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Biomedical subjects

D Lazarus

Publications and source records attributed to D Lazarus.

At least 19 recordsLinked to original sources
PubMed2000

One-stage immediate breast and nipple-areolar reconstruction with autologous tissue I: a preliminary report.

This preliminary report discusses 7 patients with early breast cancer (mean age, 48 years) who underwent one-stage breast reconstruction. Reconstruction was achieved using a deepithelialized transverse rectus abdominis musculocutaneous (TRAM) flap placed in a pocket created by a skin-sparing mastectomy. Areolar reconstruction is performed by harvesting the areola as a full-thickness graft from the mastectomy specimen, and nipple reconstruction is achieved with a CV flap (in zone II of the TRAM flap), which is deepithelialized and covered with a full-thickness graft from the areola. In all patients a contralateral reduction or mastopexy was performed. Recent evidence suggests that not all patients with early breast cancer have areolar involvement, and that certain prognostic factors can be used to predict the likelihood of tumor involvement. A number of large studies have shown that in patients with early breast cancer, when the tumor is situated more than 5 cm from the nipple-areolar complex, tumor involvement of the nipple-areolar complex is most unlikely. No patients in this study had histological evidence of nipple involvement by cancer. The aesthetic results were very satisfactory in 5 of 7 patients. One patient who developed sepsis of the TRAM flap had an unsatisfactory result. The other complications that occurred were minor and self-limiting. The advantages of single-stage breast reconstruction are financial and psychological. In addition, the patient attains homogenous nipple-areolar reconstruction. Areolar reconstruction is achieved with the best possible option--areola. This preliminary report suggests that in a select group of patients with early breast cancer, when the tumor is more than 5 cm from the nipple-areolar complex, the areola may be preserved. The aesthetic results in these patients was considered satisfactory. However, long-term studies are required to confirm the oncological safety of this technique.

Adult↗
PubMed2000

The use of serial tissue expansion in pediatric plastic surgery.

There are clinical situations in which even despite the use of simultaneous multiple tissue expanders, complete coverage of a defect cannot be achieved. In this situation, serial, repeated tissue expansion may be indicated. There are few studies that have reported repeated tissue expansion in pediatric plastic surgery. Twelve children (6 girls, 6 boys) with a mean age of 7 years underwent serial tissue expansion for giant hairy nevus (N = 3) or burn reconstruction (N = 9). A total of 63 tissue expanders were used. Serial expansion of the expanded flap was performed a second time in 12 children, a third time in 6 children, and a fourth time in 2 children. The major complication rate was 4% for the first expansion, and 20%, 18%, and 0% for the second, third, and fourth expansions respectively. Clinically, at the time of expander reinsertion, there was no evidence of capsule from the previous expander in any patient. This was confirmed on histological examination of 12 biopsy specimens. Repeated tissue expansion is a safe and effective procedure for use in pediatric plastic surgery.

Burns↗
PubMed1998

Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis.

The transcription factor NF-kappaB activates a number of genes whose protein products are proinflammatory. In quiescent cells, NF-kappaB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IkappaB is degraded by the ubiquitin-proteasome pathway. Consequently, inhibition of the proteasome suppresses activation of NF-kappaB. This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect. To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed. The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin-proteasome pathway. PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-kappaB and the subsequent transcription of genes that are regulated by NF-kappaB. Significantly, PS-341 displayed similar effects in vivo. Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats. The attenuation of inflammation in this model was associated with an inhibition of IkappaBalpha degradation and NF-kappaB-dependent gene expression. These experiments clearly demonstrate that the ubiquitin-proteasome pathway and NF-kappaB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect.

Animals↗
PubMed1997

Fatal rhabdomyolysis in a flame burn patient.

Rhabdomyolysis due to flame burns is not well described. A case of fatal rhabdomyolysis in an epileptic patient who sustained 65 per cent body surface area, very deep, flame burns is described. It appears as if the sustained muscle compression from the restrictive, circumferential eschar was the major factor in the aetiology of the rhabdomyolysis. Despite aggressive fluid management, the patient died of acute renal failure and adult respiratory distress syndrome. We have subsequently identified three other cases of pigmenturia occurring following burns. It would seem as if rhabdomyolysis following extensive full thickness burns may be more common than previously suggested. Fluid requirements are in excess of those proposed by traditional protocols. Rhabdomyolysis in flame burn patients indicates a poor prognosis.

Accidents, Home↗
PubMed1997

Cancrum oris--a 35-year retrospective study.

OBJECTIVES: To determine the factors predisposing to cancrum oris and its frequency, clinical features, treatment and outcome. Cancrum oris is a gangrenous condition of the face usually occurring in poorly nourished children in a Third-World setting. DESIGN: Retrospective review of clinical data on children with cancrum oris. SETTING: All children with cancrum oris seen over a 35-year period, from 1960 to 1995, at Red Cross War Memorial Children's Hospital (RXH) in Cape Town. SUBJECTS: Twenty-six patients (16 female and 10 male) with cancrum oris. Their average age at presentation was 4 years and 4 months (range 1-15 years). RESULTS: The peak incidence was between 1971 and 1975 (11 cases); subsequently only 1 new case was seen at RXH in every 5-year period. Most children were referred from rural areas. Associated conditions could only be determined in 11 of the 26 patients. In order of frequency, these were malnutrition, gastro-enteritis, measles and anaemia. Twenty-three of the 26 children had soft-tissue involvement affecting the lips, cheek, chin, nose or other structures. Eighteen had bony or cartilaginous involvement; the maxilla was affected in 15, the palate in 7, the vomer in 5, the mandible in 3 and the nasal septum in 7. Three children had bony involvement only, the soft tissues being spared. Operative records were available for 18 children. These 18 children had a total of 84 operations, with an average of 4.7 per child (range 0-12). CONCLUSIONS: Cancrum oris is a devastating condition affecting malnourished children. Reconstruction is complex and demanding, involving both soft tissue (23 of 26 cases) and bone (18 of 26 cases). Most children require multiple procedures. Prevention is best effected by comprehensive primary health care.

Adolescent↗
PubMed1994

Relative quantification of angiotensin-converting enzyme mRNA in human smooth muscle cells, monocytes, and lymphocytes by the polymerase chain reaction.

A method was developed for relative quantification of angiotensin-converting enzyme (ACE) mRNA in as few as 100 cells. After reverse transcription of total RNA to cDNA, multiplexed polymerase chain reaction with two sets of primers amplified ACE cDNA and that of an internal standard glyceraldehyde phosphate dehydrogenase (GAPDH) simultaneously. By adjusting primer pair concentrations, both ACE and GAPDH were amplified with constant efficiencies. Macrophage-like U937 histiocytic lymphoma cells expressed ACE mRNA constitutively. Freshly isolated human monocytes did not express ACE mRNA initially, but after 4 days in culture had 8% of the amount found in U937 cells. After phorbol ester stimulation, monocytes transcribed ACE at levels comparable to U937 cells. Human smooth muscle cells had ninefold more ACE mRNA than 4-day monocytes, but 30% less than U937 cells. In contrast, a mixed population of lymphocytes was devoid of ACE mRNA.

Base Sequence↗
PubMed1991

Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model.

Growth hormone (hGH) has been reported to improve nitrogen balances and accrue lean mass tissue in stable subjects. However, the ability of hGH to positively influence host preservation in stressed catabolic states such as cancer-induced cachexia remains unproven. Thirty-seven sham or tumor implanted Fischer 344 rats were randomized to receive either 0.5 mg/kg/day hGH or saline (SAL) subcutaneously from Days 14 to 23 postimplantation. Plasma levels of hGh and somatomedin C/insulin-like growth factor I (IGF I) as well as IGF I bioactivity were determined at sacrifice. Gastrocnemius muscle protein content was used as a index of host lean tissue mass and the tumor response was evaluated via flow cytometry for analysis of cell-cycle distribution. Host cachexia was not attenuated by hGH as muscle protein content was similar in hGH and saline-treated groups. Despite elevated hGH levels (range, 77-222 ng/ml (GH) vs less than 2 ng/ml (SAL], IGF I levels and bioactivity were not elevated in GH-treated groups. In contrast, cancer-induced anorexia markedly decreased IGF I levels (4 U/ml vs 9 U/ml, NTB; P less than 0.01) and this response remained refractory to hGH administration. While final tumor weights were similar between GH- and SAL-treated groups, hGH treatment caused a twofold increase in the proportion of aneuploid cells (P less than 0.05). In conclusion, hGH failed to attenuate lean mass dissolution in the tumor bearing host and this response may be related to the failure of IGF I induction. Conversely, the altered proportion of tumor aneuploid cells suggests a direct influence on tumor cell-cycling populations.

Animals↗
PubMed1991

Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities.

Dendritic cells are specifically adapted to provide accessory signals for the growth of T lymphocytes. Ia+ dendritic cells are present within the normal lung; however, little is known concerning their regulation in vivo. Interferon-gamma (IFN-gamma) is a proinflammatory lymphokine that augments the expression of Ia antigens and promotes the accessory activities of a variety of cells. In order to determine whether IFN-gamma regulates pulmonary dendritic cells in vivo, Lewis rats were injected intraperitoneally with recombinant murine IFN-gamma (2 x 10(5) U/rat/day) or with buffered saline for 5 consecutive days. Following sacrifice, the lungs were excised, and the distribution and number of Ia (OX-6)+ cells was determined in situ. Dendritic cells were localized in the mucosal lining of the tracheobronchial tree, in pulmonary capillaries, as well as in the alveolar septal interstitium and subjacent to the pleural surfaces. IFN-gamma yielded a specific increase in Ia+ dendritic cells in alveolar septa and in pulmonary airways. Purified Ia+ dendritic cells from enzymatic digests of lung were excellent accessory cells for the proliferative responses of both antigen-primed and naive T lymphocytes. IFN-gamma did not, however, further augment the expression of Ia antigens or the accessory activities of pulmonary dendritic cells. These results suggest that IFN-gamma may promote pulmonary T cell-mediated inflammatory responses in vivo by increasing the number of Ia+ dendritic accessory cells in the lung.

Animals↗
PubMed1990

Anti-RMA: a murine monoclonal antibody that activates rat macrophages. I. Distribution and characterization of the RMA antigen.

Activated macrophages participate in inflammation by eliminating foreign cells, promoting wound healing, and modulating the immune response. A murine monoclonal antibody, designated anti-rat macrophage activator (RMA), was raised against alveolar macrophages (AM) activated with interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA). The RMA antigen is expressed by resident macrophages but not by other cells. Binding to AM by anti-RMA is not competitively inhibited by the murine monoclonal antibodies MRC OX-41, OX-42, and OX-43. Surface membrane expression of RMA antigens is upregulated by lipopolysaccharide, PMA, and tumor necrosis factor-alpha but not by IFN-gamma. Stimulation of AM with anti-RMA yields distinct ultrastructural alterations, as well as de novo protein and DNA synthesis. Immunoprecipitation of [35S]methionine metabolically labeled AM yields a 120 kD protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that is not altered by chemical reduction. We conclude that the RMA antigen is macrophage specific and that binding of anti-RMA to AM promotes functional activities in a subset of these cells.

Animals↗
PubMed1990

Anti-RMA, a murine monoclonal antibody, activates rat macrophages: II. Induction of DNA synthesis and formation of multinucleated giant cells.

Anti-RMA is a murine anti-rat monoclonal antibody that binds to a 120-kD surface membrane antigen expressed primarily by alveolar macrophages. Saline-lavaged alveolar macrophages (AM) formed clusters after incubation with anti-RMA. Anti-RMA produced multinucleated giant cells (MGC) in approximately 15% of adherent AM, and the F (ab')2 fragment of anti-RMA yielded MGC in approximately 9% of AM. The Fab fragment of anti-RMA did not promote MGC formation, nor did the murine anti-rat monoclonal antibodies OX41 and W3/25 (anti-CD4). Although anti-RMA produced a tenfold increase in [3H]thymidine incorporation by AM, it yielded a minimal increase in the number of AM. Autoradiography of AM stimulated with anti-RMA showed heterogeneous labeling of nuclei in MGC, suggesting that 3H-labeled AM may fuse with AM that are not actively synthesizing DNA. These findings suggest that binding of anti-RMA to AM may activate DNA synthesis, and promote clustering and fusion of AM, leading to MGC formation.

Animals↗
PubMed1989

Adoptive immunotherapy with interleukin-2 (IL-2) results in diminished IL-2 production by stimulated peripheral blood lymphocytes.

We examined the responses of peripheral blood lymphocytes (PBL) to a panel of T-cell mitogens in patients receiving adoptive transfers of tumor-infiltrating lymphocytes and continuous infusions of interleukin-2 (IL-2) for treatment of advanced cancer. All patients showed diminished proliferative responses to soluble and alloantigens, lectins, anti-CD3, and IL-2 during therapy. The non-major histocompatibility complex (MHC)-restricted cytolytic activities of PBL were increased by treatment and were further augmented by IL-2 in vitro. The expression of approximately 55-kd low-affinity IL-2 receptors (IL-2R) by PBL increased during treatment but functional IL-2R were simultaneously down-regulated. Proliferative responses were partially restored to pretreatment levels when PBL were costimulated with recombinant IL-2 and mitogens. Lectin stimulation of PBL produced little IL-2 secretion during treatment, while IFN-gamma secretion persisted. We conclude that infusions of IL-2 down-regulate the expression of functional IL-2R, decrease the secretion of IL-2, and lead to decreased mitogen responses by PBL.

Antigens, Surface↗