Biomedical subjects

Sadik Khuder

Publications and source records attributed to Sadik Khuder.

13 recordsLinked to original sources

PubMed2006

Predicting AIDS-related events using CD4 percentage or CD4 absolute counts.

BACKGROUND: The extent of immunosuppression and the probability of developing an AIDS-related complication in HIV-infected people is usually measured by the absolute number of CD4 positive T-cells. The percentage of CD4 positive cells is a more easily measured and less variable number. We analyzed sequential CD4 and CD8 numbers, percentages and ratios in 218 of our HIV infected patients to determine the most reliable predictor of an AIDS-related event. RESULTS: The CD4 percentage was an unsurpassed predictor of the occurrence of AIDS-related events when all subsets of patients are considered. The CD4 absolute count was the next most reliable, followed by the ratio of CD4/CD8 percentages. The value of CD4 percentage over the CD4 absolute count was seen even after the introduction of highly effective HIV therapy. CONCLUSION: The CD4 percentage is unsurpassed as a parameter for predicting the onset of HIV-related diseases. The extra time and expense of measuring the CD4 absolute count may be unnecessary.

Journal Article↗

PubMed2006

Analysis of the young and elderly variable gene repertoire in response to pneumococcal polysaccharides using a reconstituted SCID mouse model.

Significant changes in anti-pneumococcal polysaccharide (PPS) variable gene usage occur with aging and may be influenced by changes in cytokine environment. Severe combined immunodeficient (SCID) mice were engrafted with B cells obtained from young and elderly donors, supplemented with human cytokines and immunized with the pneumococcal polysaccharide vaccine. B cells specific for PPS serotypes 4 and 14 were isolated from mice and immunized donors, and variable region sequences analyzed. Significant differences in variable heavy and light chain gene usage were observed between young and elderly adults despite a more constant cytokine environment. Due to the limitations of the hu-PBL-SCID model, the use of alternative systems would be beneficial in the elucidation of mechanisms underlying the reduced vaccine efficacy in the elderly.

Adult↗

PubMed2006

Comparison of the human immune response to conjugate and polysaccharide pneumococcal vaccination using a reconstituted SCID mouse model.

The pneumococcal conjugate vaccine (CV), although highly immunogenic in infants and young children, does not consistently demonstrate an advantage over the pneumococcal polysaccharide vaccine (PPV) in older adults. To further elucidate the adult immune response to CV, we compared its response to PPV on a molecular level using a severe combined immunodeficient (SCID) mouse model. This model allowed us to analyze a single individual's response to two different forms of antigen and define differences in gene usage elicited by these vaccines. We reconstituted SCID mice with human lymphocytes derived from an unimmunized donor; the mice were divided into two groups and immunized with either the PPV or CV. Our results demonstrate significant differences in variable gene usage in SCID mice immunized with PPV versus CV and suggest that the nature of the immunizing agent has a significant impact on gene usage and therefore influences antibody function and vaccine efficacy.

Adult↗

PubMed2005

Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults. I. Antibody concentrations, avidity and functional activity.

Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS) 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA) absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS), or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age) were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides.

Journal Article↗

PubMed2005

Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults: analysis of the variable heavy chain repertoire.

Streptococcus pneumoniae is a leading cause of morbidity and mortality in both developed and developing countries. The current pneumococcal polysaccharide (PPS) vaccine is highly effective in young adults; however, vaccine efficacy is dramatically decreased in the elderly population. We hypothesized that the decreased vaccine efficacy in the elderly results from altered variable gene family usage. We have characterized the immunoglobulin G gene usage of the antibody response to PPS4 and PPS14 in 20 young and 20 elderly adults. The variable heavy (V(H)) gene repertoire of human peripheral B cells was amplified by using PCR. A total of 364 heavy chain sequences with specificity for PPS4 and 305 heavy chain sequences for PPS14 were analyzed from young adults. In addition, a total of 325 sequences for PPS4 and 291 sequences for PPS14 were obtained from elderly adults. Complete sequence identity, somatic mutation frequencies, and V(H) gene usage was determined in response to PPS4 and PPS14. In all volunteers, the immune response to both polysaccharides consisted predominantly of heavy chains belonging to the V(H)3 gene family. There were significant differences in the variable gene repertoire between young and elderly adults. Somatic mutation occurred more frequently in sequences derived from young compared to elderly derived sequences. With aging, a loss of oligoclonality was noted in response to PPS4 and PPS14 compared to young adults. The observed differences in V(H) repertoire, somatic mutation, and loss of oligoclonality may contribute to decreased vaccine efficacy in the elderly.

Adult↗

PubMed2005

Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults: analysis of the variable light chain repertoire.

Streptococcus pneumoniae is a human bacterial pathogen responsible for serious infections including pneumonia. The currently licensed polysaccharide vaccine provides 60 to 80% protection in young adults, but in the elderly the vaccine efficacy is drastically reduced despite normal antibody levels. We hypothesized that the reduced vaccine efficacy in the elderly results from altered variable gene family usage. We have analyzed the light chain gene usage in 20 young (20 to 30 years of age) and 20 elderly (65 to 86 years of age) adults in response to pneumococcal polysaccharide 4 (PPS4) and PPS14. We generated a variable light chain library using B cells specific for PPS4 and PPS14 from each vaccinated individual. We determined complete sequences and somatic mutation frequencies in all isolated variable light chain fragments. Six gene families, kappa1, kappa2, kappa3, kappa4, lambda1, and lambda3, were identified in response to PPS4 and PPS14 in both age groups. Comparison of young and elderly adults demonstrated significant differences in kappa4, lambda1, and lambda3 gene usage in response to PPS4 and PPS14. With aging, there was a significant increase in kappa4 gene usage and a significant decrease in lambda1 and lambda3 gene usage in response to both PPS4 and PPS14. Although both Vkappa1 and Vlambda3 gene products demonstrated extensive mutations, there was no age-related difference in mutational frequency per gene family. These findings suggest an age-related change in light chain gene usage in response to PPS4 and PPS14.

Adult↗

PubMed2005

Comparing Rasch analyses probability estimates to sensitivity, specificity and likelihood ratios when examining the utility of medical diagnostic tests.

INTRODUCTION: Medical diagnostic tests are evaluated based on measures of sensitivity (Sn), specificity (Sp), and likelihood ratios (LR). These procedures are limited in the event of a biased gold standard or missing data. Interpretations of these measures are frequently inappropriate. PURPOSE: The Rasch measurement model (RMM) was examined as a method to provide evidence of diagnostic test utility in order to overcome the limitations of Sn, Sp, and LR. METHODS: Patients suspected of a knee ligament tear (n = 825) were studied, by evaluating four diagnostic tests. The RMM probability estimates for each test were compared to estimates of Sn, Sp, and LR. RESULTS: The RMM provided probability estimates for the diagnosis that were comparable to likelihood ratios. These probability estimates correlated with the estimates of Sn, Sp, and LR. The RMM estimates were not affected by missing data. DISCUSSION: The RMM may provide an alternative means to study the utility of medical diagnostic tests to estimate the probability of disease presence/absence.

Anterior Cruciate Ligament Injuries↗

PubMed2003

Elective management of the clinically negative neck by otolaryngologists in patients with oral tongue cancer.

BACKGROUND: The treatment of patients with squamous cell carcinoma of the head and neck who have a clinically negative (cN0) neck remains controversial. Furthermore, the treatment delivered to patients with a cN0 neck by practicing otolaryngologists is not known. OBJECTIVE: To determine the variability in the management of the cN0 neck in the otolaryngology community. DESIGN, SETTING, AND PARTICIPANTS: A random survey of 763 board-certified otolaryngologists in the United States. MAIN OUTCOME MEASURES: Physician respondents' preferences for observation vs treatment of the cN0 neck and the treatment modalities chosen. RESULTS: Forty-one percent of the surveyed physicians responded. Nearly 10% of the respondents observed all patients with a cN0 neck. Otolaryngologists who treat 35 or more new patients with cancer each year were more likely to perform elective treatment of the neck for a T2 lesion of the oral tongue than those who treat 10 or fewer patients each year (P =.03). They were also more likely to treat patients with a cN0 neck when the risk of occult cervical metastases was greater than 15% to 20% (P =.04). A comprehensive neck dissection was the preferred lymphadenectomy procedure for 21% of the otolaryngologists surveyed. CONCLUSIONS: Variations in the treatment of the cN0 neck are associated with differences in the frequency of treatment of patients with head and neck cancer by otolaryngologists. Uniformity of care must be established within the otolaryngology community by developing widely accepted evidence-based guidelines and referring patients to surgeons who routinely treat head and neck cancer.

Adult↗

PubMed2003

HIV/AIDS knowledge among female migrant farm workers in the midwest.

The rate of HIV infection in the migrant farm worker community is 10 times the national average. A survey was conducted of 106 female migrant farm workers in rural Northwest Ohio to assess HIV knowledge. The average participant's age was 28.7 years, 78 spoke Spanish, and 47 had an < or =8th- grade education. Fifty-six women received their information on HIV/AIDS from television. Eighty-seven women identified sexual contact as the major source of HIV transmission and 54 women identified the combination of sex, use of needles, and blood contact as the important routes. Sixty-nine women identified both homosexual and heterosexual intercourse as risk factors. Only 58 women identified perinatal infection as a route of HIV transmission and 59 women knew that treatment was available to prevent perinatal transmission. Although the majority of women had a good general knowledge of HIV transmission, further prevention education on perinatal transmission is needed among this population.

Adolescent↗

PubMed2003

A survey of herbal product use in a dialysis population in Northwest Ohio.

OBJECTIVE: To identify herbal product use in a dialysis population. DESIGN AND SETTING: Cross-sectional survey conducted at 2 freestanding dialysis centers in Northwest Ohio. PATIENTS: Two hundred and sixteen hemodialysis and peritoneal dialysis patients who provided informed consent. INTERVENTION: All patients were surveyed by personal interview regarding use of herbal products. Patients identified as current users were asked questions about specific agents. Respondents reporting past but not current use were questioned about specific agents and reasons for discontinuation. RESULTS: Thirty-one patients reported taking herbal therapies. Twenty-six patients discontinued use before the survey. Sixteen different herbal products were reported being used in our study population. Those who reported ever using an herbal product were more likely to be employed or disabled and have higher education when compared with nonusers. CONCLUSION: Our data suggest a lower frequency of herbal product use in the dialysis population as compared with the general population and other chronically ill populations. Education and employment are factors associated with use. Many of the herbal therapies used potentially could have significant adverse effects in dialysis patients. These include effects on blood pressure, blood glucose, coagulation parameters, and electrolyte disturbances. Dialysis patients currently taking herbal products may not be reevaluating their need for continuation and may not be informing members of the nephrology care team about their use.

Cross-Sectional Studies↗

PubMed2003

Survey of physician attitudes toward HIV testing in pregnant women in Ohio.

HIV infection among women of childbearing age is still increasing in the United States. In most states, HIV testing of women or neonates during pregnancy is not mandatory. The current study assessed HIV prenatal testing practices among obstetrician-gynecologists and primary care physicians listed in a regional physician referral data base in a predominantly rural region. Between December 2000 and March 2001 a 20-question survey was sent by mail to regional physicians in obstetrics/gynecology and primary care regarding physician practice demographics and prenatal HIV testing practices. Of 1116 surveys sent, 431 were returned (38.6% response). Only 42% of physicians offered universal HIV prenatal testing. Factors associated with universal testing (p < 0.5) included obstetrics/gynecology as the practice specialty (90%) physicians' age younger than 50 years, and a practice with predominantly Medicaid or African American patients. Further educational and public health initiatives may be needed to increase nonselective, universal HIV testing in pregnant women.

Adult↗

PubMed2002

Physician specialty is associated with differences in the evaluation and management of acute bacterial rhinosinusitis.

BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a common illness that is routinely managed by physicians from several different specialties. However, the actual diagnostic and treatment preferences of physicians from these different specialties are not known. OBJECTIVE: To determine whether the radiographic evaluation and management of community-acquired ABRS differs according to medical specialty. DESIGN, SETTING, AND PARTICIPANTS: Randomized survey of 450 board-certified physicians in the United States from family medicine, general internal medicine, and otolaryngology. MAIN OUTCOME MEASURES: Responding physicians' use of diagnostic radiography as well as choice and duration of antimicrobial and adjunctive treatments of ABRS. RESULTS: Otolaryngologists were more likely to use supportive diagnostic radiography (P =.04). They were also more likely to treat patients with adjunctive therapy, such as topical decongestants (P =.01), guaifenesin (P =.01), and saline nasal irrigation (P =.01), in addition to antibiotics. Otolaryngologists prescribed more medications to treat patients with ABRS than primary care physicians (P =.01). There were no significant differences in diagnosis and management by family physicians and general internists. CONCLUSIONS: Otolaryngologists use more health care resources to diagnose and treat ABRS than primary care physicians despite an absence of evidence that such tests and treatments lead to better outcomes. Otolaryngologists typically treat a patient population with a higher prevalence of ABRS and frequently see referred patients with recurrent acute sinusitis and chronic rhinosinusitis, which may explain their tendency to treat patients more aggressively. Nevertheless, these survey results illustrate a lack of consensus within the medical community regarding the evaluation and management of community-acquired ABRS, suggesting that widely accepted evidence-based practice guidelines need to be developed.

Acute Disease↗

PubMed2002

The effect of dynamic versus isometric resistance training on pain and functioning among adults with osteoarthritis of the knee.

OBJECTIVE: To compare 16 weeks of isometric versus dynamic resistance training versus a control on knee pain and functioning among patients with knee osteoarthritis (OA). DESIGN: Randomized clinical trial. SETTING: Outpatient setting. PARTICIPANTS: A total of 102 volunteer subjects with OA of the knee randomized to isometric (n=32) and dynamic (n=35) resistance training groups or a control (n=35). INTERVENTIONS: Strength exercises for the legs, 3 times weekly for 16 weeks. Dynamic group: exercises across a functional range of motion; isometric: exercises at discrete joint angles. MAIN OUTCOME MEASURES: The time to descend and ascend a flight of 27 stairs and to get down and up off of the floor. Knee pain was assessed immediately after each functional task. The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess perceived pain, stiffness, and functional ability. RESULTS: In the isometric group, time to perform all 4 functional tasks decreased (P<.05) by 16% to 23%. In the dynamic group, time to descend and ascend stairs decreased by 13% to 17%. Both groups decreased knee pain while performing the functional tasks by 28% to 58%. Other measures of pain and functioning were significantly and favorably affected in the training groups. The improvements in the 2 training groups as a result of their respective therapies were not significantly different. The control group did not change over the duration of the study. CONCLUSION: Dynamic or isometric resistance training improves functional ability and reduces knee joint pain of patients with knee OA.

Analysis of Variance↗