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Biomedical subjects

S Malek

Publications and source records attributed to S Malek.

At least 19 recordsLinked to original sources
PubMed2004

Emergency repair of groin herniae: outcome and implications for elective surgery waiting times.

Patients with groin herniae do not always seek medical advice and, when listed for surgery, often wait many months for elective repair. We audited our emergency admissions for complicated groin herniae to establish whether a change in policy for elective surgery could lower their incidence. We performed a retrospective review of all admissions for complicated groin herniae from 1 January 2000 to 31 December 2001. Besides outcome, we recorded patients' awareness of their diagnosis before admission and whether they had been listed for elective surgery. We identified 19 patients (16 men and three women) with an inguinal and 19 (four men and 15 women) with a femoral hernia. Sixteen (42%) knew of their hernia before admission (11 inguinal and five femoral), but only three had been awaiting surgical repair for 1, 7 and 26 weeks, respectively. The median (interquartile range) age was 70 (54-84) years in inguinal and 79 (64-88) years in femoral herniae. Surgery was performed in all but an 84-year-old man who died pre-operatively. Two patients with inguinal and 11 with femoral herniae required a laparotomy (p = 0.006). Bowel resection was necessary in one patient with an inguinal and 12 with femoral herniae (p = 0.001). Complications occurred in 12 cases (31%). Four patients, all with femoral herniae, died post-operatively, for an overall mortality of 13% (5/38). Morbidity and mortality for complicated groin hernia, particularly femoral, remain high. As most patients were elderly and unaware of their diagnosis, reducing waiting times for elective repair is unlikely to influence the incidence of complicated herniae.

Aged↗
PubMed2001

IkappaBbeta, but not IkappaBalpha, functions as a classical cytoplasmic inhibitor of NF-kappaB dimers by masking both NF-kappaB nuclear localization sequences in resting cells.

NF-kappaB dimers, inhibitor IkappaB proteins, and NF-kappaB.IkappaB complexes exhibit distinct patterns in partitioning between nuclear and cytoplasmic cellular compartments. IkappaB-dependent modulation of NF-kappaB subcellular localization represents one of the more poorly understood processes in the NF-kappaB signaling pathway. In this study, we have combined in vitro biochemical and cell-based methods to elucidate differences in NF-kappaB regulation exhibited by the inhibitors IkappaBbeta and IkappaBalpha. We show that although both IkappaBalpha and IkappaBbeta bind to NF-kappaB with similar global architecture and stability, significant differences exist that contribute to their unique functional roles. IkappaBbeta derives its high affinity toward NF-kappaB dimers by binding to both NF-kappaB subunit nuclear localization signals. In contrast, IkappaBalpha contacts only one NF-kappaB NLS and employs its carboxyl-terminal proline, glutamic acid, serine, and threonine-rich region for high affinity NF-kappaB binding. We show that the presence of one free NLS in the NF-kappaB.IkappaBalpha complex renders it a dynamic nucleocytoplasmic complex, whereas NF-kappaB.IkappaBbeta complexes are localized to the cytoplasm of resting cells.

Animals↗
PubMed2001

Physical properties of root cementum: Part I. A new method for 3-dimensional evaluation.

Cementum is a nonuniform connective tissue that covers the roots of human teeth. Investigation of the physical properties of cementum may help in understanding or evaluating any possible connection to root resorption. A variety of engineering tests are available to investigate these properties. However, the thickness of the cementum layer varies, and this limits the applicability of these techniques in determining the physical properties of cementum. Hardness testing with Knoop and Vickers indentations overcame some of these limitations, but they prohibited the retrieval and retesting of the sample and therefore the testing was restricted to one area or section of the tooth. Another limiting factor with the existing techniques was the risk of artifacts related to the embedding material such as acrylic. A new method to investigate the physical properties of human premolar cementum was developed to obtain a 3-dimensional map of these properties with the Ultra Micro Indentation System (UMIS-2000; Commonwealth Scientific and Industrial Research Organization, Campbell, Australia). UMIS-2000 is a nano-indentation instrument for investigation of the properties of the near-surface region of materials. Premolars were harvested from orthodontic patients requiring extractions and then mounted on a newly designed surveyor that allowed sample retrieval and 3-dimensional rotation. This novel method enabled the quantitative testing of root surface cementum, on all 4 root surfaces, extending from the apex to the cementoenamel junction at 60 different sites.

Bicuspid↗
PubMed2001

Varying treatments of Class II malocclusions: two case reports.

Two female patients, JH aged 13 years 5 months and CN, aged 13 years 10 months, presented at the Sydney University Orthodontic Clinic, Australia. Patient JH complained that her lower teeth were "too far back behind her top teeth". She was treated using the Speed Appliance. Patient CN complained that her teeth were "crooked". The main point of interest of her case is the mechanics used following the extraction of her four first molar teeth. Both patients were keen to improve their appearance.

Adolescent↗
PubMed2001

[Predictive factors of normal coronary angiography].

The aim of this study is to compare two groups of patients Group A consisted of 120 patients (70 men and 50 women) hospitalised for anginal symptoms, with either clinical or electrical positive exercise test and/or ischemic events on a 24 H electrocardiography and having angiographically normal coronaries Group B consisted of 120 patients (102 men and 18 women) hospitalised for an acute coronary syndrome with pathological coronaries. The analysis of the 2 groups showed that in the group A the average age was lesser (56 years vs 60 years), women's percentage was higher (41% vs 15%) and cardiovascular risk factors were less frequent. Data from non invasive tests was significantly different in the 2 groups: the exercise test showed both clinical and electrical ischemic events in 35% of the patients in group A versus 75% in group B (p < 0.01) and the 24 h electocardiography showed ST depression in 9% of patients in group A versus 25% in group B (p < 0.01%). The coronary angiography is an invasive and an expensive procedure. The results of our study allow us to modulate its indications, especially in young women patients, with few or no cardivascular risk factors and with only electrical positive exercise test.

Adult↗
PubMed2001

[Dumesnil's method: is it viable?].

BACKGROUND: Left ventricular (LV) ejection fraction (EF) is an indicator of left ventricular systolic function and is a potent predictor of cardiovascular mortality. LVEF is assessed by a variety of methods, however echocardiography is the most used in clinical practice. Simpson biplane multiple disc method (BMDM) is recommended by the American Society of Echocardiography; Dumesnil's method based on doppler echocardiography seems to be simpler and theoritically less influenced by distortion of LV geometry. OBJECTIVE AND METHODS: To assess the accuracy and reproducibility of Dumesnil's method a group of 100 patients proposed for coronarography with left ventricular angiography, prospectively underwent LVEF measurements by both BMDM and Dumesnil's method. RESULTS: Compared with LV angiography, the correlation coefficient for the Dumesnil's method was r = 0.85 and it was r = 0.9 for BMDM. Correlation in patients with LV regional asynergy were respectively r = 0.69 and r = 0.85. Intraobserver and interobserver variabilities were less then 7% for both echocardiographic methods. CONCLUSION: Although Dumesnil's method is less accurate than BMDM, it is simpler, more rapid with a satisfactory reliability and reproducibility.

Adult↗
PubMed2000

Preparation and crystallization of dynamic NF-kappa B.Ikappa B complexes.

The formation of single, well-diffracting crystals is a requirement for any molecular structure determination by x-ray crystallography. Crystallization of biological macromolecules can represent a significant obstacle when the subject exhibits internal flexibility or indiscriminate self-association. In such cases, the removal of inherently flexible regions and the addition of stabilizing ligands can improve the probability of crystal formation and ordered growth. We have applied these principles in order to form crystals of the Rel homology region of transcription factor NF-kappaB in complex with its inhibitors IkappaBalpha and IkappaBbeta. None of these molecules crystallizes in the absence of a binding partner. Recombinant overexpression of truncated IkappaBalpha required selection of the correct start site. NF-kappaB.IkappaBalpha complex crystals formed under relatively stringent conditions. NF-kappaB. IkappaBbeta complex crystals were formed by analogy to NF-kappaB. IkappaBalpha, although some modifications in purification and complex formation were necessary due to differences between the inhibitors.

Animals↗
PubMed2000

Mechanism of kappa B DNA binding by Rel/NF-kappa B dimers.

The DNA binding of three different NF-kappaB dimers, the p50 and p65 homodimers and the p50/p65 heterodimer, has been examined using a combination of gel mobility shift and fluorescence anisotropy assays. The NF-kappaB p50/p65 heterodimer is shown here to bind the kappaB DNA target site of the immunoglobulin kappa enhancer (Ig-kappaB) with an affinity of approximately 10 nm. The p50 and p65 homodimers bind to the same site with roughly 5- and 15-fold lower affinity, respectively. The nature of the binding isotherms indicates a cooperative mode of binding for all three dimers to the DNA targets. We have further characterized the role of pH, salt, and temperature on the formation of the p50/p65 heterodimer-Ig-kappaB complex. The heterodimer binds to the Ig-kappaB DNA target in a pH-dependent manner, with the highest affinity between pH 7.0 and 7.5. A strong salt-dependent interaction between Ig-kappaB and the p50/p65 heterodimer is observed, with optimum binding occurring at monovalent salt concentrations below 75 mm, with binding becoming virtually nonspecific at a salt concentration of 200 mm. Binding of the heterodimer to DNA was unchanged across a temperature range between 4 degrees C and 42 degrees C. The sensitivity to ionic environment and insensitivity to temperature indicate that NF-kappaB p50/p65 heterodimers form complexes with specific DNA in an entropically driven manner.

Amino Acid Substitution↗
PubMed2000

[Cardiogenic shock in the acute phase of myocardial infarction].

Cardiogenic shock (CC) is the most common cause of death in acute myocardial infarction (MI) and it has been often associated with fatal evolution. The aim of this study is to emphasize the positive impact of myocardial revascularisation especially percutaneous coronary angioplasty (PTCA) on short and mid term survival of 35 patients hospitalised for acute MI with CC. All the 11 patients who were on conventional therapy died, whereas the hospital mortality rate of the 24 patients who underwent primary PTCA was 41%. PTCA in CC complicating MI is highly effective and reduces the mortality rate in the literature from 80% to 40%. For this reason PTCA should be performed in each case of MI with CC seen in the first 6 hours.

Aged↗
PubMed1998

Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice.

We have used a mouse model of allergen-induced airway hyperresponsiveness to demonstrate that immunostimulatory DNA sequences (ISS) containing a CpG DNA motif significantly inhibit airway eosinophilia and reduce responsiveness to inhaled methacholine. ISS not only inhibited eosinophilia of the airway (by 93%) and lung parenchyma (91%), but also significantly inhibited blood eosinophilia (86%), suggesting that ISS was exerting a significant effect on the bone marrow production of eosinophils. The inhibition of the bone marrow production of eosinophils by 58% was associated with a significant inhibition of T cell-derived cytokine generation (IL-5, granulocyte-macrophage CSF, and IL-3). ISS exerted this inhibitory effect on T cell cytokine production indirectly by stimulating monocytes/macrophages and NK cells to generate IL-12 and IFNs. The onset of the ISS effect on reducing the number of tissue eosinophils was both immediate (within 1 day of administration) and sustained (lasted 6 days), and was not due to ISS directly inducing eosinophil apoptosis. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (i.p.), or mucosally (i.e., intranasally or intratracheally). Interestingly, a single dose of ISS inhibited airway eosinophilia as effectively as daily injections of corticosteroids for 7 days. Moreover, while both ISS and corticosteroids inhibited IL-5 generation, only ISS was able to induce allergen-specific IFN-gamma production and redirect the immune system toward a Th1 response. Thus, systemic or mucosal administration of ISS before allergen exposure could provide a novel form of active immunotherapy in allergic diseases.

Adjuvants, Immunologic↗
PubMed1998

The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation.

IkappaBalpha regulates the transcription factor NF-kappaB through the formation of stable IkappaBalpha/NF-kappaB complexes. Prior to induction, IkappaBalpha retains NF-kappaB in the cytoplasm until the NF-kappaB activation signal is received. After activation, NF-kappaB is removed from gene promoters through association with nuclear IkappaBalpha, restoring the preinduction state. The 2.3 A crystal structure of IkappaBalpha in complex with the NF-kappaB p50/p65 heterodimer reveals mechanisms of these inhibitory activities. The presence of IkappaBalpha allows large en bloc movement of the NF-kappaB p65 subunit amino-terminal domain. This conformational change induces allosteric inhibition of NF-kappaB DNA binding. Amino acid residues immediately preceding the nuclear localization signals of both NF-kappaB p50 and p65 subunits are tethered to the IkappaBalpha amino-terminal ankyrin repeats, impeding NF-kappaB from nuclear import machinery recognition.

Amino Acid Sequence↗
PubMed1998

Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB.

We have determined the binding energies of complexes formed between Ikappa Balpha and the wild type and mutational variants of three different Rel/NF-kappaB dimers, namely, the p50/p65 heterodimer and homodimers of p50 and p65. We show that although a common mode of interaction exists between the Rel/NF-kappaB dimers and Ikappa Balpha, IkappaB alpha binds the NF-kappaB p50/p65 heterodimer with 60- and 27-fold higher affinity than the p50 and p65 homodimers, respectively. Each of the three flexibly linked segments of the rel homology region of Rel/NF-kappaB proteins (the nuclear localization sequence, the dimerization domain, and the amino-terminal DNA binding domain) is directly engaged in forming the protein/protein interface with the ankyrin repeats and the carboxyl-terminal acidic tail/PEST sequence of Ikappa Balpha. In the cell, Ikappa Balpha functions to retain NF-kappaB in the cytoplasm and inhibit its DNA binding activity. These properties are a result of the direct involvement of the nuclear localization sequences and of the DNA binding region of NF-kappaB in complex with Ikappa Balpha. A model of the interactions in the complex is proposed based on our observations and the crystal structures of Rel/NF-kappaB dimers and the ankyrin domains of related proteins.

Base Sequence↗
PubMed1998

[Sinus node dysfunction after complete correction of tetralogy of Fallot. Report of a case].

Atrioventricular conduction defects after complete correction of tetralogy of Fallot are well known and their prevalence is decreasing with improved operative techniques. On the other hand, sinus node dysfunction has not been described after this type of surgery. The authors report the case of a 24 year old patient operated at the age of 2 for a favourable form of tetralogy of Fallot. In the long-term, this patient had a minimal anatomical sequel (mild pulmonary insufficiency) and first degree AVB with complete right bundle branch block with sinus bradycardia on the surface ECG. A recent aggravation of the patient's functional status led to rhythmological investigation which showed chronotropic atrial incompetence with nodal atrioventricular delay. The patient was implanted with a permanent DDD cardiac pacemaker programmed in the DDDR mode with a good outcome. Atrial chronotropic incompetence is one of the modes of expression of sinus node dysfunction. This has not been previously described in this context. This form of sinus node dysfunction should be systematically excluded after surgical cure of tetralogy of Fallot by exercise stress testing and 24 hour Holter ECG. Symptomatic patients are greatly improved by permanent cardiac pacing with hysteresis.

Adult↗
PubMed1997

A prospective study of the effect of I.V. pentamidine therapy on ventricular arrhythmias and QTc prolongation in HIV-infected patients.

STUDY OBJECTIVES: I.V. pentamidine therapy in HIV-infected patients has been associated in case reports and one uncontrolled prospective series with frequent prolongation of the rate-corrected QT interval (QTc) and a high risk for potentially lethal ventricular arrhythmias, especially torsade de pointes. The aim of this study was to prospectively examine in a controlled manner the effect of I.V. pentamidine therapy on the QT interval and the incidence of ventricular arrhythmias. DESIGN: Open, nonrandomized, prospective evaluation of ventricular arrhythmia incidence in HIV-infected patients receiving pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) utilizing Holter monitoring prior to and during therapy with these agents. SETTING: Staten Island University Hospital, Staten Island, NY. PATIENTS: Twenty-seven HIV-infected patients, of whom 16 received I.V. pentamidine and 11 received I.V. TMP-SMX. MEASUREMENTS AND RESULTS: Study patients underwent Holter monitoring prior to therapy and during the first 3 days and last 2 days of therapy with pentamidine or TMP-SMX, 12-lead ECG prior to and every 24 to 48 h, serum electrolytes prior to and on days 3, 6, 9, and 12 of therapy, and baseline transthoracic two-dimensional and Doppler echocardiography. In the pentamidine group, the results for each monitoring period were as follows (means are presented +/- SEM): pretherapy, 1.66+/-1.03 (median=0) premature ventricular complexes (PVCs) per hour, zero nonsustained ventricular tachycardia (NSVT), zero sustained ventricular tachycardia (VT); early therapy, 1.55+/-0.91 (median=0.04) PVCs per hour, two NSVT (both < or = 5 complexes), zero sustained VT; late therapy, 1.69+/-1.17 (median=0.08) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for early or late therapy as compared to pretherapy for PVCs per hour, NSVT, or sustained VT). In the TMP-SMX group, the Holter monitoring results were as follows: pretherapy, 1.36+/-1.27 (median=0) PVCs per hour, zero NSVT, zero sustained VT; early therapy, 0.71+/-0.53 (median=0.03) PVCs per hour, two NSVT, zero sustained VT; late therapy, 0.56+/-0.51 (median=0) PVCs per hour, zero NSVT, zero sustained VT (p value not significant for pretherapy, early therapy, or late therapy with TMP-SMX as compared to pentamidine for PVCs per hour, NSVT, or VT). The QTc also did not significantly differ during therapy with pentamidine as compared to TMP-SMX. The mean QTc in the pentamidine group decreased during therapy as compared to pretherapy with the difference approaching significance for days 2, 4, and 6 with pentamidine (p<0.06). CONCLUSIONS: QTc prolongation during therapy with pentamidine in HIV-infected patients is not as frequent an occurrence as has been reported previously. In the absence of QTc prolongation, pentamidine therapy was not associated with a significant increase in PVCs, NSVT, or sustained VT as compared to pretherapy recordings or as compared to therapy with TMP-SMX.

Adult↗
PubMed1995

The status of local smoking regulations in North Carolina following a state preemption bill.

OBJECTIVE: To determine the number and protectiveness of local smoking regulations adopted before the implementation of a preemptive statewide smoking control bill. METHOD: Review of local smoking control regulations from all 100 counties and 85 municipalities with populations greater than 5000 in North Carolina. MAIN OUTCOME MEASURES: Adoption of local smoking control regulations before and during the 3-month delay in enactment of the preemptive bill. Protectiveness of regulations was based on restrictions on smoking and requirements for separate ventilation systems at private work sites: none (smoking unrestricted); minimal (smoking restricted to designated areas); partial (smoking restricted to designated areas served by separate ventilation systems); and complete (smoking prohibited). Because some regulations would be phased in gradually over the next 5 years, we evaluated the requirements that will be in effect by January 1, 2000. RESULTS: Between July 15 and October 15, 1993, the number of local smoking regulations in North Carolina increased from 16 to 105. By the year 2000, 59% of private employees still will not be guaranteed any protection from work site environmental tobacco smoke; 19% will have minimal protection, 22% will have partial protection, and none will have complete protection. CONCLUSIONS: The 3-month delay in preemption created an unnatural time frame for communities to organize, debate, and adopt smoking restrictions. Despite the adoption of 89 new regulations, no private employees will be guaranteed complete protection from work site environmental tobacco smoke by the year 2000; new regulations can no longer be adopted. HB 957 has been a setback for public health in North Carolina.

Humans↗