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Biomedical subjects

K Andrews

Publications and source records attributed to K Andrews.

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

Sensory threshold changes without initial pain or alterations in cutaneous blood flow, in the area of secondary hyperalgesia caused by topical application of capsaicin in humans.

Changes in von Frey hair perception, pricking pain, and vibration thresholds were examined in six healthy human adults, in the zone of secondary hyperalgesia, 45 min following the topical application of capsaicin at concentrations of 0.05 and 0.1 mg/ml. In two of these subjects, cutaneous blood flow was monitored at 10-min intervals, before, during and after capsaicin application, using laser Doppler perfusion imaging. Thresholds for all three parameters were significantly reduced after capsaicin treatment, in a dose-dependent manner. However, there was no visible skin flare, and no change in cutaneous blood flow at these doses of capsaicin. The effects on von Frey perception threshold and vibration threshold have not been demonstrated previously, and may be indicative of central changes, initiated by afferent fibres (presumably C fibres) that are not vasoactive.

Administration, Topical↗
PubMed1999

Cutaneous flexion reflex in human neonates: a quantitative study of threshold and stimulus-response characteristics after single and repeated stimuli.

The cutaneous flexion reflex has been used to study spinal sensory processing in 68 infants (37 female, 31 male) aged between 28 and 42 weeks postconceptional age (PCA). Mechanical and electrical stimuli were singularly and repeatedly applied to the foot, and single-surface EMG responses were recorded from the biceps femoris muscle. A clear correlation was demonstrated between the mechanical stimulus intensity and latency and the amplitude of the reflex. Mechanical threshold normally increased with age, but the flexion-reflex threshold was lowered by local limb-tissue damage in the contralateral limb. The incidence of response to repeated mechanical stimulation at 2.8 x threshold decreased significantly with increasing age. Repeated mechanical stimulation at 2.8 x threshold caused a build-up in the size of the response followed by a diminution. The flexion reflex can, therefore, be used to investigate sensory processing in the neonate, and the effects of tissue damage. The importance of using natural rather than electrical stimulation is highlighted.

Electric Stimulation↗
PubMed1999

Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells.

To identify genes upregulated during the process of ciliated cell differentiation of airway epithelial cells, differential display was used to compare RNA from rat tracheal epithelial (RTE) cells cultured under conditions that inhibit/promote ciliated cell differentiation. Several partial complementary DNAs (cDNAs) were identified whose expression was regulated coordinately with ciliated cell differentiation. One of these, KPL2, detected a messenger RNA transcript of approximately 6 kb when used as a probe on Northern blots of RNA from ciliated cultures but was undetectable in RNA from nonciliated cultures. Sequencing of overlapping clones obtained by a modified rapid amplification of cDNA ends procedure generated a complete cDNA sequence that exhibited no significant homology to sequences in GenBank, indicating that KPL2 is a novel gene. Southern analysis demonstrated that KPL2 exists as a single-copy gene. KPL2 contains a long open reading frame predicted to code for a protein of > 200 kD. Several putative functional motifs are present in the protein, including a calponin homology domain, three nuclear localization signals, a consensus P-loop, and a proline-rich region, suggesting that KPL2 has a unique function. KPL2 was undetectable in heart and liver samples, but was expressed in brain and testis, tissues that contain axonemal structures. In seminiferous tubules of the testis, KPL2 expression was stage-specific and appeared to be highest in spermatocytes and round spermatids. During differentiation of RTE cells, the expression of KPL2 closely paralleled that of an axonemal dynein heavy chain. These results suggest that KPL2 plays an important role in the differentiation or function of ciliated cells in the airway.

Amino Acid Sequence↗
PubMed1998

Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis.

PURPOSE: To investigate prospectively the utility of plasma transforming growth factor beta1 (TGFbeta1) as a marker for the development of symptomatic radiation pneumonitis. MATERIALS AND METHODS: Seventy-three patients with lung cancer treated with curative intent are reported herein. Plasma TGFbeta1 samples were obtained before, weekly during, and at each follow-up after radiation therapy (RT). TGFbeta1 was extracted using an acid/ethanol method. An enzyme-linked immunosorbent assay was used to quantify plasma TGFbeta1 concentrations. The TGFbeta1 level at the end of RT was considered "normal" if it was both < or = 7.5 ng/ml and less than the pretreatment value. All patients were followed for at least 6 months, unless symptomatic pneumonitis developed sooner. Pneumonitis was defined by National Cancer Institute (NCI) common toxicity criteria. RESULTS: Fifteen of the 73 patients (21%) developed symptomatic pneumonitis and the remaining 58 (79%) did not. A normal plasma TGFbeta1 by the end of RT, as defined above, was more common in patients who did not develop pneumonitis. A return of the plasma TGFbeta1 to normal accurately identified patients who would not develop pneumonitis with both a sensitivity and positive predictive value of 90%. CONCLUSION: Plasma TGFbeta1 levels appear to be a useful means to identify patients at low risk for the development of pneumonitis from thoracic RT. Thus, monitoring of plasma TGFbeta1 levels may identify candidates for dose escalation studies in the treatment of lung cancer.

Adult↗
PubMed1997

New England eye care survey.

BACKGROUND: Descriptive statistics on patient or consumer use of eye care are important for health care policy and professional development. Most survey research has been through doctors or doctors' offices. Some consumer surveys have been completed by direct mail, but information from direct mail surveys suffers from respondent self selection. This study joins a growing number of surveys designs that use random-digit telephone survey methods, which have less self-selection bias. METHODS: This study describes patient use and perceptions of eye care services in three New England areas using random-digit telephone survey. Nine hundred eighteen calls were attempted. A standardized interview and survey questionnaire was used for each phone contact. RESULTS: Of 163 respondents (18% response rate), it was found that most patients were satisfied with the care, time, discussion, and fees provided by their eye care practitioner. Most (78%) planned on returning to the same practitioner in the future. Sixty percent of participants saw an optometrist, 29% saw an ophthalmologist, and 11% were unsure. In a subsample, differences in perception between optometric and ophthalmologic care was investigated, and no statistically significant differences (p < 0.05) were found. CONCLUSIONS: The study findings are similar to others in terms of market share between optometric and ophthalmologic settings for primary eye care. Several new findings were measured and discussed, and the data may be helpful for policy decisions.

Adolescent↗
PubMed1996

Bent pseudoknots and novel RNA inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase.

The reverse transcriptase (RT) of the human immunodeficiency virus (HIV) is a proven target for therapeutic intervention of HIV infections. We have found several new RNA inhibitors of HIV-1 RT that differ significantly from the pseudoknot ligands found previously, along with a wide variety of pseudoknot variants. One pseudoknot variant and three novel ligands were studied in more detail. Each specifically inhibits DNA polymerization by HIV RT (half-maximal inhibition at 0.3 to 20 nM inhibitor), but not that of RTs derived from MMLV or AMV. The minimal binding element of each isolate was determined by deletion analysis and by gel electrophoresis of protein-bound, partially alkaline-hydrolyzed RNA. Truncations of three of the isolates bound nearly as well as (or better than) the parental sequences, while most deletions in the fourth caused substantial disruption of binding. The truncated versions of two isolates were subjected to six rounds of secondary SELEX after resynthesizing them mutagenically. Patterns of conserved and covarying nucleotides yielded structural models consistent with 5' and 3' boundary determinations for these molecules. Among the four isolates studied in detail, the first is confirmed as being a pseudoknot, albeit with substantial structural differences as compared to the canonical pseudoknots identified previously. The second forms a stem-loop structure with additional flanking sequences required for binding. Tentative structural models for the other two isolates are presented. The minimal fully active truncations of each of these four isolates compete with each other and with a classical RNA pseudoknot for binding to HIV RT, suggesting that they all recognize the same or overlapping sites on the protein, in spite of their apparently dissimilar structures. We model their interactions with RT as mimicking the 40 to 45 degrees bend in dsDNA co-crystallized with RT.

Anti-HIV Agents↗
PubMed1996

Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit.

OBJECTIVE: To identify the number of patients who were misdiagnosed as being in the vegetative state and their characteristics. DESIGN: Retrospective study of the clinical records of the medical, occupational therapy, and clinical psychology departments. SETTING: 20 bed unit specialising in the rehabilitation of patients with profound brain damage, including the vegetative state. SUBJECTS: 40 patients admitted between 1992 and 1995 with a referral diagnosis of vegetative state. OUTCOME MEASURES: Patients who showed an ability to communicate consistently using eye pointing or a touch sensitive single switch buzzer. RESULTS: Of the 40 patients referred as being in the vegetative state, 17 (43%) were considered as having been misdiagnosed; seven of these had been presumed to be vegetative for longer than one year, including three for over four years. Most of the misdiagnosed patients were blind or severely visually impaired. All patients remained severely physically disabled, but nearly all were able to communicate their preference in quality of life issues-some to a high level. CONCLUSIONS: The vegetative state needs considerable skill to diagnose, requiring assessment over a period of time; diagnosis cannot be made, even by the most experienced clinician, from a bedside assessment. Accurate diagnosis is possible but requires the skills of a multidisciplinary team experienced in the management of people with complex disabilities. Recognition of awareness is essential if an optimal quality of life is to be achieved and to avoid inappropriate approaches to the courts for a declaration for withdrawal of tube feeding.

Awareness↗
PubMed1996

Euthanasia in chronic severe disablement.

One of the major dilemmas for the clinician caring for people with chronic disabling conditions is how to provide not only a good quality of life but also the best quality of dying. It is my view that the clinician should provide the opportunity for living before giving the opportunity to die. By this I mean that the clinician has the responsibility to ensure that efforts have been made to improve the quality of life by controlling clinical situations and providing psychological and emotional support. Once the decision has been made by patient, family and clinical team that it is inappropriate that life should continue, then the quality of the dying process should be of the highest standard. The present attitude of ending the patient's life by withdrawal of nutrition and fluids is highly unsatisfactory, if not inhumane, and the option of euthanasia would be by far a more satisfactory solution. In addition, a more satisfactory procedure than application to the High Court for a directive on withdrawal of tube feeding needs to be found. This method is very stressful for family and staff already in distress and is an extremely expensive approach. An independent ethical panel to ensure that the decision to end the patient's life is clinically appropriate, is being carried out purely for the best interests of the patient and is not influenced by the other considerations.

Chronic Disease↗
PubMed1995

Enrichment of fetal nucleated cells from maternal blood: model test system using cord blood.

The presence of small numbers of fetal nucleated red cells in the maternal circulation has been a stimulus for the development of technologies for non-invasive prenatal genetic analysis. Our laboratory has been assessing the feasibility of density gradient centrifugation followed by magnetic activated cell sorting (MACS) of cells expressing CD32 and CD45, to deplete maternal nucleated blood cells. We have examined the efficiency of each of the steps of this procedure using cord blood from term pregnancies as a source of nucleated red blood cells. Cord blood was shown to contain highly variable numbers of nucleated red cells. Three different density gradients were examined. There was no major difference in the performances of the double and triple gradients. Density gradient centrifugation resulted in enrichments of nucleated red blood cells of about 1000-fold relative to the total cell count. However, it was apparent that the selection of the cell layers which were most enriched for these cells would result in significant losses of nucleated red cells in other layers. MACS sorting of cells using CD45 resulted in white cell depletions ranging from 7 to 34-fold. These data provide a foundation for comparison with other methods and for optimization of the MACS technique.

Cell Separation↗