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Biomedical subjects

F Haddad

Publications and source records attributed to F Haddad.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ischio-vertebral dysplasia: a distinct entity.

BACKGROUND: Kyphoscoliosis is a complication of some bone dysplasias, including cleidocranial dysplasia. OBJECTIVES: We report a distinct disorder with defective ossification of the ischial rami, severe kyphoscoliosis and normal clavicles. Early recognition of this syndrome allows prevention of complications. MATERIALS AND METHODS: All patient cases (aged 1 day to 33 years) were selected according to the above criteria, with special attention to radiological findings, family history and follow-up (5-30 years). RESULTS: In all eight patients, we observed the following: (a) Severe thoracic scoliosis of early onset and rapid progression, leading to rotatory dislocation. Spinal cord compression occurred in four cases with respiratory problems related to chest deformity. (b) Bilateral and symmetrical incomplete ossification of the ischial rami. (c) Peculiar facies with retrognathia. (d) Normal clavicles. Three patients were from the same family (grandmother, mother and daughter). CONCLUSION: Ischio-vertebral dysplasia seems to represent a true entity, with radiological and genetic findings that make it distinct from cleidocranial dysostosis. The association of kyphoscoliosis and these pelvic abnormalities is specific for this condition. Neurological and respiratory complications can be avoided if the condition is recognised early and early treatment is instituted.

Abnormalities, Multiple↗
PubMed1999

Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat.

BACKGROUND & AIMS: A reduction in nitric oxide (NO) has been implicated as a cause of intrahepatic vasoconstriction in cirrhosis, but the regulatory mechanisms remain undefined. The aim of this study was to examine a contributory role for caveolin-1, a putative negative regulator of endothelial NO synthase, in mediating deficient intrahepatic NO production in the intact cirrhotic liver. METHODS: Cirrhosis was induced by carbon tetrachloride inhalation. Flow regulation of NO production and perfusion pressure was examined in the perfused rat liver. Protein expression of endothelial NO synthase (eNOS), caveolin, and calmodulin was examined by Western blotting and immunohistochemistry. NOS activity and NO production were assessed by citrulline generation and chemiluminescence, respectively. Protein-protein interactions were examined using whole tissue protein immunoprecipitation. RESULTS: In response to incremental increases in flow, cirrhotic animals produced significantly less NO(x) than control animals. NOS activity was significantly reduced in liver tissue from cirrhotic animals compared with control animals in the presence of similar eNOS protein levels. Deficient eNOS activity was associated with a severalfold increase in binding of eNOS with caveolin. Protein levels of caveolin-1 were markedly increased in the cirrhotic liver. CONCLUSIONS: These studies provide evidence that enhanced expression and interaction of caveolin with eNOS contribute to impaired NO production, reduced NOS activity, and vasoconstriction in the intact cirrhotic liver.

Animals↗
PubMed1999

Lymphatic mapping in breast cancer.

The most accurate predictor of survival in breast cancer is the presence or absence of lymph node metastases. Lymphatic mapping with sentinel node biopsy is a new technique that provides more accurate nodal staging compared with routine histology for women with breast cancer, but without the morbidity of a complete lymph node dissection. Sentinel lymph node (SLN) biopsy is a more conservative approach to the axilla that requires close collaboration from the surgical team, nuclear medicine, and pathology. National trials are investigating the clinical relevance of the upstaging that occurs with a more intense examination of the SLN. As is the case with breast preservation as a viable alternative to mastectomy for the definitive treatment of the primary node, selective lymphadenectomy has the ability to decrease morbidity without compromising patient care.

Breast Neoplasms↗
PubMed1999

In vivo regulation of beta-MHC gene in rodent heart: role of T3 and evidence for an upstream enhancer.

Cardiac beta-myosin heavy chain (beta-MHC) gene expression is mainly regulated through transcriptional processes. Although these results are based primarily on in vitro cell culture models, relatively little information is available concerning the interaction of key regulatory factors thought to modulate MHC expression in the intact rodent heart. Using a direct gene transfer approach, we studied the in vivo transcriptional activity of different-length beta-MHC promoter fragments in normal control and in altered thyroid states. The test beta-MHC promoter was fused to a firefly luciferase reporter gene, whereas the control alpha-MHC promoter was fused to the Renilla luciferase reporter gene and was used to account for variations in transfection efficiency. Absolute reporter gene activities showed that beta- and alpha-MHC genes were individually and reciprocally regulated by thyroid hormone. The beta-to-alpha ratios of reporter gene expression demonstrated an almost threefold larger beta-MHC gene expression in the longest than in the shorter promoter fragments in normal control animals, implying the existence of an upstream enhancer. A mutation in the putative thyroid response element of the -408-bp beta-MHC promoter construct caused transcriptional activity to drop to null. When studied in the -3, 500-bp beta-MHC promoter, construct activity was reduced ( approximately 100-fold) while thyroid hormone responsiveness was retained. These findings suggest that, even though the bulk of the thyroid hormone responsiveness of the gene is contained within the first 215 bp of the beta-MHC promoter sequence, the exact mechanism of triiodothyronine (T3) action remains to be elucidated.

Animals↗
PubMed1999

Time course of changes in markers of myogenesis in overloaded rat skeletal muscles.

During the process of compensatory muscle hypertrophy, satellite cells are thought to proliferate, differentiate, and then fuse with existing myofibers. We hypothesized that early in this process changes occur in the expression of cellular markers indicative of the onset of myogenic processes. The plantaris muscles of rats were overloaded via the unilateral ablation of synergists. Groups of rats were killed at time points from 6 h to 12 days. Changes in muscle gene expression (mRNA) of cyclin D1, p21, myogenin, MyoD, and insulin-like growth factor I (IGF-I, mRNA and peptide) were measured. Cyclin D1 (a cell cycle marker) was increased after 24 h of overloading and corresponded with changes in muscle DNA content. In contrast, p21 and myogenin, markers of cellular differentiation, were increased after just 12 h. Muscle IGF-I peptide levels were also increased at early time points. The results of this study indicate that myogenic processes are activated in response to increased loading at very early time points (e.g., 12 h) and that IGF-I may be modulating this response. Furthermore, these findings suggest that some cells may have been differentiating very early in the adaptation process before events leading to cellular proliferation have been initiated.

Animals↗
PubMed1998

Detection of Leishmania DNA by polymerase chain reaction in scars of treated human patients.

Leishmaniasis is an endemic disease in developing countries. The efficacy of therapy is usually evaluated through clinical parameters. To define the parasitologic cure, 20 patients were biopsied before and 1 month to 8 years after treatment. Paraffin-embedded tissue was used for DNA isolation. All patients had a positive polymerase chain reaction (PCR) result before therapy, except 1, for whom no histopathologic material was available. The causative agent was identified as belonging to the Leishmania (Viannia) subgenus by hybridization. Despite clinical healing and absence of reactivation or development of mucosal lesions, PCR was positive in scars of 16 patients (80%). The results suggest that parasites persist in the skin for many years despite treatment. Depending on specific pathogenetic features of the parasite and the immune status of the host, this phenomenon might result in mucosal lesions. Alternatively, it could have a role in the maintenance of immunologic memory in patients living in areas in which leishmaniasis is endemic.

Animals↗
PubMed1998

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.

OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. METHODS: Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.

Biopsy↗
PubMed1998

Prognostic importance of automated ST-segment monitoring after coronary artery bypass graft surgery.

BACKGROUND: Automated ST-segment monitors are widely used in cardiac surgery units. The purpose of this study was to determine if cardiac morbidity and mortality, after CABG surgery, are predicted by ECG ST-segment changes on automated monitors. METHOD: One hundred patients, who underwent CABG, were included in this prospective study. ST-segment deviations were recorded by an automated ST monitor, in the ICU, for 24 h after surgery. A reversible ST depression of more than 0.1 mV or a ST elevation of more than 0.2 mV and for at least 1 min were considered as significant episodes. Adverse cardiac outcomes were defined as: myocardial infarction (MI), severe left ventricular failure, ventricular fibrillation (VF) and cardiac-related death. RESULTS: Sixty patients (group 1) presented significant episodes of ST deviation (6+/-5 episodes per patient). Forty patients (group 2) were free from ST changes. Eight patients from group 1 had postoperative adverse cardiac outcomes: 5 MI, 2 VF and 1 cardiac-related death. Patients from group 2 were all free from adverse cardiac outcomes. Automated ST-segment analysis during the first 24 h had a positive predictive value of 13% and a negative predictive value of 100%. CONCLUSION: Automated ST analysis is a non-invasive, sensitive and very easy-to-use monitoring system to screen patients who may develop myocardial ischemia and cardiac complications after CABG surgery.

Automation↗
PubMed1998

Thyroid receptor plasticity in striated muscle types: effects of altered thyroid state.

This study examined nuclear thyroid receptor (TR) maximum binding capacity (Bmax), dissociation constant (Kd), and TR isoform (alpha1, alpha2, beta1) mRNA expression in rodent cardiac, "fast-twitch white," "fast-twitch red," and "slow-twitch red" muscle types as a function of thyroid state. These analyses were performed in the context of slow-twitch type I myosin heavy-chain (MHC) expression, a 3,5,3'-triiodothyronine (T3)-regulated gene that displays varying responsiveness to T3 in the above tissues. Nuclear T3 binding analyses show that the skeletal muscle types express more TRs per unit DNA than cardiac muscle, whereas the latter has a lower Kd than the former. Altered thyroid state had little effect on either cardiac Bmax or Kd, whereas hypothyroidism increased Bmax in the skeletal muscle types without affecting its Kd. Cardiac muscle demonstrated the greatest mRNA signal of TR-beta1 compared with the other muscle types, whereas the TR-alpha1 mRNA signals were more abundant in the skeletal muscle types, especially fast-twitch red. Hyperthyroidism increased the ratio of beta1 to alpha1 and decreased the ratio of alpha2- to alpha1+beta1-mRNA signal across the muscle types, whereas hypothyroidism caused the opposite effects. The nuclear T3 affinity correlated significantly with the TR-beta1 mRNA expression but not with TR-alpha1 mRNA expression. Collectively, these findings suggest that, despite a divergent pattern of TR mRNA expression in the different muscle types, these patterns follow similar qualitative changes under altered thyroid state. Furthermore, TR expression pattern cannot account for the quantitative and qualitative changes in type I MHC expression that occur in the different muscle types.

Animals↗
PubMed1998

Effects of isometric training on skeletal myosin heavy chain expression.

This study tested the hypothesis that an isometric resistance-training program induces upregulation of slow myosin heavy chain (MHC) expression in a fast-twitch skeletal muscle. Thus we studied the effects of two resistance-training programs on rodent medial gastrocnemius (MG) muscle that were designed to elicit repetitive isometric contractions (10-12 per set; 4 sets per session) of different duration (8 vs. 5 s) and activation frequency (100 vs. 60 Hz) per contraction during each training session (total of 6 and 12 sessions). Results showed that both training paradigms produced significant increases in muscle weight ( approximately 11-13%) after completion of training (P < 0.05). Significant transformations in MHC expression occurred and involved specifically a decrease in the relative expression of the fast type IIb MHC and concomitant increased expression of the fast type IIx MHC. These adaptations were observed in both the "white" and "red" regions of the MG, and they occurred at both the mRNA and protein levels. These adaptations were detected after only six training sessions. Neither of the training programs produced any change in the relative expression of either the slow type I MHC or the moderately fast type IIa MHC, which can be upregulated in the red MG by chronic functional overload. These findings show that the isometric protocols used in this investigation were not sufficient to induce the hypothesized changes in the myosin heavy chain isoform expression in rodent skeletal muscle.

Animals↗
PubMed1998

Interaction of hyperthyroidism and hindlimb suspension on skeletal myosin heavy chain expression.

We examined the novel interaction of hyperthyroidism and hindlimb suspension on the pattern of myosin heavy chain (MHC) expression (mRNA and protein) in skeletal muscles. Female Sprague-Dawley rats were assigned to four groups: 1) normal control (Con); 2) thyroid hormone treated [150 micrograms 3,5,3'-triiodothyronine (T3). kg-1. day-1] (T3); 3) hindlimb suspension (HS); or 4) T3-treated and HS (T3 + HS). Results show for the first time the novel observation that the combination T3 + HS induces a rapid and sustained, marked (80-90%) downregulation of type I MHC gene expression that is mirrored temporally by concomitant marked upregulation of type IIb MHC gene expression, as evidenced by the de novo synthesis of type IIb MHC protein in the soleus. The fast type IIx MHC isoform showed a differential response among the experimental groups, generally increasing with the separate and combined treatments in both the soleus and vastus intermedius muscles while decreasing in the plantaris muscles. The fast type IIa MHC was the least responsive to suspension of the MHCs and reflected its greatest responsiveness to T3 treatment while also undergoing differential adaptations in slow vs. fast muscle (increases vs. decreases, respectively). These results confirm previous findings that all four adult MHC genes are sensitive to T3 and suspension in a muscle-specific manner. In addition, we show that T3 + HS can interact synergistically to create novel adaptations in MHC expression that could not be observed when each factor was imposed separately.

Animals↗
PubMed1998

[Werner's syndrome].

BACKGROUND: Werner's syndrome associates early aging in young adults, small height, cataract, glucose intolerance, hypogonadism, skin ulcers, vascular calcifications and osteoporosis. CASE REPORT: We report a new case of Werner's syndrome in a 34-year-old man with suggestive alterations of the skin and endocrine anomalies in addition to hypospadias, urethral stenosis, bilateral mega-ureter and chronic renal failure. DISCUSSION: The diagnosis of Werner's syndrome in our patient was unquestionable because of the clinical presentation and the familial context. However, the urology anomalies have not been reported in this syndrome. A simple coincidence cannot be excluded.

Adult↗
PubMed1998

Lymphatic mapping in the treatment of breast cancer.

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested sentinel lymph nodes are evaluated more thoroughly by detailed pathologic examination using serial sectioning, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. This allows for the detection of smaller tumor volumes and leads to more accurate staging. Lymphatic mapping has a 68% to 98% success rate in identifying the sentinel lymph node. The false-negative rate (defined as a negative sentinel lymph node while a higher node or nodes in the axilla are positive) is between 0% and 2%. The morbidity associated with this procedure is minimal. We believe that lymphatic mapping and sentinel lymph node biopsy will ultimately lead to more conservative treatment of patients with breast cancer. This article describes the historical background and technical aspects of the procedure. This is followed by updated, prospectively collected outcomes data from 466 consecutive breast cancer patients who underwent lymphatic mapping at the H. Lee Moffitt Cancer Center, as well as an up-to-date review of the literature.

Biopsy↗