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Biomedical subjects

J Foote

Publications and source records attributed to J Foote.

At least 19 recordsLinked to original sources
PubMed2001

Structural effects of framework mutations on a humanized anti-lysozyme antibody.

A humanized version of the mouse anti-lysozyme Ab D1.3 was previously constructed as an Fv fragment and its structure was crystallographically determined in the free form and in complex with lysozyme. Here we report five new crystal structures of single-amino acid substitution mutants of the humanized Fv fragment, four of which were determined as Fv-lysozyme complexes. The crystals were isomorphous with the parent forms, and were refined to free R values of 28-31% at resolutions of 2.7-2.9 A. Residue 27 in other Abs has been implicated in stabilizing the conformation of the first complementarity-determining region (CDR) of the H chain, residues 31-35. We find that a Phe-to-Ser mutation at 27 alters the conformation of immediately adjacent residues, but this change is only weakly transmitted to Ag binding residues in the nearby CDR. Residue 71 of the H chain has been proposed to control the relative disposition of H chain CDRs 1 and 2, based on the bulk of its side chain. However, in structures we determined with Val, Ala, or Arg substituted in place of Lys at position 71, no significant change in the conformation of CDRs 1 and 2 was observed.

Amino Acid Substitution↗
PubMed2001

Polysubstance use among alcoholics.

Contemporary alcoholics often use multiple substances, but there is little systematic research on this. This study examines the drug use comorbidity of alcoholics (DSM diagnosis, frequency and quantity of drug use); the relationship between drinking and drug use; the relative severity of alcohol- and drug-related problems; and the validity of reports of illicit drug use. Data on substance use were collected from 248 treatment-seeking alcoholics using an expanded Time-line Follow-Back (TLFB) interview. Self-reports of substance use were validated with data from biological specimens (urine and hair). Lifetime diagnosis of joint alcohol and drug dependence/abuse was 64%. Two-thirds (68%) reported using drugs in the past 90 days: 33% powder cocaine; 29% crack cocaine; 15% heroin, and 24% cannabis. The mean proportions of exposed days on which users reported consuming a substance were 57% (alcohol), 26% (powder cocaine), 46% (crack cocaine), 47% (heroin), and 29% (cannabis). Subjects reported consuming an average of 14 standard drinks on a drinking day and $67 worth of drugs on a using day. Drug users reported drinking less than nonusers on a drinking day. Frequency of drinking and drug use were positively correlated; almost all drug users reported simultaneous drinking and drug use; and they rated drugs as the bigger problem. Considerable under-reporting of drug use occurred for the previous 3-4 days, but was more accurate for the previous month.

Adult↗
PubMed2001

Collagen implant for treating stress urinary incontinence in women with urethral hypermobility.

PURPOSE: We evaluated the use of collagen in women with stress urinary incontinence and urethral hypermobility. MATERIALS AND METHODS: We treated 90 patients with stress urinary incontinence and urethral hypermobility with 1 to 3 injections of Contigen implant (C. R. Bard, Inc., Covington, Georgia) between June 1996 and October 1998. Observations at 3, 6 and 12 months included continence grade, 7-day voiding diaries and quality of life questionnaires. Abdominal leak point pressure was determined at baseline and 12 months. RESULTS: At the 6-month followup 68 patients remained in the study, of whom 30 (44%) were dry and 24 (35%) were improved. Of the 58 patients who reached the 12-month followup 19 (33%) were dry and 19 (33%) were improved. Considering all patients entered into the study at 6 months 30 (33%) were dry and 24 (27%) were improved. Of the original 90 patients 19 (21%) were dry and 19 (21%) were improved at 12 months. The probability of maintaining initial improvement for 12 months was 44%. The success of bulking agent therapy was not predicted by the initial incontinence grade. Improved continence grade correlated with improved leak point pressure. CONCLUSIONS: This therapy is appropriate in women with urethral hypermobility who wish to avoid surgical risks and in those in whom surgery is ill advised.

Adult↗
PubMed2000

A relation between the principal axes of inertia and ligand binding.

The principal axes of inertia are eigenvectors that can be calculated for any rigid body. We report studies of the position of the principal axes in crystallographically solved protein molecules. We find with high frequency that at least one principal axis penetrates the surface of the respective protein in a region used for ligand binding. In antibody variable regions, an axis goes through the third hypervariable loop of the heavy chain. In major histocompatibility complex proteins, an axis goes through the peptide-binding groove. In protein-protein heterodimers, a principal axis of one subunit will often penetrate the interface formed with the other subunit. In many of these protein-protein complexes, the axis specifically intersects residues known to be critical for molecular recognition.

Algorithms↗
PubMed2000

Removal of UroLume endoprosthesis: experience of the North American Study Group for detrusor-sphincter dyssynergia application.

PURPOSE: We present the experience of the North American UroLume Multicenter Study Group with removal of the UroLume endoprosthesis. MATERIALS AND METHODS: A total of 160 neurologically impaired patients were enrolled in the North American UroLume Multicenter Study Group for detrusor external sphincter dyssynergia application. Analysis was performed in 2 groups of patients in which the device was removed during insertion and after implantation, respectively. RESULTS: Device retrieval was required during insertion in 21 patients (13%) mainly due to misplacement or migration in 17. Extraction was done with minimal complications and in all but 2 cases subsequent UroLume implantation was successful. Of 158 men with the device in place 31 (19.6%) required removal. In 34 procedures 44 devices were removed, mainly due to migration. Time from implantation to removal ranged from 4 days to 66 months (mean 22 months). The UroLume was removed en bloc in 20 cases and in parts or wire by wire in 19. The majority of patients had no or minimal complications after extraction. Only 2 patients had serious temporary complications, including bleeding and urethral injury, with no lasting consequences. No malignancy developed as a result of UroLume insertion. CONCLUSIONS: While there is a potential for urethral injury and bleeding, UroLume endoprosthesis removal is largely a simple procedure with minimal complications and consequences.

Humans↗
PubMed2000

Terazosin for vesicosphincter dyssynergia in spinal cord-injured male patients.

PURPOSE: Evaluation of the role of the long-acting alpha-adrenergic blocker, terazosin, in the treatment of vesicosphincter dyssynergia (VSD) in spinal cord-injured male patients. PATIENTS AND METHODS: Sixty spinal cord-injured male patients with VSD were recruited prospectively. Their mean age was 37 years (range 15-70 years). Baseline evaluation included a thorough medical history, clinical examination, blood pressure measurement, intravenous urogram, and videourodynamics. The patients received terazosin for a 90-day period. Videourodynamic evaluation after completion of the study included cystometrogram, sphincter electromyography, maximum urethral pressure gradient (MUPG), and measurement of post voiding residual (PVR) urine volume. The findings were compared with the pretreatment values. RESULTS: Of the 60 patients, 35 completed the study. According to response to treatment, two groups were identified: Group A = responders (N = 17; 49%) and Group B = nonresponders (N = 18, 51%). In Group A, there was a significant decrease in the maximum detrusor pressure, from a mean of 105.3 to 73.9 cm H(2)O, and in MUPG, from a mean of 84.7 to 54.1 cm H(2)O. The bladder capacity and PVR did not change significantly in either group. The time since injury was significantly longer in Group A than in Group B. CONCLUSIONS: Terazosin in a dose of 10 mg/day was well tolerated and effective in reducing bladder outlet obstruction in many spinal cord-injured patients, as reflected by a decrease in maximum detrusor pressure and MUPG in 49% of the patients. Patients with a weak or negative response initially may respond later. Terazosin should be considered a first-line treatment of VSD prior to contemplating surgery.

Adolescent↗
PubMed1999

Enhanced treatment outcomes for cocaine-using methadone patients.

Cocaine dependent methadone patients were randomly assigned to 6 months of high intensity cognitive-behavioral therapy or low intensity therapy. A repeated measures ANOVA was conducted with patients stratified on severity of cocaine use at baseline. Both treatment groups showed significant and equivalent reductions in cocaine use during the post-treatment period. Completing either therapy and lower cocaine severity at baseline were associated with lower proportion of cocaine-positive urines across a 48-week post-treatment period. Examination of the treatment x cocaine severity interaction provided some evidence that high-severity patients improved more if exposed to high intensity treatment than to low intensity treatment. Positive outcomes for therapy completers relative to non-completers increased over time. The results are consistent with several clinical trials showing that: (1) participation in treatment is associated with reductions in cocaine use; and (2) the relationship between treatment intensity and outcome is not linear and may better be explained by an interaction between patient and treatment factors.

Adult↗
PubMed1999

A group motivational treatment for chemical dependency.

Patient "motivation" has been implicated as a critical component in addiction treatment outcomes. To date, treatments utilizing motivational elements have been conducted as individual interventions. We describe the development of a Group Motivational Intervention (GMI), a four-session, manual-driven group approach that employs key hypothesized motivational elements. These include the six motivational elements derived by Miller and Sanchez (1994) from successful alcoholism treatments, described with the acronym, FRAMES (feedback, responsibility, advice, menu of options, empathy, and self-efficacy). GMI is additionally informed by concepts derived from "self-determination theory" (Deci & Ryan, 1985), concerned with understanding motivation as either internal/autonomous or external/controlled. Evidence indicates that people will value and persist longer in behaviors that they perceive as autonomously motivated. GMI techniques utilize the interpersonal factors found to be autonomy-supportive in self-determination theory. Preliminary results from a randomized clinical trial suggest that key motivational processes are affected by GMI: patients perceive the GMI environment and group leader as significantly more "autonomy supportive" than treatment "as usual."

Alcoholism↗
PubMed1999

The autonomy of mood disorders among cocaine-using methadone patients.

This study uses an algorithm to determine whether patients dually diagnosed with a mood disorder and cocaine dependence have either (a) an autonomous mood disorder (onset of mood disorder prior to substance use disorder (SUD) or mood disorder symptoms persist during periods of abstinence or (b) a nonautonomous mood disorder (onset of SUD preceded mood disorder and mood disorder symptoms remit during periods of abstinence). The relationship among autonomy, patient characteristics, and treatment completion is examined. The sample included 67 methadone patients with a mood disorder (87% major depression, 13% bipolar) who were enrolling in a 6-month psychosocial treatment for cocaine use. Of these subjects, 27% were rated as having an autonomous mood disorder and 73% a nonautonomous mood disorder. Mean age was 37 years; 55% were female and 82% were Hispanic or African-American. All subjects had been stabilized on methadone (mean = 70 mg). During the 30 days prior to study intake, subjects with an autonomous mood disorder, compared to subjects with a nonautonomous mood disorder, reported fewer days using cocaine (12.5 versus 21.1) and fewer days drinking four or more drinks of alcohol (1.1 versus 6. 1). Treatment completion was associated with less cocaine use, autonomy, and African-American ethnicity. However, when these variables were controlled using logistic regression, only autonomous mood disorder and ethnicity predicted treatment completion. These results suggest that autonomy may be a useful construct to measure, and that subjects with nonautonomous mood disorders may need special efforts to ensure treatment retention.

Adult↗
PubMed1999

Long-term followup of the North American multicenter UroLume trial for the treatment of external detrusor-sphincter dyssynergia.

PURPOSE: We determine the long-term efficacy and safety of the UroLume stent as minimally invasive treatment for external detrusor-sphincter dyssynergia in spinal cord injured men. MATERIALS AND METHODS: A total of 160 spinal cord injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1 years (range 16 to 74) were prospectively treated with an endoprosthesis at 15 centers as part of the North American UroLume trial for external detrusor-sphincter dyssynergia. Urodynamic parameters, including voiding pressure, residual urine volume and bladder capacity, were compared before treatment and at 1, 2, 3, 4 and 5 years after treatment. RESULTS: Mean voiding pressure was 75.1 +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3 +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent insertion (p <0.001). Residual urine volume decreased after stent placement and was maintained throughout the 5-year followup (p <0.001). Mean cystometric capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5 years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or stabilized in most patients with functioning stents. Stent explant was necessary in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS: The UroLume stent demonstrates long-term safety and efficacy for the treatment of external detrusor-sphincter dyssynergia. The outcome was similar in men with and without previous sphincterotomy.

Adolescent↗
PubMed1998

Conformational correction mechanisms aiding antigen recognition by a humanized antibody.

The crystal structure of the complex between hen egg lysozyme and the Fv fragment of a humanized antilysozyme antibody was determined to 2.7-A resolution. The structure of the antigen combining site in the complex is nearly identical to that of the complexed form of the parent mouse antibody, D1.3. In contrast, the combining sites of the unliganded mouse and humanized antilysozymes show moderate conformational differences. This disparity suggests that a conformational readjustment process linked to antigen binding reverses adverse conformations in the complementarity determining regions that had been introduced by engineering these segments next to human framework regions in the humanized antibody.

Animals↗
PubMed1998

Medicinal herb use and the renal patient.

Medicinal herb use, although a popular branch of alternative medicine, may be inappropriate for the renal patient. The pharmacological activity, chemical components, and microbial content of herbs, as well as their ability to interfere with prescription medications, make medicinal herbs potentially dangerous for the renal patient. The purpose of this report is to inform the medical professional of the implications of renal patients using medicinal herbs.

Complementary Therapies↗
PubMed1998

Gender differences in psychiatric comorbidity among cocaine-using opiate addicts.

Psychiatric comorbidity was examined for a sample of 212 methadone patients dually addicted to opiates and cocaine, focusing on gender differences. Diagnoses were determined by the SCID for DSM-III-R. Men displayed more lifetime (but not current) substance use disorders, while women displayed more lifetime and current non-substance use disorders. There were several significant interactions among psychiatric disorders and gender. Women were more likely than men to present with concurrent mood and anxiety disorders. Women with ASPD were unlikely to have alcohol use disorder, but likely to have opioid use disorder. Men with anxiety were likely to be diagnosed with ASPD. Treatment implications of the findings are discussed.

Adult↗
PubMed1997

Structural consequences of humanizing an antibody.

We have determined the crystal structure of the Fv fragment of a humanized anti-hen eggwhite lysozyme Ab (HuLys). This molecule is a composite of known structures: complementarity-determining regions (CDRs) were from the mouse anti-lysozyme Ab D1.3, heavy chain framework regions were from the human myeloma protein NEW, and the light chain framework regions were consensus sequences similar to the Bence Jones protein REI. HuLys crystallized in space group P4(3)2(1)2, with two Fv molecules in the crystallographic asymmetric unit. The structure was solved by molecular replacement, using a composite of the parent structures as a search model. The resolution of the structure was 2.87 A, with an R factor of 22%. There were several unanticipated structural similarities and differences between HuLys and the mouse and human structures. The framework regions of HuLys were as close or closer in conformation to D1.3 than to the NEW or REI protein, despite overwhelming sequence identity with the human framework regions. The effect was most pronounced at the CDR-framework junction, showing that the CDRs can induce structural changes in framework residues, having the net effect in HuLys of reconforming the framework into a conformation more like D1.3. In the combining site, the grafted CDRs retained conformational equilibria seen in D1.3, demonstrating that humanizing can be applied to Abs that bind Ags through isomeric equilibrium or induced fit mechanisms. In addition, HuLys showed systematic differences from D1.3 that resembled domain rotations reported for other Abs. However, the V(H)-V(L) interface itself was unaffected, and the apparent movement was actually caused by rearrangements distant from this surface.

Amino Acid Sequence↗
PubMed1997

Recurrent synovial chondromatosis treated with meniscectomy and synovectomy.

Synovial chondromatosis is a rare benign intraarticular metaplasia of synovium. This process may result in the production of detached particles of highly cellular cartilage in the involved joint spaces. It is most often reported in the larger joints of the body including the knee, hip, elbow, and ankle. Since Axhausen in 1993 reported the first case affecting the temporomandibular joint, several articles have been listed in the literature regarding the presentation, diagnosis, and management of this form of an arthropathy. This is a case of a recurrent synovial chondromatosis that was approached with a meniscectomy and a complete synovectomy.

Arthroscopy↗
PubMed1997

Bromocriptine for cocaine dependence. A controlled clinical trial.

On the basis of the dopamine depletion theory, bromocriptine has been tested to treat cocaine withdrawal and dependence. The authors conducted a 6-week study with 1 week of pretreatment observation and 5 weeks of a randomized, double-blind, placebo-controlled clinical trial of bromocriptine for DSM-III-R-defined cocaine dependence in methadone-maintained male patients. The bromocriptine group (n = 24) did not differ from the placebo group (n = 26) in self-reported cocaine use, proportion of positive urine toxicology samples, craving for cocaine, resistance to cocaine use, or mood symptoms between the pretreatment baseline and the last week of the clinical trial. Both groups showed significant reduction in self-reported frequency of cocaine use, resistance to craving, and mood symptoms during participation in the protocol. The results of this study are consistent with recent clinical and laboratory findings in primary cocaine users. Despite initially promising pilot studies, recent evidence does not support the efficacy of bromocriptine to reduce cocaine use or craving.

Adult↗