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Biomedical subjects

S Hammer

Publications and source records attributed to S Hammer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120.

A phase I dose escalation study was conducted with the human monoclonal anti-gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional activity of F105 in HIV-1-infected individuals. F105 is an IgG1(kappa) antibody reactive with a discontinuous epitope that overlaps the CD4-binding site of gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates, and synergizes with other antibodies in neutralizing an expanded spectrum of isolates. Four patients each with CD4 counts between 200 and 500/mm3 received a single dose of F105 at 100 or 500 mg/m2, intravenously. Sustained levels of F105 were obtained in plasma, and there was no evidence of an immune response to F105 as determined by a double-antigen immunoassay. No patient experienced any toxicity. Infused antibody retained full functional activity as detected by the ability of sera to block the binding of labeled F105 to HIV-1-infected cells. Of note, all patients had preexisting antibody to the gp120 CD4-binding site. The ability to culture virus by quantitative microculture remained unchanged by this single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic as a single injection at the doses tested. Furthermore, the antibody retains full gp120-binding activity. In these patients, with preexisting CD4-binding site antibody, there is no evidence of anti-HIV-1 activity following a single antibody infusion.

Adult↗
PubMed1998

Procalcitonin: a new marker for diagnosis of acute rejection and bacterial infection in patients after heart and lung transplantation.

UNLABELLED: The aim of the study was to investigate the reliability of procalcitonin (PCT), a new potential marker for detection of bacterial, fungal and protozoal infections, in order to differentiate these from viral infections and early rejections in heart, heart-lung and lung transplanted patients. PCT is a propeptide of calcitonin with unknown origin which is not detectable in plasma of healthy subjects. It increases rapidly and significantly under severe microbial infections. METHODS: PCT plasma levels were measured using an immuno-luminescence assay. C-reactive protein and white blood cells were quantified to validate the PCT values. RESULTS: Increased levels of PCT were found in all transplant patients with bacterial, fungal and protozoal infections. The magnitude of the values were clearly associated with the severity of the infection. Trauma of operation or inflammatory events such as viral infections and rejections did not trigger PCT-production. The release of PCT did not depend on the type of pathogens even though Aspergillum resulted in the highest levels measured. Sensitivity, specificity and prognostic value of PCT for systemic infections were higher than of the other parameters investigated. CONCLUSION: PCT is a highly specific analyte which shows significant diagnostic validities when nonviral infections are compared with rejection episodes. PCT discriminates between inflammatory events such as rejection or viral infections and nonviral-infections including bacterial, fungal and protozoal infections. The half-life of PCT is 24 h indicating clearly a competent antibiotic treatment. Unnecessary antibiotic therapy can be avoided due to the early exclusion of bacterial and fungal infections.

Adolescent↗
PubMed1998

Perspective: human immunodeficiency virus type 1 (HIV-1) RNA end points in HIV clinical trials: issues in interim monitoring and early stopping.

Due to the desire to both shorten the length and reduce the size of clinical trials in human immunodeficiency virus (HIV) disease, the use of surrogate end points such as HIV-1 RNA is becoming increasingly standard. While these end points may be reasonable surrogates for the clinical effectiveness of drugs, a key point in their use as trial end points is the definition of a relevant duration of antiviral response. This definition is often complicated by the desire to perform interim reviews of ongoing laboratory end point trials. Unlike clinical end point trials, in which early clinical response is generally indicative of longer-term follow-up, it is yet to be determined whether short-term viral response adequately predicts the long-term durability of that response.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Efficient trial designs for studying combination antiretroviral treatments in patients with various resistance profiles.

Selecting antiretroviral therapies for human immunodeficiency virus type 1-infected persons is complicated by the availability of a vast number of potentially useful drug combinations and by extensive variation among patients in their resistance to various drugs. AIDS clinical trials have used designs in which a handful of drug regimens in a few patient classes can be compared. Here is proposed implementation of innovative designs with factorial structure that permit assessment of many treatment arms and patient classes in a single trial; when and how they can be appropriately used are discussed. These designs are efficient, permit systematic investigation of correlations between genetic mutations and in vivo drug resistance, and provide insight into important drug interactions in people that conventional designs are unable to provide. Through creative application of these designs, identification of superior drug combinations and the science of understanding in vivo joint drug dynamics and genotypic resistance will progress at an optimum pace.

Anti-HIV Agents↗
PubMed1998

Intra-abdominal Candida infection during acute necrotizing pancreatitis has a high prevalence and is associated with increased mortality.

OBJECTIVES: To analyze the frequency of intra-abdominal Candida infection during acute necrotizing pancreatitis and to compare the outcome to patients without Candida infections. DESIGN: Retrospective analysis of data from 37 patients with and without Candida infection. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: Thirty-seven patients with acute necrotizing pancreatitis. INTERVENTIONS: Patients were subject to necrosectomy and programmed lavage. MEASUREMENTS AND MAIN RESULTS: Clinical parameters contained in the Acute Physiology and Chronic Health Evaluation (APACHE) II score were monitored, as were microbiological results from the intra-abdominal primary focus and from sites of secondary infections. Body mass index, distribution of underlying diseases, length of ICU stay, number of operations, and outcome were recorded. Multivariate logistic regression analysis for mortality as the dependent variable was performed. Intra-abdominal Candida infection was observed in 13 of 37 cases and was associated with a four-fold greater mortality rate compared with intra-abdominal bacterial infection alone. Multivariate logistic regression analysis demonstrated that Candida infection contributed to mortality significantly (p < .025) and independently from APACHE II (p < .006; mortality odds ratio for the two parameters=12.5). Lack of antimycotic treatment was associated with an increase to 29.2 (p<.001) in the odds ratio. CONCLUSIONS: Given the impact of Candida infection on mortality to acute necrotizing pancreatitis and the apparent benefit from antimycotic chemotherapy, the data argue for an early fungicide chemotherapeutic intervention.

APACHE↗
PubMed1997

Measuring quality of life in early HIV disease: the modular approach.

RATIONALE: to examine the reliability and validity of the General Health Self-assessment, a modular questionnaire for self-assessment of quality of life (QoL) in human immunodeficiency virus (HIV) clinical trials and to describe the baseline QoL of participants in a large HIV clinical trial. DESIGN: the domains assessed include health perceptions, physical, psychological and role/social functioning, health care utilization and symptom distress. METHOD: 1,694 subjects with early HIV infection enrolled in the AIDS Clinical Trials Group Protocol 175 completed the scale at baseline. RESULTS: the domains demonstrated reliability, construct and discriminant validity. A worse QoL was associated with recent hospitalization and symptomatic status. Prior antiretroviral therapy was associated with higher health perceptions and well-being. The presence of symptom distress was related to lower QoL on the other scales. There was no relationship between QoL scales and the baseline CD4 count. Women showed a lower QoL than men on all scales, while ethnicity was related to differences in health perceptions and physical and psychological functioning. CONCLUSIONS: the General Health Self-assessment shows excellent potential as a measure of QoL for HIV-infected patients in clinical trials. Further research is necessary to determine the responsiveness of the scale to clinical and immunological changes in HIV-infected individuals.

Adolescent↗
PubMed1997

Effects of the non-peptide B2 antagonist FR173657 on kinin-induced smooth muscle contraction and relaxation, vasoconstriction and prostaglandin release.

1. The non-peptide bradykinin (BK) antagonist (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657) was tested in intestinal, uterine, tracheal and vascular in vitro preparations. The investigation aimed at determining the antagonistic potency, duration of action, specificity for BK receptors and apparent mode of antagonistic action of FR173657. 2. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by FR173657 (10-300 nM) in a concentration-dependent manner. The inhibition lasted for up to 90 min after wash-out of FR173657. Cumulative concentration-response curves to BK were shifted to the right with a concomitant decrease in the maximum effect. A pKB value of 8.7 was determined. FR173657 had no effect on contractions induced by acetylcholine, histamine, 5-hydroxytryptamine, substance P, angiotensin II or caerulein. 3. The concentration-response curves for B2 receptor-mediated relaxations of the rat isolated duodenum induced by BK were shifted to the right together with a concomitant reduction of the maximum BK effect in the presence of FR173657 (10-300 nM). A pKB of 9.0 +/- 0.2 was calculated. FR173657 had no effect on B1 receptor-mediated relaxations in response to des-Arg9-BK. 4. The concentration-response curves for BK-induced contractions of the rat isolated uterus were shifted to the right by FR173657 (3-300 nM) in a concentration-dependent and parallel manner. The Schild plot for the inhibition caused by FR173657 had a slope of -0.98 indicating a competitive mode of antagonism. A pA2 value of 9.1 was determined. 5. Contractions of the circular smooth muscles of the guinea-pig isolated trachea in response to BK were concentration-dependently inhibited by FR173657 (10-100 nM). An affinity estimate of 9.3 was calculated for FR173657. Contractions induced by acetylcholine and relaxations in response to isoprenaline remained completely unaffected by FR173657. 6. In the rabbit isolated perfused ear, BK (0.01-10 nmol) produced a dose-dependent vasoconstriction. In the presence of 30 nM FR173657, the effects of BK were reduced by at least 60%, while FR173657 completely abolished the effects of all BK doses at 300 nM. FR173657 did not affect vasoconstriction induced by noradrenaline or angiotensin II. 7. The arterial injection of BK (10 nmol) into the rabbit isolated perfused ear caused an approximately three fold increase in the release of the prostaglandins E2 and I2 into the venous effluent. The BK-stimulated prostaglandin release was completely abolished in the presence of FR173657 (300 nM) while the basal prostaglandin release was unchanged. 8. In summary, FR173657 was shown to be a highly potent and selective BK antagonist which was active on B2, but not B1, receptors. FR173657 was a competitive antagonist in the rat uterus but showed a deviation from competitive inhibition in the other preparations studied similar to other second generation peptide antagonists. The inhibitory action in vitro was long-lasting, but was fully reversible.

Animals↗
PubMed1997

Stabilities of free and complexed human immunodeficiency virus p24 antigens during short- and long-term storage.

By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C. There was no loss at either temperature by the immune complex dissociation (ICD) procedure. Furthermore, there was no significant loss of detectable p24 in serum by either the ICD or the standard p24 assay after 700 days of storage at -70 degrees C.

Antigen-Antibody Complex↗
PubMed1996

Pharmacokinetics of F105, a human monoclonal antibody, in persons infected with human immunodeficiency virus type 1.

F105 is a human monoclonal antibody that binds to the CD4 binding site of human immunodeficiency virus type 1 gp120 and neutralizes clinical and laboratory isolates of the human immunodeficiency virus. This phase I study investigated the disposition of the antibody in humans. F105 was administered over a 60-minute period at two dose levels, 100 and 500 mg/m2. Blood samples were obtained for up to 56 days. The clearance of the antibody was 0.33 ml/min with a corresponding half-life of approximately 13 days. Peak concentrations achieved at the higher dose level were 216.19 +/- 9.62 micrograms/ml. The disposition of the drug was linear for the doses studied. Simulations were performed to design future studies aimed at investigating the efficacy of the antibody. This study concluded that F105 can be administered as a bolus dose every 21 days.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Isokinetic muscle performance in healthy female handball players and players with a unilateral anterior cruciate ligament reconstruction.

A total of 114 healthy female European team handball players in the elite to second division with no previous ACL injury, and the uninjured legs of 22 females with a unilaterally reconstructed ACL (the injury sustained while playing handball; mean time from reconstruction 15 months) were examined with a Biodex isokinetic testing device. Five extensions and flexions at lower speed (60 degrees/s) and 15 repetitions at higher speed (240 degrees/s) were performed. Gravity-corrected peak torque values for flexion and extension were obtained, and hamstrings-to-quadriceps ratios (H/Q) were calculated at both speeds. Compared with the control group, the uninjured legs of the injury group showed 8% weaker quadriceps muscles and 14% higher H/Q ratios at higher speed. The other between-group comparisons were not significant. These differences could have been developed by strength reduction after the injury in the noninjured limb due-to-insufficient rehabilitation, by a weaker musculature in the patient group already initially, or by both mechanisms. If the second option is true, the finding may indicate that weak quadriceps musculature is one of the risk factors for anterior cruciate ligament injuries. The study establishes additional normative data on hamstrings and quadriceps torque on high-level female handball players.

Adolescent↗
PubMed1995

Can a regular leg extension bench be used in testing deficits of the quadriceps muscle during rehabilitation?

Fifty-nine people, 31 healthy subjects with no previous knee injuries and 28 who had undergone an intra-articular anterior cruciate ligament reconstruction 6-12 months prior to testing took part in the study. The subjects were randomly tested bilaterally on a Cybex 6000 isokinetic testing device (ITD) and on an ordinary leg extension bench (LEB). Strength and endurance were tested with both methods. The linear relationships for paired strength and endurance differences between ITD and LEB were found to be acceptable for the operated group. The LEB alone explained 57% and 38% of the ITD outcome for strength and endurance, respectively. The agreement between observed and predicted ITD values based on the LEB measurements was found satisfactory with a positive standardized agreement index. This indicates that the LEB can be used as a helpful tool in evaluation of quadriceps muscle strength deficits.

Adolescent↗
PubMed1995

Surgical treatment of medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg.

From September 1988 to June 1990, 35 athletes were treated for medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg. Thirty-two patients were available for the follow-up, including self-assessment, clinical examination and activity scoring. The mean postoperative observation time was 16 months. Thirteen patients were performing sports at top international or top national level; 19 patients were competing at different lower levels. Twenty-three patients improved, 7 were unchanged and 2 had poor results.

Adolescent↗
PubMed1993

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Acyclovir↗
PubMed1993

Effects of dehydration and rehydration on plasma vasopressin and aldosterone in horses.

We have investigated the change in plasma vasopressin and aldosterone concentrations in Namib (desert-adapted) and in control horses from a subtropical region, during an acute 12% dehydration and during rehydration, while food was available. During dehydration, vasopressin concentrations increased significantly in both groups of horses, but the increase was significantly greater in Namib horses than in control horses. During rehydration, vasopressin levels fell, but fell significantly less in Namib horses. The change in vasopressin concentration correlated significantly with plasma osmolality (r = 0.88, p < 0.001), and the relationship between these two variables was the same for both groups of horses during the dehydrated and rehydrated states. Aldosterone concentrations fell up to 48-h dehydration in both groups, but decreased significantly more in desert horses. From 48-h dehydration and during rehydration, aldosterone concentrations increased and the increase was sustained longer in Namib than in control horses. Changes in plasma osmolality did not correlate significantly with changes in aldosterone concentration. There were significant correlations between faecal moisture (%) and both vasopressin and aldosterone concentrations (r = -0.72, p < 0.008; r = 0.80, p < 0.002, respectively). During the 12% dehydration, the Namib horses sustained higher plasma osmolalities and consequently vasopressin levels than the control horses. We conclude that plasma osmolality in conjunction with these two hormones plays a significant role in water homeostasis in horses.

Acclimatization↗