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Biomedical subjects

P H Gordon

Publications and source records attributed to P H Gordon.

At least 19 recordsLinked to original sources
PubMed2006

Development and evaluation of a self-administered version of the ALSFRS-R.

We evaluated the reliability and sensitivity to change over time of a newly developed self-administered version of the ALS functional rating scale-revised (ALSFRS-R) in 60 consecutive patients from an ALS clinic. The self-administered ALSFRS-R showed excellent reliability (intraclass correlation = 0.93, 95% CI: 088 to 0.96) and similar sensitivity to change over time vs the standard evaluator-administered ALSFRS-R.

Activities of Daily Living↗
PubMed2006

Randomized controlled phase II trial of glatiramer acetate in ALS.

The authors conducted a randomized controlled trial to test the safety and immunology of glatiramer acetate in ALS. Twenty treated patients were randomly assigned to daily or biweekly injections. Ten control patients were selected from another trial and followed up concurrently. Injection reactions were the only common adverse event (p = 0.01). Treated patients showed enhanced lymphocyte proliferation (p = 0.02). The safety profile and immune effects support conducting larger trials of dose selection and efficacy.

Drug Administration Schedule↗
PubMed2006

The natural history of primary lateral sclerosis.

OBJECTIVE: To define the syndrome of primary lateral sclerosis (PLS) and disorders that contain features of both ALS and PLS, to determine the time beyond which PLS is less likely to become ALS clinically, and to determine the outcome of people with PLS and those who develop lower motor neuron (LMN) signs. METHODS: The authors reviewed the records of all 39 patients initially diagnosed with PLS in 1984 to 2004. Diagnostic subgroups were defined based on clinical features. The authors used Kaplan-Meier methods to estimate the time to diagnosis, linear regression analyses to assess function, and a Cox proportional hazard model to assess survival in subgroups. RESULTS: Of the 39 patients, 29 had only upper motor neuron (UMN) signs on initial evaluation. Thirteen of the 29 were later classified as having UMN-dominant ALS (UMN-D) because they acquired evidence of denervation by EMG (3.17 years) or examination (3.67 years). Sixteen of the 29 patients, classified as clinically pure PLS, retained only UMN signs and a normal EMG (mean follow-up 8.7 years). Ten patients who met criteria for ALS at the initial visit were used as controls. The UMN-dominant ALS group had lower functional scores (p = 0.033) than the PLS group, and similar scores to those with ALS. Survival was longer in both the PLS group (p = 0.027) and the UMN-D group (p = 0.067) than the ALS group. CONCLUSIONS: Clinically pure PLS can be defined by isolated UMN signs 4 years after symptom onset, and is a syndrome of slow progression with high levels of function. Prior to the fourth year, the diagnosis of PLS cannot be made with certainty because many patients develop LMN signs. UMN-dominant ALS, defined by predominantly UMN disease with minor LMN signs, has disability similar to ALS, but slower progression.

Adult↗
PubMed2005

Injuries sustained by colorectal surgeons performing colonoscopy.

BACKGROUND: Repetitive tasks in the workplace are one cause of injury. This study aimed to identify injuries specific to physicians routinely performing colonoscopy, and to identify prevention strategies. METHODS: A survey was sent to all 2,173 worldwide members of the American Society for Colon and Rectal Surgery to investigate injuries or disabilities that resulted from performing colonoscopy and the methods used to prevent and alleviate symptoms related to the procedure. RESULTS: The response rate was 28%. Of the respondents, 96% performed colonoscopy. At least one injury or pain believed to result from performing colonoscopy was reported by 39% of the respondents. The most frequently reported injuries were to hands and fingers (n = 257), neck (n = 65), and back (n = 52). The methods adopted to alleviate injury included changing the height of the stretcher or video monitor, changing from a standing to a sitting position, minimizing torque on the colonoscope, having an assistant perform the torque maneuver, and resting or taking time off from colonoscopy. Two respondents also created devices to make the instrument more ergonomic. CONCLUSION: The number of colorectal surgeons encountering injury from colonoscopy highlights the need for preventive strategies. The study results suggest that it may be necessary to improve the design of colonoscopes to make them more ergonomic. Appropriate positioning of the endoscopist, patient, and monitors may diminish some of the injuries encountered.

Colonoscopy↗
PubMed2005

Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family.

BACKGROUND: A 3 bp deletion located at the 5' end of exon 3 of MLH1, resulting in deletion of exon 3 from RNA, was recently identified. HYPOTHESIS: That this mutation disrupts an exon splicing enhancer (ESE) because it occurs in a purine-rich sequence previously identified as an ESE in other genes, and ESEs are often found in exons with splice signals that deviate from the consensus signals, as does the 3' splice signal in exon 3 of MLH1. DESIGN: The 3 bp deletion and several other mutations were created by polymerase chain reaction mutagenesis and tested using an in vitro splicing assay. Both mutant and wild type exon 3 sequences were cloned into an exon trapping vector and transiently expressed in Cos-1 cells. RESULTS: Analysis of the RNA indicates that the 3 bp deletion c.213_215delAGA (gi:28559089, NM_000249.2), a silent mutation c.216T-->C, a missense mutation c.214G-->C, and a nonsense mutation c.214G-->T all cause varying degrees of exon skipping, suggesting the presence of an ESE at the 5' end of exon 3. These mutations are situated in a GAAGAT sequence 3 bp downstream from the start of exon 3. CONCLUSIONS: The results of the splicing assay suggest that inclusion of exon 3 in the mRNA is ESE dependent. The exon 3 ESE is not recognised by all available motif scoring matrices, highlighting the importance of RNA analysis in the detection of ESE disrupting mutations.

Adaptor Proteins, Signal Transducing↗
PubMed2005

The ALSFRSr predicts survival time in an ALS clinic population.

OBJECTIVE: To determine whether the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRSr), a predictor of survival time in ALS clinical trials, predicts survival time in an ALS clinic population. METHODS: The authors prospectively evaluated 267 consecutive patients with ALS at first visit to an ALS clinic using the ALSFRSr and pulmonary function testing. The association of ALSFRSr score at baseline with death or tracheostomy in ALS was examined using Cox proportional hazards models, adjusting for age at baseline, sex, and symptom duration. RESULTS: Of 267 patients with ALS, 103 (39%) reached the endpoint, defined as either death (79 patients) or tracheostomy (24 patients), during a mean follow-up of 1.0 +/- 0.7 years. Among the 103 patients who reached the endpoint during follow-up, 77 (75%) had a baseline ALSFRSr score of less than 38 (the median baseline score of all patients), compared to 53 of 164 (32%) who remained alive without tracheostomy. Patients with a total ALSFRSr score below the median had a 4.4-fold increased risk of death or tracheostomy compared to those who scored above the median (HR: 4.38, 95% CI: 2.79 to 6.86, p < 0.001). Both the total ALSFRSr score at baseline (HR: 0.94, 95% CI: 0.91 to 0.98, p < 0.001) and forced vital capacity at baseline (HR: 0.99, 95% CI: 0.98 to 1.00, p = 0.02) were associated with death or tracheostomy when included in the same Cox model. CONCLUSIONS: In an ALS clinic population, the total Amyotrophic Lateral Sclerosis Functional Rating Scale-revised score at baseline is a strong predictor of death or tracheostomy independently of forced vital capacity and after adjustment for age at baseline, sex, and symptom duration.

Age of Onset↗
PubMed2005

Novel genomic insertion-- deletion in MLH1: possible mechanistic role for non-homologous end-joining DNA repair.

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited cancer syndrome caused by a defect in the mismatch repair pathway. The majority of HNPCC mutations have been detected in MLH1 and MSH2. Most reported mutations are substitutions, small insertions and deletions, but standard methods of mutation analysis do not detect large rearrangements. It is now established that large deletions, insertions and rearrangements account for a significant proportion of MLH1 and MSH2 mutations. We report an unusual rearrangement resulting in the deletion of exons 6, 7 and 8 of MLH1, with the retention of part of intron 6 and insertions of two nucleotides each flanking the retained sequence. The 349-bp-retained sequence is made up of two closely spaced Alu sequences. The mutation was initially detected by protein truncation test and cDNA sequencing. Multiplex ligation-dependent probe amplification confirmed the deletion of three exons. PCR and sequencing were used to characterize the breakpoint. Despite the high density of Alu elements in MLH1, there is no homology at the deletion breakpoints or insertion junctions in this case to suggest that homologous recombination has occurred. We propose a mechanism involving non-homologous end joining to explain the occurrence of this complex deletion.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Undergraduate orthodontic teaching in the new millennium--the Newcastle model.

This paper identifies the main factors which have influenced the nature of the undergraduate orthodontic curriculum presently taught at Newcastle University. It also outlines the philosophy that underpins the teaching, states the professional aims of the tutors and spells out the clinical objectives set for the students.

Curriculum↗
PubMed2004

Placebo-controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis.

Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or placebo for 6 months; there were no significant differences in adverse events (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover trial. The mean tolerated dose was 387 mg/day, there was a trend toward more gastrointestinal AE (p = 0.057), and blood urea nitrogen and liver enzymes became elevated (p < 0.05). Using these data, the authors have designed and launched a phase III trial.

Adult↗
PubMed2004

Long-term outcome of rubber band ligation for symptomatic primary and recurrent internal hemorrhoids.

PURPOSE: Rubber band ligation therapy for symptomatic hemorrhoidal disease has been used for many years and is a well-accepted treatment modality, but information on long-term outcome is limited. Our goals were to determine safety and long-term efficacy of this treatment. METHODS: A retrospective chart review of patients undergoing rubber band ligatures for symptomatic internal hemorrhoids in a single practice was conducted. Information on presenting symptoms, number of bands applied, response to therapy, complications encountered, length of follow-up, interval to recurrent symptoms when applicable, and subsequent therapy were documented. Supplemental information was obtained from telephone follow-up. Outcome was categorized as success or failure, in which success was defined as: permanent relief of symptoms for follow-up period; marked improvement in symptomatology with rare manifestation of bleeding (< or = 1/month); symptom relief for a limited period of time (> or = 100 days), and failure was defined as: modest improvement (decreased but not relief of symptoms); or no improvement in symptoms. RESULTS: A total of 805 patients underwent 2,114 rubber band ligatures. Most common presenting symptoms were bleeding in 731 patients (90.8 percent) and prolapsing in 382 patients (47.5 percent). The median number of bands placed was two (range, 1-17). The median time between bandings was 4.7 (range, 1.1-35.6) weeks. Median follow-up time was 1,204 (range, 14-9,571) days. Excluding 104 patients lost to follow-up (never returned after initial treatment), success was obtained in 70.5 percent (494/701) and failure in 29.5 percent (207/701) of patients. Success rates were similar for all degrees of hemorrhoids. Hemorrhoidal disease requiring the placement of four or more bands was associated with a trend in higher failure rates and greater need for subsequent hemorrhoidectomy. Complications per treatment series included bleeding (2.8 percent), thrombosed external hemorrhoids (1.5 percent), and bacteremia (0.09 percent). Higher bleeding rates were encountered with the use of acetylsalicylic acid/nonsteroidal anti-inflammatory drugs and warfarin. Time to recurrence was less with subsequent treatment courses. Treatment of recurrent symptoms with rubber band ligation resulted in success rates of 73.6, 61.4, and 65 percent for first, second, and third recurrences respectively. This resulted in a cumulative success rate of 80.2 percent for this method of treatment. CONCLUSIONS: Rubber band ligatures are safe and effective therapy for symptomatic internal hemorrhoids. It can be used to treat all degrees of hemorrhoids with similar effectiveness. The likelihood of success is lower if more than four bands are needed to eliminate symptoms. The use of acetylsalicylic acid/nonsteroidal anti-inflammatory drugs and warfarin is associated with higher bleeding rates. Rubber band ligatures for recurrence of symptoms is effective; however, time to recurrence is less with subsequent treatments.

Adult↗
PubMed2004

Smile aesthetics and malocclusion in UK teenage magazines assessed using the Index of Orthodontic Treatment Need (IOTN).

OBJECTIVE: There is a significant demand for orthodontic treatment within the UK from adolescent girls, a group known to be influenced by the media portrayal of body form and body image, which may extend to the presentation of malocclusions. This study examined the portrayal of malocclusion in a media type that targets teenage girls under 16 years of age. MATERIALS AND METHODS: A representative selection of 1 month's magazines targeting this group were investigated, and the frequency and severity of malocclusions displayed were assessed. Two calibrated examiners viewed all the smiles (on two occasions) using a modification of Index of Orthodontic Treatment Need (IOTN) and assigned an Aesthetic Component Score to each smile. RESULTS: It was found that the aesthetic score is low (less than 7) for the majority of models (92.8%) indicating no need or a borderline need for treatment. Only 7.2% of models exhibited a definite need for treatment. CONCLUSION: It appears that the portrayal of malocclusion in teenage magazines does not reflect the general treatment need of the adolescent population.

Adolescent↗
PubMed2003

Do distal adenomas mandate total colonoscopy?

BACKGROUND: Distal adenomas have been considered markers of proximal neoplasms. It also has been suggested that patients with small, distal adenomas do not require proximal examination of the colon. This study was conducted to determine the validity of the latter recommendation. METHODS: From a total of 5,132 colonoscopies performed between 1976 and 1999, all patients from whom adenomas were removed were included. Those with previous colon resections or incomplete cecal intubation were excluded. Proximal adenomas were defined as those proximal to the sigmoid colon. Adenomas were considered advanced if they were 1 cm or larger, contained any villous component, or demonstrated severe dysplasia. RESULTS: The study included 226 patients. Overall, 98 patients had distal adenomas, and there was a synchronous proximal adenomas rate of 23.4%. Patients with single, small, rectosigmoid, tubular adenomas had proximal adenomas at a rate of 28.8%, and 9.6% were advanced adenomas. Patients with advanced distal adenomas had synchronous proximal adenomas at a rate of 18.9%, and 10.8% of these were advanced adenomas. According to multiple logistic regression, the strongest predictor of proximal neoplasia was the absence of distal polyps. CONCLUSION: These data confirm the necessity for total colonoscopy in all patients with distal adenomas regardless of size. In addition, the high proportion of proximal neoplasia without distal markers suggests that full colonoscopy may be warranted as a screening tool in all patients.

Adenoma↗
PubMed2003

Dental erosion -- changing prevalence? A review of British National childrens' surveys.

OBJECTIVES: To investigate the change in the prevalence of dental erosion, over time, by a review of the data from the published national dental surveys of young people in the UK. A subsidiary objective was to investigate the relationship between erosion and possible associated risk factors. DESIGN: The review was based on cross-sectional prevalence studies incorporating a clinical dental examination and structured interviews. SAMPLE: The data were collated from the 1993 UK childrens' dental health survey and the dental report of the two National Diet and Nutrition Surveys (NDNS) of children aged 1(1/2)-4(1/2) in 1992/3 and 4-18 years in 1996/7. The criteria used for data collection were comparable between the three different studies. RESULTS: Comparing the data from the different studies, the prevalence of erosion was seen to increase from the time of the childrens' dental health survey in 1993 and the NDNS study of 4-18-year-olds in 1996/7. There was a trend towards a higher prevalence of erosion in children aged between 3(1/2) and 4(1/2) and in those who consumed carbonated drinks on most days compared with toddlers consuming these drinks less often. Drinks overnight were associated with an increased prevalence of erosion. More 4-6-year-olds with reported symptoms of gastro-oesophageal reflux had erosion compared with symptom-free children. On multivariate analysis, the strongest independent association with erosion was geography, with children living in the North having twice the odds of having erosion compared with those in London and the South-east. CONCLUSIONS: Comparing prevalence data from cross-sectional national studies indicates that dental erosion increases between different age cohorts of young people over time. Dietary associations with erosion are present but weak. Similarly, there is an association apparent between erosion, symptoms of gastro-oesophageal reflux and socio-demographic variables such as region of domicile, social class, and receipt of social benefits.

Adolescent↗
PubMed2003

An ex vivo investigation to compare orthodontic bonding using a 4-META-based adhesive or a composite adhesive to acid-etched and sandblasted enamel.

OBJECTIVE: This study investigates the shear-peel orthodontic bond strengths of brackets bonded with an unfilled acrylic resin containing 4-META (MCP Bond or a no-mix composite adhesive (Right On) to acid-etched or sandblasted enamel. DESIGN: Ex vivo. MATERIALS AND METHODS: Eighty human pre-molar teeth were separated into four equal groups, according to the adhesive used and method of enamel pre-treatment. Group I-Right On with enamel etched using phosphoric acid for 30 seconds. Group II-Right On with enamel sandblasted using 50- microm alumina particles at 80 psi for 3 seconds. Group III-MCP Bond with enamel etched using phosphoric acid for 30 seconds. Group IV-MCP Bond with enamel sandblasted using 50- microm alumina particles at 80 psi for 3 seconds. Subsequently, the specimens were stored in distilled water for 24 hours prior to bond strength testing using an Instron universal testing machine. Each debonded tooth was scored using the adhesive remnant index (ARI) to determine the site of bond failure. RESULTS: The mean bond strength (1 SD) were Group I: 10.7 (2.7) MPa, Group II: 5.3 (1.3) MPa, Group III: 15.9 (3.4) MPa, Group IV: 15.0 (2.2) MPa. Statistical analysis using one-way analysis of variance and Tukey test found no statistical difference between Group III and Group IV (P > 0.05), but the other groups were statistically different from each other (P < 0.05). The data were found to fit the Weibull distribution and Weibull analysis showed stress required for a 5 per cent probability of failure was: Group I: 5.77 MPa; Group II: 3.32 MPa; Group III: 10.31 MPa; Group IV: 10.58 MPa. Chi-square test showed a statistically significant difference existed between the ARI scores (P < 0.001), principally through less adhesive remnants being observed on the sandblasted specimens. CONCLUSION: The adhesive containing 4-META achieved significantly higher bond strengths than the composite adhesive, particularly in the case of sandblasted enamel.

Acid Etching, Dental↗
PubMed2002

The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906G-->C, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (P=.042), and those with colorectal cancer who carried the mutation were, on average, younger than affected individuals who did not carry it (P=.033). The mutation was not detected in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is <60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Alanine↗
PubMed2001

The changed histologic paradigm of colorectal polyps.

BACKGROUND: Previous literature has recorded the preponderance of hyperplastic over neoplastic polyps. This study evaluated the histopathologic characteristics of colonic polyps, excised during colonoscopic polypectomy, and further determined their relationship to age, location, and gender. METHODS: Of 5132 colonoscopies reviewed between 1976 and 1999, 757 were performed on 582 patients who had polyp removal. Patients with previous colon resection or incomplete cecal intubation were excluded. RESULTS: The mean age was 67 +/- 11 years for men and 66 +/- 11 years for women. Of the 1050 lesions histologically analyzed, 871 (83.0%) were neoplastic, 129 (12.3%) were hyperplastic, and 50 (4.8%) were miscellaneous lesions (29 inflammatory polyps, 14 lipomas, 2 leiomyomas, 1 juvenile polyp, and 4 no pathology identified). Hyperplastic polyps were always less than 1 cm (with one exception) and were located predominantly in the left colon, the majority residing in the sigmoid colon. Peak prevalence of hyperplastic polyps occurred in the 50-70 years old age group. Of the neoplastic polyps, 566 (65.0%) were tubular, 225 (25.8%) villotubular, 63 (7.2%) villous adenomas, 4 (0.5%) mixed adenomatous hyperplastic polyps, and 12 (1.4%) invasive carcinomas. The peak prevalence of neoplastic polyps occurred in the same age group as did hyperplastic polyps. Even though adenomatous polyps outnumbered hyperplastic polyps throughout the colon and within each age group, a greater percentage of hyperplastic polyps were found distally and in younger patients compared to location and age groups for neoplastic polyps. CONCLUSION: Adenomatous polyps outnumber hyperplastic polyps 7:1, even in the distal colon. Even small polyps seen during colonoscopy should be removed and subjected to histologic analysis because of the advisability of follow-up examinations of patients with neoplastic polyps. The increase in the incidence of neoplastic polyps beginning at the age of 50 years supports the need for colonoscopy in these individuals.

Adenomatous Polyps↗
PubMed2001

Early electrodiagnostic findings in Guillain-Barré syndrome.

CONTEXT: Guillain-Barré syndrome (GBS) is the foremost cause of acute, generalized, peripheral neuropathic weakness. Although nerve conduction studies are a diagnostic aid, the characteristic electrical changes may not evolve for several weeks. Early diagnosis of GBS is important, however, because early treatment has been shown to improve outcome. OBJECTIVES: To describe the electrodiagnostic abnormalities detectable in the first week of GBS, to determine if there are early patterns suggestive of GBS, and to identify the percentage of patients whose condition can be diagnosed with reasonable certainty in the first week. DESIGN AND SETTING: We retrospectively reviewed the medical records of all patients admitted to the Cleveland Clinic Foundation, Cleveland, Ohio, having the discharge diagnosis GBS during the past 16 years. Patients who underwent nerve conduction studies within 7 days of muscle weakness were selected for this study. RESULTS: The H reflex was absent in 30 (97%) of 31 patients. Nineteen patients (61%) had low-amplitude or absent sensory nerve action potential (SNAP) in the upper extremity. Fifteen patients (48%) overall, including 21 (67%) of the 31 patients, including 14 (67%) of the 21 patients younger than 60 years, had an abnormal upper extremity SNAP combined with a normal sural SNAP. Other findings included an abnormal F wave (25 patients [84%]), reduced compound muscle action potential amplitude (22 patients [71%]), prolonged distal latency (20 patients [65%]), temporal dispersion (18 patients [58%]), slowed motor conduction velocity (16 patients [52%]), and motor conduction block (4 patients [13%]). Definite diagnosis was possible in 17 patients (55%), but not commonly until the fifth day. CONCLUSIONS: The H reflex is the most sensitive test for early GBS. Upper extremity SNAPs are also frequently abnormal in early GBS. Absent H response, abnormal F wave, and abnormal upper extremity SNAP combined with a normal sural SNAP are characteristic of early GBS. If multiple nerves are tested, definite diagnosis is possible in half the patients, but not until the fifth day after the onset of symptoms.

Action Potentials↗