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Kazim Sheikh

Publications and source records attributed to Kazim Sheikh.

17 recordsLinked to original sources

Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy.

Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute motor axonal form of the post-infectious paralysis, Guillain-Barre syndrome. Development of a disease model in mice has been impeded by the weak immunogenicity of gangliosides and the apparent resistance of GD1a-containing neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with altered ganglioside biosynthesis to generate such a model at motor nerve terminals. First, we bypassed immunological tolerance by immunizing GD1a-deficient, beta-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a ganglioside-mimicking antigens from Campylobacter jejuni and generated high-titer anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposed ex vivo nerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock-out mice to the anti-GD1a mAbs in the presence of a source of complement and investigated morphological and electrophysiological damage. Dense antibody and complement deposits were observed only over presynaptic motor axons, accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function. Perisynaptic Schwann cells and postsynaptic membranes were unaffected. In contrast, normal mice were not only unresponsive to immunization with GD1a but also resistant to neural injury during anti-GD1a Ab exposure, demonstrating the central role of membrane antigen density in modulating both immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated injury. Identical paralyzing effects were observed when testing mouse and human anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via molecular mimicry and are likely to be clinically relevant in injuring peripheral nerve axonal membranes containing sufficiently high levels of GD1a.

Animals↗

Evaluation of quality improvement interventions for reducing adverse outcomes of carotid endarterectomy.

BACKGROUND: Clinical and health services interventions should be evaluated for their effectiveness. OBJECTIVES: The objectives of this study were to evaluate the effectiveness of quality improvement interventions for reducing the adverse outcome of the carotid endarterectomy (CEA) procedure, and to study the relationship between pre- and postintervention 30-day mortality and stroke rates. These interventions were implemented in 1997-1998 by the Peer Review Organizations (PRO) for 7 states. RESEARCH DESIGN: In a quasiexperimental study, a control state was matched with each of the 7 intervention states. Pretest-posttest analyses compared the preintervention outcome rates in each intervention and control state with the corresponding postintervention rates. In a time (1991-2001) series analysis, the trends in the preintervention 30-day, 7-state mortality in intervention and control states were compared with the trends in the corresponding postintervention rates. STUDY POPULATION: We studied Medicare beneficiaries aged 65 years and older who had a CEA procedure in 14 states during 1991-2001. RESULTS: There was no correlation between the state-specific, preintervention 30-day mortality and the corresponding postintervention mortality. After interventions, there was no significant decline in 30-day mortality in any intervention or control state, or in all 7 intervention states combined or all control states combined. Similarly, the 30-day stroke rate did not decrease after interventions in any state. The trend in the 7-state, 30-day mortality also did not show further decline after interventions. CONCLUSION: After PRO interventions, the post-CEA 30-day mortality and stroke rates did not decrease in any individual intervention state or in all states combined.

Aged↗

Sex differences in carotid endarterectomy utilization and 30-day postoperative mortality.

OBJECTIVE: To study trends, and sex and regional differences in utilization of the carotid endarterectomy (CEA) procedure and 30-day postoperative mortality from 1991 to 1999. METHODS: Retrospective analysis of fee-for-service claims and mortality data for Medicare beneficiaries aged 65 years and older in the United States. RESULTS: The male and female CEA rates and 30-day mortality increased with age up to the age of 79 years. From 1991 to 1995, the age-adjusted male and female CEA rates increased 72% from 26.6 and 14.2 procedures per 10,000 beneficiaries. Thereafter, the CEA rates slightly decreased except for the 80 years and older age group, which increased through 1999. In each year from 1991 to 1999, the age-adjusted male CEA rates were approximately 1.9 times higher than the corresponding female rates. From 1991 to 1998, the age-adjusted male and female 30-day mortality decreased 29.3% and 46.4% from 19.2 and 18.1 deaths per 1,000 procedures. From 1992 to 1997, except 1994, 30-day mortality was higher in men than in women. This sex difference was not present in the 65 to 69 years age group. There were small differences in CEA rates between two of the four regions of the United States in 3 of the 9 years. CONCLUSIONS: Increasing CEA rates with decreasing postoperative mortality suggest that CEA may have been more frequently performed on low-risk patients. The apparent sex differences in CEA rates may not be true differences.

Age Distribution↗

Variation and changes in state-specific carotid endarterectomy and 30-day mortality rates, United States, 1991-2000.

OBJECTIVES: The objectives of this study were to investigate variations between states and changes in state-specific carotid endarterectomy (CEA) and 30-day mortality rates. Cross-sectional variations and changes over time in such measures may be indicative of improvement in the quality of care. METHODS: We performed retrospective analyses of pre-existing administrative data on Medicare beneficiaries aged 65 years and older in the United States. Age-adjusted, state-specific CEA rates and 30-day postoperative mortality rates in 1991, 1995 and 2000 were examined, as well as changes in these rates from 1991 to 1995 and from 1995 to 2000. Stroke mortality in the general population of each state was used as a crude measure of the need for CEA procedure in the state. The Spearman rank correlation analysis was used to study correlations between rates. Oldham's method was used to avoid the effect of regression to the mean. RESULTS: There were wide variations in the state-specific CEA rates, 30-day mortality, and in changes in these rates over time. The states with relatively low procedure rates in 1991 also had low rates in 1995 and 2000, and relatively higher increases in the rates. The states with relatively high 30-day mortality in 1991 or 1995 had lower increases or greater decreases in the rate. CEA rates were not correlated with any measure of surgical mortality, but they were correlated with stroke mortality in the general population. CONCLUSIONS: The inter-state variation in CEA rates has not changed much since 1991, but variation in 30-day mortality decreased through 2000. The states with low procedure rates in 1991 did not have sufficient increase to catch up with the high-rate states by 1995, but they were prone to experience a higher increase in the subsequent 5 years. The validity of stroke mortality in a state as a measure of the need for CEA is questionable. Further research using clinical data is needed to better explain variations between states.

Aged↗

Rise and fall of radical prostatectomy rates from 1989 to 1996.

OBJECTIVES: To describe the changes in the rates of radical prostatectomy procedures, prostate-specific antigen (PSA) screening tests among Medicare beneficiaries, and the incidence of prostate cancer in the United States and to explain the exaggerated increase and decrease in the frequency of radical prostatectomy from 1989 to 1996. METHODS: Medicare claims data on radical prostatectomy procedures and screening PSA tests and the National Cancer Institute's Surveillance, Epidemiology, and End Results prostate cancer incidence data were used to estimate the rates of PSA testing and radical prostatectomy among Medicare beneficiaries aged 65 to 74 years and 75 years and older (population rates). The age-specific true rates of the procedure were also estimated for the incident cases of prostate cancer (the population at risk of undergoing radical prostatectomy) among the beneficiaries. RESULTS: The PSA test, prostate cancer incidence, and radical prostatectomy rates increased from 1989 to 1992. Thereafter, the incidence of prostate cancer, and the population and true rates of radical prostatectomy declined. The percentage of increase and decrease in the population rate of radical prostatectomy was approximately twice that in its true rate. CONCLUSIONS: The radical prostatectomy rates based on all Medicare beneficiaries grossly exaggerated the changes in the use of the procedure. Where possible, true rates, using the population at risk as the denominator, should be used in the studies of diagnostic and therapeutic procedures, complications, and adverse effects.

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Campylobacter jejuni from patients with Guillain-Barré syndrome preferentially expresses a GD(1a)-like epitope.

GM(1)- and GD(1a)-like ganglioside mimicry in Campylobacter jejuni lipooligosaccharide (LOS) is considered to be involved in the pathogenesis of Campylobacter-induced Guillain-Barré syndrome (GBS). Compared with gastroenteritis-related isolates, GBS-related C. jejuni isolates were strongly associated with the expression of GD(1a)-like mimicry. The presence of a few genes involved in LOS ganglioside mimicry, cst-II, cgtA, and cgtB, was also associated with GBS-related strains. GD(1a)-like epitope expression may be an important virulence phenotype associated with the risk of developing GBS following campylobacter infection.

Antigens, Bacterial↗

Effectiveness of interventions for reducing the frequency of radical prostatectomy procedures in the elderly: an evaluation.

Between 1993 and 1997, the Peer Review Organizations (PROs) implemented interventions for reducing radical prostatectomy rates in 50 selected hospitals in 10 states and all hospitals in an additional 4 states. Control hospitals and states were matched with the intervention hospitals and states. Prostate cancer incidence rates were used to estimate the number of Medicare beneficiaries aged 75 years and older with prostate cancer, the denominators for the procedure rates, in the hospital service area of each intervention and control hospital, and in each state and their controls. After interventions, significant reductions in the state-specific radical prostatectomy rates were achieved in the intervention hospitals in 2 states and in 1 of the 4 intervention states where statewide interventions had been implemented. Similar reductions were seen in the control hospitals in 3 other individual states and 8 states combined where hospital-based interventions were implemented. These changes in the procedure rates were most likely due to the national decline in the incidence of prostate cancer, not the PRO interventions.

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