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Biomedical subjects

S Nasser

Publications and source records attributed to S Nasser.

At least 19 recordsLinked to original sources

Antibiotic allergy in cystic fibrosis.

Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30-50%). There is a low risk of cross reactions between penicillins and other non-beta-lactam classes of antibiotics in penicillin skin prick positive patients. Carbapenems should only be used with extreme caution in patients with positive skin prick tests to penicillin. However, aztreonam can be used safely in patients who are penicillin allergic with positive skin prick reactions. The aminoglycosides are a relatively uncommon cause of allergic reactions, but patients who react to one member of the family may cross react with other aminoglycosides. Desensitisation relies on the incremental introduction of small quantities of the allergen and has been used for penicillins, ceftazidime, tobramycin and ciprofloxacin and must be repeated before each course. Personalized cards should be regularly updated for patients who develop allergic reactions. Written instructions on the emergency treatment of allergic reactions should be provided to patients self-administering intravenous antibiotics at home. Further research is required to identify risk factors and predictors for antibiotic allergy.

Anti-Bacterial Agents↗

A SAGE (serial analysis of gene expression) view of breast tumor progression.

To identify molecular alterations involved in the initiation and progression of breast carcinomas, we analyzed the global gene expression profiles of normal mammary epithelial cells and in situ, invasive, and metastatic breast carcinomas using serial analysis of gene expression (SAGE). We identified sets of genes expressed only or most abundantly in a specific stage of breast tumorigenesis or in a certain subtype of tumors through the pair-wise comparison and by hierarchical clustering analysis of these eight SAGE libraries (two/stage). On the basis of these comparisons, we made the following observations: Normal mammary epithelial cells showed the most distinct and least variable gene expression profiles. Many of the genes highly expressed in normal mammary epithelium and lost in carcinomas encoded secreted proteins, cytokines, and chemokines, implicating abnormal paracrine and autocrine signaling in the initiation of breast tumorigenesis. Very few genes were universally up-regulated in all tumors regardless of their stage and histological grade, indicating a high degree of diversity at the molecular level that likely reflects the clinical heterogeneity characteristic of breast carcinomas. Tumors of different histology type and stage had very distinct gene expression patterns. No genes seemed to be specific for metastatic or for in situ carcinomas. We found that the most dramatic and consistent phenotypic change occurred at the normal-to-in situ carcinoma transition. This observation, combined with the fact that many of the genes involved encode secreted, cell-nonautonomous factors, implies that the normal epithelium-to-in situ carcinoma transition may be the most promising target for cancer prevention and treatment.

Adult↗

Odour discrimination in the olfactory bulb of goldfish: contrasting interactions between mitral cells and ruffed cells.

Anatomical differences characterizing mitral cells and ruffed cells have been published by T. Kosaka and K. Hama in three teleost species. Physiological responses from both types of relay neurons were recorded extracellularly and simultaneously in the plexiform layer, using a single tungsten microelectrode. During interstimulus intervals mitral cells responded with higher, frequently burst-like impulse rates triggered by the activity of epithelial receptor neurons. Mitral cell activity could be totally suppressed by local anaesthesia of the olfactory epithelium. Ruffed cell impulse rates were low, and each action potential triggered a long-lasting (3-5 ms), continuously varying, summed granule cell potential. During olfactory stimulation with non-familiar stimuli and important biological stimuli such as amino acids, preovulatory and ovulatory pheromones, and a probable alarm pheromone, contrasting interactions between mitral cells and ruffed cells were recorded frequently, which resulted in a drastic intensification of centrally transmitted information. An excitation of mitral cells' activity via granule cells laterally inhibited the ruffed cells' activity, and an inhibition of mitral cells' activity simultaneously 'released' an excitation of ruffed cells.

Animals↗

Pheromone discrimination ability of olfactory bulb mitral and ruffed cells in the goldfish (Carassius auratus).

Significant anatomical differences characterizing mitral cells and ruffed cells were published by Kosaka and Hama in three teleost species. Physiological responses from both types of relay neurons have now been recorded extracellularly and simultaneously in the plexiform layer using a single tungsten microelectrode. During interstimulus intervals mitral cells responded with higher, frequently burst-like impulse rates triggered by the activity of epithelial receptor neurons. Ruffed cell impulse rates were low, and each action potential triggered a long-lasting, continuously variable, integrated granule cell potential. During olfactory stimulation with important biological stimuli such as preovulatory and ovulatory pheromones, a probable alarm pheromone and amino acids contrasting interactions between mitral cells and ruffed cells resulting in a drastic intensification of centrally transmitted information were frequently recorded. Individual neurons excellently discriminated stimuli. Irrespective of the physiological relevance of stimuli, however, similarities were recorded in the distribution of excitatory, inhibitory and indifferent responses.

Animals↗

Egyptian medical women, past and present.

In ancient Egypt, at least one woman carried the title of physician. University education for women started in 1930. Today, women are practicing in all disciplines and are effective in health care. Egyptian medical women represent 35% to 45% of the staff of faculties of medicine and about one-third of all medical graduates. They have contributed to the improvement of health, particularly in maternal and child health, and are role models for young girls in rural areas.

Egypt↗

Experimental acute hematogenous osteomyelitis in mice. I. Histopathological and immunological findings.

This study investigated immunological responses to Staphylococcus aureus bone infection. Because considerable immunological information is available on the mouse, a murine model of acute hematogenous osteomyelitis was established. Osteomyelitis was created in the proximal tibia of C3H/HeJ mice by a tibial epiphyseal fracture followed by intravenous bacterial inoculation with Staphylococcus aureus (strain LS-1). Swelling and warmth of the limb was found, and following limb exposure, abscess formation was evident in the proximal tibia. Histological examination revealed distortion primarily at the hypertrophic zone of the physis and polymorphonuclear leukocyte infiltration throughout the damaged area of the proximal tibia. Local infection was demonstrated at the fracture site, evidenced by the recovery of Staphylococcus aureus following microbiological analysis of tissue specimens. Polymerase chain reaction was utilized to detect 16S ribosomal prokaryotic nucleic acid to demonstrate that the diagnosis of osteomyelitis could be established in the absence of conventional microbiological techniques. The infected mice had an increase of circulating large leukocytes (granulocytes) and an elevation of total serum immunoglobulin. Flow cytometry revealed significant increases in splenic B lymphocytes and in lymph-node CD4+ T lymphocytes. These results indicate that an experimental model of acute hematogenous osteomyelitis that closely resembles the pathology of the disease in humans may be consistently induced in mice. Furthermore, marked immunological changes may be observed in response to the Staphylococcus aureus bone infection.

Acute Disease↗

Inexpensive methods of repairing cortical defects in cemented total joint replacement.

Inexpensive methods to augment cement pressurization in the face of cortical defects are presented. The first two methods involve the use of disposable plastic syringes and the foil packaging from suture material. The third uses screws that were removed with hardware. The techniques prevent cement extrusion from the cortical defects with minimal stripping of the remaining soft tissues. Methods for using foil packaging to form templates for accurate production of well-fitting cortical inlay grafts and the use of plastic wire ties as temporary fixation devices are also described.

Arthroplasty, Replacement, Hip↗

Proteins bound to polyethylene components in patients who have aseptic loosening after total joint arthroplasty. A preliminary report.

BACKGROUND: Immunological responses to proteins that adhere to ultra-high molecular weight polyethylene have not, to our knowledge, been examined previously in patients who have aseptic loosening. In the current study, polyethylene components from forty-nine failed prostheses recovered during revision procedures were examined for the presence of antibodies that were bound to the polyethylene surface or that were reactive with other proteins that were bound to the polyethylene surface. METHODS: The polyethylene components consisted of thirty acetabular cups recovered during revision total hip arthroplasties and nineteen tibial components recovered during revision total knee arthroplasties. After extensive washing, bound proteins were extracted from the polyethylene components with use of 0.1-molar glycine-hydrogen chloride solution followed by four-molar guanidine hydrochloride solution. RESULTS: Sufficient protein for analysis was recovered from forty-two polyethylene components. Polyacrylamide gel electrophoresis demonstrated a minimum of one and a maximum of twelve protein bands, with molecular weights ranging from thirteen to 231 kilodaltons. Immunoblotting revealed the presence of type-I collagen in most (thirty-four) of the forty-two explants, whereas aggrecan proteoglycans were detected in eight samples. Immunoglobulin also was detected in most (thirty-three) extracts, whereas type-II collagen was consistently absent. The presence of autologous antibodies directed against polyethylene-bound proteins in sera drawn at the time of the revision was investigated. Antibodies that were reactive against the ultra-high molecular weight polyethylene-bound proteins were detected in twenty-six of the forty-two patients with use of the Western blot technique. The number of reactive bands ranged from one to six, and the strongest binding was directed against a 103-kilodalton protein. Assays for specificity revealed that these sera autologous antibodies were reactive against the type-I collagen that was present in the explant solutions. CONCLUSIONS: We hypothesize that immunoglobulin complexed with polyethylene may fix complement and that the complement cascade may in turn attract inflammatory cells to the polyethylene surface. Our data support the hypothesis that an immunological response to antigens bound to the polyethylene surface may contribute to aseptic loosening. CLINICAL RELEVANCE: Despite improvements in materials and designs of prostheses, aseptic loosening is the most common complication of total joint replacement, frequently leading to revision operations. We examined the immunological response to proteins that bind to ultra-high molecular weight polyethylene in patients who had aseptic loosening and discovered a high prevalence of antibodies to polyethylene-bound proteins. This immunological response may contribute to an inflammatory reaction in the periprosthetic tissue, ultimately leading to increased bone resorption around the prosthesis.

Antigen-Antibody Complex↗

Pristane-induced arthritis in mice. V. Susceptibility to pristane-induced arthritis is determined by the genetic regulation of the T cell repertoire.

OBJECTIVE: Pristane-induced arthritis (PIA) is an experimental seropositive arthritis that is characterized by serologic and cellular immune abnormalities and is dependent on the presence of a competent CD4+ T cell population. We examined the regulation of PIA by genes of the major histocompatibility complex (MHC) and the Mls-1 loci to determine whether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility. METHODS: Genetic regulation of PIA was investigated using F1 hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor Vbeta phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcription-polymerase chain reaction techniques. RESULTS: F1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-1 loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1a mice, where T cells expressing the Vbeta8.1 and Vbeta6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed toward Vbeta8.1 and Vbeta6 compared with the population observed in lymph nodes from either PIA or normal control DBA/1 mice. CONCLUSION: The data support the hypothesis that PIA is a T cell-mediated disease. While pristane causes a polyclonal T cell expansion that gives rise to lymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with the capacity to infiltrate synovial joints.

Alleles↗

Long-term effectiveness of translational manipulation for adhesive capsulitis.

Long term effects of glenohumeral joint translational (gliding) manipulation on range of motion, pain, and function in patients with adhesive capsulitis were studied. Thirty-one patients underwent brachial plexus block followed by translational manipulation of the glenohumeral joint. Changes in range of motion and pain were assessed before manipulation with the patient under anesthesia, immediately after manipulation with the patient still under anesthesia, at early followup (5.3 +/- 3.2 weeks), and at long term followup (14.4 +/- 7.3 months). Passive range of motion increased significantly for flexion, abduction, external rotation, and internal rotation. Significant decreases in visual analog pain scores between initial evaluation and the followup assessments also occurred. Furthermore, Wolfgang's criteria score increased significantly between initial evaluation and followup assessments. Translational manipulation provides a safe, effective treatment option for adhesive capsulitis.

Arthralgia↗

Direct-exchange arthroplasty for the treatment of infection after total hip replacement. An average ten-year follow-up.

Twenty consecutive patients who had a direct-exchange total hip arthroplasty, performed by one surgeon between October 1979 and July 1990, were prospectively followed and data were collected. The most common infecting organism was Staphylococcus epidermidis (nine patients), followed by Streptococcus species and Staphylococcus aureus (five patients each). Three patients (15 per cent) had a draining sinus tract at the time of the operation. The operation and the postoperative management included meticulous débridement, administration of appropriate systemic antibiotic therapy, and use of antibiotic-loaded cement. By an average of 9.9 years (range, 3.5 to 17.1 years) postoperatively, no patient had had recurrence of the infection. Two patients had a revision for aseptic loosening nine and seventeen years after the direct exchange. Although the present series is relatively small, our experience has shown that direct exchange, which is associated with less morbidity and is less expensive than delayed exchange, can be successful in carefully selected patients.

Adult↗

Cellular immune responses to orthopaedic implant materials following cemented total joint replacement.

In vitro cellular immune responses to metallic and polymeric implant materials in particulate form were measured preoperatively in 185 patients. The patients were candidates for either primary total joint replacement (n = 65) or revision arthroplasty (n = 120). Proliferative cellular responses to polymethylmethacrylate particles in patients with osteoarthritis at revision surgery for aseptic loosening were significantly higher than the responses of patients with osteoarthritis at either primary surgery or surgical revision for mechanical failure of the prosthesis or sepsis. The responses to particles of cobalt-chromium alloy at revision surgery were also higher than the responses at primary surgery. The responses were reevaluated in 32 patients after a minimum of 10 months following surgery to correlate individual changes in the biological responses with clinical progress. Reevaluation at early follow-up of patients who had undergone primary surgery revealed significantly elevated proliferative responses and in vitro cytokine production in response to polymethylmethacrylate and cobalt-chromium alloy particles compared with their preoperative responses. In contrast, the response at follow-up to polymethylmethacrylate was significantly reduced in patients who had undergone revision surgery, and this reduction corresponded with a marked improvement in pain, joint motion, and function following revision surgery. These data suggest that specific cellular responses to polymethylmethacrylate or cobalt-chromium alloy particles, or both, may be associated with loose or painful prostheses.

Arthroplasty, Replacement↗

Total joint arthroplasty and the immune response.

Total joint replacement arthroplasty has proved highly successful in the management of osteoarthritis and rheumatoid arthritis. The cause of aseptic loosening of prosthetic joint replacement components is unclear. Early experience with total joint arthroplasty was plagued by a number of problems that no longer exist as major impediments to long-term success. Improvement in the operating room environment and the use of prophylactic antibiotics have substantially reduced the high incidence of infection to less than 1%. Implant materials have long been considered biologically inert, but recent studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Currently, particulate debris from cement or polyethylene causing loosening of the prosthesis is the major problem in total joint arthroplasty. Significant data suggest a progression from a simple inflammatory reaction to complex immune responses against the biomaterials. The cellular responses to particles of polymethylmethacrylate, ultra-high-molecular-weight polyethylene, and alloys of cobalt-chromium and titanium have been assayed in vitro in patients with osteoarthritis, rheumatoid arthritis, and avascular necrosis who had total joint replacement. Elevated immunologic cell proliferation responses to both acrylic and cobalt chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.

Arthritis, Rheumatoid↗

The immune response to implant materials in humans.

The etiology of aseptic loosening of prosthetic joint replacement components is unclear. Implant materials have been considered biologically inert, but recently studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Data suggesting a progression from a simple inflammatory reaction to complex immune responses against the biomaterials are reviewed. The cellular responses to particles of polymethylmethacrylate, ultrahigh molecular weight polyethylene, and alloys of cobalt-chromium and titanium were assayed in vitro to determine cell proliferation in patients with underlying diagnoses of osteoarthrosis, rheumatoid arthritis, and avascular necrosis who had joint replacement. Control populations were provided by patients with similar diagnoses who were preoperative surgical candidates. The underlying diagnoses did not seem to influence responses to particle stimulation. Elevated responses to both acrylic and cobalt-chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.

Biocompatible Materials↗