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Biomedical subjects

G Kearns

Publications and source records attributed to G Kearns.

At least 19 recordsLinked to original sources
PubMed2006

Association between paclitaxel and necrotic pancreatitis.

To our knowledge this is the first reported case of paclitaxel associated necrotic pancreatitis requiring a pancreatic necrostomy. This was a near fatal complication associated with paclitaxel with a high resulting morbidity. Although this is a rare association physicians should be wary of the potential to develop severe pancreatitis in patients receiving this therapeautic agent. Monitoring of serum amylase during therapy is therefore warranted.

Adult↗
PubMed2003

Role of the research-subject locator (RSL) in the performance of a pediatric drug trial.

This article examines the feasibility, effectiveness, and ethical constraints relevant to appropriate financial compensation of the pediatric house officer who functions as a research-subject locator (RSL). When carefully trained and supervised, the RSL can facilitate timely enrollment of research subjects in pediatric drug trials, augment the house officer training experience, and advocate for children to increase therapeutic options available for pediatric care. When monitored within the clinical trial schema, the RSL has no direct link to the study outcome and thus performs within ethical standards for subject enrollment and study participation.

Child↗
PubMed2001

Exacerbated physical fatigue and mental fatigue in Parkinson's disease.

OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND: Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in the mental realm. Fatigue has not been characterized in PD. METHODS: We characterized fatigue in 39 PD patients and 32 age-matched normal controls using five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which measures five dimensions of fatigue independently including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. B. The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The Profile of Mood States (POMS), which assesses six subjective subscales: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity, and confusion-bewilderment. D. Center for Epidemiological Studies-Depression Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD patients scored higher in all of the five dimensions of fatigue in the MFI including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The severity of physical fatigue did not correlate with that of mental fatigue. PD patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The scores in the FSI correlated with general fatigue, physical fatigue, reduced activity, and reduced motivation but not with mental fatigue in the MFI. Depression correlated with all dimensions of fatigue except physical fatigue in the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did not correlate with any of the measures. CONCLUSIONS: PD patients have increased physical fatigue and mental fatigue compared to normals. Physical fatigue and mental fatigue are independent symptoms in PD that need to be assessed and treated separately.

Aged↗
PubMed2000

A financial analysis of maxillomandibular fixation versus rigid internal fixation for treatment of mandibular fractures.

PURPOSE: The aim of this study was to compare the cost-effectiveness of mandibular fracture treatment by closed reduction with maxillomandibular fixation (CRF) with open reduction and rigid internal fixation (ORIF). PATIENTS AND METHODS: This was a retrospective study of 85 patients admitted to the Oral and Maxillofacial Surgery Service at San Francisco General Hospital and treated for mandibular fractures from January 1 to December 31, 1993. The patients were divided into 2 groups: 1) those treated with CRF and 2) those treated with ORIF. The outcome variables were length of hospital stay, duration of anesthesia, and time in operating room. The charge for primary fracture treatment included the fees for the operation and hospitalization without any complications. Within the group of 85 patients treated for mandibular fractures in 1993, 10 patients treated with CRF and 10 patients treated with ORIF were randomly selected, and hospital billing statements were used to estimate the average charge of primary treatment. The average charge to manage a major postoperative infection also was estimated based on the billing statements of 10 randomly selected patients treated in 1992 (5 treated with CRF, 5 with ORIF) who required hospital admission for the management of a complication. The average total charge was computed by using the average charge for primary treatment plus the incidence of postoperative infection multiplied by the average charge for management of that complication. RESULTS: Eighty-five patients were included in the study. The average charge for primary treatment was $10,100 for the CRF group and $28,362 for the ORIF group. The average charge for the inpatient management of a major postoperative infection was $26,671 for the CRF group and $39,213 for the ORIF group. The average total charge for management of a mandible fracture with CRF was $10,927; the total charge for the ORIF group was $34,636. CONCLUSION: The results of this retrospective study suggest that the use of CRF in the management of mandibular fractures at our institution provides considerable savings over treatment by using ORIF. The use of ORIF should be reserved for patients and fracture types with specific indications.

Adult↗
PubMed2000

Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network.

In this study, the authors evaluate the pharmacodynamics, safety, and acceptability of a new cherry-flavored oral syrup formulation of midazolam. This randomized, double-blind, parallel-group, dose-ranging clinical trial of oral midazolam was conducted at seven U.S. health care institutions focused on pediatric clinical pharmacology research (i.e., the PPRU Network). Pediatric patients (n = 85, ages 6 months through 15 years) underwent invasive procedures and were randomized to a single oral dose of midazolam syrup (0.25, 0.5, or 1.0 mg/kg). Patient taste acceptability of midazolam syrup was evaluated at the time of oral administration. Pharmacodynamic measurements included (1) sedation score using a 5-point scale at baseline and 10-, 20-, and 30-minute postdose intervals and (2) anxiety score using a 4-point scale at the time of separation from caretakers and, when applicable, at the time of mask anesthetic induction. Midazolam and alpha-hydroxymidazolam plasma concentrations were measured at all pharmacodynamic measurement time points. Adverse events were monitored continuously during the study. Most patients (99%) accepted the syrup without difficulty. Satisfactory sedation was achieved within 30 minutes by 81% of patients. The anxiety score at the time of caretaker separation and mask anesthetic induction was satisfactory for 87% and 91% of patients, respectively. A significant linear relationship between plasma drug concentration and maximal sedation score, but not anxiety score, was observed. The occurrence of adverse events was consistent with the known safety profile of midazolam. The most commonly reported adverse events were hiccoughing, hypoxemia, nausea, and emesis. It was concluded that a new oral syrup formulation of midazolam, 0.25 to 1.0 mg/kg, effectively induced rapid-onset, dose-related, adequate, and safe sedation and anxiolysis in pediatric patients who underwent operative procedures. Sedative effects were related to plasma concentrations of both midazolam and the primary metabolite, alpha-hydroxymidazolam. Oral midazolam, 1.0 mg/kg, administered within 30 minutes of the expected procedure or anesthetic induction should provide safe and effective sedation to a majority of children ages 6 months to 16 years.

Administration, Oral↗
PubMed1999

Placement of endosseous implants in children and adolescents with hereditary ectodermal dysplasia.

OBJECTIVE: The purposes of this investigation were to study the feasibility of placing endosseous implants in children and adolescents with ectodermal dysplasia and to assess the position and stability of such implants during growth. This article reports on 6 subjects with long-term follow-up. Study design. A prospective study was commenced in 1991. Patients with hereditary ectodermal dysplasia who were over the age of 5 years and who presented to the University of California San Francisco Ectodermal Dysplasia Clinic for dental treatment were included and maintained in the study. In each case, clinical and radiographic records were obtained before treatment, immediately after implant placement, at delivery of the prosthesis, and subsequently at yearly intervals. Six subjects are reported, 4 as members of the prospective study group and 2 who had been treated before the study began. RESULTS: A total of 41 implants (19 maxillary, 22 mandibular) were placed. The average follow-up after implant placement was 7.8 years (range, 6-11 years), and the average time since restoration was 6 years (range, 5-10 years). Forty implants successfully integrated and have been restored. There was no evidence that implant placement or prosthetic rehabilitation resulted in restriction of transverse or sagittal growth. One mandibular implant, placed in a partially dentate 5-year-old, became submerged because of adjacent alveolar development and required placement of a longer abutment. Four maxillary implants placed in a partially dentate 7-year-old also became submerged and required prosthetic revision and the placement of longer abutments. CONCLUSIONS: This preliminary report suggests that endosseous implants can be successfully placed and can provide support for prosthetic restoration in patients with hereditary ectodermal dysplasia. However, vertical dentoalveolar growth results in submergence of the implant relative to the adjacent natural dentition when implants are placed adjacent to erupting permanent teeth.

Adolescent↗
PubMed1999

The role of cisapride in the treatment of pediatric gastroesophageal reflux. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. METHODS: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. RESULTS: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. CONCLUSIONS: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Arrhythmias, Cardiac↗
PubMed1998

The removal of plates and screws after Le Fort I osteotomy.

PURPOSE: This study is a retrospective chart review designed to evaluate the incidence and reasons for removal of plates and screws after Le Fort I osteotomy. PATIENTS AND METHODS: The study sample consisted of patients who underwent Le Fort I osteotomy at the University of California, San Francisco, and Northwestern University in Chicago between December 1985 and December 1994. All patients in the study were treated with internal fixation using 2.0-mm plates and screws. All data were obtained from medical records and operative reports. The following intraoperative variables were evaluated: hardware material, plate size and shape, plate location, screw size, graft material, and intraoperative complications. For patients requiring removal of hardware, the number, location and type of plates and screws removed were recorded, as well as the reasons for removal. RESULTS: A total of 738 plates were placed in 190 patients. Twenty-one of the 190 patients (11.1%) had at least a portion of the hardware removed because they either requested removal or required removal secondary to complications related to the plate or screw. This represented 70 of 738 plates (9.5%). The percentage of titanium plates removed was greater than the percentage of Vitallium plates removed. The reasons for removal included pain, palpation by the patient, sinusitis, temperature sensitivity, infection, and patient request. CONCLUSION: Only a small number of patients (10.6%) develop complications from plates or screws that required their removal. In each case, prompt removal constituted adequate management.

Adult↗
PubMed1998

The distribution of the auriculotemporal nerve around the temporomandibular joint.

OBJECTIVE: The purpose of this cadaver dissection was to study the position of the auriculotemporal nerve in relation to the mandibular condyle, capsular tissues, articular fossa, and lateral pterygoid muscle and to evaluate the anatomic possibility of nerve impingement or irritation by the surrounding structures. STUDY DESIGN: Eight cadaveric heads (16 sides) were dissected. The auriculotemporal nerve was identified by following its course around the middle meningeal artery. The course of the nerve trunk was dissected from the middle meningeal artery to the terminal branches within the temporomandibular disk. The horizontal distance between the auriculotemporal nerve and the medial portion of the condyle/condylar neck was measured. The vertical distance from the most superior portion of the articular condyle to the superior border of the auriculotemporal nerve was measured. RESULTS: The auriculotemporal nerve was identified on each side, and a single trunk was evident along the medial aspect of the condylar neck. At the posterior border of the lateral pterygoid muscle, the nerve trunk was in direct contact with the condylar neck in every specimen. The average vertical distance between the superior condyle and the nerve was 7.06 mm (+/- 3.21 mm); the range was 0 to 13 mm. The vertical distance between the nerve and the superior condyle on one side of the specimen did not correlate with the distance on the contralateral side. CONCLUSION: The auriculotemporal nerve trunk has a close anatomic relationship with the condyle and the temporomandibular joint capsular region, and there is evidence of a possible mechanism for sensory disturbances in the temporomandibular joint region. In all cases, the nerve was in direct contact with the medial aspect of the capsule or condylar neck. Because there is no correlation between the positions of the nerves on the right and left sides, only one side may be affected. The nerve was also observed to course in direct apposition to the lateral pterygoid muscle. The findings support the hypothesis that the anatomic and clinical relationship of the auriculotemporal nerve to the condyle, articular fossa, and lateral pterygoid muscle may be causally related to compression or irritation of the nerve, producing numbness or pain, or both, in the temporomandibular joint region.

Adult↗
PubMed1997

Two novel routes of transporter associated with antigen processing (TAP)-independent major histocompatibility complex class I antigen processing.

Jaw1 is an endoplasmic reticulum (ER) resident protein representative of a class of proteins post translationally inserted into membranes via a type II membrane anchor (cytosolic NH2 domain, lumenal COOH domain) in a translocon-independent manner. We found that Jaw1 can efficiently deliver a COOH-terminal antigenic peptide to class I molecules in transporter associated with antigen processing (TAP)-deficient cells or cells in which TAP is inactivated by the ICP47 protein. Peptide delivery mediated by Jaw1 to class I molecules was equal or better than that mediated by the adenovirus E3/19K glycoprotein signal sequence, and was sufficient to enable cytofluorographic detection of newly recruited thermostabile class I molecules at the surface of TAP-deficient cells. Deletion of the transmembrane region retargeted Jaw1 from the ER to the cytosol, and severely, although incompletely, abrogated its TAP-independent peptide carrier activity. Use of different protease inhibitors revealed the involvement of a nonproteasomal protease in the TAP-independent activity of cytosolic Jaw1. These findings demonstrate two novel TAP-independent routes of antigen processing; one based on highly efficient peptide liberation from the COOH terminus of membrane proteins in the ER, the other on delivery of a cytosolic protein to the ER by an unknown route.

Antigen Presentation↗
PubMed1997

Comparison of full thickness skin graft "take" after excision with the carbon dioxide laser and scalpel.

SPECIFIC AIM. To evaluate the take of skin grafts on conventionally prepared beds and on beds prepared by a carbon dioxide laser, with and without abrasion of the bed. SIGNIFICANCE. Graft take is dependent on hemostasis, immobility, and nutrition of the graft. Scalpel excision of the skin graft can be associated with hemostatic difficulties and laser treatment of the skin graft bed can provide hemostasis. Abrasion of the bed after laser treatment may then be a means of opening small lymphatic and blood vessels to maintain the graft. Laser treatment followed by abrasion of the bed may provide an ideal graft base before suturing of the skin graft. MATERIAL AND METHODS. Full-thickness skin grafts were taken with a scalpel at three sites on the dorsal skin of 24 guinea pigs. The three beds were prepared with pressure alone to provide hemostasis, laser vaporization followed by abrasion with gauze to produce pinpoint bleeding, and laser vaporization alone. The original skin from each of the sites was then sutured back in place. At postoperative days 1, 3, 5, 10, 21, and 35 the graft sites were assessed clinically for "take." Laser Doppler measurements were also made to evaluate blood flow. Histologic sections of the three sites were prepared. Immunohistochemical analysis was performed to evaluate cell proliferation and angiogenesis. RESULTS. For the animals sacrificed through day 10 the rate of take for the sites that were not lased was 100%. For the sites that were lased alone and lased and abraded the rate of take was 71% with no difference between the two techniques. The lased sites demonstrated increased inflammatory response and graft necrosis. Immunohistochemical analysis showed increased cellular proliferation and angiogenesis in the bed. DISCUSSION. Grafts take best on a scalpel-prepared bed. Laser preparation of the bed, with or without abrasion, demonstrates decreased "take." Therefore the carbon dioxide laser is not a recommended means to take a graft or prepare the graft bed.

Animals↗
PubMed1997

Placement of endosseous implants in grafted alveolar clefts.

OBJECTIVE: The purpose of this study was to determine the optimal timing for placement and to evaluate short- and long-term outcomes of endosseous implants in bone-grafted alveolar clefts. DESIGN: Fourteen patients who underwent alveolar cleft bone grafting (ACBG) and closure of an oronasal fistula followed by restoration of the missing lateral incisor tooth using endosseous implants (EI) were studied. The oronasal fistulae were closed using local flaps, and the alveolus was grafted with fresh autogenous iliac marrow. Endosseous implants were placed a minimum of 4 months following ACBG. The average age at ACBG was 20.35 years (range, 12-65 yr), and at implant placement 22.2 years (range, 15-66 yr). It was necessary to regraft the alveolar cleft region in six patients to provide adequate bone volume for implant placement. Those who required alveolar regrafting had an increased mean interval between the initial ACBG and planned implant placement compared to the patients with adequate bone available for implant placement 26.4 months (range, 4-46 mo) versus 15.75 months (range, 4-36 mo). RESULTS: Twenty-nine implants were placed in 14 patients, 9 outside of the cleft region and 20 in grafted alveolar clefts. Eighteen of 20 (90%) implants in the bone-grafted alveolar clefts have been successfully restored. The mean follow-up after implant placement was 39.1 months (range, 1-54 mo), and after restoration 28.5 months (range, 1-47 mo). CONCLUSIONS: Endosseous implants can be placed in bone-grafted alveolar clefts. Consideration should be given to the adequacy of graft volume and ridge morphology at the time of ACBG. The interval between ACBG and implant placement is important. The greater the interval beyond 4 months, the more likely there will be inadequate bone volume to accept an implant.

Adolescent↗
PubMed1995

Infection following treatment of mandibular fractures in human immunodeficiency virus seropositive patients.

PURPOSE: There are little data available on the prevalence of human immunodeficiency virus (HIV) disease and its relationship to postoperative infection in patients presenting with mandibular fractures. This retrospective study assesses these parameters. PATIENTS: The study population consisted of 251 patients treated for mandibular fractures at San Francisco General Hospital (SFGH) between January 1990 and December 1993. Group 1 (n = 20) was composed of patients with documented HIV infection and group 2 (n = 231) served as controls. The groups were comparable with regard to age, sex, etiology, and number and types of fractures. RESULTS: HIV prevalence for this population was 7.9%, and was consistent with previously documented prevalence studies in SFGH surgical patients. In the HIV-positive group, 6 of 20 patients (30%) developed postoperative infection: 2 soft tissue (10%) and 4 bone-related (20%). In the control group, 22 of 231 patients (9.5%) developed postoperative infections: 16 soft tissue (6.9%) and 6 bone-related (2.6%). Statistical analysis showed a significant difference between the two groups with regard to overall (P = .016) and to bone-related (P = .001) infection rates. There was no statistically significant difference in soft tissue infections between the two groups (P = .953). The rate of postoperative infection was significantly higher in those patients (both HIV-positive and controls) who had open reduction and internal fixation (ORIF; 25/155; 16%) versus those who had closed reduction and maxillomandibular fixation (3/96; 3.1%; P = .003). The postoperative infection rate after ORIF was significantly higher in the HIV-positive (5/11; 45%) compared with the control group (20/144; 13.9%; P = .02). CONCLUSIONS: The results of this study indicate that the overall rate of postoperative infection after treatment of mandibular fractures is significantly higher in HIV-positive than in HIV-negative patients. Specifically, the use of ORIF in HIV-positive patients represents a significant risk.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Expression of CD44 on rheumatoid synovial fluid lymphocytes.

OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.

Arthritis, Rheumatoid↗
PubMed1994

Jaw1, A lymphoid-restricted membrane protein localized to the endoplasmic reticulum.

Jaw1 is a novel lymphoid-restricted gene that is expressed in a developmentally regulated fashion in both the B and T cell lineages. Jaw1 mRNA is abundantly expressed in pre-B and B cell lines with minimal or undetectable expression in plasma cell lines. Pre-T cell lines and normal mouse thymocytes express high levels of Jaw1 mRNA, whereas most mature T cell lines express low levels. Comparison of the mouse and human genes reveals that Jaw1 encodes a 539 amino acid protein with a highly conserved coiled-coil domain in the middle third of the protein and a COOH-terminal transmembrane domain. Jaw1 was localized to the endoplasmic reticulum (ER) of lymphocytes by indirect immunofluorescence and confocal microscopy. When overexpressed in HeLa cells, Jaw1 protein targeted to the ER. In vitro translation of Jaw1 in the presence of canine microsomes demonstrated that Jaw1 is an integral membrane protein of the ER and is oriented on the ER membrane facing the cytosol. Jaw1 is a member of a class of proteins with COOH-terminal hydrophobic membrane anchors and is structurally similar to proteins involved in vesicle targeting and fusion. These findings suggest that the function and/or the structure of the ER in lymphocytes may be modified by lymphoid-restricted resident ER proteins.

Amino Acid Sequence↗