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Biomedical subjects

R Allen

Publications and source records attributed to R Allen.

At least 55 records · Page 3Linked to original sources

Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma.

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.

Antibodies, Monoclonal↗

Investigation of tuberculosis transmission in Canadian Arctic Inuit communities using DNA fingerprinting.

OBJECTIVE: To understand the transmission of tuberculosis in Inuit communities in the Baffin region of the Canadian Arctic. METHODS: Twenty-one isolates of Mycobacterium tuberculosis from 19 Inuit patients diagnosed with tuberculosis between February 1991 and September 1993 were analyzed by DNA fingerprinting. The DNA fingerprints were achieved by the standard restriction fragment length polymorphism (RFLP) technique, with subsequent probing using the repetitive insertion segment IS6110. RESULTS: The isolates could be divided into three DNA types. The DNA types generally corresponded to the geographic origins of the patients. In most instances only one DNA type of M. tuberculosis was identified in each community. This suggests that a single case was the start of each of the three clusters, most likely due to reactivation. CONCLUSIONS: The results show that molecular typing of M. tuberculosis was useful in determining the mode of transmission of tuberculosis in a remote area of the Canadian Arctic where the disease is endemic. In addition, the information provides useful information for planning interventions in this setting.

Adolescent↗

Characterization of Sm13, a tegumental antigen of Schistosoma mansoni.

Sm13, a 13-kDa Schistosoma mansoni tegumental antigen, is one of the principal polypeptides recognized by antibodies from mice protectively vaccinated with adult-worm tegumental membranes. To obtain the complete gene encoding Sm13 we subcloned and sequenced a cDNA and a fragment of a genomic clone. The collated sequence contains 1,088 nucleotides and represents the full-length open reading frame of the gene, encoding a protein of 104 amino acids with a calculated molecular mass of 11,923 Da, compatible with the native protein identified in the tegumental membranes. The sequence derived from genomic DNA contains a 45-nucleotide intron. The analysis of the predicted protein suggests the presence of both N- and C-terminal hydrophobic membrane-spanning segments, and the coding region contains no homology in the currently available data bases. Additionally, the coding region is preceded by putative CCAAT and TATA boxes that may be involved in the control of expression. Western-blot analysis and indirect immunofluorescence resulted in the identification of a 13-kDa protein (Sm13) in the tegument of adult worms. The present study reveals that Sm13 behaves as an integral membrane protein upon partitioning in Triton X-1 14 and that it is present in worms of 3 weeks or older but not in schistosomula or miracidia. Moreover, it is also specifically recognized by sera from some schistosomiasis patients in enzyme-linked immunosorbent assay and Western-blot analysis, suggesting that it is immunogenic in human schistosomiasis.

Amino Acid Sequence↗

Improved patient outcome after surgical treatment for loculated empyema.

BACKGROUND: Empyemas complicate the hospital course of many patients. Advanced stages of empyema often require surgical intervention. METHODS: A retrospective review of 70 adult patients with empyema, hospitalized between the years of 1992 and 1997, was performed. Data on age, length of stay, comorbidities, diagnostic studies, and treatment was obtained. We compared patient outcome from patients with loculated empyemas who had surgical treatment and those who were managed nonsurgically. RESULTS: Seventy patient records were reviewed, 37 of which were of patients with loculated empyemas. Parapneumonic empyemas comprised 60% of all cases. Chest radiographs, computed tomography scan, and thoracentesis were the most common studies performed in both groups. Thirty-three patients with the radiographic finding of a loculated empyema were treated with either surgical decortication or tube thoracostomy. CONCLUSION: Empyemas at various stages of development require different forms of therapy; advanced empyemas treated early with decortication have a shorter duration of treatment, lower incidence of recurrence and fewer complications.

Adult↗

Molecular cloning and characterisation of a venom allergen AG5-like cDNA from Meloidogyne incognita.

RNA fingerprinting was used to identify RNAs that were expressed in parasitic second-stage juveniles of Meloidogyne incognita, but absent from or reduced in preparasitic second-stage juveniles. A cDNA encoding a putative secretory protein was cloned from a M. incognita second-stage juvenile cDNA library by probing with a 0.5kb fragment derived from fingerprinting that was more strongly expressed in parasitic second-stage juveniles. The cDNA, named Mi-msp-1, contained an open reading frame encoding 231 amino acids, with the first 21 amino acids being a putative secretory signal. In Southern blot analysis the Mi-msp-1 hybridised with genomic DNA from M. incognita, Meloidogyne arenaria, Meloidogyne javanica, but not Meloidogyne hapla, Heterodera glycines or Caenorhabditis elegans. In Northern blot analysis a 1kb transcript was detected in both preparasitic and parasitic second-stage juveniles, but not in adult females of M. incognita. Comparing the predicted amino acid sequence with protein databases revealed significant similarity to the venom allergen antigen 5 family of proteins in hymenoptera insects and homologues found in several other nematode species.

Allergens↗

Use of complementary and alternative medicine among Dominican emergency department patients.

This small, pilot study examined presenting complaint, brief health history, use of complementary and alternative medicine (CAM), and sociodemographic characteristics, among patients attending the emergency department (ED) of a large urban hospital. The sample (n = 50) was primarily Dominican and of low socioeconomic status. Almost half had used CAM for their presenting complaint or another health problem during the past year, most commonly in the form of medicinal plants made into herbal teas. CAM users were more likely to be female, longer-term residents of the United States, and to have also used religious practices for health problems. Subjects who had used CAM for any problem other than the presenting complaint during the past year rated its effectiveness higher than subjects who had used CAM for their presenting complaint. In conclusion, it is likely that a significant proportion of Dominican ED patients use CAM, suggesting that they should be asked about their CAM use during triage.

Adult↗

Author's reply

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Journal Article↗

Body image: gender, ethnic, and age differences.

Using figure drawings (E. Fallon & P. Rozin, 1985), 120 male and female U.S. college students--African American, Hispanic, and Caucasian--indicated their current and ideal figures, the figures that they considered most attractive to the opposite sex, and the opposite-sex figures most attractive to themselves. Dissatisfaction with body shape was greater among the women regardless of ethnicity. Both the men and the women misjudged which shapes the opposite sex would rate as most attractive: The women guessed that the men preferred shapes thinner than those that they actually reported. The African American women had the most accurate perceptions of what the men found attractive, whereas the Caucasian women had the most distorted views. The men guessed that the women preferred shapes bulkier than those that they actually indicated. These findings may be relevant to the lower incidence of eating disorders among African American women and the higher incidence of such disorders among Caucasian women.

Adult↗

Spinal fusion for lumbar instability: does it have a scientific basis?

The validity of spinal fusion for lumbar instability is considered. Some difficulty lies in the interpretation of the term instability. The differing interpretations in the clinical, radiologic, and biomechanical contexts are discussed. These interpretations may only be reconciled if the confusion between hypermobility and instability is removed and some recourse is made to soft tissue integrity. Fusion is considered in the context of the functioning spine as a whole. Although the aim of the surgery is usually to produce a solid arthrodesis, some studies show that this can compromise the functioning of the rest of the spine. Furthermore, there is some evidence that pseudarthrosis itself may not be detrimental. Dynamic imaging offers the potential for improved diagnosis and assessment, but further work is needed to pave the way for better selection criteria and treatment strategies.

Humans↗

Immunoflow cytometry and cell block immunohistochemistry in the FNA diagnosis of lymphoma: a review of 73 consecutive cases.

AIMS: To review the results of 73 consecutive fine needle aspirations (FNAs) that were collected by a pathologist and analysed by immunoflow cytometry. Material for a cell block was also collected from some of these lesions. METHODS: The setting was a large general hospital in rural New Zealand. The FNAs were performed by a pathologist, or a radiologist for image guided localisations. Material for immunoflow cytometry was collected into RPMI and, when required, material for a cell block was collected into formalin. RESULTS: Of the 73 samples collected by FNA nine were inadequate. Light chain restriction could be demonstrated in most FNA samples from B cell lymphomas (28 of 30 adequate samples). The exceptions were two cases of T cell rich B cell lymphoma. Artefactual light chain restriction was seen occasionally in T cell lymphomas, presumably as a result of autoantibodies binding to the cell surfaces. It was possible to subtype most (18 of 30 adequate samples) B cell lymphomas as chronic lymphocytic leukaemia (CLL), follicle centre cell lymphoma (FCCL), or mantle cell lymphoma. The CD4 to CD8 ratio was not usually restricted in T cell lymphomas and coexpression of CD4 and CD8 was not usually found. Loss of pan-T cell antigens was seen in some T cell lymphomas. Four of the six T cell lymphomas and three of the four non-lymphoid malignacies were diagnosed with the aid of cell block immunohistochemistry. Only one of the four cases of Hodgkin's lymphoma showed Reed-Sternberg cells in the FNA smears. CONCLUSIONS: It is not always possible to characterise lymphomas as fully with FNA and immunoflow cytometry as is possible with biopsy histology and a full battery of modern investigations. Nevertheless, in the setting of a large rural general hospital immunoflow cytometry on FNA samples is a highly effective method of diagnosing and typing B cell lymphomas. Immunoflow cytometry is of little use for T cell lymphomas or Hodgkin's lymphomas. We advocate the use of cell block immunohistochemistry in preference to immunoflow cytometry for cases in which the cytological appearance of the specimen is overtly malignant but the differential diagnosis includes non-lymphoid malignancy.

Biopsy, Needle↗

Risk and prevalence of treatable sexually transmitted diseases at a Birmingham substance abuse treatment facility.

OBJECTIVES: We evaluated the prevalence of gonorrhea, chlamydia, trichomoniasis, and syphilis in patients entering residential drug treatment. METHODS: Data on sexual and substance abuse histories were collected. Participants provided specimens for chlamydia and gonorrhea ligase chain reaction testing. Trichomonas vaginalis culture, and syphilis serologic testing. RESULTS: Of 311 patients, crack cocaine use was reported by 67% and multisubstance use was reported by 71%. Sexually transmitted disease (STD) risk behaviors were common. The prevalence of infection was as follows: Chlamydia trachomatis, 2.3%; Neisseria gonorrhoeae, 1.6%; trichomoniasis, 43%; and syphilis, 6%. CONCLUSIONS: STD counseling and screening may be a useful adjunct to inpatient drug treatment.

Adolescent↗

The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review.

A task force consisting of six authors reviewed the published literature on the therapy of the restless legs syndrome or periodic limb movements in sleep available in indices through April, 1998. They selected the 45 articles for detailed review which presented original investigations of therapeutic impact on the restless legs syndrome (RLS) or periodic limb movements (PLM) and which met minimal standards. These articles dealt with a range of pharmacological and other treatment modalities, although most dealt with medications and almost half of those concentrated on dopaminergic agents, especially levodopa in various formulations. Almost half of the articles reviewed used controlled methodologies, most commonly cross-over methodologies with randomized allocation of subjects. Multi-center studies with large numbers of subjects and long-term controlled studies were not found. Information was extracted from the articles and study design, clinical definition, evaluative measures, side effects, and outcomes were tabulated in 6 evidence tables and summarized in the accompanying text. This literature was evaluated for the nature of the studies performed and its coverage of potential therapies. The review concludes with comments on possible future directions for therapeutic investigation based on the current state of the literature.

Diagnosis, Differential↗

Inhibitors of Src-family tyrosine kinases favour Th2 differentiation.

Two potent pyrazolo-pyrimidine inhibitors of Src-family kinases were found to enhance interleukin 4 (IL-4) and reduce interferon gamma(IFN-gamma) production in cultures of splenocytes from ovalbumin-specific TCR-transgenic BALB/c mice. The effect was increased by addition of a monoclonal antibody binding to domains 3/4 of CD4, while other antibodies binding to domain 1 had the opposite effect. The inhibitors suppressed CD40 ligand (CD40L) expression on activated CD4 T cells, which may explain this Th2 differentiating effect. More generally, the effect fits within the overall framework of signal attenuation in T cells driving this form of differentiation. The inhibitors did not revert previously induced Th1 differentiation in serial cultures of the TCR-transgenic cells. Drugs with this activity are of obvious interest as probes and potential therapeutic agents in autoimmune disease.

Animals↗

The effects of venting on in-the-ear, in-the-canal, and completely-in-the-canal hearing aid shell frequency responses: real-ear measures.

The acoustic effects of 1-, 2-, and 3-mm vents were investigated with in-the-ear, in-the-canal, and completely-in-the-canal hearing aid shells. Real-ear sound pressure level measures were obtained from unvented and vented shells with 12 adults. In general, with increasing vent size, a statistically significant (p < .05) increase in the amount of low-frequency reduction, an upward shift in vent cutoff frequencies, and an upward shift in vent-associated resonances occurred for all hearing aid shell styles. There was no significant change in the slope of the low-frequency reduction across all hearing aid shell styles (p > .05), albeit the frequency response curves were shifted upward in frequency with increasing vent diameters. Only with the in-the-ear and completely-in-the-canal hearing aid shells were statistically significant (p < .05) differences found with the magnitude of vent-associated resonance as a function of vent diameter, and these differences were not consistent across the different styles. These findings suggest that venting may be used effectively to tune low-frequency responses in custom in-the-ear hearing instruments.

Adult↗