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Biomedical subjects

S Waller

Publications and source records attributed to S Waller.

At least 19 recordsLinked to original sources
PubMed1999

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair.

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.

Animals↗
PubMed1998

Regulation of the synthesis and secretion of vasopressin.

We have developed a transgenic system that, for the first time, facilitates the monitoring of the regulatory dynamics of a central peptidergic system from transcription of a neuropeptide gene to the storage and release of the mature secretory product. Here we describe novel studies on the regulation of this system by physiological stimuli. The rat hypothalamic vasopressin (VP) mRNA responds in two ways to the functional demand imposed by an osmotic challenge. Firstly, the abundance of the VP RNA increases, and secondly, the size of the VP transcript increases as a consequence of a lengthening of the poly(A) tail. We have previously shown that chronic ingestion of 6-n-propyl-2-thiouracil (PTU), while not affecting plasma osmolality or VP mRNA size, results in a significant increase in the abundance of the hypothalamic VP mRNA. We now show that chronic PTU ingestion results in a dramatic increase in the abundance of the mRNA encoded by a modified rat vasopressin transgene that is expressed in rat vasopressinergic magnocellular neurons. This is accompanied by a significant depletion in neural lobe stores of a VP. However, this increase in transgene expression is accompanied by an increase in the proportion of transgene encoded products reaching the neural lobe--the pituitary content of a unique peptide encoded by the modified transgene does not change. These observations are further evidence in support of models of neurohypophyseal homeostasis that suggest that pituitary VP peptide levels passively reflect changes in hormone release and synthesis and that the availability of mRNA is the primary determinant of pituitary VP content in the basal state.

Animals↗
PubMed1998

Higher level practice in nursing: a prerequisite for nurse consultants?

The Prime Minister has stated that he wishes nurse consultant posts to be introduced in the NHS. The UKCC is currently consulting on a framework for recognizing nurses who are working at a higher level of practice, and this work could form the professional standards infrastructure for those seeking a nurse consultant post.

Education, Nursing, Continuing↗
PubMed1996

Neurohypophyseal and fluid homeostasis in transgenic rats expressing a tagged rat vasopressin prepropeptide in hypothalamic neurons.

We have developed a transgenic system that, for the first time, facilitates monitoring of the regulatory dynamics of a central peptidergic system from transcription of a neuropeptide gene to the storage and release of the mature secretory product. A rat vasopressin (VP) transgene (5-VCAT-3), the expression of which is restricted to hypothalamic vasopressinergic magnocellular neurons in rats, contains a sequence that, if translated, would place a unique hexadecapeptide (DRSAGYYGLFKDRKEK, abbreviated to DR-12-EK) at the C-terminus of the VP precursor. We have raised an antibody against this "tag" and, using immunohistochemistry, electron microscopy, RIA, and HPLC, have shown for the first time that a VP transgene RNA is translated into a protein product found, in a processed form, in secretory granules in the posterior pituitaries of transgenic rats. Disruption of the C-terminus of the VP precursor by the peptide tag is well tolerated and does not disrupt VP production or disturb salt and water balance. An osmotic stimulus increased hypothalamic DR-12-EK levels, but changes in posterior pituitary DR-12-EK levels were more complex. After 5 days of salt-loading, DR-12-EK levels fell, as would be expected if its release was coordinate with that of VP. However, after 10 days of salt-loading, posterior pituitary DR-12-EK levels increased, despite the lower level of VP. This probably reflects the greater response of the transgene to osmotic challenge at the RNA level, increasing the proportion of DR-12-EK-containing translation products transported to the posterior pituitary relative to those derived from the endogenous gene. The exaggerated response of the tagged transgene to osmotic challenge at both RNA and protein levels affords a new opportunity to study the regulatory dynamics of the VP system at the molecular level, but within the physiologically advantageous context of the intact animal.

Amino Acid Sequence↗
PubMed1994

Efficient and rapid affinity purification of proteins using recombinant fusion proteases.

In the affinity purification of recombinant fusion proteins, the rate-limiting step is usually the efficient proteolytic cleavage and removal of the affinity tail and the protease from the purified recombinant protein. We have developed a rapid, convenient and efficient method of affinity purification which can overcome this limitation. In one example of the method, the protease 3C from a picornavirus (3Cpro), which cleaves specific sequences containing a minimum of 6-7 amino acids, has been expressed as a fusion with glutathione S-transferase. The resultant recombinant 'fusion protease' cleaves fusion proteins bearing (from the amino-terminus) the same affinity tail as the fusion protease, a 3Cpro cleavage recognition site, and the recombinant protein of interest. The recombinant protein is purified in a single chromatographic step which removes both the affinity tail and the fusion protease. The advantages over existing methods include much improved specificity of proteolytic cleavage, complete removal of the protease and the affinity tail in one step, and the option of adding any desired amount of fusion protease to ensure efficient cleavage. The potential flexibility of the method is shown by the use of various affinity tails and alternative fusion proteases.

3C Viral Proteases↗
PubMed1994

Tiapride in the prevention of relapse in recently detoxified alcoholics.

BACKGROUND: The aim was to investigate the effect of tiapride (100 mg three times a day for at least one month) on outcome following detoxification. METHOD: The setting was a tertiary referral centre. The study design was randomised, double-blind, and placebo-controlled. One hundred routinely admitted alcohol-dependent patients were entered, and 54 completed the trial. Outcome was assessed by considering drinking status at three months and six months follow-up, and by comparing psychological status at intake and follow-up using the Crown-Crisp Experiential index, the Litman Self-esteem scale and a Satisfaction with Life Situations scale. We also compared performance over the six months before admission with the three and six months of follow-up on measures of health, social and drinking variables. RESULTS: Tiapride proved better (usually at statistically highly significant levels) than placebo at promoting: abstinence, self-esteem, and satisfaction with life situations; and at reducing: alcohol consumption, use of health service resources, and levels of neuroticism. CONCLUSIONS: Tiapride merits serious consideration in the longer-term treatment of alcoholic patients.

Alcohol Drinking↗
PubMed1993

Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute.

The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits. Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups. Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect. The animals were observed for 40 days after the primary debridement and then were killed. The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material. At primary debridement, all of the animals in each group were equally infected. At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001). In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity.

Animals↗
PubMed1992

Neuroretinitis: an unusual presentation of ocular toxoplasmosis.

Neuroretinitis is a clinical condition usually seen in young healthy adults that is characterized by rapid profound unilateral loss of vision. Funduscopic findings include swollen disc, splinter hemorrhages, and macular star. Catscratch fever and leptospirosis have been suggested as possible etiologies in this condition. We report a case of a patient with neuroretinitis whose only laboratory abnormality was an elevated enzyme-linked immunosorbent assay immunoglobulin G Toxoplasma titer. The patient responded favorably to treatment with clindamycin, triple sulfa, and systemic corticosteroids. We recommended toxoplasmic serology be added to the workup of patients with neuroretinitis.

Adult↗
PubMed1991

The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients.

The Karnofsky Performance Scale (KPS) was evaluated in a geriatric outpatient population with regard to three issues: its strength of association with widely used and validated geriatric instruments; its ability to predict patient outcomes; and its ability to serve as an identifier of high-risk patients. The 134-patient sample was given a comprehensive geriatric assessment which included the KPS, the Activities of Daily Living (ADL) scale, the Instrumental Activities of Daily Living (IADL) scale, and other psychosocial and sensory tests. The KPS, ADL, and IADL were significantly correlated with each other, and the KPS showed the strongest associations with other functional measures. The KPS was also highly predictive of outcomes, performing better or equally well as the ADL and IADL. The KPS designation of high- and low-risk groups resulted in statistically significant score differences between groups in all but one assessment area, demonstrating better ability to discriminate than either the ADL or IADL. Thus, the KPS was shown to serve as an effective proxy score for a patient's health and functional status. It also was a significant predictor of hospitalizations, survival time, community residence, and institutionalization. Finally, the KPS was shown to adequately distinguish risk groups to aid in the targeting of services to ambulatory geriatric patients.

Activities of Daily Living↗
PubMed1990

Alcoholism: a follow-up study of participants in an alcohol treatment programme.

One hundred and twelve alcoholic patients treated by an intensive one-month residential programme were followed up for one year. As a group, they were socially disadvantaged and highly dependent on alcohol. Outcome of treatment was assessed at six months and one year following discharge by multiple measures which included assessments of drinking behaviour, measurements of social stability, neuroticism and self-esteem, and self-ratings of satisfaction with important aspects of day-to-day living. During the first six months following treatment, 37% were abstinent or drinking in controlled fashion; during the second six months, 53% achieved this status. Improvement in drinking status was positively related to improvements in all other outcome variables.

Adult↗
PubMed1989

Age-dependent vulnerability of brain choline acetyltransferase activity to transient cerebral ischemia in rats.

Male Fischer-344 rats aged 6, 12, or 24 months were subjected to four-vessel occlusion cerebral ischemia to assess age-dependent ischemic vulnerability of cholinergic and GABAergic neurons based on choline acetyltransferase (EC 2.3.1.6) and glutamic acid decarboxylase (EC 4.1.1.15) activities. Activities of both enzymes were similar (p greater than 0.05) in 6- (n = 5) and 12- (n = 5) month-old rats. Mean +/- SEM choline acetyltransferase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 75 +/- 5, 123 +/- 9, 415 +/- 9, and 50 +/- 4 nmol acetylcholine/hr/mg protein, respectively, and were 20-30% lower (p less than 0.05) in all brain regions except the cerebellum in 24-month-old controls. Choline acetyltransferase activity was unaffected by ischemia in 6- and 12-month-old rats but was reduced by 30-60% in 24-month-old rats. Mean +/- SEM glutamic acid decarboxylase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 98 +/- 8, 86 +/- 7, 144 +/- 13, and 125 +/- 9 nmol gamma-aminobutyric acid/hr/mg protein, respectively, and 25-35% lower in all regions of 24-month-old controls. After 30 minutes of ischemia and 5 days of recovery, glutamic acid decarboxylase activities were reduced (p less than 0.05) in all brain regions and age groups. However, its activity was decreased (p less than 0.05 compared with age-matched controls) by 55% in the cortex and 79% in the hippocampus of 24-month-old rats compared with 30% and 45% in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

Tiapride in the long-term management of alcoholics of anxious or depressive temperament.

Thirty-two chemically dependent alcoholics with significant levels of anxiety or depression were admitted to a double-blind randomised study in which the effect of the substituted benzamide tiapride was compared with that of placebo over a 6-month period. Twenty patients completed the study. Assessments included relevant biochemical and haematological tests, drinking levels and associated behaviour, expressed satisfaction with various areas of life, the Crown-Crisp Experimental Index of neurotic symptoms and questionnaires on self-esteem and alcohol dependence. The results indicated that in comparison with the placebo group, patients treated with tiapride drank less and had longer periods of abstinence. This was associated with improvements in laboratory tests, reduction in neurotic symptoms, gains in self-esteem and increased levels of expressed satisfaction with life situation. The drug was well tolerated and no deleterious effects were noted, suggesting its potential usefulness for this patient group.

Adult↗
PubMed1986

Lactobacillemia of amniotic fluid origin.

Four cases of amnionitis due to Lactobacillus sp and three cases of bacteremia are reported. Postpartum endometritis developed in all four cases. Lactobacillus bacteremia occurred in two infants. A review of the literature on serious infections due to Lactobacillus sp is also presented. The importance of considering the clinical role of any microorganism isolated in pure culture from symptomatic patients is discussed.

Adolescent↗