The dog-ear rotation flap for the repair of large surgical defects on the head and neck.

BACKGROUND: The Mohs micrographic surgeon is often faced with the daunting challenge of having to repair very large surgical defects on the head and neck where cosmesis and maintenance of normal function are of paramount importance. OBJECTIVE: We describe a novel flap, the dog-ear rotation flap, for the repair of such defects. We will demonstrate that this flap offers superior cosmetic and functional results to many other closure options, particularly for extensive defects of the cheek, temple, forehead and scalp. METHODS: The dog-ear rotation flap is a combination repair. It is executed by first closing one end of the surgical defect in a primary side-to-side-fashion, to a point at which tension across the wound precludes any further closure. A rotation flap is then developed to close the remaining defect, using tissue from the large dog-ear created at the distal end of the wound. RESULTS: In our experience, the dog-ear rotation flap is able to close substantial head and neck defects with less tension across the wound edges when compared to other closure types, resulting in diminished scarring and little to no distortion of surrounding anatomic structures. It also provides an excellent tissue match, is relatively quick and easy to perform, and has an extremely low incidence of flap necrosis. CONCLUSIONS: The dog-ear rotation flap is an excellent choice for the repair of very large surgical defects on the head and neck, particularly the cheek, temple, forehead and scalp, and, in our experience, provides a superior cosmetic and functional result to other closure options.

Standardized neurologic evaluations of 128 patients with Wegener granulomatosis.

OBJECTIVE: To assess the frequency and type of neurologic involvement in a cohort of patients with generalized Wegener granulomatosis (WG). PATIENTS AND METHODS: In a prospective analysis the clinical, electrophysiologic, radiological, and serologic data of 128 patients have been studied over a median observation period of 19 months (range, 1-60 months). RESULTS: Sixty-four patients (50%) revealed central or peripheral nervous system involvement. Peripheral neuropathy (PN) affected 56 patients, in 9 cases the central nervous system was involved, and in 6 cases the cranial nerves were involved. Thirty-one patients showed a distal symmetrical polyneuropathy, 25 a mononeuritis multiplex. Within the first 2 years of the disease course 47 of the 56 patients had developed their PN, sometimes as the initial symptom of WG. Patients with PN were significantly more often male (34 of 65 patients) than female (22 of 63 patients, P =.04), were significantly older at the onset of WG (median age, 53 vs 44 years; P =.001), had a significantly larger disease extent (P =.001), and had higher classic antineutrophil cytoplasmic antibody titers (P =.002) than neurologically unaffected patients. Response to immunosuppression was moderate concerning peripheral nervous system manifestations. CONCLUSIONS: Peripheral neuropathy is frequent in generalized WG, occurring early in the disease course. As PN can be the first and sole symptom of a beginning systemic vasculitis, it is important that in cases of PN of an unclear origin, interdisciplinary investigations are initiated to detect, treat, and closely follow-up a possible underlying WG, especially as these patients seem to have a more severe disease course.

Cerebral and subcutaneous cysticercosis treated with albendazole.

BACKGROUND: Cysticercosis is the most common parasitic disease of the central nervous system in the world, but cysticercosis cutis has been reported much less frequently. Because 54% of patients present with subcutaneous nodules, we report here the association of cysticercosis cutis in a patient with neurocysticercosis and review the literature and treatment options. CASE REPORT: The patient presented with multiple, asymptomatic subcutaneous nodules over the trunk and the extremities, associated with central nervous system involvement. Examination of an excised nodule by light microscopy revealed a larval cyst in the deep dermis surrounded partly by a fibrous pseudocapsule. Computed tomographic scanning af the skull showed multiple, nonenhancing, and calcified cycts in both cerebral hemispheres. Treatment with albendazole, 15 mg/kg/day for 30 days, was highly effective. At follow-up 6 months later, most subcutaneous nodules had disappeared or were markedly reduced in size, and the cerebral lesions had much improved. CONCLUSIONS: Albendazole, a newer paracidal drug, seems to be more effective and less expensive than some other drugs in use for the treatment of neurocysticercosis.

Purification and characterization of transforming growth factor-beta 2.3 and -beta 1.2 heterodimers from bovine bone.

A unique form of transforming growth factor-beta (TGF-beta), TGF-beta 2.3 heterodimer, has been purified from bovine bone extract. TGF-beta 2.3 migrated as a single 25-kDa band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas under reducing conditions it migrated as a 12.5 kDa band. The TGF-beta 2.3 reacted positively with anti-TGF-beta 2 and anti-TGF-beta 3 antibodies on immunoblots. Equal levels of TGF-beta 2 and TGF-beta 3 sequences were detected by N-terminal sequencing. TGF-beta 2.3 eluted as a single sharp peak by reverse-phase high performance liquid chromatography. However, prior reduction of the protein with dithiothreitol resulted in the protein eluting in two peaks, one containing predominantly TGF-beta 3 and the other containing predominantly TGF-beta 2. TGF-beta 2.3 inhibited proliferation of mink lung epithelial cells and promoted the formation of colonies of normal rat kidney fibroblasts in culture with specific biological activity similar to those of TGF-beta 1 and TGF-beta 2. These results demonstrate that the protein is TGF-beta 2.3 heterodimer, consisting of one polypeptide chain each of TGF-beta 2 and TGF-beta 3 linked by one or more disulfide bonds. In addition, TGF-beta 1.2 heterodimer, previously found only in porcine platelets, has also been purified from bovine bone extract.

Study of long-term cultures of simian immunodeficiency virus (SIVmac 251)-infected peripheral blood lymphocytes.

A culture of rhesus monkey peripheral blood lymphocytes was divided into two parts; one was kept as an uninfected control, and the other was infected with a strain of simian immunodeficiency virus (SIVmac251) originally isolated from a rhesus monkey that died of a malignant lymphoma associated with acquired immune deficiency syndrome. Both cultures were sampled at successive intervals from 1 to 40 days postinfection. Each sample was subjected to in situ hybridization for detection of viral mRNA, immunocytochemical detection of viral core protein (p27), reverse transcriptase assay, electron microscopy, and immunophenotypic characterization of infected cells. These techniques were used to define viral growth kinetics of this novel lentivirus in peripheral blood lymphocytes. The first evidence of SIVmac251 replication was obtained by an in situ hybridization signal for viral mRNA at 2 days postinoculation. This was followed by detection of viral p27 core protein by immunocytochemistry on day 4. Reverse transcriptase activity above control values was not detected until day 8. Budding particles were not found in the infected cultures until 14 days postinfection. Results of in situ hybridization, immunocytochemistry, and reverse transcriptase assay indicated that two bursts of viral replication occurred during the course of this study. The first, at 3 weeks postinfection, was due to infection and subsequent depletion of CD4+ lymphocytes, while the second, 3 weeks later, resulted from a cycle of replication in CD8+ lymphocytes and the remaining CD4+ cells, culminating in the death of all cells on day 39 postinoculation.

Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac.

Infection of macaque monkeys with simian immunodeficiency virus (SIV) is probably the best animal model currently available for studying acquired immunodeficiency syndrome. In this report, we describe three infectious molecular clones of SIVmac and one of human immunodeficiency virus type 2 (HIV-2) and their use in the study of cell and species specificity, animal infection, and the relationship of gene sequence to function. Replication of the cloned viruses in different cell lines varied dramatically. Some human CD4+ cell lines (HUT 78 and MT-4) supported the replication of SIVmac and HIV-2, while others (CEM and Jurkat-T) supported the replication of HIV-2 but not SIVmac. Growth of cloned virus in macaque lymphocytes in vitro was predictive of macaque infection in vivo. Macaque lymphocytes supported the replication of SIVmac239 and SIVmac251 but not SIVmac142 or HIV-2ROD. Using virus recovery and antibody response as criteria for infection, macaques that received cloned SIVmac251 and SIVmac239 became infected, while macaques receiving cloned SIVmac142 and HIV-2ROD did not become infected. Nucleotide sequences from the envelope region of all four cloned viruses demonstrated that there is considerable flexibility in the location of the translational termination (stop) signal. These infectious molecular clones will be very useful for future studies directed at the molecular basis for persistence, pathogenicity, tropism, and cell and species specificity.

Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus.

Juvenile rhesus macaques 6 to 18 months of age were experimentally infected by intravenous inoculation with the simian immunodeficiency virus (SIV), the T cell-tropic retrovirus of monkeys related to the human acquired immunodeficiency syndrome (AIDS) virus HIV. The SIV used for inoculation was grown either in normal human peripheral blood lymphocytes in the presence of interleukin 2 or in the human tumour cell line HUT-78. Eight of the macaques died 129 to 352 days post-inoculation with a variety of clinical and pathological findings paralleling those of AIDS in humans. However eight other animals became persistently infected for prolonged periods; these eight macaques remained alive at 537 and 820 days post-inoculation despite persistent lymphadenopathy and our continued ability to isolate SIV. The ability of these monkeys to survive infection correlated directly with the strength of their antibody response to SIV. Infection was also established in macaques using approximately 100 tissue culture infectious doses of HUT-78-grown SIV. There was no correlation between the dose of virus inoculum and either the strength of the antibody response or clinical outcome. These results demonstrate that SIV infection of macaques can be used not only to study acute AIDS but also to mimic the long-term persistent infection seen in carriers of HIV.

Simian models for AIDS.

The macaque immunodeficiency syndrome has many parallels to AIDS in humans. Affected monkeys develop profound, prolonged T lymphocyte dysfunction and die of lymphomas or opportunistic infections. We recently isolated a virus that we call SIV from four sick macaque monkeys. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of human AIDS. The pathogenicity of this newly isolated virus was tested in macaque monkeys. Five of six died between 127 and 352 days following inoculation. The animals developed a wasting syndrome and died with adenovirus pancreatitis and/or pneumonia and primary retroviral encephalitis. Immunological abnormalities in these animals included a decrease in circulating T4+ lymphocytes and depressed peripheral blood lymphocyte proliferative response to pokeweed mitogen. The SIV monkey model holds great promise for testing antiviral agents and for the development of vaccines against AIDS.

Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III.

The T-cell tropic retrovirus of macaque monkeys STLV-III has morphologic, growth, and antigenic properties indicating that it is related to HTLV-III/LAV, the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Four of six rhesus monkeys died within 160 days of STLV-III inoculation with a wasting syndrome, opportunistic infections, a primary retroviral encephalitis, and immunologic abnormalities including a decrease in T4+ peripheral blood lymphocytes. These data show that an immunodeficiency syndrome can be produced experimentally in a nonhuman primate by an agent from the HTLV-III/LAV group of retroviruses. The STLV-III-macaque system will thus provide a useful model for the study of antiviral agents and vaccine development for human AIDS.

Retrovirus D/New England and its relation to Mason-Pfizer monkey virus.

Seventeen isolates of retrovirus D/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was prepared from Hirt supernatants of cells infected with one of these isolates (D/New England 398). By restriction endonuclease analysis, cloned pD398 DNA represented full-length viral DNA with one long terminal repeat. A detailed restriction endonuclease map of pD398 was derived and compared with a map of the cloned Mason-Pfizer monkey virus genome. Forty-six percent (13 of 28) of restriction endonuclease sites were found to be conserved when these related viruses were compared. Five of the D/New England isolates, including those from three different macaque species, were examined for strain variability by restriction endonuclease typing. Comparison of over 30 restriction endonuclease sites has not distinguished any of these D/New England isolates. It thus appears that a single strain of type D retrovirus is infecting three different species of macaques in the New England colony. Markedly reduced cross-hybridization was observed between cloned pD398 and Mason-Pfizer monkey virus DNAs at high stringency; this reduced cross-hybridization was localized to the pol-env regions of the genome. Only very weak hybridization of D/New England DNA to cloned squirrel monkey type D retrovirus DNA could be detected even at low-stringency conditions. What role type D retrovirus plays in the immunodeficiency syndrome of macaques remains to be determined.

Experimental infection of rhesus monkeys with type D retrovirus.

The naturally occurring immunodeficiency syndrome of macaque monkeys is an important animal model for the acquired immunodeficiency syndrome in humans. A new type D retrovirus, distinct from Mason-Pfizer monkey virus, has been isolated from affected animals at the New England Regional Primate Research Center. We now report the results of experimental infection of macaques with retrovirus D/New England after 13 months of study. Inoculated macaques developed lymphadenopathy without follicular hyperplasia, profound neutropenia, and a transient decrease in peripheral blood lymphocyte blastogenic responsiveness. Despite our varying the strain of virus, the manner in which the virus was grown, the size of the inoculum, and the age of the inoculated animals, infected macaques have not developed opportunistic infections or profound, prolonged loss of T cell function, key features of the macaque immunodeficiency syndrome. Therefore, experimental infection of naive macaques with D/New England has not reproduced the naturally occurring macaque immunodeficiency syndrome.