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Biomedical subjects

D J Watson

Publications and source records attributed to D J Watson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of the amyloid precursor protein Glu693-->Gln 'Dutch' mutation on the production and stability of amyloid beta-protein.

Hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D), is a cerebral amyloidosis characterized by prominent vascular deposits and fatal haemorrhages. The disorder is caused by a point mutation in codon 693 of the gene encoding the amyloid precursor protein (APP), resulting in a Glu-->Gln amino acid substitution at position 22 of the amyloid beta-protein (Abeta) region. The pathogenetic mechanisms of HCHWA-D are unknown but could involve alterations in the proteolytic processing of APP and in amyloid fibril formation. We examined Abeta production and stability by using cultured human embryonic kidney 293 cells stably expressing wild-type or 'Dutch' APP. Radiosequencing and quantitative immunoprecipitation experiments showed that cells expressing Dutch APP secreted increased quantities of Abeta peptides beginning at Asp1, and of truncated peptides beginning at Val18 and Phe19. The ratio of levels of 4 kDa (Abeta) to 3 kDa (p3) peptides remained constant due to co-ordinate decreases in other peptide species. Novel truncated or elongated peptides were not observed. Pulse-chase experiments showed that the Dutch mutation did not affect the stability of the Abeta or p3 populations. These results are consistent with a disease process in which the Dutch mutation results in the production of Abeta peptides with enhanced propensities for fibrillogenesis, leading to accelerated vascular deposition and disease.

Amino Acid Sequence↗
PubMed1999

Comparison of the responsiveness and relative effect size of the western Ontario and McMaster Universities Osteoarthritis Index and the short-form Medical Outcomes Study Survey in a randomized, clinical trial of osteoarthritis patients.

OBJECTIVE: This study compares the responsiveness and relative effect sizes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) with the Medical Outcomes Study Short Form Health Survey (SF-36) in a randomized clinical trial for treatment of osteoarthritis (OA). METHODS: Patients with OA of the knee or hip were randomized to receive either placebo or 2,400 mg/day of ibuprofen for 28 days. Patients completed the WOMAC and SF-36 at baseline and days 7, 14, and 28 of the trial. RESULTS: Patients receiving ibuprofen showed significant improvement in WOMAC pain, physical functioning, and the total score, while improvement was detected only for bodily pain on the SF-36. The WOMAC detected significant differences between ibuprofen and placebo for pain and physical functioning, whereas the SF-36 detected differences for the bodily pain subscale. CONCLUSION: These results suggest the WOMAC has greater power to detect treatment differences than the SF-36, with respect to pain and physical functioning, in OA clinical trials.

Activities of Daily Living↗
PubMed1998

Diabetes mellitus and its complications in an African-American community: project DIRECT.

Project DIRECT (Diabetes Intervention Reaching and Educating Communities Together) is a multilevel community-based intervention project designed to address diabetes and its complications in an African-American community. This article presents results of the Project DIRECT pilot study and describes risk factors for diabetes, diabetes prevalence, complications, and care practices. During 1993, a pilot study was conducted among persons 20 to 74 years of age in Wake County, North Carolina. The study involved household interviews and examinations, and more extensive health center interviews and examinations based on the race of the head of the household, previous diagnosis of diabetes, and results of capillary glucose tests done in the household. Of the black population aged 20 to 74 years, 52 +/- 3% reported being inactive and 51 +/- 3% were overweight; the prevalence of diagnosed diabetes was 5.2 +/- 0.9%; the prevalence of undiagnosed diabetes was 5.7 +/- 2.7%; and the prevalence of impaired glucose tolerance was 11.4 +/- 7.5%. Blacks with diabetes were significantly more likely than nonblacks with diabetes to have uncontrolled hypertension and to smoke cigarettes. Blacks with diabetes were significantly less likely to report having health insurance or to have a private health-care provider. Diabetes mellitus is a major public health problem in the African-American community of Wake County. Modifiable risk factors for diabetes and undiagnosed diabetes are common. Project DIRECT is attempting to improve the health-related quality of life of this population by reducing the burden of diabetes and its complications through a multilevel, community-based intervention.

Adult↗
PubMed1997

Heparin-binding properties of the amyloidogenic peptides Abeta and amylin. Dependence on aggregation state and inhibition by Congo red.

Aggregation and deposition of the 40-42-residue amyloid beta-protein (Abeta) are early and necessary neuropathological events in Alzheimer's disease. An understanding of the molecular interactions that trigger these events is important for therapeutic strategies aimed at blocking Abeta plaque formation at the earliest stages. Heparan sulfate proteoglycans may play a fundamental role since they are invariably associated with Abeta and other amyloid deposits at all stages. However, the nature of the Abeta-heparan sulfate proteoglycan binding has been difficult to elucidate because of the strong tendency of Abeta to self-aggregate. Affinity co-electrophoresis can measure the binding of proteoglycans or glycosaminoglycans to proteins without altering the physical state of the protein during the assay. We used affinity co-electrophoresis to study the interaction between Abeta and the glycosaminoglycan heparin and found that the aggregation state of Abeta governs its heparin-binding properties: heparin binds to fibrillar but not nonfibrillar Abeta. The amyloid binding dye, Congo red, inhibited the interaction in a specific and dose-dependent manner. The "Dutch" mutant AbetaE22Q peptide formed fibrils more readily than wild type Abeta and it also attained a heparin-binding state more readily, but, once formed, mutant and wild type fibrils bound heparin with similar affinities. The heparin-binding ability of aggregated AbetaE22Q was reversible with incubation in a solvent that promotes alpha-helical conformation, further suggesting that conformation of the peptide is important. Studies with another human amyloidogenic protein, amylin, suggested that its heparin-binding properties were also dependent on aggregation state. These results demonstrate the dependence of the Abeta-heparin interaction on the conformation and aggregation state of Abeta rather than primary sequence alone, and suggest methods of interfering with this association.

Amino Acid Sequence↗
PubMed1997

Ritodrine- and terbutaline-induced hypokalemia in preterm labor: mechanisms and consequences.

The effects of ritodrine and terbutaline on potassium homeostasis, renal function, and cardiac rhythm were assessed in women treated with these drugs for preterm labor. Timed blood and urine samples were obtained for two hours before and during six hours of intravenous ritodrine (N = 5) and terbutaline (N = 5) administered in pharmacologically equivalent doses. No differences were found in any parameters affecting potassium homeostasis or renal function between these drugs. A decrease in mean plasma potassium of 0.9 mEq/liter occurred after 30 minutes of drug infusion (4.2 +/- 0.1 to 3.3 +/- 0.1 mEq/liter, P < 0.005) before any significant changes in plasma glucose (75.0 +/- 4.7 to 93.7 +/- 6.1 mg/dl, P = NS) or plasma insulin (12.4 +/- 6.0 to 28.4 +/- 5.1 mU/ml, P = NS). The mean plasma potassium after four hours of drug infusion was 2.5 +/- 0.1 mEq/liter. Plasma insulin rose to a level known to induce cellular potassium uptake (39.2 +/- 7.7 mU/ml) after 60 minutes of drug therapy and remained at this level for four hours. Hyperlactatemia occurred at four hours (4.7 +/- 0.8 mmol/liter) and the plasma lactate/pyruvate ratio increased in a 10:1 ratio. Both drugs significantly reduced glomerular filtration rate, sodium, potassium, and chloride excretion and urinary flow rate. Changes in acid-base homeostasis, plasma aldosterone, or renal potassium excretion did not contribute to ritodrine-or terbutaline-induced hypokalemia. In 83 women with preterm labor randomly assigned to ritodrine (N = 42) or terbutaline (N = 41), the maximum decrease in plasma potassium occurred after six hours of drug infusion. During Holter monitoring, 3 of 14 women treated with ritodrine or terbutaline developed symptomatic cardiac arrhythmias at the lowest plasma potassium while no women treated with saline and morphine (N = 12) developed cardiac arrhythmias (P = 0.14). We conclude that ritodrine and terbutaline induce profound hypokalemia by stimulating cellular potassium uptake and both drugs cause significant renal sodium and fluid retention and cardiac arrhythmias. Careful monitoring of electrolytes, fluid balance, and cardiac rhythm should occur during tocolytic therapy with ritodrine or terbutaline.

Adolescent↗
PubMed1996

Timing of hard palatal closure: a critical long-term analysis.

The controversy about timing of cleft palate surgical procedures is focused on early palatoplasty for improved speech versus delayed hard palate repair for undisturbed facial growth. Timing and technique of palate repair are the most important influences on speech and facial growth, yet there is no consensus on the age or technique for surgery. The Oxford Cleft Palate Study was initiated to evaluate critically the long-term follow-up of 44 patients with early versus late closure of the hard palate. A multidisciplinary approach was used to determine the incidence of speech deficiencies, palatal fistulas, maxillofacial growth disturbances, and hearing abnormalities and to assess objectively the long-term effects of two different treatment modalities on the cleft palate patient. The 44 patients were selected randomly, interviewed, and examined by the multidisciplinary Oxford Cleft Palate Study team. The average age at follow-up in the early closure group was 17.0 years versus 18.2 years in the late closure group. There was a similar number of unilateral and bilateral clefts in both the early and late closure groups. The hard palate was closed in the early group at an average age of 10.8 months versus 48.6 months in the late closure group. All operative procedures in each group were performed by the same senior plastic surgery consultant. Both consultants have since retired and did not participate in the study. Each patient was evaluated by the same plastic surgeon, speech pathologist, orthodontist, and otologist. All examiners were blinded in that they were unaware of the type or timing of the surgical technique and had no prior knowledge of or access to the patient's medical records. Furthermore, none of the examiners participated in the initial care and surgery of these patients. Statistically significant greater speech deficiencies were noted with delayed hard palate closure, especially in articulation, nasal resonance, intelligibility, and substitution pattern assessment (overall intelligibility, p < 0.01). Likewise, the persistent palatal fistula rate in the late closure group was 35 percent in comparison with 5 percent for the early closure group (p <0.02). No significant differences in hearing or maxillofacial growth impairment were delineated in either group. Our data suggest that delaying hard palate closure results in significant speech impairment without a beneficial maxillofacial growth response.

Adolescent↗
PubMed1992

Fractured-nose reduction under local anaesthesia. Is it acceptable to the patient?

This article examines patients' acceptance of fractured-nose reduction under local anaesthesia, both objectively and subjectively. At each stage of the reduction the level of the discomfort, the patients' experiences were recorded. The success rate of complete reduction of the nasal fracture was found to be 71% and this was similar to that obtained in other studies that have used general anaesthesia. An overall level of discomfort for the procedure in terms a layman can understand was obtained by comparing the manipulation with that of having a tooth filled at the dentist. Sixty-three percent of the patients said that the nasal fracture reduction was no worse or the same as a dental filling. Our study showed that 96% of patients would be willing to undergo the same local anaesthetic procedure if they fractured their nose a second time. We conclude that it is possible to reduce the majority of fractured noses adequately with little inconvenience to the patient under local anaesthesia, and so we recommend that this procedure should be considered in the first-line treatment of the displaced fractured nose.

Adolescent↗
PubMed1990

Lymphogranuloma venereum of the tonsil.

A case of lymphogranuloma venereum of the tonsillar lymph tissue is presented. The similarities of tonsils to cervical lymph nodes are discussed and the importance of histological examination of abnormal tonsil tissue is reiterated.

Adult↗
PubMed1990

Death following suspected alprazolam withdrawal seizures: a case report.

This is a case report of severe psychosis and seizures following abrupt discontinuation of alprazolam and then the recurrence of seizures at the end of a gradual tapering schedule. The last of these seizures appeared to be a contributing factor in the patient's death. To the authors' knowledge, this is the first published report of a fatality associated with alprazolam withdrawal.

Alprazolam↗
PubMed1988

The safety and efficacy of intra-nasal ethmoidectomy.

Each of the three types of ethmoidectomy: intra-nasal, trans-antral and external, has its supporters and detractors who argue about the efficacy and safety of the procedures. One hundred and five ethmoidectomies for nasal polyps are reviewed retrospectively. Regardless of the approach used, approximately half of these had recurrence of polyps and some patients had several revision operations. There were six complications specific to the surgery. None was serious but most occurred with external ethmoidectomy. The limitations of ethmoidectomy for nasal polyps, the reasons for the good safety record and the best means of training juniors in the procedures are discussed.

Ethmoid Bone↗
PubMed1988

Local versus general anaesthetic in the management of the fractured nose.

Displaced fractured noses are usually manipulated under general anesthetic. The appearances of fractured noses were assessed and the airways measured by rhinomanometry before and after nasal manipulation in 29 patients. Seventeen received a local anaesthetic (LA) and 12 a general anaesthetic (GA) for the manipulation. Patients were generally pleased with the outcome and there were no significant differences between results in the 2 groups. Bony manipulation did not affect the nasal airway. Local anaesthesia was acceptable to all but one patient. The benefits, including those of cost and safety, of local anaesthetic for manipulation of almost all fractured noses are discussed.

Adolescent↗