to flap transfer.


Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe "boomerang dysplasia"?

The authors report a case of lethal neonatal dwarfism characterized by striking micromelia, fused rudimentary and supernumerary digits, large, soft head, pronounced hypertelorism, protruding eyes set laterally, enormous omphalocele and severe deficiency of tubular bone and spine ossification. Histologic examination showed lack of ossification of the cartilaginous anlage of many tubular bones. The cartilage had irregularly distributed chondrocytes. The matrix contained hypocellular and degenerated areas with scattered large chondrocytes. In a few bones a very disorganized growth cartilage was present. The case is similar to that described by Piepkorn et al. (1977) and may represent a severe form of "boomerang dysplasia" (Kozlowski et al., 1981; Tenconi et al., 1983; Kozlowski et al., 1985; Winship et al., 1990).


Cytogenetic and molecular investigations of an abnormal Y chromosome: evidence for a pseudo-dicentric (Yq) isochromosome.

A derivative Y chromosome was found in a 55-year-old man with Lambert-Eaton paraneoplasic pseudomyastheniform disease. Small testicles, azoospermia were noticed and hormonal level values were as in the Klinefelter syndrome. A 45,X/46,XYp+ mosaïcism was described on peripheral blood lymphocytes. Cytogenetic investigations with R-G-C- and Q-banding have been performed. In situ hybridization with the GMGY 10 DNA probe showed two copies of proximal Yp sequences. Southern blot analyses were performed using the Y DNA probes 27a, 47z, 64a7, 50f2 disclosing specific Yp and Yq sequences from the pseudoautosomal boundary to the Yq proximal portion. The der(Y) has been defined as a dicentric isochromosome for the long arm with one active and one apparently suppressed centromere. The breakpoint leading to the der(Y), has been located in the pairing segment of the Y short arm (i.e. Yp11.32). So the der(Y) was interpreted as a psu dic(Y) (qter-->cen-->p11.32 ::p11.32-->qter). There was thus an almost complete duplication of the Y chromosome.


Molecular studies of a translocated (X;22) DiGeorge patient using somatic cell hybridization.

In order to better characterize the chromosomic rearrangement of an unbalanced 45XX t(X;22) (q28;q11) DiGeorge patient, a somatic hybrid clone segregating the translocated chromosome was constructed and investigated using X and 22 linked markers. Our study demonstrated that this de novo translocation was from paternal origin. The breakpoint was assigned between DXS296 and IDS loci at Xq28 and between D22S9 and BCRL2 at 22q11. This observation and published data allow to locate a "critical region" for DiGeorge syndrome between these two last loci on 22q11. Our hybrid clone may be a useful tool for mapping new probes arising in this region.


Interstitial deletion of the proximal region of the long arm of chromosome 18, del(18q12) a distinct clinical entity? A report of two new cases.

Two unrelated mentally retarded patients were found to have an interstitial deletion of 18q12. They were a 2-year-old, short, macrocephalic and autistic girl, and a 5-year-old boy. Six other liveborn patients with comparable deletion have been so far identified. The common findings are mild dysmorphic features (telecanthus, epicanthal folds, flaring eyebrows, small mouth with thin upper lip), hypotonia, behavioural disorders, mental retardation with speech delay and lack of major malformation.


Mapping of the Darier's disease gene by serogenetic markers: results in two large British kindreds.

The authors have carried out genetic linkage studies in 57 subjects from two large kindreds of Darier's disease, using a range of serological and biochemical polymorphisms of known chromosomal location. In these kindreds, about 7% of the genome has been excluded for close linkage to the Darier's disease gene. However, one family showed positive lod scores for linkage with the Duffy blood locus (1p13); lod scores were negative in the other family, but in the combined families the total score for this marker was still positive and does not completely exclude linkage.


A small one-band paracentric inversion inv (4) (p15.3p16.3).

A neonate with aniridia was found to have a one band paracentric inversion of the short arm of chromosome 4. This was initially difficult to interpret on high resolution banding. The inversion was present in three generations of the family.


An apparent balanced translocation [t(9;11)(p21.2;p14.2)] in a neonate with dysmorphic features.

The role of so called balanced translocations in human morphogenesis remains puzzling. An eleven month old hispanic female was referred for neurological evaluation. The major dysmorphic features include: epicanthal folds, flat nasal bridge, small mouth, micrognathia, low set ears and cleft-palate. The cytogenetic findings by multiple banding techniques revealed an apparent balanced translocation involving chromosomes 9p and 11p i.e. 46,XX,t(9;11)(p21.2;p14.2) which, according to the authors, has not been previously reported.


Distal deletion of the long arm of chromosome number 1 (q43-->qter) associated with severe mental retardation and a nonspecific dysmorphic syndrome.

A 6 8/12-year-old girl with severe mental retardation, multiple congenital malformations and a de novo distal deletion of the long arm of chromosome 1 [del 1 (q43-->qter)] is here described. A review of the reported patients does not allow to distinguish different phenotypes related to distal deletion 1q42 and/or 1q43.


Trisomy 18q: 46,XX,-10,+der(10) t(10;18) (p15;q12) pat: a case report.

A 2-month-old female with intrauterine and postnatal growth retardation, multiple congenital anomalies, absent right kidney, congenital heart disease was investigated. Her karyotype revealed, 46,XX,-10,+der(10), t(10;18) (p15;q12) pat. The child died at 2 months 2 weeks. This is the third case of trisomy 18q resulting from translocation of chromosome 10 and 18.


fra(1) (p11), fra(1) (q22) and r(1) (p11q22) in a retarded girl.

A mentally retarded girl with a 46,XX/47, XX+r(1) (p11q22q22p11)/47, XX+r(1) (p11q22) fra(1) (p31) fra(1) (p11) fra(1) (q22) karyotype who inherited the fragile sites from the normal mother was studied. The conicidence of fra(1) (p11) and fra(1) (q22) with the ring chromosome breakpoints strongly suggests a cause-effect relationship. This finding agrees with other reported associations between fragile sites and structural chromosome abnormalities and constitutes the fourth reported of a de novo structurally abnormal chromosome as a consequence of presumed in vivo fragile sites instability. Although risk figures for chromosome anomalies and cancer associated with fragile sites are lacking, carriers of fra (1) (p11) may have a higher risk for abnormalities of chromosome 1 in somatic and gonadal cells than the general population.


C-anaphases: a mitotic variant.

In order to assess the frequency of C-anaphases in colchicine-arrested lymphocyte cultures, the authors studied 100 patients classified in four groups: spontaneous abortion (n = 17), subfertility (n = 12), aneuploidy (n = 18) and miscellaneous (n = 53). At least 300 mitotic G-banded cells were scored by individual. In 12 individuals no C-anaphases were observed; in 87 individuals the range was 1-7 with a mode of 2 and a mean of 2.14; the remaining individual had 19 C-anaphases in 330 cells (5.7%). The statistical analysis did not show significant differences between the groups (p > 0.05). These data along with previous studies indicate that normally most individuals have < or = 3% of C-anaphases in habitual lymphocyte cultures. Moreover, there exists an autosomal dominant form in which individuals with the trait have > 5% of the cells with such mitotic configurations. We conclude that both the low frequency common and the high frequency familiar forms are mitotic variants without pathological significance.


[Laparoscopic ileal conduit].

The authors describe an experimental model for performing the Bricker procedure endoscopically. After placing the operating table in the Trendelenburg position, the trocars are inserted through the incisions at the level of the umbilicus, the right and left flanks and the hypogastrium. Both ureters are dissected free from the inferior pole of the kidney up to a short distance from the bladder, clamped and cut. The right flank incision is extended a few cms longitudinally and the right ureter and ileal loop are brought out through the incision. Once exteriorized, a segment of the ileum is separated and intestinal continuity reestablished. The right ureter is then attached to the distal end of the ileal segment. The other end of the loop is brought to the left flank and exteriorized together with the left ureter, as described above. Once the ureter has been attached, they are passed inside. The incisions are sutured and a stoma is created in the right flank. The authors recommend the application of this simple technique in the clinical setting.


[Conservative treatment of ureteral iatrogenesis of gynecologic origin].

Five patients with iatrogenic ureteral injuries are described herein. Two patients had a vesicoureteric fistula and the remaining three patients had obstructive uropathy secondary to ligation with resorbable material during hysterectomy for a benign uterine condition, which spontaneously resolved with conservative management. Classically, the approach of this type of lesion was interventional and careful patient selection afforded the possibility of definitive resolution. US, CT and modern endourological technology have facilitated temporary diversion via percutaneous nephrostomy (or surgery, if the foregoing is not possible) to protect renal function during the process of recanalization of the injured ureter. Furthermore, it permits radiological control of the course and functional assessment of the excretory tract.


[Flurbiprofen: therapeutic alternative in nephritic colic].

A double blind randomized study was conducted in 52 patients with renoureteric colic to compare the therapeutic efficacy of two analgesics given in a single intramuscular dose. Following the administration of 2 gm dipirone plus 20 mg hyoscine N-butylbromide (n = 26) or 150 mg flurbiprofen (n-26), the patients were assessed for pain intensity, relief and pain status for a period of one hour. Both treatments afforded a similar analgesic effect, with pain remitting in 76.9% of the cases. No significant differences were observed for the latency periods or degree of pain at 5, 10, 30 and 60 minutes following treatment. Additional analgesic therapy was required in 34.6% of the patients who received dipirone and 26.9% of the flurbiprofen group, the difference not being statistically significant. Overall both drugs were well tolerated and only local adverse effects were observed, pain being the most frequent.


[Carcinosarcoma of the prostate. Immunophenotype, morphologic course and clinico-pathologic differential diagnosis].

The observation of a patient with a malignant tumor of the prostate initially classified as adenocarcinoma with desmoplasia, reclassified as adenocarcinoma with a malignant spindle cell component of uncertain cell line following two large tumor recurrences over a period of 4 months, and subsequently as carcinosarcoma with heterologous mesenchymal areas has prompted us to review the 11 reported cases of prostatic carcinosarcoma and the diagnostic algorithm of the proliferative processes of the prostate with elongated cells in order to recognize (from the histological features and the inclusion and exclusion immunophenotypes) the pseudosarcomatous stromal reactions, fusicellular changes of the carcinoma, benign and malignant phyllodes tumors and carcinosarcoma.


[Renal angiomyolipoma: a cause of massive retroperitoneal hemorrhage].

Five patients were diagnosed as having angiomyolipoma. Evidence or signs of tuberous sclerosis were observed in no patient. In 2 patients the presenting symptoms was massive retroperitoneal hemorrhage which required emergency surgery. The kidney could be preserved in 4 cases. One underwent nephrectomy for synchronous clear cell renal tumor. CT and US afford a diagnostic accuracy of nearly 100 percent. According to the data reported in the literature, tumors larger than 4 cm are amenable to treatment by conservative surgery. Smaller tumors can be followed carefully. However, surgical exploration is warranted not only in patients with pain and hemorrhage, but also in those cases with complex lesions less than 4 cm.


[Test with vasoactive drugs: its predictive value in the diagnosis of erectile sexual dysfunction of venous origin].

The practicability and sensitivity of the test with vasoactive drugs, the first method performed in our flow studies, make it an invaluable method for orienting the diagnosis. Our findings show that in 65% of the patients with a partial response to the drug-induced erectile test, dysfunction may arise from pure or associated venous leakage, which must be confirmed by dynamic cavernosometry and/or cavernosography.


[Priapism induced by intracavernous injection].

We report 16 cases of priapism in 13 of 404 patients who received intracavernous injection of vasoactive drugs to induce erection. In 10 patients the complication presented following injection of papaverine and phentolamine in combination. Despite reducing the dose of both agents, one patient had another episode of priapism. One patient who had been receiving papaverine alone in increasing doses with no results, developed priapism after the first injection of the combined treatment modality and again after the dose of both drugs had been reduced. Three cases presented priapism after injection with papaverine alone. One presented the complication again after injection of a reduced dose. The patients were seen after a sustained erection of 20 hours maximum on 15 occasions and one patient was seen after a sustained erection of 36 hours.


[Basis for the study of erectile dysfunction with pudendal evoked potentials].

The evaluation of erectile dysfunction by popliteal and pudendal evoked potentials is not widely utilized in our country, although the foregoing has proved to be a useful technique in the evaluation of a possible neurological etiology. This study describes this simple, fast and low cost method of evaluation and reports the normal ranges. The study comprised 40 subjects; 15 were healthy volunteers and the remaining had consulted for impotence and referred antecedents suggesting a neurological etiology. The results show that a latency of 40.9 +/- 2.1 msec in P1 for the pudendal evoked potentials is normal. Concerning the popliteal evoked potentials, the normal latency for P1 is 38.07 +/- 2.8 msec.


[High-flow priapism: diagnostic-therapeutic management].

We report a case of traumatic priapism with an evolution of three weeks at the time of the diagnosis. The foregoing condition had been caused by an arteriocavernal fistula. Several arteriograms and selective embolization of the compromised area were required for treatment. The etiological, pathophysiological and therapeutic aspects are discussed.


[Leydig cell tumor].

We report on a 44-year-old patient with Leydig cell tumor of the testis that had been incidentally detected following orchidectomy for a tumor. The clinical, hormonal and histological criteria currently used to distinguish the malignant from the benign form of this tumor and the different therapeutical alternatives are discussed.


[Bladder sarcomatoid carcinoma: report of a case].

A case of sarcomatoid carcinoma of the bladder is described. Its interest basically stems from the fact that this extremely aggressive tumor is uncommon in the bladder and there is existing controversy as to its anatomopathological distinction from other carcinosarcomas, spindle cell sarcoma and pseudosarcomatous bladder lesions.


[Medico-surgical management of renal leiomyosarcoma].

Because renal leiomyosarcoma is extremely rare, the experience in the management of this tumor type is necessarily scant. Our surgical and chemotherapeutic approach in a 17-year-old male patient with renal leiomyosarcoma achieved partial remission of tumor recurrence and a survival of 31 months following diagnosis.


[2 new cases of ++urethral diverticuli in women].

The first two cases of diverticulum of the female urethra seen in our Service are described. The secretion of purulent material from the urethra on vaginal compression prompted us to suspect this condition, which could not be confirmed radiologically in one case and a urethroscopy procedure was required. The etiopathogenesis of this disease is briefly reviewed and the therapeutic possibilities depending on the location of the urethral diverticulum are discussed.


[Focal urinary Salmonella infection].

A case of focal Salmonella sp. urinary infection in an elderly diabetic patient is described herein. The therapeutic approach in this uncommon type of infection is discussed.


[Vulvar metastasis in renal adenocarcinoma].

We report an additional case of vulvar metastasis as the presenting symptom of renal adenocarcinoma. The hypothesis that have been put forward relative to the route of spread of this type of metastasis are discussed and the literature reviewed.


When and how to treat caliceal stones.

Currently, there are no guidelines for the selection of patients for caliceal stone removal, although there is no doubt that urologists are taking a more aggressive approach now that treatments with low morbidity are available. We discuss when and how to treat patients with symptomatic and asymptomatic caliceal stones.


Invasive bladder cancer in women.

A total of 84 radical cystectomies were performed for invasive bladder cancer in 67 men (79.8%) and 17 women (20.2%). The present study investigated the possible sex-dependent differences in the pattern of invasive bladder cancer. More than 40% of the women presented lower urinary tract syndrome alone or with haematuria, giving a clinical picture similar to acute cystitis. This caused an average time-lag in diagnosis of 18.5 months in the women and 8 months in the men. There was a higher frequency of non-transitional cell carcinoma in the women (17.6%) than in the men (2.9%). We found statistically significant differences (p < 0.005) in tumor grade: 35.2% of the women had low grade tumors, compared to 7.4% of the men. However, no significant differences in staging or survival rate were found when comparing the two sexes. This leads us to believe that bladder cancer is less aggressive in women.


Measurement of cold challenge responses in primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis.

Using computed thermography continuous temperature recordings were made before and after cold challenge of the fingers of control subjects and patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Basal skin temperature measurements (Tpre) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in the controls. Temperatures immediately after cold challenge (T0) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The lag phase before the start of temperature recovery (Tlag) was significantly greater in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in control subjects. The maximum recovery index (R%) was significantly less in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The maximum rate of change of temperature during the rapid phase of rewarming (Gmax) was significantly greater in controls than in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Discriminant analysis showed that the dynamic parameters of rewarming (Tlag, Gmax, and R%) showed greater variation between the patients with primary Raynaud's phenomenon and those with Raynaud's phenomenon associated with systemic sclerosis than did Tpre or T0. This method of analysis of cold challenge will be used in studies of the effects of treatment of Raynaud's phenomenon.


Systemic lupus erythematosus on the Caribbean island of Curaçao: an epidemiological investigation.

To determine the incidence, prevalence, and outcome of systemic lupus erythematosus (SLE) in a well delineated black population in the Caribbean basin data were collected on the disease course of all patients with definite SLE seen during a 10 year period (1980-9) using three different sources of information (hospital records, private practice records, and death certificates). Ninety four patients were identified giving an average annual incidence rate of 4.6/100,000 (95% confidence interval (CI) 0.4 to 8.8), which showed little variation during the study period. Twenty five patients (27%) died during the study period, giving a point prevalence of 47/100,000 (CI 34.1 to 51.1) in 1990. In women aged 15-44 years the annual incidence (12/100,000; CI 5.3 to 18.9) was highest, whereas in women aged 44-65 years the 1990 point prevalence rate (one in 526; CI 469 to 625) was highest. Annual mortality was 1.7/100,000 (CI -0.8 to 4.2) with a female to male ratio of 5.3. Renal disease was the most common complication, occurring in 73 (78%) patients. Thus the transatlantic movement from an area with a (presumably) low prevalence of SLE (Central Africa) has been accompanied by an increase in the prevalence of SLE in the black population of Curaçao, indicating that environmental factors may prevail over genetic factors in the expression of this disease.


Comparison of two approaches to measuring change in health status in rheumatoid arthritis: the Health Assessment Questionnaire (HAQ) and modified HAQ.

As an alternative to the calculation of change scores for health status questionnaires used in clinical trials or longitudinal studies, transitional questions have been developed for patients to assess changes directly themselves. Here the original Health Assessment Questionnaire (HAQ) is compared with a modified version of the HAQ (MHAQ) which contains transition questions used at follow up. These, together with a set of standard rheumatological tests, were all completed by 100 patients with rheumatoid arthritis on two occasions, three months apart. Change scores were calculated for the HAQ and for the clinical measures and compared with the MHAQ. The results were strikingly in favour of encouraging patients to assess their own degree of change through the use of transition questions in the MHAQ.


Specificity of the proteus antibody response in rheumatoid arthritis.

Antibodies to proteus were determined by indirect immunofluorescence in 146 serum samples from patients with rheumatoid arthritis (RA). An autoantibody screen was performed in the same samples and in 52 of these antibody titres to the viruses influenza A, adenovirus, rubella, and parvovirus were determined. There was no significant correlation between proteus antibodies and any of the other antibodies tested. Dividing the samples into those from patients with active (C reactive protein > 10 mg/l) and inactive RA showed that the only antibodies to be significantly increased in active RA were the proteus antibodies. These observations suggest that the proteus antibody response in RA is specific.


Aetiological role of bacteria associated with reactive arthritis in pauciarticular juvenile chronic arthritis.

The cause of juvenile chronic arthritis (JCA) is unknown. Pauciarticular JCA is the most common subtype and can be subdivided into early (type I) and late onset (type II) forms, the latter clinically resembling reactive arthritis. The cellular immune responses to bacteria associated with reactive arthritis in blood and synovial fluid from 39 children with pauciarticular JCA, three children with classical reactive arthritis, and two children with psoriatic arthritis were examined. Specific titres of antibodies to bacteria in serum samples were measured in all patients. A bacteria specific synovial cellular immune response was found in two of three (67%) patients with reactive arthritis and 14 of 28 (50%) patients with pauciarticular JCA type II but only in one of 11 (9%) patients with pauciarticular JCA type I and none in patients with psoriatic arthritis. Six patients responded specifically to Chlamydia trachomatis and 11 to Yersinia enterocolitica. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. These findings suggest that bacteria with associated reactive arthritis may have a causative role in pauciarticular JCA type II but not in JCA type I.


Effect of intravenous iron-dextran (Imferon) infusion on antigen induced monarticular arthritis in rabbits.

The effect of intravenously infused iron-dextran (Imferon) on the progression of antigen induced monarticular arthritis in rabbits was studied. A rapid deposition of iron and apoferritin in the synovia of arthritis joints occurred after infusion of iron-dextran during either the acute or chronic phases of the disease. This coincided with the appearance of catalytic (bleomycin reactive) iron in the synovial fluid. There was no evidence, however, for an exacerbation of the antigen induced arthritis as a result of the iron-dextran, and synovial and bleomycin reactive iron concentrations decreased with time after administration, indicating a redistribution of the synovial iron load. Thus although intravenously infused iron-dextran appears to 'prime' the rabbit arthritic joint transiently with the potential for iron stimulated oxygen free radical damage, other factors may determine its occurrence.


Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.

Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations in patients with RA and OA were significantly higher than in controls. In both disease groups synovial fluid nitrite was significantly higher than serum nitrite, implying nitric oxide synthesis by the synovium. Serum and synovial fluid nitrite concentrations in RA were also significantly higher than those in OA. These data show increased nitric oxide production in RA and OA and suggest a role for nitric oxide as an inflammatory mediator in rheumatic diseases.


P blood group phenotype, proteus antibody titres, and rheumatoid arthritis.

The interrelationships between P blood group phenotype, proteus antibodies and rheumatoid arthritis (RA) were investigated in 140 patients with RA and 114 of their siblings who did not have RA. In the group with RA P2 subjects had significantly higher titres of proteus antibodies than P1 patients. This was not observed in the group without RA, or for antibodies to Escherichia coli. Although C reactive protein was the best predictor of proteus antibodies in the group with RA, the P blood group had an independent and significant influence. These observations suggest a testable model in which asymptomatic carriage of proteus in the urinary tract may lead to antibody production, which in turn may be important in the pathogenesis of RA.


Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis and proteus/serratia membrane haemolysins.

Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has been identified which resembles biochemically, and discriminates by charge, between HLA types associated with RA (DR1, Dw4, Dw14, Dw15), and those not linked with the disease (Dw10, Dw13).


Antibody response against 26 and 46 kilodalton released proteins of yersinia in yersinia triggered reactive arthritis.

Using an inhibition enzyme linked immunosorbent assay (ELISA) the serum antibody responses against released proteins of yersinia of molecular weights 26 and 46 kilodaltons were studied in 37 patients with and in 21 patients without reactive arthritis following yersinia infection. Although no difference was seen for the 46 kilodalton released protein, patients with yersinia triggered reactive arthritis had higher levels of antibodies against the 26 kilodalton released protein at the beginning of the disease than patients with uncomplicated yersiniosis. This may indicate an increased production of this protein in the early infection leading to poorer phagocytosis of the bacteria and thereby to the persistence of yersinia organisms within the arthritic host.


Does the locus on chromosome 11 implicated in susceptibility to HLA-DR4 dependent type I diabetes mellitus also affect susceptibility to rheumatoid arthritis?

There is a polygenic component to rheumatoid arthritis (RA) in addition to the known association with HLA-DR4. It has previously been shown in another autoimmune disease (type I diabetes mellitus) that a gene on chromosome 11p can act with HLA-DR4 to enhance susceptibility (relative risk 5-6). It is therefore possible that this locus may also affect the development of RA. Genotype frequencies at this locus, defined by a dimorphic Fok 1 restriction site, were compared in 139 healthy controls and 213 patients with classical/definite RA. In contrast with diabetes there was no increase in genotypes lacking the Fok 1 site, either in the rheumatoid group overall (125/211 compared with 86/139 controls) or in the DR4 positive rheumatoid group (76/140 compared with controls). These results indicate that the interaction between DR4 and a locus on chromosome 11p is not common to all DR4 associated autoimmune diseases.


Use of a risk factor and dietary calcium questionnaire in predicting bone density and subsequent bone loss at the menopause.

One hundred and thirty six healthy white females within 30 months of their last menstrual period (mean age 52 years) were examined to determine the usefulness of a risk factor questionnaire in predicting bone density and subsequent loss. Bone density was assessed at baseline and at 12 monthly intervals. None of the proposed risk factor variables with the exception of nulliparity correlated with the baseline spinal or femoral bone density. As a predictor of bone loss only drinking alcohol (more than four units/day) was significant. A risk factor score derived from the questionnaire before its administration did not correlate with baseline bone density or subsequent bone loss. In most normal women questioned soon after a natural menopause, an estimate of bone density and subsequent bone loss and hence osteoporotic risk cannot be reliably made using a simple risk factor questionnaire.


Recent results of elective open cholecystectomy in a North American and a European center. Comparison of complications and risk factors.

Results of elective open cholecystectomy in 1252 patients treated in a North American and a European center were examined using a recent standardized classification of complications. Although there were significant differences between centers in population age, rate of concomitant disorders, and numbers of operators, the frequency and severity of complications were comparable. There were no deaths, but 12% and 14% of the patients developed complications in the two centers. About 6% of the patients developed grade I complications. Grade II complications were noted in 6% and 8%, and grade III in 0% and 0.3%. Using univariate and multivariate analysis, individual risk factors for developing complications were found to be different in the two centers. Two preoperative scoring systems, ASA and a simplified APACHE II, were predictive for complications in both centers, but did not account for all risk in these patients. Data from the two centers could not be combined because of significant interaction between risk factors and center. Elective open cholecystectomy is a safe procedure, particularly in terms of highly morbid complications and death. Generalization of risk factors identified in a particular center may be misleading because local conditions may significantly affect risk factors for complications. The data also demonstrate the advantages of a uniform way of reporting surgical complications, which may permit meaningful comparisons among centers.


Intraoperative detection of colorectal cancer with radioimmunoguided surgery and CC49, a second-generation monoclonal antibody.

Radioimmunoguided surgery (RIGS) has been employed intraoperatively in cases of colorectal cancer to assess the extent of local tumor spread and metastatic disease. This technique uses radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens, and a hand-held gamma-detection probe to detect the radiolabel fixed to tumor tissue. Recently introduced is an MAb directed against tumor-associated glycoprotein (anti-TAG), CC49. Sixty patients were entered into the initial study. Eighteen of 21 (86%) primary tumors were localized by the CC49 MAb and the gamma-detecting probe. Twenty-nine of 30 (97%) recurrent tumors were localized. Antibody dose did not affect localization. Specimens were divided into tissue types I through IV, based on antibody localization and hematoxylin and eosin (H&E) staining: type I, RIGS (-) and histologically (-); type II, RIGS (-) and histologically (+); type III, RIGS (+) and histologically (-); type IV, RIGS (+) and histologically (+). Type IV tissue were further classified by whether they were grossly apparent, IVa, or grossly inapparent, IVb (occult). Occult tumor found by RIGS and confirmed by H&E staining (type IV) had localization ratios similar to RIGS-positive, histology-negative tissue (type III). Traditionally found cancer (type IV) had significantly higher ratios. In 12 of 24 patients (50%) with primary tumors and 14 of 30 patients (47%) with recurrent tumors, RIGS with CC49 altered the planned operative procedure. Radioimmunoguided surgery with CC49 provides useful, immediate intraoperative information not available by other techniques.


The association of perioperative blood transfusion with colorectal cancer recurrence.

The relationship between blood transfusion, disease-free survival, and other potential prognostic factors was prospectively studied in 339 consecutive patients with colorectal cancer. Admission and discharge hematocrit, Dukes' stage, and blood loss were significantly related to both blood transfusion and disease-free survival. Using Cox proportional hazards model, however, the association of transfusion with disease-free survival was significant (p = 0.0196) after controlling for age, sex, blood loss, procedure, tumor differentiation, stage, admission hematocrit, duration of surgery, length of the specimen, and tumor size. Dukes' stage (p < 0.0001) and blood transfusion (p < 0.0001) were the only variables independently related to disease-free survival. Forty per cent (44) of the 110 patients who received transfusions developed cancer recurrence, compared with 22% (50) of the 229 patients who did not receive blood (p < 0.0001). Five-year disease-free survival of the transfused patients was 57%, compared with 77% for nontransfused patients. Patients who developed recurrence received an average of twice as much blood as patients without recurrence (1.26 versus 0.61 units, p = 0.0128). Perioperative blood transfusion is a significant independent prognostic factor for colorectal cancer.


Undergraduate surgical education for the twenty-first century.

This article addresses the problems associated with current undergraduate surgical education and discusses the requirements necessary for its improvement during the third and fourth years of medical school. It asserts that, coincident with the emphasis on faculty research and publication and expanded resident patient care duties, teaching, particularly medical student teaching, has assumed a very low priority. Third-year medical students are attached to surgical teams, where their education is haphazard and disorganized. Furthermore, because any teaching that occurs is teacher oriented rather than student centered, knowledge is accumulated passively and is not well retained. Traditional evaluation using shelf multiple choice examinations and ward ratings by residents and faculty may provide inaccurate assessments of the students' performance. The undergraduate surgical education program should be directed by a faculty member who has been grounded in educational techniques and research and supported by a department chairman committed to bettering the program. In the clerkship, medical students should be assigned to faculty rather than to services and should be presented problems that require solution. Students also should be provided with the resources to solve the problems and should be given sufficient time to solve them. Some operating room experience and bedside teaching should occur during the clerkship. A variety of evaluation and testing methods based on the learning objectives of the clerkship should be used. Third-year students should not be promoted until they have demonstrated their acquisition of appropriate knowledge and skills.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of recombinant human growth hormone in patients with severe sepsis.

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.


Pancreatic exocrine and endocrine function after operations for chronic pancreatitis.

Exocrine and endocrine function of the pancreas was assessed in the early postoperative period (< or = 2 months) and subsequently (mean, 25 months; range, 3 to 120) in 103 patients (69 men, 34 women; mean age, 42.4 +/- 11.6 years) undergoing operation for chronic pancreatitis. Alcohol was the main causative agent (69%) and pain the most frequent indication (87%) for operation. Drainage procedures (n = 23) did not alter pancreatic function either initially or on long-term follow-up. In the early postoperative period, distal pancreatectomy (n = 42) often impaired endocrine function without affecting exocrine function; seven patients (17%) became diabetic, and results of oral glucose tolerance test showed deterioration in 23 of 28 patients (82%, p < 0.05). On subsequent follow-up, 11 patients developed exocrine failure (p < 0.01) and 10 patients endocrine (p < 0.01) failure. Proximal pancreatectomy (n = 38) precipitated clinical exocrine failure in 14 patients (37%, p < 0.01), yet pancreolauryl tests in 18 patients showed little objective change in exocrine status (0.50 > p > 0.10). Endocrine function was initially spared after proximal pancreatectomy, but six additional patients (16%, p < 0.05) required treatment for diabetes at a mean of 19 months (range, 3 to 34). Deterioration in pancreatic function is thus not an invariable immediate consequence of pancreatic drainage procedures or partial pancreatectomy for chronic pancreatitis. Progression of disease must account, in part, for failure of both exocrine and endocrine function on long-term follow-up. Drainage operations appear to delay this progressive decline in pancreatic function.


Conversion of exocrine secretions from bladder to enteric drainage in recipients of whole pancreaticoduodenal transplants.

Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas recipients, however, have lost graft function (follow-up, 10 to 36 months). The only pancreas allograft loss was in an SPK recipient who also rejected the kidney 6 months after conversion. She received a second SPK transplant with enteric drainage, and is insulin independent and normoglycemic 10 months after retransplantation. Patients converted for metabolic acidosis tended to have impaired renal function (mean creatinine, 2.14 +/- 0.98 mg/dL at time of conversion) due to chronic rejection, progression of native kidney diabetic nephropathy, or cyclosporine toxicity, and possibly could not compensate for bicarbonate loss from the pancreas allograft.(ABSTRACT TRUNCATED AT 400 WORDS)


Enucleation of giant hemangiomas of the liver. Technical and pathologic aspects of a neglected procedure.

Cavernous hemangiomas are the most common benign tumors of the liver. Giant cavernous hemangiomas, defined as those larger than 4 cm in diameter, can reach enormous proportions. Newer imaging modalities, although often demonstrating characteristic features that strongly suggest the diagnosis, should not be augmented by biopsy because of the risk of hemorrhage. Elective surgical resection may be indicated for symptomatic giant lesions and for those with an atypical appearance where the diagnosis is in doubt. Between October 1986 and May 1991, we treated 10 patients with giant hemangiomas by enucleation or enucleation plus resection. Median operative blood loss was 800 mL (range, 200 to 3000 mL). One patient required reoperation for control of postoperative hemorrhage. Detailed pathologic examination has demonstrated an interface between hemangiomas and the normal liver tissue that allows enucleation. Enucleation is an underused procedure that if carefully performed allows resection of giant hemangiomas with a reduced blood loss and the preservation of virtually all normal hepatic parenchyma.


Collagen types I and III propeptides as markers of healing in chronic leg ulcers. A noninvasive method for the determination of procollagen propeptides in wound fluid--influence of growth hormone.

A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.


Surgical aspects of subungual malignant melanomas. The Scottish Melanoma Group.

The incidence, treatment, and survival of subungual malignant melanomas in Scotland is reviewed from the Scottish Melanoma Group database. Between 1979 and 1989, 100 cases of subungual melanoma were identified (2.8% of all malignant melanomas in Scotland). The tumors tended to be locally advanced at the time of presentation (mean Breslow depth, 4.7 mm +/- 3.0 mm), and this is reflected in an overall 5-year survival of 41%. There was no difference in the survival of patients treated with local/proximal interphalangeal (PIP) joint amputation compared with those having more proximal amputations. Because nearly 70% of these tumors arose on the thumb or hallux, it is concluded that, provided adequate clearance could be obtained, less radical excision should be performed for these lesions to maintain maximum function.


Management of groin hernias in patients with ascites.

The records of 18 cirrhotic patients with ascites and groin hernias (20 inguinal and one femoral) were retrospectively reviewed. Eleven patients underwent repair of their groin hernias (total of 13 repairs). Ten herniorrhaphies were performed electively, two were performed urgently because of recent difficult reduction, and one was performed emergently for incarceration without strangulation. No major and four minor postoperative complications occurred. There were no perioperative deaths or ascites leaks. Of the 13 hernias in 11 patients undergoing repair, 12 (92%) were available for follow-up. In this group, the 12 groin hernia repairs were followed for a mean of 25 months. One recurrence (8%) occurred 11 months after repair. In this same group of patients, five umbilical hernias were repaired, with three recurrences (60%). From this retrospective study, it appears that serious complications from groin hernias in cirrhotics are not common, and elective repair can usually await control of ascites. Additionally, for appropriately selected patients with ascites, elective inguinal hernia repair can be performed safely, with an acceptable rate of recurrence.


Laparoscopic colectomy.

Fifty-one laparoscopic colectomies were attempted at two institutions. The clinical results and methods are presented. Seven cases (14%) were converted to facilitated procedures, and four cases (8%) were converted to "open." Cases of cancer, diverticulitis, endometriosis, regional enteritis, villous adenomas, and sessile polyps were operated. Right, transverse, left, low anterior, and abdominoperineal colectomies were performed. Colotomies and wedge resections were also performed. Laparoscopic suturing was required in five cases of incomplete anastomosis by circular stapler (18%). Suturing was required in all right, transverse colectomies and colotomies. Operative time averaged 2.3 hours. Hospitalization averaged 4.6 days. Four patients had complications (8%), and one 95-year-old died of pneumonia (2%). Laparoscopic colectomies can be performed safely, but require two-handed laparoscopic coordination, as well as suturing and knot-tying skills.


Synthesis of biologically active [2.2]paracyclophanes.

Claisen reaction of 4-acetyl[2.2]paracyclophane (1) with ethyl acetate and diethyl oxalate affords 4-acetoacetyl[2.2]paracyclophane (2) and ethyl (4-oxaloacetyl[2.2]paracyclophane) (6), respectively. Reaction of 2 and 6 with hydrazines and CuCl2 gave the pyrazole derivatives 4 and 8 in addition to the metal complexes 5 and 9. Mannich reaction of 2 with benzylamine and paraformaldehyde yielded the piperidinone derivative 3. The biological activity of all new compounds was tested.


Psychological and ergonomic aspects of work with video display terminals.

Forty-nine operators of video display terminals were administered a questionnaire on subjective complaints in connection with work conditions. Measurements of non-ionizing and ionizing radiation emissions during normal operation of video display terminals showed them to be within permissible levels. A detailed ergonomic analysis of equipment and workstations was also performed. Results showed a high occurrence of subjective complaints, significant differences between age subgroups in a few variables, and significant correlation between sets of variables of some perceived ergonomic features and subjective complaints.


[Interindividual differences in tolerance to shift work and characteristics of shift workers: relation between the quality and duration of sleep and certain worker characteristics].

The investigation aimed at examining the relationship between the quality and duration of sleep on the one hand and various shift workers' characteristics on the other, as well as establishing whether sleep characteristics were congruent with some other indices of night shift tolerance. A total of 604 rotating shift workers working in a fast rotating shift system were administered a battery of questionnaires. The results showed that sleep quality was related to their many characteristics, especially to neuroticism, rigidity of sleeping habits, flexibility of habits, and relaxedness. Actually, the shift workers' characteristics accounted for a notable percentage (48%) of interindividual differences in sleep quality. However, there were fewer traits related to sleep duration than to sleep quality so that only a small percentage of interindividual differences in sleep duration could be explained (12-30%). Sleep quality proved to be a good indicator of night shift tolerance. The results concerning sleep duration indicated only sleep duration on the afternoon shift and days off, as well as average sleep duration in the complete shift cycle, to be relatively good indices of night shift tolerance.


[Monitoring of respiratory function in hemp-processing workers].

In a follow-up study the prevalence of chronic respiratory symptoms and changes in ventilatory capacity were followed over a period of three years in 38 female and 28 male hemp workers in a textile industry. The prevalence of all respiratory symptoms was found to be increased. Significant acute reductions of ventilatory capacity were recorded during the work shift. The measured ventilatory capacity values were significantly decreased in comparison to predicted normal values. The mean annual decline of FVC (range: 0.014-0.065 L), FEV1 (range: 0.041-0.068 L), FEF50 (range: 0.020-0.220 L/s) and FEF25 (range: 0.030-0.140 L/s) was considerably greater than in healthy non-exposed subjects. The mean annual decline of all tests was considerably larger in workers with the symptoms of byssinosis than in those without such symptoms. Our data suggest that long-term exposure to hemp dust may cause the development of chronic respiratory symptoms and impairment of ventilatory capacity.


Contact allergy and psoriasis.

The study was conducted over a two-year period and included 48 psoriatic patients with palmar and plantar lesions and 61 psoriatic patients without palmar and plantar lesions who served as controls. The objective was to establish the incidence of contact sensitization and its importance as the causative factor in palmar and plantar psoriasis. The most frequent contact allergens were: nickel sulphate, mercapto mix, balsam of Peru, potassium dichromate, mercury mix and fragrance mix. Patch tests were positive in 41.7% psoriatics with palmar-plantar psoriasis and in only 6.6% of psoriatics without palmar-plantar involvement. The study showed an increased incidence of contact allergy in patients with palmar-plantar psoriasis.


Cervicobrachial syndrome--work and disability.

The subjects in the study were 114 persons receiving a disability pension or referred for disability assessment. They were placed in two groups of 57 persons each, one with marked cervicobrachial syndrome and the other without. The latter group was chosen by the method of equivalent pairs with regard to sex and age. All subjects underwent a clinical examination and a standardized questionnaire was completed. The questionnaire pertained to the state of health, focussing on the amount and type of physical burdening at the workplace and on activities outside the workplace. Sixty-five percent of the subjects were aged from 51 to 60 years. A statistically significant difference was established between earlier occupation and cervicobrachial syndrome. Cervicobrachial syndrome was found in 31.6% of unskilled workers and 12.3% of the controls (P < 0.05). A forced body posture during work was recorded in 74% of the subjects with the syndrome and in 50% of the control subjects (P < 0.05). Repetitive movements at work were reported by a large number of subjects with cervicobrachial syndrome (71.9:49.1%; P < 0.05) who also claimed to strain the arms (84.2:61.4%; P < 0.05) and burden the cervical spine (68.5:40.4%; P < 0.05) during household activities to a significantly greater extent than the controls. A possible preventive approach to the occurrence and progression of cervicobrachial syndrome is discussed.


[Evaluation of ventilatory function of the small airways].

The results of functional tests and the values of flow-volume and spirometric parameters were reevaluated in 1174 randomly selected patients with no evidence of heart disease. There were 533 patients with normal ventilation and 327 patients with no restrictive disorders. In the latter group 11% of the patients had normal FEV1 and lowered FEF50 and FEF75 values. In those patients obstructive changes would not have been found if expiratory flow rates had not been taken into account as one of the criteria for evaluating airway obstruction. In further 13% of the patients a mild airway obstruction would have been found had only FEV1 been evaluated without taking account of expiratory flow rates. It is concluded that expiratory flow rates along with anamnestic data and clinical status are important indicators of obstructive changes of ventilation, especially as they serve to identify functional disorders while these are still reversible and therapy can be useful.


[Early detection of the toxic effects of benzene on the hematopoietic system--the imperative of modern occupational medicine].

Surveillance of workers exposed to benzene calls for a complex approach. This includes the determination of benzene concentration in the working atmosphere, which, according to standards applied in Croatia, should not exceed 15 ppm. In the developed countries the allowable workplace level has been reduced to 1 ppm. The monitoring of benzene metabolites in the organism of exposed workers is also necessary. As an indicator of benzene exposure, the urinary phenol concentration determined before and after work in the middle of the week has been generally accepted in Croatia. An essential laboratory test is a complete blood count including red cell indices. Other haematological tests that might be valuable early indicators of benzene haematotoxicity need to be more fully evaluated. Alterations in any of these indicators are not pathognomonic and all findings should therefore be interpreted at the same time and with caution. Early detection of benzene haematotoxicity can be accomplished by continuous health monitoring of exposed workers through preplacement and periodic health examinations. This is in accordance with the principles of modern occupational medicine which requires identification of early changes and prevention of irreversible benzene induced toxic changes in the haematopoietic system.


[Work-related diseases].

The different causal factors of work and work environment which contribute to the development of work-related diseases are discussed. The diseases such as locomotor disorders, chronic non-specific respiratory diseases, arterial hypertension, disorders connected with psychosocial factors and the use of video display terminals are separately analysed. Special emphasis is placed on the importance of epidemiological and clinical approach in the prevention and control of work-related diseases with regard to the different causal factors. Criteria for diagnosis of work-related diseases are suggested to serve as basis for preparation of the List of work-related diseases.


Effect of tooth temperature on activities of slowly adapting periodontal mechanoreceptors in the cat.

The mass response of a nerve bundle and the unitary discharges from a functional single nerve fibre evoked by mechanical stimulation of the upper canine tooth were recorded from the superior alveolar nerves of 10 anaesthetized cats. When the pulpal cavity of the mechanically stimulated tooth was perfused with a 0.9% NaCl solution at temperatures from 10 to 45 degrees C, the mass response of the nerve bundle to that stimulation increased linearly with the rise in perfusate temperature (hereafter, tooth temperature). In the unitary discharge recordings, the activities of 30 (88%) of 34 slowly adapting periodontal mechanosensitive units were modulated by tooth temperature. The optimal temperature, at which the periodontal mechanoreceptor shows extreme excitation by mechanical tooth stimulation, was distributed widely from 10 to < or = 45 degrees C with a peak at < or = 45 degrees C. A shift in tooth temperature away from the optimal value caused a decrease in, or sometimes the disappearance of, the response. This decrease was the result of the decrease in the excitability of the periodontal mechanoreceptor; i.e. an increase in threshold stimulus intensity and a shortening of the adaptation time to sustained pressure applied to the tooth.


Histochemical characterization of masseter muscle fibres in a biopsy study of normal young women.

Muscle fibres from biopsies of the anterior part of the masseter muscle (pars superficialis) were histochemically characterized in 13 healthy female students. They were 21-28 yr old with a full complement of teeth, and normal facial and occlusal relations. Before surgery, normal masseter muscle function was demonstrated by bite-force measurements and recordings of electromyographic activity. After staining for myosin ATPase activity, the relative mean areas of muscle fibres were: type I 82.9%, type IM 9.5% and type II 8.3%. The intraindividual (18-155% of mean) and interindividual (0-216% of mean) variation of the fibre size was large. The type I fibres had the largest diameter (10-80 microns, mean: 39 microns), the type II fibres (6-47 microns, mean: 21 microns) and the IM fibres (8-54 microns, mean: 28 microns) the smallest. The biopsy technique and the histochemical characterization will be suitable for reference in women with functional changes or diseases of the masseter muscle.


Associations among different orofacial dysfunctions in 6-8 year olds.

Associations among several orofacial dysfunctions such as articulatory speech disorders, craniomandibular disorders (CMD) and problems in coordinating the orofacial muscles were examined in two groups of Finnish first-graders, i.e. children with and without speech disorders. In the whole sample of 287 subjects the mean age was 7.5 yr. A speech therapist diagnosed articulatory speech disorders and a phoniatrician examined the morphology and function of the articulators. Signs and symptoms of CMD, capacity for mandibular movement, and prevalence of occlusal interferences were examined by a dentist. Deviations in motor skills, but not in morphology of the articulators, were associated with speech disorders. The findings also suggested that capacity for mandibular movement, deviation of the jaw during maximal mouth opening and occlusal interferences were related to certain speech disorders among these 6-8 yr olds. Different orofacial dysfunctions appear to be associated with each other during growth.


pH responses to sucrose and the formation of pH gradients in thick 'artificial mouth' microcosm plaques.

Artificial microcosm plaques were grown in a five-plaque culture system for up to 6 weeks, reaching a maximum depth of several mm. Procedures for long-term pH measurement with glass electrodes were established; they showed that the application of 5 or 10% sucrose for 6 min with a slow continuous flow of a basal medium containing mucin (BMM) generated the pH changes characteristic of in vivo Stephan curves. These pH responses were reproducible between plaques. Plaque mass and thickness were critical variables. Successive, sucrose-induced pH curves in plaques up to 4 mm thickness showed minor reductions only in the amplitude and rates of pH change. In plaques over 4 mm thick there was a pronounced reduction in pH response to successive sucrose applications, indicating increased diffusion limitations--a result of plaque growth to seal in the freshly-inserted pH electrode. In plaques of 6 mm maximum thickness, 10% sucrose induced a decrease to below pH 5.5 lasting 24 h, compared to the pH response in 2 mm thick plaque, which returned to the resting pH in 2 h. Differences in pH of up to 0.9 units were identified in thick plaques between inner and outer layers. The BMM flow rate was a critical determinant of the amplitude of the pH response to sucrose and subsequent return to resting pH. These results confirm, for microcosm plaque, the importance of clearance dynamics and diffusion-limited gradients in regulating plaque pH.


A study in 47,XYY men of the expression of sex-chromosome anomalies in dental occlusion.

Occlusal traits were determined for 47,XYY men and compared with previous determinations of occlusal morphology in other sex-chromosome anomalies and in normal women and men. The 47,XYY men, like 47,XXY men, tended to have a mesial molar occlusion and a mandibular overjet more often than did other groups, while 45,X women (Turner patients) clearly had the highest frequency of distal occlusion and large overjet. The 47,XXY men had the highest frequency of most occlusal anomalies. As a whole, these and earlier findings suggest that the number of X or Y chromosomes is associated negatively with distal occlusion and lateral crossbite, whereas a positive association was found with mesial molar occlusion and scissors bite.


Fluoride uptake in hard tissues of fetal guinea pigs in response to various dose regimens.

This study was designed to explore various aspects of maternal-fetal fluoride metabolism. In its first phase, 57 female guinea pigs were bred and randomly assigned to a control group (I) or one of three experimental groups: (II) 3 parts/10(6) fluoride in drinking water, (III) a single daily oral dose and (IV) 3 parts/10(6) fluoride in water and a single daily oral fluoride dose. The total mean doses received by groups II and III were similar. The total mean dose received by group IV was approximately double that for groups II and III. Samples of maternal plasma, and fetal bone and enamel were collected on the 57th day of gestation. In its second phase, 53 pregnant guinea pigs were given drinking water containing 0, 2, 4, 6 or 8 parts/10(6) fluoride during gestation. On the 57th day of gestation samples of maternal and fetal enamel were collected. All samples in both phases of the study were assayed for fluoride using the microdiffusion, ion-selective electrode method. In the first part of the study, mean fetal enamel fluoride by group was: I, 21.6 parts/10(6); II, 38.6 parts/10(6); III, 33.5 parts/10(6); IV, 54.9 parts/10(6). In the second phase, maternal enamel was linearly related to the fluoride dose. The same was true for fetal enamel except at the 8 parts/10(6) fluoride level in the water where there was no increase over the 6 parts/10(6) group. At all dose levels, fetal enamel fluoride uptake was approximately an order of magnitude less than maternal enamel fluoride uptake.(ABSTRACT TRUNCATED AT 250 WORDS)


Interleukin-1: the principal osteolytic cytokine produced by keratocysts.

Fragments of keratocysts removed at operation were maintained in explant culture and the media were assayed for the biological activity of the potent osteolytic cytokines--interleukin (IL)-1, interleukin (IL)-6 and tumour necrosis factor (TNF). Media were also assayed for their ability to stimulate bone resorption. All six cysts examined released IL-1 and IL-6 bioactivity but TNF bioactivity was unmeasurable. Dialysed cyst media stimulated bone resorption and this could be completely inhibited by a monospecific antibody which neutralized IL-1 alpha and IL-1 beta. Immunohistochemical staining of cryostat sections of keratocysts revealed the presence of IL-1 alpha and IL-6 in cyst epithelial cells but not in other cell types. Sections did not react with antibodies to IL-1 beta or TNF. It is therefore proposed that IL-1 alpha is the major osteolytic cytokine produced by keratocysts and that IL-6 and IL-1 may contribute to keratocyst growth by promoting epithelial cell proliferation and bone resorption, respectively.


The distribution of the antimicrobial protein, calprotectin, in normal oral keratinocytes.

Calprotectin is a heterodimeric peptide isolated from neutrophil cytosol that exhibits profound antimicrobial effects. Using monoclonal antibody MAC 387, calprotectin was found to be expressed in oral keratinocytes from normal, non-inflamed oral mucosa. Orthokeratinized sites including the attached gingiva and hard palate expressed low levels of calprotectin with a restricted pattern; immunoreactants were identified only within subcorneal keratinocytes. Parakeratinized mucosa from the lips, soft palate, tongue and buccal mucosa expressed calprotectin in a more widespread, yet variable pattern, immunoreactants being detectable in only a portion of the spinous layer in some cases whereas in others the pattern of expression was more topographically diffuse. Antigen was not detected in basilar and lower strata cells. Both cytoplasmic and nuclear decoration could be identified. The results indicate that oral mucosa harbours an antimicrobial deterrent to micro-organisms that may enhance the physical epithelial barrier of host defence.


The validity of the masseteric post-stimulus electromyographic complex: a twin study.

The twin model was used to assess the validity of an electromyographically recorded, masseter muscle reflex by measuring the sensitivity and specificity. Results were satisfying, implying that in future studies this reflex could be used to calculate heritability estimates between monozygotic and dizygotic twins.


Effects of lipid-lowering diets enriched with monounsaturated and polyunsaturated fatty acids on serum lipoprotein composition in patients with hyperlipoproteinaemia.

Controlled comparisons of the effects of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) as a part of lipid-lowering diets in persons with hyperlipoproteinaemia are sparse. The present study was carried out at a metabolic ward. Forty hyperlipidaemic patients (25 hypercholesterolaemic and 15 hypertriglyceridaemic) were given a 3-week diet rich in either MUFA (saturated fatty acids 7.3 energy% (E%), MUFA 14.6 E%, PUFA 4.8 E%) or PUFA (saturated fatty acids 7.8 E%, MUFA 8.4 E%, PUFA 10.4 E%), but otherwise with an identical composition. The mean serum cholesterol reduction on the MUFA diet was 12% (P < 0.001), with a low density lipoprotein cholesterol reduction of 11% (P < 0.001). The corresponding reductions on the PUFA diet were 15% (P < 0.001) and 16% (P < 0.001). The serum apolipoprotein B and A-I concentrations decreased highly significantly by 13% and 11% on the MUFA diet and by 14% and 11% on the PUFA diet. None of these changes differed between the two diets. Neither were there any differences between the diets regarding the effects on blood glucose, serum insulin and plasma fibrinogen, but there was a significant decrease in serum insulin with a significant reduction of the insulin/glucose ratio after the MUFA diet. The results of this study indicate that MUFA and PUFA are interchangeable within the given frames in lipid lowering diets even in patients with hyperlipidaemia.


Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.


Effect of a novel series of macrocyclic hypolipidemic agents on plasma lipid and lipoprotein levels of four non-primate species.

The ansamycins are structurally novel hypolipidemic agents derived from rifampicin, but lacking antibacterial activity. Oral or intravenous administration resulted in rapid lowering of plasma cholesterol in rats, hamsters, guinea pigs and dogs. In the chow-fed rat, three related compounds (CGP 43371, CGS 23810 and CGS 24565) exhibited ED50 values of 13.7, 3.1 and 0.18 mg/kg, respectively. A feature common to the lipid lowering documented in these four species was the concomitant reduction of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. In the chow-fed rat, however, apolipoprotein AI (apo AI) levels were much less affected than were those of HDL cholesterol. CGP 43371 at 3 and 10 mg/kg, lowered HDL cholesterol by 20% and 39%, respectively, whereas plasma apo AI was reduced by only 1% and 12%. Similarly, in lipoprotein fractions separated by ultracentrifugation, apo AI was unchanged in the d = 1.019-1.21 g/ml fraction after treatment with 3 or 10 mg/kg of CGP 43371, but HDL cholesterol was reduced 12% and 26% in this fraction at the two dose levels. Plasma and lipoprotein apo B levels, on the other hand, were reduced to a level equivalent to that of the reduction in cholesterol. The ansamycins thus represent a new structural series which may possess a novel mechanism of action as well, involving differential effects on HDL cholesterol and protein.


The influence of dietary olive oil and margarine on aortic cholesterol accumulation in cholesterol-fed rabbits maintained at similar plasma cholesterol level.

The present study compares the atherogenicity of a standard diet and diets with 10% olive oil or 10% margarine added, in rabbits maintained at a mean plasma cholesterol level of about 20 mM for 13 weeks. Each group consisted of 15 animals. The distribution of cholesterol in plasma between VLDL, IDL, LDL and HDL was similar in the 3 groups. The thoracic aortic cholesterol accumulation was 16.6 +/- 1.6, 11.4 +/- 1.0 (P < 0.05) and 12.6 +/- 1.7 (P > 0.05) nmol/mg wet weight for the group receiving standard diet, diet with 10% olive oil added and diet with 10% margarine added, respectively. There was no significant difference between groups in the occurrence of the atherosclerotic changes in the proximal and distal parts of coronary arteries, abdominal aorta and renal arteries. The occurrence of atherosclerotic changes in the pulmonary arteries was equal in the groups receiving standard diet and diet with 10% margarine added while it was significantly lower (P < 0.05) in the group receiving diet with 10% olive oil added. The atherosclerotic changes at the aortic orifice of coronary arteries were quanticated morphometrically and were most severe in the group on the standard diet. The results indicate a comparable atherogenic effect of 10% olive oil or margarine addition to standard diet on development of atherosclerosis in rabbits maintained at a similar plasma cholesterol level. The study also suggests that supplementation of olive oil or margarine to standard rabbit diet leads to lower cholesterol accumulation in the thoracic aorta compared with standard diet, an effect not modulated by changes in plasma cholesterol concentrations.


Effect of vitamin E on acute iron load-potentiated aggregation, secretion, calcium uptake and thromboxane biosynthesis in rat platelets.

In the present study performed on rats, we investigated the influence of an in vivo acute iron load on several platelet parameters and their modification after vitamin E supplementation. Iron load was achieved by injecting iron dextran corresponding to 0.1 mg Fe3+ per kg in the gluteus muscles. Control rats were injected with an equal amount of a dextran solution. Analyses were performed 18 h after injection. By comparison with controls, in iron-injected animals, we found significant increases of: (1) serum total iron (by 110%); (2) aggregation of isolated platelets induced by low concentration of thrombin and ADP (by 350% and 120%, respectively); (3) thrombin-induced endogenous serotonin secretion (by 94%). We also studied the mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids. The results indicated that the thrombin-stimulated release of arachidonate and formation of cyclooxygenase and lipoxygenase products (particularly thromboxane B2), were significantly increased. We also found in plasma an increase (by 67%) of malondialdehyde (MDA) as well as a decrease of vitamin E (by 60%). When vitamin E was injected the day before iron injection, platelet hyperactivity and thromboxane biosynthesis were reduced as well as the plasma MDA concentration. Consequently, given the key role of calcium flux in the activation processes in platelets, we also investigated the thrombin-induced Ca2+ uptake by means of radiocalcium. We found that in platelets from iron-treated rats the Ca2+ uptake amounted to 3670 +/- 201 pmol/10(9) platelets (plt) and was significantly different from controls (1680 +/- 192 pmol/10(9) plt, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


EDTA reduces liver cholesterol content in cholesterol-fed rabbits.

A study conducted in 1953 by one of the authors (H.S.M. Uhl) reported that orally administered ethylenediamine tetraacetic acid (EDTA) both prevented the accumulation of cholesterol in the liver of cholesterol-fed rabbits and caused the removal of accumulated cholesterol from the liver. These observations were made in rabbits fed high concentrations of cholesterol and have never been confirmed in the literature. The purpose of the present study was to determine if this original observation could be confirmed using lower amounts of dietary cholesterol and more modern and comprehensive methods for analysis of tissue lipids and plasma lipoproteins. New Zealand White rabbits were fed diets containing 0.1% cholesterol with or without EDTA (3 g/day). After 16 weeks, significantly lower concentrations of hepatic cholesterol were found in rabbits fed EDTA (6.95 mg/g wet weight) compared with controls fed the same cholesterol-containing diet without EDTA (16.6 mg/g wet weight). Plasma cholesterol levels in both groups of animals were not significantly different from one another; therefore, the effect of EDTA in reducing liver cholesterol accumulation was independent of changes in plasma cholesterol concentrations. Although the mechanism of this EDTA effect is unknown, it may provide a tool to gain further insight into mechanisms of regulation of hepatic lipoprotein and cholesterol metabolism.


Phenotype related changes of intimal smooth muscle cells from human aorta in primary culture.

To study the functional characteristics of smooth muscle cell (SMC) phenotypes, we have investigated myosin expression, cell proliferation, collagen production and low-density lipoprotein (LDL) receptor activity in intimal SMCs of normal human aorta during their growth in primary culture. By staining with rabbit antibodies to smooth muscle myosin (ASMM) 3 cell types could be distinguished in culture: homogeneously stained cells, cells with discontinuous myosin fibrils and myosin-negative cells. The ratio of cell types greatly changed with culture growth: on days 5, 7 and 14 it was 82:1:17%, 70:5:25% and 10:30:60%, respectively. After 5-6 days of culture intimal SMCs began to proliferate and DNA-synthesizing nuclei were seen 1.5-4.3 times more frequently in myosin-negative cells than in cells with homogeneous myosin distribution. At that time the number of cells reacted with monoclonal antibody (MAb) to an epitope shared collagen types I and III started to increase. By double immunofluorescence staining it was shown that the cultured cells containing both ASMM and MAb markers were found 2.0-4.8 times more rarely than MAb-positive staining in myosin-negative cells. During the first 5 days in culture LDL binding and uptake were diminished in intimal cells with intercellular lipid inclusions independently of their myosin staining pattern, but their activity increased with culture growth. Thus, SMCs from human aortic intima change their phenotype on days 6 and 7 in primary culture as manifested by alteration of myosin expression, increased cell proliferation, collagen production and LDL receptor activity. Changes in myosin expression, however, are not an essential prerequisite for cell proliferation and collagen production.