Biomedical subjects

D Harari

Publications and source records attributed to D Harari.

At least 19 recordsLinked to original sources

PubMed2005

Health risk appraisal for older people in general practice using an expert system: a pilot study.

The prevention of disability in later life is a major challenge facing industrialised societies. Primary care practitioners are well positioned to maintain and promote health in older people, but the British experience of population-wide preventive interventions has been disappointing. Health risk appraisal (HRA), an emergent information-technology-based approach from the USA, has the potential for fulfilling some of the objectives of the National Service Framework for Older People. Information technology and expert systems allow the perspectives of older people on their health and health risk behaviours to be collated, analysed and converted into tailored health promotion advice without adding to the workload of primary care practitioners. The present paper describes a preliminary study of the portability of HRA to British settings. Cultural adaptation and feasibility testing of a comprehensive health risk assessment questionnaire was carried out in a single group practice with 12,500 patients, in which 58% of the registered population aged 65 years and over participated in the study. Eight out of 10 respondents at all ages found the questionnaire easy or very easy to understand and complete, although more than one-third had or would have liked assistance. More than half felt that the length of the questionnaire was about right, and one respondent in 10 disliked some questions. Of those who completed the questionnaire and received tailored, written health promotion advice, 39% provided feedback on this with comments that can be used for increasing the acceptability of tailored advice. These findings have informed a wider exploratory study in general practice.

Aged↗

PubMed2003

[A retrospective study of orthodontic treatment of children with clefts].

OBJECTIVES: To evaluate the population of cleft patients treated in a Department of Orthodontics and the types of treatment modalities provided. METHODS: Demographic, cleft related and treatment related data existing in the patients' files were supplemented by questionnaires. Comparisons were conducted among 3 cleft groups: cleft lip (CL), cleft lip and palate (CLP) and cleft palate (CP). RESULTS: The response rate was 36% (n = 152). The distribution of the patients in the 3 cleft groups, the sidedness, the male predominance and association with additional anomalies were similar to the reports in the literature. Most of the patients were the 3rd born (or more) and were of normal birth weight. Consanguity in the cleft families was at least 2.5 times more prevalent than that of the Israeli population and 30% reported on additional cleft in the family. Low birth weight and additional anomalies were found mainly in the CP group. Orthodontic involvement spanned 3 developmental periods: immediate postnatal presurgical treatment, phase I between the ages 6-8 years and full orthodontic treatment at a later age. Up to the age of 5 years only one lip operation was performed for 60% of the lip-affected children and one palate operation for 65% of the palate affected patients. CONCLUSIONS: 1. The distribution of the various cleft-related parameters in this retrospective study was similar to the findings in the literature. 2. The high prevalence of additional anomalies found emphasizes the need for a thorough examination of the cleft babies. 3. Orthodontic treatment was rendered in one and two phase protocols in addition to immediate postnatal pre-surgical intervention.

Age Factors↗

PubMed2001

Comparative pharmacokinetics of once daily intravenous and intramuscular gentamicin in patients with post partum endometritis.

In patients with post partum endometritis once daily intramuscular administration of gentamicin may be convenient in certain clinical settings. However pharmacokinetic data on once daily intramuscular gentamicin are not reported. In this study 10 women with post partum endometritis were given once daily intravenous gentamicin (4 mg/kg ideal body weight) followed at a later day by a similar intramuscular dose. Gentamicin levels coincided at 30 min. Levels at 60 and 90 min were lower with the intravenous route. Further clinical studies are needed to confirm reduced nephrotoxicity and ototxicity with the intramuscular route.

Anti-Bacterial Agents↗

PubMed2001

A computer-based method for the assessment of body-image distortions in anorexia-nervosa patients.

A computer-based method for the assessment of body-image distortions in anorexia nervosa and other eating-disorder patients is presented in this paper. At the core of the method is a realistic pictorial simulation of lifelike weight changes, applied to a real source image of the patient. The patients, using a graphical user interface, adjust their body shapes until they meet their self-perceived appearance. Measuring the extent of virtual fattening or slimming of a body with respect to its real shape and size allows direct quantitative evaluation of the cognitive distortion in body image. In a preliminary experiment involving 33 anorexia-nervosa patients, 70% of the subjects chose an image with simulated visual weight gain between 8%-16% as their "real" body image, while only one of them recognized the original body image. In a second experiment involving 30 healthy participants, the quality of the weight modified images was evaluated by pairwise selection trials. Over a weight change range from -16% to +28%, in about 30% of the trials, artificially modified images were mistakenly taken as "original" images, thus demonstrating the quality of the artificial images. The method presented is currently in a clinical validation phase, toward application in the research, diagnosis, evaluation, and treatment of eating disorders.

Agnosia↗

PubMed2001

The effect of mechanical force on mRNA levels of collagenase, collagen type I, and tissue inhibitors of metalloproteinases in gingivae of dogs.

Orthodontic force causes an injury to and subsequent degradation of the attachment apparatus, thus leading to the transposition of the tooth. The gingiva, however, is compressed and sometimes becomes hypertrophic with tooth movement and often shrinks after treatment. To study the effect of force on the gingiva, we applied orthodontic force in dogs and analyzed gingival tissues 1, 2, 3, 7, 14, and 28 days later as well as after removing the force. The effect of force on mRNA levels of collagen type I (col-I), matrix metalloproteinase-1 (MMP- 1), and tissue inhibitors 1 and 2 (TIMPs) genes was analyzed by RT-PCR, and MMP-1 activity was determined by zymography. The results showed that force significantly increased both the mRNA levels of MMP-1 and its interstitial activity. After the removal of force, MMP-1 gene expression was significantly decreased. The results could partly explain the clinically observed shrinkage and adaptation of the gingiva during tooth movement.

Adaptation, Physiological↗

PubMed2001

Sweeping of membranes vs. intracervical prostaglandin E2 gel for cervical ripening. Randomized trial.

OBJECTIVE: To compare intracervical prostaglandin E2 gel and membrane sweeping for cervical ripening. STUDY DESIGN: Fifty patients were randomized to either intracervical prostaglandin E2 or membrane sweeping. A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure. RESULTS: The Bishop scores assigned 24 hours after prostaglandin instillation and membrane sweeping were not significantly different (3.4, SE 0.42, vs. 3.3, SE 0.37, respectively; P > .05). The proportions of women entering active labor or delivering within 24 hours were similar in the prostaglandin and membrane groups (21% and 19%, respectively; P > .05). CONCLUSION: When both intracervical prostaglandin insertion and membrane sweeping are feasible, their salutary effects are comparable.

Administration, Intravaginal↗

PubMed2000

Molecular mechanisms underlying ErbB2/HER2 action in breast cancer.

Overexpression of ErbB2, a receptor-like tyrosine kinase, is shared by several types of human carcinomas. In breast tumors the extent of overexpression has a prognostic value, thus identifying the oncoprotein as a target for therapeutic strategies. Already, antibodies to ErbB2 are used in combination with chemotherapy in the treatment of metastasizing breast cancer. The mechanisms underlying the oncogenic action of ErbB2 involve a complex network in which ErbB2 acts as a ligand-less signaling subunit of three other receptors that directly bind a large repertoire of stroma-derived growth factors. The major partners of ErbB2 in carcinomas are ErbB1 (also called EGFR) and ErbB3, a kinase-defective receptor whose potent mitogenic action is activated in the context of heterodimeric complexes. Why ErbB2-containing heterodimers are relatively oncopotent is a function of a number of processes. Apparently, these heterodimers evade normal inactivation processes, by decreasing the rate of ligand dissociation, internalizing relatively slowly and avoiding the degradative pathway by returning to the cell surface. On the other hand, the heterodimers strongly recruit survival and mitogenic pathways such as the mitogen-activated protein kinases and the phosphatidylinositol 3-kinase. Hyper-activated signaling through the ErbB-signaling network results in dysregulation of the cell cycle homeostatic machinery, with upregulation of active cyclin-D/CDK complexes. Recent data indicate that cell cycle regulators are also linked to chemoresistance in ErbB2-dependent breast carcinoma. Together with D-type cyclins, it seems that the CDK inhibitor p21waf1 plays an important role in evasion from apoptosis. These recent findings herald a preliminary understanding of the output layer which connects elevated ErbB-signaling to oncogenesis and chemoresistance.

Amino Acid Sequence↗

PubMed2000

c-Cbl is a suppressor of the neu oncogene.

A rodent oncogenic mutant of the Neu receptor tyrosine kinase is a useful experimental model because overexpression of the respective receptor, namely HER2/ErbB-2, in human malignancies is associated with relatively aggressive diseases. Here we show that the oncogenic form of Neu is constitutively associated with the product of the c-cbl proto-oncogene and is part of a large complex that includes the phosphoinositide 3-kinase and Shc. Ectopic expression of c-Cbl, a ubiquitin-protein isopeptide ligase specific to activated tyrosine kinases, causes rapid removal of Neu from the cell surface and severely reduces signaling downstream of oncogenic Neu. c-Cbl-induced down-regulation of Neu involves covalent attachment of ubiquitin molecules and requires the carboxyl-terminal domain of Neu. The negative effect of c-Cbl is antagonized by v-Cbl, a virus-encoded oncogenic truncated form of c-Cbl. In an in vivo model, infection of a Neu-transformed neuroblastoma with a c-Cbl-encoding retrovirus caused enhanced down-regulation of Neu and correlated with tumor retardation. Our results implicate c-Cbl in negative regulation of Neu and offer a potential target for treatment of HER2/ErbB-2-positive human malignancies.

3T3 Cells↗

PubMed2000

Megacolon in patients with chronic spinal cord injury.

PURPOSE: To investigate the clinical and functional correlates of megacolon in individuals with chronic spinal cord injury (SCI). PATIENTS AND METHODS: This is a cross-sectional study of 128 patients consecutively admitted to a SCI in-patient service in a US Veterans Administration Medical Centre (mean age 57+/-15 years, mean years since injury 20+/-13, 97% male) who underwent plain abdominal radiography for study purposes. Participants were characterised by radiological findings. 'Megacolon' was defined as colonic dilatation of >6 cms in one or more colonic segment(s). Clinical, functional, and medication data were abstracted from the medical and nursing records. Individual interviews were conducted with study participants regarding bowel-related symptoms and treatment over the previous 1-month period. RESULTS: Seventy-three per cent of subjects (n=94) had megacolon, and 52% of these individuals had associated radiological constipation. Subjects with megacolon were compared with those without colonic dilatation (n=34). Factors significantly associated with megacolon were older age, longer duration of injury, symptom of abdominal distension, radiological constipation, urinary outlet surgery, laxative use at least once weekly, use of anticholinergic drugs, and use of calcium-containing antacids. These factors were simultaneously included in a multiple logistic regression model. Independent correlates of megacolon were more than 10 years elapsed since acute injury, age over 50 years, and use of >/=4 laxative doses per month. CONCLUSION: Megacolon is a highly prevalent disorder in individuals with chronic spinal cord injury. Our findings suggest that the presence of megacolon may be predicted in older individuals, and in those who are more than 10 years post-SCI. We also found that clinical constipation was frequently present in individuals with megacolon, despite their significantly greater use of laxatives. SPONSORSHIP: This work was supported by a grant from the Claude D Pepper Geriatric Research and Training Center from the National Institute of Ageing-AG08812-05, and a grant from the Education and Training Foundation of the Paralyzed Veterans Association in the USA. Dr Harari is currently recipient of a grant from Action Research (UK). Spinal Cord (2000) 38, 331 - 339.

Chronic Disease↗

PubMed2000

A new multipurpose dental adhesive for orthodontic use: an in vitro bond-strength study.

The purpose of this study was to evaluate the compatibility of a new dental adhesive, High-Q-Bond (HQB) adhesive, for the bonding of orthodontic brackets by determining its bond strength and the mode of bond failure after debonding. Eighty extracted human premolars were divided into 4 groups, 20 in each group. In groups 1 and 2, stainless steel brackets were bonded to etched enamel with HQB and Right-On adhesives respectively. In groups 3 and 4, the same adhesives were used to bond stainless-steel brackets to roughened, old amalgam restorations prepared in the teeth. After 72 hours of incubation in saline solution at 37 degrees C, debonding was performed with a shearing force. The force at bond failure was recorded, and the mode of bond failure was examined. Results showed that when bonding to enamel, both the HQB and the Right-On material achieved adequate bond strength, and no significant difference was found between the two. However, after debonding, the HQB material left no adhesive on the enamel, whereas the Right-On material left significant amounts of adhesive on the enamel. When bonding to amalgam, the HQB material had a significantly higher shear bond strength than did the Right-On adhesive. It is suggested that HQB can be applied for orthodontic use, but further clinical studies are required to evaluate its efficacy.

Dental Amalgam↗

PubMed1999

Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase.

The ErbB/HER family of receptor tyrosine kinases consists of four receptors that bind a large number of growth factor ligands sharing an epidermal growth factor- (EGF)-like motif. Whereas ErbB-1 binds seven different ligands whose prototype is EGF, the three families of neuregulins (NRGs) activate ErbB-3 and/or ErbB-4. Here we characterize a fourth neuregulin, NRG-4, that acts through ErbB-4. The predicted pro-NRG-4 is a transmembrane protein carrying a unique EGF-like motif and a short cytoplasmic domain. A synthetic peptide encompassing the full-length EGF-like domain can induce growth of interleukin-dependent cells ectopically expressing ErbB-4, but not cells expressing the other three ErbB proteins or their combinations. Consistent with specificity to ErbB-4, NRG-4 can displace an ErbB-4-bound NRG-1 and can activate signaling downstream of this receptor. Expression of NRG-4 mRNA was detected in the adult pancreas and weakly in muscle; other tissues displayed no detectable NRG-4 mRNA. The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands.

Amino Acid Sequence↗

PubMed1999

Sonographically diagnosed pelvic hematomas and postcesarean febrile morbidity.

OBJECTIVE: To evaluate the incidence of ultrasonographically-diagnosed postcesarean hematomas and correlate their presence with febrile morbidity. METHODS: Prospective study of 111 consecutive patients who had a pelvic ultrasound 4-6 days post-operatively. Ultrasonographic findings were correlated with clinical data. RESULTS: Postoperative fever was diagnosed in 28 (25%) patients. Fifteen (13.5%) women had hematomas; 10 (9%) had bladder-flap and five (4.5%) had subfascial hematomas. Only subfascial hematomas were significantly associated with post-operative fever (P = 0.01). CONCLUSIONS: Postcesarean bladder-flap hematomas are not predictive of post-operative fever. The presence of subfascial hematomas should be specifically sought in the evaluation of a febrile postcesarean patient.

Adult↗

PubMed1998

Does a secular trend exist in the distribution of occlusal patterns?

The existence of a secular trend in the distribution of occlusal patterns was studied in two generations of children. Study models and demographic data of a sample of 265 children from the previous generation (group A) and recordings of clinical examinations of 988 children from the present generation (group B) served as the data base for this study. Children in whom caries affected the occlusion and those in the deciduous dentition stage were excluded. Thus, occlusal analysis was performed for 102 children in group A and 703 in group B. A dramatic decrease was found in the prevalence of caries affecting the occlusion. No difference existed between the two groups with respect to molar and canine anteroposterior relationships. However, there was a decrease in the prevalence of normal occlusion accompanied by an increase of Class I malocclusion.

Adolescent↗

PubMed1997

FGF plays a subtle role in oligodendrocyte maintenance in vivo.

Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a role in both the development and maintenance of oligodendrocytes. Addition of FGF to mature oligodendrocytes in culture was reported to downregulate the expression of genes encoding proteins of the myelin sheath and to induce a loss of myelin compaction. In this study, a model was developed to functionally block FGF signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a dominant-negative FGF receptor (FGFR1), under the control of the myelin basic protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these cells. Subsequently, five independent transgenic lines ("MBP-FRD") were generated. Three lines expressing the highest level of the transgene were further studied. Initial investigation by Western blot and light microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of myelinated optic nerve fibres from two independent MBP-FRD lines revealed a significant increase in myelin thickness as a function of fibre diameter for both transgenic lines (13% and 16% increase). This increase in myelin thickness was not accompanied by alterations in myelin compaction. These results support the idea that FGF signaling in oligodendrocytes plays a role in the modulation of axon myelination in vivo.

Animals↗

PubMed1997

Constipation-related symptoms and bowel program concerning individuals with spinal cord injury.

PURPOSE: To determine the prevalence of constipation-related symptoms in individuals with chronic spinal cord injury (SCI), to describe the bowel program as reported by patients and including use of bowel medications and evacuation techniques, and to examine the clinical, functional and pharmacological risks of difficulty with evacuation. PATIENTS AND METHODS: This is a cross-sectional study of all in-patients at least 3 months beyond acute injury, on the West Roxbury/Brockton VAMC SCI Service, during a 10 month period (n = 197). Clinical, functional, and medication data were abstracted from medical and nursing records. Individual interviews were conducted with all available participants (n = 161, 82%) regarding bowel-related symptoms and treatment over the previous 1 month period. The study definition of difficulty with evacuation was spending more than 1 h per episode of bowel evacuation. RESULTS: Forty-one percent of the 161 interview responders spent more than 1 h on bowel evacuation, 50% reported abdominal distension and 38% reported abdominal pain, 27% reported headaches or sweats relieved by having a bowel movement, and 33% reported fecal incontinence at least once a month. The bisacodyl suppository was the most commonly used laxative agent, while docusate was the most popular oral agent. Subjects with difficulty with evacuation (n = 66) were compared with those who spent less than 1 h on evacuation (n = 95). Factors associated with difficulty with evacuation were tetraplegia, Frankel grade A/B, laxative use, polypharmacy, previous urinary outlet surgery, and symptoms of abdominal pain and distension. CONCLUSION: Constipation-related symptoms are highly prevalent in individuals with spinal cord injury, despite considerable laxative use. Our findings suggest that difficulty with evacuation can be predicted on the basis of a patient's clinical profile.

Adult↗

PubMed1997

How do older persons define constipation? Implications for therapeutic management.

This study examined the relation between bowel-related symptoms and self-report of constipation in 10,875 subjects aged 60 years and over, who participated in the 1989 National Health Interview Survey. Subjects reporting constipation "always" or "mostly" over the past 12 months (n = 594) were compared with those who reported never having the symptom (n = 4,192). Straining (adjusted odds ratio 66.7; 95% confidence interval 31.5, 142.4) and hard bowel movements (25.6; 16.7, 38.7) were most strongly associated with self-report of constipation. These findings suggest that treatment for constipation in the older population should be directed as much or more at facilitating comfortable rectal evacuation, as increasing bowel movement frequency.

Aged↗

PubMed1997

Occlusal traits in a group of school children in an isolated society in Jerusalem.

The prevalence of occlusal features in 939 children, aged 6-13 years, belonging to an ultra-orthodox community of Jewish Ashkenazi descent living in Jerusalem was studied clinically. Sexual dimorphism was found for overjet, overbite, and habit practising. About one-quarter of the sample exhibited some degree of occlusal mutilation due to caries, thus creating a 'caries-affected' subgroup, the rest forming the 'caries-free' subgroup. In the latter set, normocclusion was scarce (7.4 per cent), Class I being the most frequent malocclusion (49.1 per cent). Caries had a significant effect on the symmetry of bilateral occlusal relationships, lower dental midline deviation, and on crowding/spacing conditions in the mixed dentition stage (except for the maxilla in late mixed dentition). The low prevalence of normocclusion can be attributed to genetic background, environmental influences and the definition attached to normal occlusion.

Adolescent↗

PubMed1997

The effect of nonisodiametric design on the ease of extracting chronically implanted pacemaker leads.

Extracting permanently implanted transvenous pacemaker leads is often difficult because a fibrous sheath tends to trap the lead at various points along its course. Because many leads have bulbous or nonisodiametric portions, extraction may be rendered even more troublesome, because it is difficult to pull the larger portion through the narrow areas of the sheath. Furthermore, forceful extraction may have dire consequences, such as cardiac laceration. A study was undertaken in animals to evaluate the effect of lead isodiametricity on lead extraction. The results show that any increase in the diameter of the lead tip greatly reduces the ease of its removal. Consequently, leads designed to be isodiametric throughout their entire lengths will greatly enhance their removability.

Animals↗