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Biomedical subjects

H Kaufman

Publications and source records attributed to H Kaufman.

At least 19 recordsLinked to original sources
PubMed2006

A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer.

PURPOSE: Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM. METHODS: In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 x l0(8) pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 x 10(9) pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9-1424). RESULTS: There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients. CONCLUSION: This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.

Journal Article↗
PubMed2005

Complications encountered while using thin-wire-hybrid-external fixation modular frames for fracture fixation. A retrospective clinical analysis and possible support for "Damage Control Orthopaedic Surgery".

One hundred ninety eight adult patients who had sustained long bone fractures were treated by external fixation from admission to bone healing and consolidation. Of these, 135 had sustained high-energy injuries, 39 of them had suffered multi-system injuries. Superficial pin track infection was the most common complication, occurring predominantly in pins located in the femur, upper tibia and upper humerus. There were no cases of deep infection or osteomyelitis. One patient with a femoral shaft fracture developed a DVT although he was on preventive low molecular weight heparin, i.e. sc Clexane 40 mg daily. There were no cases of PE or ARDS. External fixation systems are a minimal invasive surgical modality, which allow three-dimensional fracture fixation after closed or minimal open reduction. They require a good command of surgical anatomy, but provide an optimal preservation of the fracture's soft tissue envelope, the critical biological factor for new bone formation and fracture healing. Recent publications have suggested that in the critically ill patient, minimally invasive fracture fixation surgery may prevent the perpetuation of a reactive, life threatening inflammatory reaction (the "second hit") which may induce the development of multiple organ dysfunction (MODS).

Adult↗
PubMed2001

Effect of literacy on breast-feeding outcomes.

BACKGROUND: We studied the effect of functional health literacy on the initiation and continuance of breast-feeding in women at a public health clinic. METHODS: Subjects were 61 first-time mothers aged 18 years or older who spoke English as their first language. They were divided into two groups, one who exclusively breast-fed for at least the first 2 months and one who never initiated breast-feeding or did not exclusively breast-feed for at least 2 months. The Rapid Estimate of Adult Literacy in Medicine (REALM) was administered, providing reading grade-level estimates for each subject. RESULTS: An association between functional health literacy and breast-feeding was seen, with only 23% of the women in the lower literacy group exclusively breast-feeding during the first 2 months compared with 54% of women in the higher literacy group. CONCLUSION: Many patients need simpler health education materials encouraging breastfeeding. These materials are needed both before and during pregnancy.

Adolescent↗
PubMed2000

Calibration of near-infrared frequency-domain tissue spectroscopy for absolute absorption coefficient quantitation in neonatal head-simulating phantoms.

Frequency-domain tissue spectroscopy is a method to measure the absolute absorption coefficient of bulk tissues, assuming that a representative model can be found to recover the optical properties from measurements. While reliable methods exist to calculate absorption coefficients from source-detector measurements less than a few centimeters apart along a flat tissue volume, it is less obvious what methods can be used for transmittance through the larger tissue volumes typically associated with neonatal cerebral monitoring. In this study we compare the use of multiple distance frequency-domain measurements processed with (i) a modified Beer-Lambert law method, (ii) an analytic infinite-medium diffusion theory expression, and (iii) a numerical finite element solution of the diffusion equation, with the goal of recovering the absolute absorption coefficient of the medium. Based upon our observations, the modified Beer-Lambert method provides accurate absolute changes in the absorption coefficient, while analytic infinite-medium diffusion theory solutions or finite element-based numerical solutions can be used to calculate the absolute absorption coefficient, assuming that the data can be measured at multiple source-detector distances. We recommend that the infinite-medium multi-distance method or the finite element method be used across large tissue regions for calculation of the absolute absorption coefficient using frequency-domain near-infrared measurements at multiple positions along the head.

Absorption↗
PubMed2000

Innovations and strategies for the development of anticancer vaccines.

In 1893, William Coley reported the spontaneous regression of a soft tissue sarcoma in several patients suffering from acute bacterial infections. Although this observation occurred over a century ago, the concept of anticancer vaccines and the immunotherapy of cancer has only recently seemed plausible. A myriad of specific and non-specific immunostimulatory approaches have been tested throughout the years with only a modicum of success. Most of these approaches were doomed from the outset since they were based on false or inadequate knowledge of tumour immunology. Recent advances in our understanding, most notably the identification of genes encoding for cancer regression antigens, currently permit investigators to pursue a more cogent strategy to develop novel and specific anticancer vaccine approaches. Several of these approaches are currently being tested in clinical trials and have already yielded exciting results. However, a number of immunologic and host obstacles to the successful application of anticancer vaccines remain. This editorial will provide an update on the clinical status of anticancer vaccines and review areas of promising research initiatives.

Adjuvants, Immunologic↗
PubMed1996

Timolol hemihydrate vs timolol maleate to treat ocular hypertension and open-angle glaucoma.

PURPOSE: We compared the therapeutic efficacy and safety of timolol hemihydrate to timolol maleate in patients with ocular hypertension and chronic open-angle glaucoma. METHODS: We conducted this three-month study as a multicentered, masked, parallel group comparison. Both the 0.25% and 0.5% concentrations were evaluated against similar concentrations of timolol maleate. Dosing was twice daily. An open-label, nine-month study followed the masked portion of the protocol, in which all patients received either 0.25% or 0.5% timolol hemihydrate. A total of 371 patients were included in both the 0.25% and 0.5% studies. RESULTS: We found statistically similar intraocular pressures with both the 0.25% (18.3 and 18.6 mm Hg for the hemihydrate and maleate groups, respectively) and 0.5% (19.9 and 19.5 mm Hg for the hemihydrate and maleate groups, respectively) concentrations of timolol hemihydrate and timolol maleate after three months of masked treatment. Likewise, peak intraocular effect at two hours after taking the medication was statistically similar between medicines at both concentrations. Likewise, both ocular and systemic safety were similar between the maleate and hemihydrate preparations at both concentrations. In the nine-month open-label protocol, therapeutic efficacy (19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations, respectively) and safety of timolol hemihydrate were similar to effect and safety of the three-month protocol. CONCLUSIONS: This study suggests that timolol hemihydrate had an ocular hypotensive efficacy and safety profile statistically equivalent to that of timolol maleate for up to three months of therapy. Timolol hemihydrate showed efficacy and safety similar to that observed within the first three months, for up to one year of therapy.

Adolescent↗
PubMed1995

Neuropsychiatric evaluation in an outpatient setting.

In a retrospective case review of 336 outpatients who underwent neuropsychiatric evaluations, patients were sorted into five groups: 1) atypical psychiatric; 2) atypical neurological; 3) prior psychiatric/new-onset neurological; 4) prior neurological/new-onset psychiatric; 5) dementia versus pseudodementia. Cluster analysis of 19 presenting complaints differentiated among groups. Post-consultation changes in preconsultation diagnosis occurred frequently overall, with more new case finding for psychiatric than for neurological disorders. For example, mood disorder diagnoses increased from 7.7% to 16.1%. Overall, dementia was the most common postconsultation diagnosis (32.8%). The authors conclude that suspicion for dementia should be high in neuropsychiatric referrals and that mood disorders may be especially common in neuropsychiatric patients.

Adolescent↗
PubMed1995

Prader-Willi syndrome: effect of group home placement on obese patients with diabetes.

Morbid obesity and type II diabetes, common complications of Prader-Willi syndrome (PWS), are difficult to manage in the home setting. We assessed the effect of specialized group home placement on these complications in eight individuals with PWS, all of whom were obese and four of whom had type II diabetes. The group home provided diet restriction and control, a monitored exercise program, and a structured environment. Twelve months after admission, average weight loss in the eight individuals was 17.0 kg. Of the four with diabetes, all achieved euglycemia, and insulin and oral hypoglycemic doses were greatly reduced or discontinued. For individuals with PWS who are obese and have type II diabetes, placement in specialized group homes can be highly effective in controlling weight and diabetes.

Adolescent↗
PubMed1992

Immunogenicity and safety of a recombinant vaccinia virus vaccine expressing the carcinoembryonic antigen gene in a nonhuman primate.

We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model. Human CEA is a M(r) 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross-reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild-type vaccinia virus as control. After three vaccinations, all rV(NYC)-CEA-vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell-mediated immune response directed against human CEA.

Animals↗
PubMed1992

Antitumor activity and immune responses induced by a recombinant carcinoembryonic antigen-vaccinia virus vaccine.

BACKGROUND: Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas. Previous studies have demonstrated enhanced immune responses to other antigens presented with vaccinia virus proteins via a recombinant vaccinia virus construct. In addition, we have developed a recombinant CEA-vaccinia virus construct, designated rV(WR)-CEA, and have demonstrated humoral anti-CEA responses in mice after immunization with that virus. PURPOSE: The goals of this study were (a) to construct a recombinant CEA-vaccinia vaccine in a less virulent vaccinia strain that is potentially safe and effective for treatment of patients whose tumors express CEA and (b) to evaluate the ability of the recombinant CEA-vaccinia vaccine to prevent and reverse tumor growth in mice and to elicit cell-mediated and humoral anti-CEA immune responses. METHODS: Using the New York City strain of vaccinia virus, which is used in smallpox vaccination and is more attenuated for humans than rV(WR), we derived a recombinant CEA-vaccinia construct, designated rV(NYC)-CEA. The ability of this construct to induce antitumor immunity was evaluated in mice receiving subcutaneous injections of murine colon adenocarcinoma cells expressing the human CEA gene. RESULTS: Administration of rV(NYC)-CEA in mice induced strong anti-CEA antibody responses, as well as CEA-specific cell-mediated responses, including delayed-type hypersensitivity, lymphoproliferative, and cytotoxic responses. Vaccination of mice with the rV(NYC)-CEA rendered them resistant to the growth of subsequently transplanted CEA-expressing tumors. Moreover, when mice were vaccinated 7 days after tumor cell injection, tumor growth was either greatly reduced or eliminated. No toxic effects were observed in any of the mice. CONCLUSION: These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine.

Adenocarcinoma↗
PubMed1992

Multiple-model adaptive predictive control of mean arterial pressure and cardiac output.

A multiple-model adaptive predictive controller has been designed to simultaneously regulate mean arterial pressure and cardiac output in congestive heart failure subjects by adjusting the infusion rates of nitroprusside and dopamine. The algorithm is based on the multiple-model adaptive controller and utilizes model predictive controllers to provide reliable control in each model subspace. A total of 36 linear small-signal models were needed to span the entire space of anticipated responses. To reduce computation time, only the six models with the highest probabilities were used in the control calculations. The controller was evaluated on laboratory animals that were either surgically or pharmacologically altered to exhibit symptoms of congestive heart failure. During trials, the controller performance was robust with respect to excessive switching between models and nonconvergence to a single dominant model. A comparison is also made with a previous multiple-drug controller design.

Animals↗
PubMed1991

A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA).

Carcinoembryonic antigen (CEA) is a 180-kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL-I) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human GI cancer and other CEA expressing carcinoma types.

Adenocarcinoma↗