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Biomedical subjects

A D Allen

Publications and source records attributed to A D Allen.

At least 19 recordsLinked to original sources
PubMed2001

Generation, observation, and free radical reactivity of aliphatic bisketenes: the solution to a long-standing problem.

[reaction: see text] Bisketenes O=C=CH(CH(2))(n)()CH=C=O (1b,c,d, n = 4, 3, 6) and (E)-O=C=CHCH=CHCH=C=O (E-13) were generated in solution by dehydrochlorination of bis(acyl chlorides) and by photochemical Wolff rearrangements and identified by their characteristic IR signals. The bisketenes react with aminoxyl radicals to give tetraaddition products for 1b and conjugate 1,6-diaddition for E-13.

Journal Article↗
PubMed2001

A doubly destabilized antiaromatic cyclopentadienyl cation: solvolysis of a 5-trifluoroacetoxy-5-heptafluoropropyl 1,3-cyclopentadiene.

The 5-trifluoroacetoxy-5-heptafluoropropylcyclopentadiene 15 rearranges to the isomeric trifluoroacetate 16 with a rate constant 5 x 10(5) less than that for solvolysis of the corresponding 5-CH(3) derivative 5. Labeling of 15 with (18)O shows the rearrangement occurs by a [1,5]-sigmatropic rearrangement. Solvolysis of 16 occurs at a rate 4 times slower than its formation from 15 and leads to the extensively rearranged fulvene 18, implicating formation of the doubly destabilized cation 20. Carbocation formation from 15 is retarded by a factor of 10(20) relative to the model 11, showing cumulative destabilizing effects due to formation of the antiaromatic cyclopentadienyl carbocation and electron withdrawal by the fluoroalkyl group.

Journal Article↗
PubMed2001

Nitroxyl radical addition to pentafulvenones forming cyclopentadienyl radicals: a test for cyclopentadienyl radical destabilization.

Photochemical Wolff rearrangements in alkane solvents of the 6-diazo-2,4-cyclohexadienones 4 and 13-15 give pentafulvenone (1), 2,3-benzopentafulvenone (2), dibenzopentafulvenone (3), and 2,4-di-tert-butylpentafulvenone (16), as identified by conventional UV and IR spectroscopy. Reactions of these fulvenyl ketenes with tetramethylpiperidinyloxyl (TEMPO) proceed by addition of TEMPO to the carbonyl carbon forming delocalized radicals for 1 and 2 which add one or more further TEMPO molecules, while the initial radical products formed from 3 and 16 dimerize. The rate constants of these reactions compared to hydration rate constants for the same compounds show the benzannulated derivatives 2 and 3 fit a previous correlation k(2)(TEMPO) vs k((H(2)O), whereas for 1 and 16 there is evidence for inhibition of reactions with radicals. The deviations are consistent with an absence of aromatic stabilization of the cyclopentadienyl radicals from 1 and 16 that is compensated in the benzannulated derivatives.

Journal Article↗
PubMed2001

Nitroxyl radical reactions with 4-pentenyl- and cyclopropylketenes: new routes to 5-hexenyl- and cyclopropylmethyl radicals.

4-Pentenylketenes 4a and 9 and cyclopropylketenes 3a, 13, 14 (RCH=C=O) are generated by photochemical Wolff rearrangements and observed by IR as relatively long-lived species at room temperature in hydrocarbon solvents. The reactions of these ketenes with the nitroxyl radicals tetramethylpiperidinyloxyl (TEMPO, TO*) and tetramethylisoindoline-2-oxyl (TMIO, IO*) form carboxy substituted 5-hexenyl and cyclopropylmethyl radicals which are either trapped by a second nitroxyl radical or undergo rearrangements followed by trapping. The rate constant of the reaction of 4a with TEMPO was similar to that of n-BuCH=C=O (1b), while 3a was 4.3 times more reactive, indicating cyclopropyl stabilization of the incipient radical.

Journal Article↗
PubMed2001

Ketene reactions with the aminoxyl radical tempo: preparative, kinetic, and theoretical studies.

Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with ketenes RR(1)C=C=O generated by either Wolff rearrangement or by dehydrochlorination of acyl chlorides to give products resulting from addition of one TEMPO radical to the carbonyl carbon and a second to the resulting radical. Reactions of phenylvinylketenes 4b and 4f, phenylalkynylketene 4c, and the dienylketene AcOCMe=CHCH=CHCMe=C=O (11) occur with allylic or propargylic rearrangement. Even quite reactive ketenes were generated as rather long-lived species by photochemical Wolff rearrangement in isooctane solution, characterized by IR and UV, and used for kinetic studies. The rate constants of TEMPO addition to eight different ketenes have been measured and give a qualitative correlation of log k(2)(TEMPO) = 1.10 log k(H(2)O) -3.79 with the rate constants for hydration of the same ketenes. Calculations at the B3LYP/6-311G//B3LYP/6-311G level are used to elucidate the ring opening of substituted cyclobutenones leading to vinylketenes and of 2,4-cyclohexadienone (17) forming 1,3,5-hexatrien-1-one (18).

Journal Article↗
PubMed2001

Assessment of the endoscopic semitendinosus/gracilis autograft procedure with interference screw fixation for reconstruction of the anterior cruciate ligament.

The semitendinosus/gracilis autograft procedure with interference screw fixation was evaluated for clinical effectiveness of anterior cruciate ligament (ACL) reconstruction. Thirty patients underwent the procedure and were evaluated an average of 15 months postoperatively. Results revealed 22 (73%) patients had a standard knee evaluation form score of normal or nearly normal, and 24 (80%) patients returned to strenuous or moderate activity levels. Average Lysholm outcome score was 89, and bilateral KT-2000 differences were <3 mm at follow-up. Functional knee test symmetry index percentage outcome for the one-legged hop test was 92.6% for distance and 98% for time. Length of time (i.e., < or =90 days or > or =91 days) between injury and surgery was independent of outcome. These findings indicate the semitendinosus/gracilis autograft is a viable procedure for reconstruction of the ACL-deficient knee.

Adult↗
PubMed1996

Pitfalls in the use of surrogate markers for human immunodeficiency virus disease: further evidence on pathogenesis.

The administration of drugs to human immunodeficiency virus patients with a pronounced CD4+ T lymphocytopenia may cause non-specific binding of the murine antibodies used in flow cytometry. This has produced spurious reports of early thymocytes in the circulating blood of human immunodeficiency virus-infected individuals following treatment with an anti-adhesion monoclonal mouse antibody (Cytolin+). Recent clinical experience with Cytolin+ confirms the pathogenic role of leukocyte adhesion pathways in human immunodeficiency virus infection. However, this experience also illustrates how comparisons of viral burden can be misleading. For nine patients with low CD4 counts, Cytolin+ alone reduced the mean ribonucleic acid-polymerase chain reaction by 0.45 log to 39 800 particles per mL. Ten patients with more advanced disease added Cytolin+ to an established regimen of standard antiretroviral drugs. Their mean polymerase chain reaction was only reduced by 0.2 log to 91 501. Yet, 67% of the former patients experienced a major clinical event within seven months, whereas the latter patients remained stable during this time.

Animals↗
PubMed1996

Audit of height measurement at age 3 years: results of a survey of Scottish health boards.

Height measurement at about the age of 3 years is accepted as a routine practice by all 15 Scottish health boards and is a recommendation of the Hall report Health for all Children. As part of a Scotland-wide project to assess the feasibility of audit of preschool surveillance programmes using routinely collected data, all boards were asked for information about this procedure. The results show that, while all boards confirmed its usefulness as a screening measure, only one board was realistically able to audit height measurement at this age at all stages using routinely available data. The whole screening process, including programme management, equipment validation, staff training and referral criteria, was examined using the quality standards defined in the Hall report. Results showed a wide variation between boards. For example, fewer than half of the boards provided guidelines for height measurement at age 3 to all professionals involved. The availability of even basic outcome data, such as numbers of children measured at this age was patchy, although this will improve with the introduction of the national computerised preschool surveillance system. Two boards have no plans to record such data routinely. In conclusion, before outcome data can be used and relied on, health boards and trusts need to develop local guidelines including quality standards such as age limits for measurement, programme management, provision of equipment, and review and referral criteria for inclusion into contracts.

Age Factors↗
PubMed1996

Audit of the distraction test of hearing at about 8 months of age: results of a survey of Scottish health boards.

The distraction test of hearing at 8 months is offered in all Scottish health boards and is a recommendation of the Hall Report 'Health for all Children'. As part of a Scotland-wide project to assess the feasibility of an audit of pre-school surveillance programmes using routinely collected data, all boards were asked for information about this screening test. The results showed that all boards regarded it as a worthwhile screening test in the present circumstances for early detection of sensorineural hearing loss (SNHL). The limitations on the reliability of the test were recognized by many boards. The quality elements of the whole screening process were examined, including screening technique, recording of results, provision of equipment and suitable test conditions, and staff training. The results showed variations in the attention given to quality standards. The results also showed a number of gaps in availability of data on coverage, results, and outcomes. Only one board was realistically able to audit the distraction test at all stages using routinely collected data. Availability of data will improve with the introduction of the national computerized Pre-school Child Health Surveillance Programme (CHSP) into the majority of health boards. The reliability and validity of audit results whether at board level or Scotland-wide level will depend on maintenance and adherence to quality standards in performing the test, in recording of results and also in ensuring adequate coverage.

Health Promotion↗
PubMed1995

Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot study.

It is well known that the AIDS pandemic is a consequence of pandemic HIV infection. However, Koch's postulates are not satisfied for two reasons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV infection. It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain other conditions are satisfied, and the most common of these other conditions (but not the only one) is HIV infection. Results from microbiology make leukocyte adhesion molecules a good candidate for the HIC. We have tested this hypothesis with a pilot study in which a small number of patients with HIV disease were infused with a monoclonal mouse antibody (MmAb) directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)2' fragments that bind to the same epitope but are nonimmunogenic. Both agents reduced peripheral viral burden significantly but fragments were more effective in this respect than the MmAb due to the mitogenic properties of the latter. For the same reason, only the MmAb were highly effective in raising circulating levels of single and double-marked CD4+ T lymphocytes, with a correlated resolution of cutaneous anergy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The Oxford growth study: a district growth surveillance programme 1988-1994.

OBJECTIVES: To develop a method of community based growth assessment. SETTING: Oxford District, United Kingdom. METHODS: A system of growth surveillance involving a community consultant paediatrician, a paediatric endocrinologist, a clinical auxologist, a project coordinator, and the many primary health care teams was started. Letters and meetings were arranged to introduce the programme to general practitioners and health visitors, emphasising the importance of growth assessment in normal child development. They were asked to measure all children as part of their routine developmental checks at 3 and 4.5 years of age. Community growth assessment clinics staffed by an experienced auxologist were established. Children whose heights were more than two standard deviation (SD) scores below the mean or whose height SD score decreased between the two ages were referred to the clinic. Any child whose height was more than 3 SD scores below the mean was referred directly to the paediatric endocrinologist. Those seen in the community clinics were followed up for a year and if their velocity was > 25th centile, karyotype normal, and bone age appropriately delayed, they were discharged to the general practitioner for further follow up. Any child with an annual velocity < 25th centile was referred to the endocrinologist. RESULTS: Of 20,338 children monitored, 260 (1.3%) had heights > -2 SD scores. Seventy six were lost to follow up, 35 were measuring errors, 69 were already seeing a paediatrician, leaving 80 children to be evaluated. Of these, 69 were "short normals" and 11 were newly identified diagnoses. CONCLUSIONS: This system of secondary referral keeps normal healthy children out of hospital, avoids unnecessary over-investigation, reduces travel and anxiety for families, avoids filling specialist clinics with normal children, and provides an inexpensive system of growth surveillance.

Analysis of Variance↗
PubMed1993

HIV and AIDS.

Explore the source record for details and available documents.

AIDS Vaccines↗
PubMed1993

Evaluation of a district growth screening programme: the Oxford Growth Study.

The Oxford district growth screening programme was established in 1988 as a community based survey of the heights of children at 3 and 4.5 years of age in a district of 550,000 people. The current birthrate is 7500 births/year and over the first three years of the study 20,338 children were screened in the community; the ascertainment ranged from 61-73.9% of the total expected. Mean height SD scores were significantly greater than the British standards; mean SD scores for boys and girls were 0.33 and 0.35 respectively at age 3, and 0.20 and 0.26 at 4.5 years. Altogether 260 (1.3%) of the total cohort were found to have heights < or = -2SD scores. The mean growth velocity of 2742 children measured at 3 and 4.5 years of age was similar to that of the national standards, 7.14 cm/year in boys and 7.21 cm/year in girls. Follow up data was available from 149 children whose heights were confirmed to be < or = -2SD scores. Of these 69 were already under the care of paediatricians. Thus far diagnoses in the 149 have included growth hormone deficiency (n = 2), Turner's syndrome (n = 2), Noonan's syndrome (n = 4), and emotional deprivation (n = 1). Ways in which ascertainment and detection of treatable causes of short stature could be improved are discussed and it is concluded that community growth screening is a useful part of the child health surveillance programme.

Body Height↗