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J A Clark

Publications and source records attributed to J A Clark.

At least 55 records · Page 3Linked to original sources
PubMed1998

Comparing generic and disease-specific measures of physical and role functioning: results from the Veterans Health Study.

OBJECTIVES: This study compared the performance of generic measures of Medical Outcome Study Short Form 36-Item Health Survey physical functioning and role limitations with disease-specific measures of physical functioning and role limitations using specific disease attributions for chronic lung disease, chronic low back pain, and osteoarthritis of the knee. METHODS: Data were analyzed from the Veterans Health Study among patients receiving Veteran's Administration ambulatory care. Patients identified as having one of the three study conditions were included in the study (n = 932). RESULTS: The study revealed that the generic physical functioning and role limitations scales had higher correlations with other generic SF-36 scales, whereas disease-specific attribution measures had larger R2 values in explaining variability in symptom-based disease severity and larger t statistic values in discriminating the impacts of patients taking medications and having surgery. CONCLUSIONS: The generic measures of physical functioning and role limitations were more applicable in assessing a broad array of health-related quality-of-life issues, whereas disease-specific measures of physical functioning and role limitations were more useful in evaluating clinical management and limitations associated with specific disease conditions. The results of the study suggest that the use of disease-specific attribution assessments was more cost-efficient than the development of new disease-specific instruments. Disease-specific attribution could be used to complement generic measures in assessing patient outcomes.

Activities of Daily Living↗
PubMed1998

Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study.

PURPOSE: To assess complications of therapy for early (nonmetastatic) prostate cancer. PATIENTS AND METHODS: A prospective study of a cohort of 279 men who sought treatment advice and completed required pretreatment forms. The measures were self-reported patient symptoms and other measures of quality of life before therapy and at 3 and 12 months afterward. RESULTS: Bowel and bladder symptoms were uncommon pretreatment. Patients frequently reported irritative bowel and bladder symptoms at 3 months after radiotherapy, although these subsided somewhat at 12 months. Substantial ("a lot") urinary incontinence and wearing of absorptive pads were reported by 11% and 35% at 12 months after surgery and varied little by age. Incontinence occurred after radiotherapy infrequently, and only in men more than 65 years old. Inadequate erections, present in one third of men pretreatment, were nearly universal at 3 months after surgery, although some improvement, primarily in men under 65 years of age, was evident at 12 months. Sexual dysfunction after radiotherapy increased less but continually through 12 months, suggesting that observed treatment-related differences would decline with further follow-up. CONCLUSION: External-beam radiotherapy of early prostate cancer is followed by bowel and bladder irritability, by increasingly severe sexual dysfunction and, in men aged more than 65 years, occasional urinary incontinence. Greater sexual dysfunction and urinary incontinence occur in the year following radical prostatectomy. These postsurgical complication rates from patient questionnaires are greater than have been reported in other treatment series and confirm the results of two retrospective studies of patient-reported complications.

Adult↗
PubMed1998

Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors.

PTH and PTH-related peptide (PTHrP) bind to the PTH/PTHrP receptor and stimulate cAMP accumulation with similar efficacy. Only PTH activates the PTH2 receptor. To examine the structural basis for this selectivity, we analyzed receptor chimeras in which the amino terminus and third extracellular domains of the two receptors were interchanged. All chimeric receptors bound radiolabeled PTH with high affinity. Transfer of the PTH2 receptor amino terminus to the PTH/PTHrP receptor eliminated high-affinity PTHrP binding and significantly decreased activation by PTHrP. A PTH/PTHrP receptor N terminus modified by deletion of the nonhomologous E2 domain transferred weak PTHrP interaction to the PTH2 receptor. Introduction of the PTH2 receptor third extracellular loop into the PTH/PTHrP receptor increased the EC50 for PTH and PTHrP, while preserving high-affinity PTH binding and eliminating high-affinity PTHrP binding. Similarly, transfer of the PTH/PTHrP receptor third extracellular loop preserved high-affinity PTH binding by the PTH2 receptor but decreased its activation. Return of Gln440 and Arg394, corresponding residues in the PTH/PTHrP and PTH2 receptor third extracellular loops, to the parent residue restored function of these receptors. Simultaneous interchange of wild-type amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. Function was restored by elimination of the E2 domain in the receptor with a PTH/PTHrP receptor N terminus and return of Gln440/Arg394 to the parent sequence in both receptors. These data suggest that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHrP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHrP.

Amino Acid Substitution↗
PubMed1998

Flare during drug withdrawal as a method to support efficacy in rheumatoid arthritis: amiprilose hydrochloride as an example in a double blind, randomized study.

OBJECTIVE: To evaluate the use of a randomized, double blind, drug withdrawal design as a means to test the efficacy of longterm therapy with antirheumatic drugs. METHODS: We evaluated 286 patients with rheumatoid arthritis (RA) treated with amiprilose hydrochloride for 1-3 years, with response, with or without other antirheumatic therapy, in a double blind, 12 week withdrawal study that compared patients randomized to continue amiprilose therapy vs patients randomized to placebo. The primary efficacy variable was preventing a predefined degree of clinical reactivation, or flare; the statistical tests of success were a difference in the proportion of flares and in the mean time to flare. RESULTS: Thirty percent of patients taking amiprilose and 43% of placebo patients experienced flare (p = 0.026). Patients taking amiprilose had a longer flare-free interval compared to placebo patients (p = 0.027), with the time to reactivation or flare becoming statistically different 73 days after withdrawal. CONCLUSION: Placebo controlled withdrawal designs are useful as evidence to support the longterm effectiveness of therapy in a proportion of patients with RA.

Adolescent↗
PubMed1997

Patient-reported impotence and incontinence after nerve-sparing radical prostatectomy.

BACKGROUND: The age-adjusted rate of radical prostatectomy, the most common treatment of early (nonmetastatic) prostate cancer, increased almost sixfold between 1984 and 1990. This increase was due in part to reported improvements in postoperative sexual potency after the use of newly developed "nerve-sparing" procedures. However, published estimates from physicians of impotence following various types of radical prostatectomy may be low, since not all patients may report treatment-related complications accurately and completely to their doctors. In contrast, direct surveys of patients indicate much higher rates of postoperative sexual and urinary dysfunction. One problem with most physician and patient surveys is that they have been performed retrospectively, and pretreatment impotence and incontinence prevalent in older men cannot be assessed accurately in retrospective studies. PURPOSE: This study was initiated in a cohort of men before they underwent radical prostatectomy to assess treatment-related effects on impotence and incontinence. METHODS: The study population consisted of 94 men enrolled in a cohort study of treatment for early prostate cancer. The patients completed questionnaires about sexual and urinary functions before surgery and at 3 and 12 months after surgery and had adequate information to assess the type of surgical technique used (non-nerve-sparing, unilateral nerve-sparing, or bilateral nerve-sparing). Because items assessing sexual function were inadvertently omitted from the questionnaire in the initial months of the study, information on sexual function for all time periods was available for only 49 men. RESULTS: Compared with men who had not been treated with a nerve-sparing procedure, men who underwent nerve-sparing radical prostatectomy, particularly of the bilateral type, were younger and had better prognostic features, indicating less advanced cancers. Before surgery, nine (75%) of 12 men not treated with a nerve-sparing procedure reported erections that were usually inadequate for sexual intercourse compared with six (33%) of 18 men and one (5%) of 19 men who underwent unilateral and bilateral nerve-sparing prostatectomies, respectively. At 12 months after surgery, most men reported inadequate erections, including 15 (79%) of the 19 men who had bilateral nerve-sparing surgery; unilateral nerve preservation provided no apparent benefit. In general, nerve-sparing surgery was associated with more use of absorbent pads at 3 and 12 months following treatment, and this approach was associated with substantial urinary incontinence at 3 months but not at 12 months following surgery. CONCLUSIONS: Nerve-sparing prostatectomy, particularly when performed unilaterally, improves postoperative sexual function to a lesser extent than previously reported. Because men with preoperative impotence and more advanced cancers receive nerve-sparing surgery less often, some of the previously reported benefit of nerve preservation may be the result of patient selection and not of the technique per se.

Aged↗
PubMed1997

Analysis of the transmembrane topology and membrane assembly of the GAT-1 gamma-aminobutyric acid transporter.

The transmembrane topology of the Na+- and Cl--dependent gamma-aminobutyric acid transporter GAT-1 has been studied using protein chimeras in Xenopus oocytes. A series of COOH-terminal truncations was generated to which a prolactin epitope was fused. Following expression of transporter-prolactin chimeras in Xenopus oocytes, the transmembrane orientation of each chimera was determined by testing for protease sensitivity in an oocyte membrane preparation. Data from protease protection assays with GAT-1-prolactin chimeras has shown that residues in the loops connecting hydrophobic domain (HD)3 and HD4 and HD7 and HD8 are accessible to protease in the cytoplasm and suggest the presence of pore loop structures which extend into the membrane from the extracellular face. Such pore loop structures may be involved in the formation of the substrate-binding pocket. Studies presented herein confirm that the NH2 and COOH termini are cytosolic and hydrophobic domains span the membrane in a manner consistent with the predicted hydropathy model for Na+- and Cl--dependent transporters. These data also provide insight into GAT-1 transmembrane assembly and suggest that a complex series of topogenic sequences directs this process. A potential pause-transfer sequence has been identified and may be responsible for the translocational pausing observed in this study.

Amino Acid Sequence↗
PubMed1997

Dimensions of quality of life expressed by men treated for metastatic prostate cancer.

Men who pursue active treatment for metastatic prostate cancer face a choice between medical or surgical castration. While both alternatives have documented side-effects (e.g. loss of libido, breast enlargement and tenderness, hot flashes, and nausea), their psychosocial impacts are not well understood. As part of a study of patients' treatment decision making, we have sought to construct a patient-based measure of the salient disease and treatment-related qualities of life experienced by these men subsequent to treatment. Focus groups (15 with patients, two with wives) were used to develop candidate Likert scale questionnaire items representing quality of life issues that patients said were important. These items were combined with assessments of symptoms, comorbidity, and generic measures of functional status and well-being in a mail survey of patients treated at the Houston VAMC and two other Houston hospitals (n = 201, response rate = 63%). Psychometric analyses (principal components and multitrait scaling) were used to identify distinct dimensions of life quality; correlations with generic measures, and symptom reports were used in validation analyses. Qualitative analyses of focus group data identified three major domains of life quality: self-perceptions, anxiety about the effects of treatment, and concern with the process of decision making and treatment. Psychometric analyses identified nine reliable and valid indicators of prostate cancer-related quality of life: body image, sexual problems, spouse affection, spouse worry, masculinity, cancer-related self-image, cancer distress, cancer acceptance, and regret of treatment decision. Internal consistency (alpha) ranged form 0.71 to 0.90. Correlations with reference scales (e.g. MOS Mental Health Index, Profile of Mood States) and symptom status supported concurrent validity. Prostate cancer patients perceive a number of important psychosocial consequences of their treatment. These consequences are represented by nine scales comprising a brief (35 items) disease and treatment sensitive health-related quality of life instrument, which we will use in monitoring the outcomes of patients' treatment choices.

Adaptation, Psychological↗
PubMed1997

Impact of state mental health reform on patterns of service delivery.

Legislation enacted in 1988 in Ohio, aimed at redistributing funding from state hospitals to community support services and prioritizing the funding for treatment of individuals with severe mental disabilities (SMD), raises important questions from a service system perspective. To assess the impact of this reform legislation on Ohio's mental health service delivery system, cluster analyses of community mental health service data were conducted for five yearly samples of approximately 4,000 adults with SMD. An analysis of resulting service patterns demonstrated a decrease in service clusters comprised of individuals receiving little more than medication check-ups and an increase in clusters comprised of individuals receiving combinations of two or more services. Increases were found in most community mental health services; however, in each year, approximately 50% of the sample received few services of any kind, while approximately 10% of the sample received voluminous amounts of highly individualized services.

Adult↗
PubMed1997

The rRNA-processing function of the yeast U14 small nucleolar RNA can be rescued by a conserved RNA helicase-like protein.

The phylogenetically conserved U14 small nucleolar RNA is required for processing of rRNA, and this function involves base pairing with conserved complementary sequences in 18S RNA. With a view to identifying other important U14 interactions, a stem-loop domain required for activity of Saccharomyces cerevisiae U14 RNAs (the Y domain) was first subjected to detailed mutational analysis. The mapping results showed that most nucleotides of the Y domain can be replaced without affecting function, except for loop nucleotides conserved among five different yeast species. Defective variants were then used to identify both intragenic and extragenic suppressor mutations. All of the intragenic mutations mapped within six nucleotides of the primary mutation, suggesting that suppression involves a change in conformation and that the loop element is involved in an essential intermolecular interaction rather than intramolecular base pairing. A high-copy extragenic suppressor gene, designated DBP4 (DEAD box protein 4), encodes an essential, putative RNA helicase of the DEAD-DEXH box family. Suppression by DBP4 (initially CA4 [T.-H. Chang, J. Arenas, and J. Abelson, Proc. Natl. Acad. Sci. USA 87:1571-1575, 1990]) restores the level of 18S rRNA and is specific for the Y domain but is not allele specific. DBP4 is predicted to function either in assembly of the U14 small nucleolar RNP or, more likely, in its interaction with other components of the rRNA processing apparatus. Mediating the interaction of U14 with precursor 18S RNA is an especially attractive possibility.

Amino Acid Sequence↗
PubMed1997

Complications after treatment with external-beam irradiation in early-stage prostate cancer patients: a prospective multiinstitutional outcomes study.

PURPOSE: To use data from a prospective quality-of-life study to assess differences in disease-specific and general health-related quality-of-life changes after treatment with different external-beam irradiation techniques for prostate cancer. PATIENTS AND METHODS: Patients were divided into three groups based on their pretreatment field size and planning technique: whole pelvis, small field, or conformal. Measures of bowel, urinary, and sexual function and of global health-related quality-of-life parameters (from the Health Survey Short Form [SF-36] and the Profile of Mood States [POMS]) were obtained from self-report questionnaires completed before initiation of therapy and at 3 and 12 months after therapy. RESULTS: Irritative gastrointestinal and genitourinary side effects were frequent 3 months after treatment, but were substantially improved at 12 months. Sexual dysfunction increased steadily over the study period. The POMS and the SF-36 did not demonstrate significant changes over time. Despite small patient numbers, we found trends in favor of conformal therapy across several symptom measures, including sexual function. In the fatigue, energy, and vigor subscales, patients who received whole-pelvis treatment fared significantly worse than those in the other two groups. CONCLUSION: Prospective, detailed data from a feasibility study allowed us to assess the effect of technique on quality of life following external-beam irradiation. Although limited by the small planned sample size, these results suggest that smaller radiation fields limit treatment-related complications, including, unexpectedly, sexual dysfunction. However, confirmation in a larger study is necessary.

Affect↗
PubMed1997

Pica behavior associated with buprenorphine administration in the rat.

Marked gastric distention was-observed in rats 20 h after they underwent partial hepatectomy under isoflurane anesthesia and received buprenorphine (0.3 mg/kg of body weight) after surgery. Hardwood bedding comprised the bulk of the gastric contents. A study was undertaken to determine the cause of the pica behavior (consumption of non-nutritive substances) and resultant gastric distention. Ten-week-old male Sprague Dawley rats were randomly assigned to one of six groups. Group-1 rats (n = 11) underwent laparotomy under isoflurane anesthesia, with buprenorphine (0.3 mg/kg) administered after surgery. Group-2 rats (n = 12) underwent laparotomy under isoflurane anesthesia with buprenorphine (0.05 mg/kg) administered after surgery. Group-3 rats (n = 24) underwent laparotomy under isoflurane anesthesia, with saline administered after surgery. Isoflurane was administered at the same rate, concentration, and duration for all groups that underwent laparotomy (groups 1 to 3). Buprenorphine or saline was administered subcutaneously as a single injection when anesthesia was discontinued (groups 1 to 3). Group-4 rats (n = 6) received buprenorphine (0.3 mg/kg) only. Group-5 rats (n = 6) received buprenorphine (0.05 mg/kg) only. Group-6 rats (n = 12) received saline only. Rats not undergoing laparotomy (groups 4 to 6) received buprenorphine or saline 18 to 20 h before euthanasia. Rats were housed individually in filter-topped polycarbonate cages containing hardwood bedding. A purified, pelleted diet and water were offered ad libitum. Food and water consumption were measured over the posttreatment period. Eighteen to 20 h after treatment, rats were euthanized, each stomach and its contents were weighed, contents were examined grossly, and wet and dry gastric content weights were recorded. All weights were significantly (P < 0.05) increased in rats receiving buprenorphine administered after surgery (groups 1 and 2), compared with rats of the control group (group 3). Weights of the stomach and contents, wet gastric contents, and dry gastric contents were significantly (P < 0.05) increased in rats receiving 0.3 mg of buprenorphine/kg only (group 4), compared with values for their controls (group 6). Hardwood bedding comprised the bulk of the gastric contents in all groups receiving buprenorphine. Stomachs of rats not receiving buprenorphine contained the purified diet with little or no hardwood bedding. These results indicate that a single injection of buprenorphine at a dosage of 0.05 or 0.3 mg/kg resulted in rats ingesting hardwood bedding, leading to gastric distention. It was concluded that pica behavior associated with administration of buprenorphine should be considered when evaluating experimental data from rats housed on contact bedding.

Analgesics, Opioid↗
PubMed1997

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Aged↗
PubMed1996

The effects of moderate and low levels of acoustic overstimulation on stereocilia and their tip links in the guinea pig.

Guinea pigs were exposed to pure tones of 10 kHz at intensities between 98 and 115 dB SPL for 5-30 min, to produce varying degrees of acoustic trauma. Changes in auditory thresholds were measured electrophysiologically, and the animals were immediately fixed for scanning electron microscopy. Correlation between morphological changes to the hair bundle and losses in threshold, showed that with the smallest degrees of trauma (98 dB SPL for 15 min, mean maximum threshold loss of 22 dB), damage was confined to a small stretch of inner hair cells (IHC), with only subtle changes to the stereocilia of the outer hair cells (OHC). At exposure intensities greater than 102 dB SPL (duration: 15 min) the IHC stereocilia in the centre of the lesion were always substantially disarrayed. Substantial damage to the OHC bundles was seen only with exposures above 110 dB SPL (duration: > or = 5 min), producing threshold losses of 50 dB or more. Tip links were lost only where the stereocilia were disarrayed. It is concluded that the tip links are not the most vulnerable components of the cochlear hair cell, but that relatively low levels of acoustic stimulation can cause significant damage to the stereociliary bundle of the IHCs.

Acoustic Stimulation↗
PubMed1996

The hypertrophic scar and microcirculation properties.

Blood-flow measurements of microcirculation were used as a quantitative indicator for scar assessment and healing. A laser doppler flowmeter (LDF), giving an integrated instantaneous flux value through a measured volume of skin, was used for the measurements. It has been postulated that the degree of hypertrophy after thermal injury correlates with the degree of microvascular regeneration. This study looked quantitatively at microcirculation in normal and scarred skin of different clinical grading and investigated the comparative responses to changes in local temperature stimuli. An attempt is made to define microcirculation using the parameters of Vasodilation Index (Dli) and Vasomotion Intensity (% Vsm) as respective responses to a rise in local temperature of the skin from 36 degrees C to 44 degrees C. The improvements in both Dli and % Vsm with healing of scar relate to the degree of microvascular regeneration, which in turn correlates with the clinical assessment.

Adolescent↗
PubMed1996

Mechanical properties of normal skin and hypertrophic scars.

The non-linear viscoelastic properties of skin tissue were characterized by modulus of elasticity E, which represents stiffness, and percentage extension (strain, xi) at load intensities of 20, 40 and 100 gm. The latter property is a measure of the extensibility for both normal skin and hypertrophic scar. A quasi-static extensometer applies a standard rate of extension to the skin and its mechanical properties were obtained from 15 Chinese patients with burn injuries of superficial to full skin thickness burns. Clinical evaluation of hypertrophic scar is qualitative and depends on colour, thickness and hardness or firmness. Using mechanical properties assists in the characterization by providing a quantitative indicator. Higher scar grading is synonymous with increased stiffness and decreased extensibility. Correlation with clinical assessment was achieved with these in vivo viscoelastic properties.

Adolescent↗
PubMed1996

Impact of enteral feeding of a glutamine-supplemented formula on the hypoaminoacidemic response in trauma patients.

Plasma amino acid concentrations were measured during fasting and after 3 days of enteral feeding in 16 trauma patients on a glutamine-supplemented diet and 14 patients on an isonitrogenous control diet. During fasting, total amino acids, including glutamine, were depressed by 50% and this was attributed to a reduction in both essential and nonessential amino acids. The essential amino acid concentrations increased in both groups after feeding. The nonessential amino acid concentrations also increased in the control group but not in the glutamine group during feeding. Repletion of the glutamine extracellular pool was not evident after an average intake of 27.1 g per day of glutamine for 3 days. Nitrogen balance was similar for the two groups during feeding. We conclude that in this study, enteral glutamine did not increase the glutamine plasma concentration. In addition, both formulas improved the hypoaminoacidemia of essential amino acids but only the control diet improved the nonessential amino acids plasma concentration.

Adolescent↗