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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 109 records · Page 6Linked to original sources
PubMed2000

Isolated acute knee injuries in the general population.

OBJECTIVE: Knee injuries are common in the general population, yet most studies have concentrated on special populations. The purpose of this study was to describe the types of injuries, injury events, age, and sex distributions in a community population. METHODS: The medical records of all residents of Olmsted County, Minnesota, 17 years of age or older who had a first visit for an isolated acute knee (acute was defined as occurring within 60 days of the physician visit) injury between January 1, 1993, and January 1, 1996, were abstracted. RESULTS: A total of 664 patients (4/1,000 community adults, 46% women and 54% men) presented to a physician for evaluation and treatment of an isolated acute knee injury. Injured men were on average younger than women and more likely to have an injury during a sports activity, whereas women's injuries were more likely to be the result of non-sports-related falls. Knee sprain or strain was the most common final diagnosis (36%). Approximately half (49%) of the patients had a single visit. The likelihood of orthopedic surgeon's care (37% overall) increased with injury severity and age of the patient. Overall, 12% of subjects had surgical treatment recommended. CONCLUSION: Knee injuries are common, often result in a single visit, seldom receive surgical intervention, and the majority are cared for entirely by generalist physicians.

Accidental Falls↗
PubMed2000

Permanent transfemoral pacemaker implantation is the technique of choice for patients in whom the superior vena cava is inaccessible.

We describe transfemoral pacemaker implantation in three patients in whom pacing via the superior vena cava was not possible or suboptimal. The first was an 88-year-old man with superior vena cava obstruction presenting with fractured epicardial pacing leads. Recent pneumonia increased the risks of a general anesthetic. The second patient was a 57-year-old man who was intolerant of a pectorally sited pacemaker because of the thinness of his anterior chest wall. The third patient was a 69-year-old woman who presented with an infected eroding pectorally sited pacemaker. Scarring secondary to a previous pacemaker infection rendered the contralateral pectoral site inaccessible. Since the subclavian route was inaccessible (case 1) or suboptimal (case 2 and 3), we implanted transvenous pacemakers via the femoral route, which was safe, and effective, during a 6-month follow-up period.

Aged↗
PubMed2000

Complementary approaches to the assessment of personality disorder. The Personality Assessment Schedule and Adult Personality Functioning Assessment compared.

BACKGROUND: Current concepts and measures of personality disorder are in many respects unsatisfactory. AIMS: To establish agreement between two contrasting measures of personality disorder, and to compare subject-informant agreement on each. To examine the extent to which trait abnormality can be separated from interpersonal and social role dysfunction. METHOD: Fifty-six subjects and their closest informants were interviewed and rated independently. Personality functioning was assessed using a modified Personality Assessment Schedule (M-PAS), and the Adult Personality Functioning Assessment (APFA). RESULTS: Subject-informant agreement on the M-PAS was moderately good, and agreement between the M-PAS and the APFA, across and within subjects and informants, was comparable to that for the M-PAS. This was equally the case when M-PAS trait plus impairment scores and trait abnormality scores were used. CONCLUSIONS: The M-PAS and the APFA are probably assessing similar constructs. Trait abnormalities occur predominantly in an interpersonal context and could be assessed within that context.

Adult↗
PubMed2000

Cardiac transplant vasculopathy.

STUDY OBJECTIVE: Coronary allograft vasculopathy (CAV) remains the major factor limiting long-term survival after heart transplantation. The purpose of this article is to review for the nontransplant physician the concept of CAV as a disease entity after heart transplantation. DESIGN: A MEDLINE search from 1985 to 1999 was performed. Data on cardiac transplant vasculopathy were divided into pathology, pathophysiology, presentation, diagnosis, and treatment. RESULTS: CAV manifests as a unique and unusually aggressive form of coronary artery disease that differs from traditional atherosclerosis. It is believed to be caused by immunologic mechanisms that combine with nonimmunologic factors to cause endothelial injury, resulting in smooth muscle proliferation and intimal thickening. This intimal hyperplasia leads to coronary obstruction, which ultimately results in allograft failure. Diagnosis of CAV can be difficult because transplant recipients have denervated hearts and rarely present with chest pain. Various noninvasive screening methods have not proved reliable. Therefore, most transplant centers perform periodic coronary angiography for routine CAV surveillance. Treatment of CAV involves modification of risk factors and the use of pharmacologic agents that alter vascular physiology. Revascularization procedures continue to play a role as palliative therapy, but are limited in their effectiveness by the diffuse nature of this disease. CONCLUSION: Cardiac transplant vasculopathy continues to play a major dilemma regarding posttransplant care. Further research is needed to develop successful preventive and therapeutic strategies that may alter the course of this disease.

Coronary Disease↗
PubMed2000

Different beta-casein fractions in Icelandic versus Scandinavian cow's milk may influence diabetogenicity of cow's milk in infancy and explain low incidence of insulin-dependent diabetes mellitus in Iceland.

OBJECTIVES: To compare children with insulin-dependent diabetes mellitus (IDDM) with controls in Iceland regarding their consumption of cow's milk in infancy, and to investigate the beta-casein fractions in Scandinavian and Icelandic cow's milk. The A1 variant of beta-casein has been shown to be diabetogenic in animal studies, and suggestions have been made that the B variant of beta-casein acts similarly. Differences in the relative proportions of beta-casein fractions might explain the lower incidence of IDDM in Iceland than in Scandinavia. METHODS: A retrospective case-control study on IDDM patients and matching controls was performed in Iceland to compare their diets in infancy. Fifty-five children with IDDM born in Iceland over a 16-year period and randomly collected controls (n = 165) were recruited to the study. Mothers of the children answered questions on breastfeeding habits and on when cow's milk products were introduced. Samples of cow's milk from randomly selected milk batches from the largest consumption areas in Iceland and Scandinavia were collected. The milk samples were freeze-dried and their beta-casein fractions were analyzed using capillary electrophoresis. RESULTS: No significant difference was found between IDDM patients and controls in the frequency and duration of breastfeeding or the first introduction of cow's milk products. The analyses of milk samples showed that the percentage of the A1 and B variants of beta-casein in Icelandic milk was significantly lower than in the milk from the Scandinavian countries. CONCLUSIONS: Cow's milk consumption in infancy is not related to IDDM in Iceland. The lower fraction of A1 and B beta-caseins in Icelandic cow's milk may explain why there is a lower incidence of IDDM in Iceland than in Scandinavia.

Adolescent↗
PubMed2000

Body mass index in patients with amputations on peritoneal dialysis: error of uncorrected estimates and proposed correction.

UNLABELLED: "Weight-height" indices including percent of ideal weight (%IW) and body mass index (BMI) are used to estimate degree of obesity in populations and are predictors of survival in dialysis patients. Amputation affects the relationship between weight and height independently of the degree of obesity. Corrections of both %IW and BMI for amputation have been published, but a National (U.S.) computer nutrition program used in the authors' institution uses only the correction for %IW. This study had two parts: (1) To test whether the weight-height cut-off values for weight deficit (%IW 90%, BMI 20 kg/m2) and obesity (%IW 120%, BMI 30 kg/m2) are compatible, we performed linear regression of BMI on %IW in peritoneal dialysis (PD) patients without amputations. In 349 men, BMI = 0.834 + 0.226 (%IW), r = 0.979. From this regression, the 95% confidence interval (CI) of BMI is 19.2-23.1 kg/m2 if %IW is 90%, and 26.1-29.9 kg/m2 if %IW is 120%. In 260 women, BMI = 2.194 + 0.184 (%IW), r = 0.974. From this regression, the 95% CI of BMI is 15.7-21.8 kg/m2 if %IW is 90%, and 21.3-27.3 kg/m2 if %IW is 120%. (2) To identify the direction and magnitude of the error of uncorrected BMI (BMIu) in dialysis patients with amputations, we analyzed weight-height indices in two groups of men by the computer nutrition program, which corrects %IW, but not BMI for amputation, and by the corrected BMI (BMIc) formula. In group A (amputation without height loss, n = 11), %IW = 110.2% +/- 16.9%, BMIu = 23.6 +/- 2.7 kg/m2, BMIc = 26.4 +/- 3.8 kg/m2 (p < 0.001, BMIc vs BMIu), and 5 of the 11 BMIu values fell below the 95% confidence band of the regression of BMI on %IW in patients without amputations. In group B (amputation with loss of height, n = 6), %IW = 92.7% +/- 19.9%, BMIu = 33.9 +/- 10.7 kg/m2, BMIc = 22.1 +/- 4.4 kg/m2 (p < 0.005, BMIc vs BMIu), and 5 of the 6 BMIu values fell above the 95% confidence band of the regression of BMI on %IW in patients without amputations. CONCLUSIONS: (1) The weight deficit cut-offs for %IW and BMI are compatible in non amputated men and women. (2) The obesity cut-offs for %IW and BMI are compatible in non amputated men, but not in non amputated women. (3) Amputation without height loss decreases BMIu, while amputation with height loss increases, in general, BMIu. (4) BMI should be corrected in PD patients with amputations.

Amputation, Surgical↗
PubMed2000

A guide for diagnosis of patients with arterial and venous thrombosis.

Inasmuch as coagulation laboratories are involved in providing a diagnosis for underlying causes of venous and arterial thrombosis, we present a comprehensive review of the biological properties and functions of the components of the hemostatic system as they relate to the diagnosis of arterial and venous thrombosis. Moreover, as coagulation laboratories are necessary to evaluate the success of initial treatment modalities and to provide guidance for supplemental therapeutic intervention, we include information on antiplatelet and antithrombotic therapy. Included in clinical coagulation testing are assays that evaluate the potential of blood to form clots and tests for platelet numbers and platelet functions. Clot-based assays directly detect the biological activity of procoagulant factors and fibrinogen; chromogenic substrate assays evaluate proteolytic activities of clotting as well as fibrinolysis enzymes; and specific antibodies measure the concentrations of coagulation and fibrinolysis enzymes in plasma. Genetic testing is rapidly becoming incorporated into the clinical routine. The prothrombin time (PT), activated partial prothrombin time (APTT), and thrombin time (TT) are screening assays that measure the clotting times of recalcified whole blood or platelet-poor plasma. In addition to their function as screening assays, PT, APTT, and TT are the backbone of all the specialized clot-based assays for factor activities and for the indirect measurement of inhibitory antithrombin and protein C activities. Molecular markers related to hemostasis and fibrinolysis consist of proteins or peptides that indicate an ongoing physiological or abnormal process related to clot formation, thrombosis, vascular damage, or drug effect. Molecular markers are currently identified by means of specific antibodies prepared against them. The list of hemostatic molecular markers is rapidly growing. Most of the assays developed for molecular marker measurement, with the notable exception of the d-dimer assay, are typically used in clinical research.

Antifibrinolytic Agents↗
PubMed1999

Anti-CD154 or CTLA4Ig obviates the need for thymic irradiation in a non-myeloablative conditioning regimen for the induction of mixed hematopoietic chimerism and tolerance.

BACKGROUND: Thymic irradiation (TI) or repeated administration of T cell-depleting monoclonal antibodies (TCD mAbs) is required in a previously described non-myeloablative regimen allowing allogeneic marrow engraftment with stable mixed chimerism and tolerance. As both treatments might be associated with toxicity in the clinical setting, we evaluated whether T-cell costimulatory blockade could be used to replace them. METHODS: C57BL/6 mice received depleting anti-CD4 and anti-CD8 mAbs on day -5, 3 Gy whole body irradiation (day 0), and 15x10(6) fully MHC-mismatched, B10.A bone marrow cells. In addition, hosts were injected with an anti-CD154 mAb (day 0) and/or CTLA4Ig (day +2). Chimerism in peripheral blood was followed by flow cytometric (FACS) analysis, and tolerance was assessed by skin grafting, and also by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. The frequency of certain Vbeta families was determined by FACS to assess deletion of donor-reactive T cells. RESULTS: Chimerism was transient and tolerance was not present in animals receiving TCD mAbs on day -5 without costimulatory blockade. The addition of anti-CD154 and CTLA4Ig, alone or in combination, reliably permitted induction of high levels of stable (>6 months) multi-lineage chimerism, with specific tolerance to skin grafts and donor antigens by MLR and CML assays. Long-term chimeras showed deletion of donor-reactive CD4+ peripheral blood lymphocytes, splenocytes, and mature thymocytes. Administration of TCD mAbs only 1 day before bone marrow transplantation plus anti-CD154 also allowed induction of permanent chimerism and tolerance. CONCLUSIONS: One injection of anti-CD154 or CTLA4Ig overcomes the need for TI or prolonged host TCD in a preclinical model for the induction of mixed chimerism and deletional tolerance and thus further decreases the toxicity of this protocol. Achievement of tolerance with conditioning given over 24 hr suggests applicability to cadaveric organ transplantation.

Abatacept↗
PubMed1999

Immunization of rhesus monkeys with a mucosal prime, parenteral boost strategy protects against infection with Helicobacter pylori.

Rhesus monkeys were immunized with recombinant Helicobacter pylori urease vaccine given solely by the parenteral route or preceded by a priming dose given by the oral route. Two groups of monkeys received parenteral urease with either a synthetic glycolipid adjuvant (Bay) or aluminum hydroxide (alum) as adjuvants. A third group of monkeys received a priming dose of oral urease given with the mucosal adjuvant LT (Escherichia coli heat labile enterotoxin), followed by parenterally administered booster doses of urease adsorbed to alum. Monkeys receiving placebo served as controls. The monkeys received a total of 4 doses of vaccine with the first 3 doses given every 3 weeks and the last booster dose administered 14 weeks later. The monkeys were challenged orally with H. pylori one week after the last vaccine dose and euthanized 10 weeks after challenge, at which time, their stomachs were collected for determination of bacterial colonization and histopathology. Monkeys primed with the oral vaccine and boosted with the parenteral vaccine showed a statistically significant reduction in bacterial colonization when compared to sham-immunized control animals (P = 0.05; Wilcoxon rank sums test). Monkeys receiving parenteral only regimes of urease plus Bay or alum showed no difference in bacterial colonization compared with sham-immunized controls (P = 1.00 and P = 0.33, respectively). The mucosal prime-parenteral boost regime did not cause gastropathy. There was no difference in any of the 3 treatment groups with respect to gastric epithelial changes compared to control animals. There was also no difference in the type and extent of gastric inflammatory cell infiltrates between animals vaccinated by the mucosal prime-parenteral boost strategy and sham immunized controls. However, monkeys receiving the two parenteral-only regimens had slightly elevated gastritis scores.

Adjuvants, Immunologic↗
PubMed1999

Adenylyl cyclase, a coincidence detector for nitric oxide.

Nitric oxide (NO) donors inhibit hormone- and forskolin-stimulated adenylyl cyclase activity in purified plasma membrane preparations from N18TG2 neuroblastoma cells. Northern blot analyses indicate that the predominant isoform of adenylyl cyclase in N18TG2 cells is the type VI. Our experiments eliminate all the known regulatory proteins for this isoform as possible targets of NO. NO decreases the Vmax of the enzyme without altering the Km for ATP. Occupancy of the substrate-binding site protects the enzyme from the inhibitory effects of NO, suggesting that the conformation of the enzyme determines its sensitivity. The inhibition is reversed by reducing agents, implicating a Cys residue(s) as the target for nitric oxide and an S-nitrosylation as the underlying modification. These findings implicate NO as a novel cellular regulator of the type VI isoform of adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1999

The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye's syndrome patients and controls.

The effects of aspirin metabolites on beta-oxidation were studied in skin fibroblasts from eight typical Reye's syndrome (RS) patients and controls. RS patients' cells did not differ from controls in rates of palmitate oxidation or in the three component activities of the mitochondrial trifunctional enzyme (MTE), indicating no inherited beta-oxidation defect. Aspirin metabolites salicylate, hydroxyhippurate and gentisate, but not aspirin, directly inhibited palmitate oxidation in control and RS cells. RS cells were significantly more sensitive to inhibition than controls at 0.5 to 5 mM salicylate. Inhibition was concentration-dependent and reversible. Inhibition did not occur in fibroblasts lacking activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of MTE. Salicylate was therefore inhibiting beta-oxidation at this step. Hydroxyhippurate and salicylate reversibly inhibited HAD activities in extracts of control and RS cells. Studies with pure short-chain HAD and LCHAD (MTE) showed hydroxyhippurate and salicylate were competitive inhibitors of the former but mixed (not competitive) inhibitors of the latter. Both compounds inhibited the combined, three-step, MTE reaction measured in the physiological direction. We conclude that (1) salicylate and hydroxyhippurate decrease beta-oxidation in intact cells by reversible inhibition of LCHAD activity of the MTE, and (2) beta-oxidation in RS cells is inherently more sensitive to inhibition by low concentrations of salicylate than controls.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

The role of GMXCXXC metal binding sites in the copper-induced redistribution of the Menkes protein.

The Menkes protein (MNK or ATP7A) is a transmembrane, copper-transporting CPX-type ATPase, a subgroup of the extensive family of P-type ATPases. A striking feature of the protein is the presence of six metal binding sites (MBSs) in the N-terminal region with the highly conserved consensus sequence GMXCXXC. MNK is normally located in the trans-Golgi network (TGN) but has been shown to relocalize to the plasma membrane when cells are cultured in media containing high concentrations of copper. The experiments described in this report test the hypothesis that the six MBSs are required for this copper-induced trafficking of MNK. Site-directed mutagenesis was used to convert both cysteine residues in the conserved MBS motifs to serines. Mutation of MBS 1, MBS 6, and MBSs 1-3 resulted in a molecule that appeared to relocalize normally with copper, but when MBSs 4-6 or MBSs 1-6 were mutated, MNK remained in the TGN, even when cells were exposed to 300 microM copper. Furthermore, the ability of the MNK variants to relocalize corresponded well with their ability to confer copper resistance. To further define the critical motifs, MBS 5 and MBS 6 were mutated, and these changes abolished the response to copper. The region from amino acid 8 to amino acid 485 was deleted, resulting in mutant MNK that lacked 478 amino acids from the N-terminal region, including the first four MBSs. This truncated molecule responded normally to copper. Moreover, when either one of the remaining MBS 5 and MBS 6 was mutated to GMXSXXS, the resulting proteins were localized to the TGN in low copper and relocalized in response to elevated copper. These experiments demonstrated that the deleted N-terminal region from amino acid 8 to amino acid 485 was not essential for copper-induced trafficking and that one MBS close to the membrane channel of MNK was necessary and sufficient for the copper-induced redistribution.

Adenosine Triphosphatases↗
PubMed1999

Administration of oxytocin immediately after insemination does not improve pregnancy rates in mares bred by fertile or subfertile stallions.

It is probable that reduced pregnancy rates in mares bred to subfertile stallions is attributable, in part, to the reduced number of normal spermatozoa that colonize the oviduct. Administration of oxytocin stimulates both uterine and oviductal contractility. The hypothesis that oxytocin may enhance sperm transport to/into the oviducts, and thereby increase pregnancy rates, was tested in 2 trials. For both trials, fertile estrous mares with follicles > or = 35 mm in diameter were inseminated once at 24 h after administration of 1500 to 2000 U hCG. The inseminate dose was limited to 100 million spermatozoa in order to lower pregnancy rates and thus increase the chance of detecting a treatment effect. Pregnancy status was determined by transrectal ultrasound examination 14 to 16 d after insemination. In Trial 1, 49 mares were inseminated with 4 mL extended semen from 1 of 3 stallions (1 fertile and 2 subfertile males). Immediately after insemination, the mares were administered either 20 U oxytocin or 1 mL saline intravenously. In Trial 2, 51 mares were inseminated with 4 mL extended semen from 1 of 4 stallions (1 fertile and 1 subfertile male used in Trial 1, and 2 additional fertile males). Immediately after insemination, and again 30 min later, mares were administered either 5 U oxytocin or 0.25 mL saline intramuscularly. To test for effects of treatment with oxytocin and for the interaction between semen quality and treatment, a generalized linear mixed regression model was used that accounted for the split-plot design (treatment within stallions), the random effect of stallion, the fixed effect of semen quality, the binary outcome of a single breeding trial, and the varying number of trials per stallion/treatment groups. Three treatment protocols or regimens were used: placebo, 5 U oxytocin injected twice intramuscularly, and 20 units oxytocin injected twice intravenously. Semen was classified as high (fertile stallions) or low (subfertile stallions) quality. No interaction between semen quality and treatment was detected (P > 0.10). The pregnancy rate of mares treated with oxytocin immediately after insemination was 30% (15/50) compared with 50% (25/50) for mares treated with saline immediately after breeding. Administration of oxytocin did not affect pregnancy rates (P > 0.10).

Animals↗
PubMed1999

Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys.

Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 microg Escherichia coli heat-labile enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered over an 8 week period. All five vaccinated monkeys had a greater than two-fold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori colonization. H. pylori was eradicated from these monkeys with a course of antimicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H. pylori. Necropsy was performed 23 weeks after rechallenge and H. pylori colonization was determined by histological examination of 12 individual gastric sites. A significant reduction in colonization (p < or = 0.0001; Friedman's analysis of variance) was found in the vaccinated animals. Histopathologic examination of necropsy tissues also revealed a trend towards reduced gastritis and epithelial alterations in the vaccinated group compared to animals receiving LT alone. This study provides the first evidence for effective vaccination of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gastric inflammation.

Adjuvants, Immunologic↗
PubMed1999

The variability of practice in interviews used by professionals to investigate child sexual abuse.

OBJECTIVE: The study aimed to examine: (1) the variability of interview practice among professionals who interview children to investigate suspected sexual abuse; (2) the relationship between interview practice and respondent characteristics; (3) the characteristics of interviewers who used the anatomically correct dolls in the course of their interviews. METHOD: Sixty investigatory interviewers completed questionnaires focusing on professional background, training, and interview practice. RESULTS: Interview practice varied considerably and some practices were at odds with the recommendations of the literature. Most of this variability was not accounted for by the respondent variables examined. Where there was evidence for an association, the interviewers' professional background, number of interviews conducted in the previous year, and whether or not they used the anatomically correct dolls appeared to influence practice, whereas general training and specific training in child sexual abuse had no significant effect. Only a minority (36%) used the anatomically correct dolls and none of the interviewer characteristics evaluated differentiated them from non doll-users. CONCLUSIONS: In this sample interview practices varied considerably and did not appear to be influenced by the interviewer's specific or general training. Further research is needed to focus on the comparative effectiveness of different interview techniques and the comparative effectiveness of different training programs in influencing interviewing practice.

Child↗
PubMed1999

The V-antigen of Yersinia is surface exposed before target cell contact and involved in virulence protein translocation.

Type III-mediated translocation of Yop effectors is an essential virulence mechanism of pathogenic Yersinia. LcrV is the only protein secreted by the type III secretion system that induces protective immunity. LcrV also plays a significant role in the regulation of Yop expression and secretion. The role of LcrV in the virulence process has, however, remained elusive on account of its pleiotropic effects. Here, we show that anti-LcrV antibodies can block the delivery of Yop effectors into the target cell cytosol. This argues strongly for a critical role of LcrV in the Yop translocation process. Additional evidence supporting this role was obtained by genetic analysis. LcrV was found to be present on the bacterial surface before the establishment of bacteria target cell contact. These findings suggest that LcrV serves an important role in the initiation of the translocation process and provides one possible explanation for the mechanism of LcrV-induced protective immunity.

Antibodies, Bacterial↗