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Biomedical subjects

J Jacobs

Publications and source records attributed to J Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acoustic and mechanical properties of artificial stones in comparison to natural kidney stones.

PURPOSE: Standardized and reproducible artificial kidney stone models are important for performing comparative studies of different lithotripsy modalities. The acoustic and mechanical properties of renal calculi dictate the manner by which stones interact with the mechanical stresses produced by shock wave lithotripsy (SWL) or intracorporeal lithotripsy modalities. We have developed a novel artificial kidney stone model that is made of natural substances found in real kidney stones. These stone models appear to be much closer in physical properties to natural kidney stones than previously used stone models. MATERIALS AND METHODS: The acoustic and mechanical properties of six groups of artificial stone models were compared to corresponding natural stones of similar compositions. Moreover, three groups of artificial stone models made of plaster-of-Paris were compared to their natural counterparts. In terms of acoustic properties, stone density was measured using a pycnometer based on Archimedes' principle, whereas longitudinal and transverse (or shear) wave propagation speeds were measured using an ultrasound pulse transmission technique. These values were used to calculate wave impedance and dynamic mechanical properties (bulk modulus, Young's modulus, and shear modulus) of the stones. The microhardness of the stones was measured and the effect of composition on stone fragility was evaluated. RESULTS: Artificial stones, when compared to natural stones of similar composition, showed similar trends in longitudinal and transverse wave speeds, wave impedance, and dynamic elastic moduli. However, values for the artificial stones were uniformly low compared to those of natural stones, suggesting that these artificial stones may be more amenable to shock wave fragmentation. The results of SWL on stone fragmentation of artificial and natural stones also revealed similar trends with the exception of artificial cystine stones which were found to be the most resistant to shock wave fragmentation. CONCLUSIONS: The results indicate that the physical properties of artificial stones made of natural stone materials are comparable to renal calculi of the same chemical composition. The data suggests that these stone phantoms are suitable for performing standardized and reproducible in vitro investigations, especially with regards to fragility of kidney stones of different chemical compositions during SWL.

Acoustics↗
PubMed1999

The impact of potent antiretroviral therapy on the characteristics of hospitalized patients with HIV infection.

OBJECTIVE: Despite advances in antiretroviral treatment, a large number of HIV-infected patients still require hospitalization. This study describes the characteristics of HIV patients requiring hospitalization before and after the advent of potent antiretroviral therapies. METHODS: Information was collected on all HIV-positive patients admitted to the New York Hospital-Cornell Medical Center in New York City. Data was collected from 1 January through 30 June 1995, and during the same 6-month interval in 1997. RESULTS: In each time period over 1500 outpatients were receiving treatment for HIV infection. There was a significant decrease in the incidence of admission [60.4 per 100 patient-years (PY) in 1995, 28.8 per 100 PY in 1997], and length of stay (10 versus 8 days). The median CD4 cell count of all HIV-infected patients admitted to the hospital doubled: 37 x 10(6)/l in 1995 versus 80 x 10(6)/l in 1997. However, there was no significant change in the median CD4 cell count of patients diagnosed with opportunistic infections. The incidence of the most common diagnosis (bacterial pneumonia, 8.0 per 100 PY in 1995 versus 3.6 per 100 PY in 1997) and the most common opportunistic infection (Pneumocystis carinii pneumonia 7.6 per 100 PY in 1995 versus 2.4 per 100 PY in 1997) decreased significantly. CONCLUSIONS: Since the introduction of potent antiretroviral therapy, a significant decrease in the incidence of hospital admission and opportunistic infections has occurred. There has been a doubling of the median CD4 cell count of inpatients. There has been no significant change in the median CD4 cell count at which patients present with opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1999

The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program.

BACKGROUND: Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children. OBJECTIVE: Our purpose was to evaluate the relationship between sensitivity and exposure to inhalant allergens and lung function and bronchial responsiveness in a group of children (n = 1041) aged 8.9 +/- 2.1 years with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). METHODS: With use of the extensive CAMP baseline cross-sectional data on spirometry, bronchial responsiveness, allergen sensitivities, and household allergen levels, the relationship of sensitization and exposure to allergens to lung function and methacholine sensitivity was evaluated. Children who enrolled in CAMP stopped all antiasthma medication except rescue use of albuterol and prednisone for exacerbations during the 5- to 16-week screening period. During the last 2 of these weeks they underwent spirometry and methacholine challenge. Indoor allergen exposures were determined from questionnaires completed by the parent. Household levels of indoor allergens (mite, cat, dog, cockroach, mold) were determined on house dust samples. Allergen sensitivity was determined by percutaneous skin testing with a standard battery of allergens plus locally important pollen and fungal spores. Lung function and bronchial hyperresponsiveness were compared for children sensitive and not sensitive to both indoor and outdoor allergens on skin testing and, if sensitive, for exposed and not exposed to the allergens to which they were positive on skin testing. RESULTS: There was a strong direct correlation between increased sensitivity to inhaled methacholine and skin test sensitivity to tree, weed, Alternaria, cat, dog, and indoor molds. When the relationship was examined by stepwise regression, the skin test sensitivities showing the strongest associations with the concentration of methacholine that caused a 20% fall in FEV(1) were dog (P =.003), Alternaria (P =.01), and cat (P =.05). Children sensitive to any one of the aeroallergens tested were compared for the presence or absence of exposure to that allergen at the time that the methacholine challenge was performed. Those who were sensitive and exposed to weed and cat had greater methacholine sensitivity than those similarly sensitive but not exposed (P =.003 and P =.02, respectively). CONCLUSIONS: Sensitivity to dog or cat dander or Alternaria by skin testing was associated with increased bronchial responsiveness but not decreased lung function in children with mild to moderate asthma. These findings support the important role that sensitization to certain allergens plays in modulating bronchial responsiveness.

Adolescent↗
PubMed1999

Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics.

Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.

Administration, Oral↗
PubMed1999

Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement.

A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months. Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. In this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop. In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop.

Adolescent↗
PubMed1998

Precisely defining high-risk operable head and neck tumors based on RTOG #85-03 and #88-24: targets for postoperative radiochemotherapy?

BACKGROUND: Local-regional recurrence of disease remains the major obstacle to cure of advanced head and neck cancers. METHODS: This investigation reviewed data derived from Radiation Therapy Oncology Group (RTOG) protocols #85-03 and #88-24 to identify characteristics of tumors that predicted local-regional recurrence of disease following surgery and postoperative radiotherapy (RT). RESULTS: The presence of tumor in two or more lymph nodes, and/or extracapsular spread of nodal disease, and/or microscopic-size tumor involvement of the surgical margins of resection imparts a high risk of local-regional (L-R) relapse. Our data also support the hypothesis that, following surgery, the concurrent addition of chemotherapy (CT) to RT may increase the likelihood of L-R control of disease for patients who have these high-risk characteristics. CONCLUSION: A prospective trial of surgery followed by concurrent RT and CT is warranted for patients who have high-risk characteristics found at surgery.

Carcinoma, Squamous Cell↗
PubMed1998

Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick hepatocytes.

In earlier studies, treatment with sodium arsenite was shown to decrease total hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting step in heme degradation to biliverdin, was considered responsible for the decrease in CYP. Here we investigated the effect of sodium arsenite on induction of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo hepatocytes. When added simultaneously with inducer, arsenite inhibited phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated increases in CYP1A, as measured enzymatically and immunochemically. Near maximal decreases were observed in these forms of CYP at a concentration of 2.5 microM sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by sodium arsenite were concomitant with increases in heme oxygenase. Sodium arsenite was not toxic at concentrations as high as 10 microM, as indicated by protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite-induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H. Combined treatment with heme and phenobarbital induced heme oxygenase to the same extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H activity was decreased only when the treatment included arsenite. These results suggest that elevated levels of heme oxygenase alone are not responsible for arsenite-mediated decreases in CYP2H.

Animals↗
PubMed1998

Oculoplastic experience with the cosmetic use of botulinum A exotoxin.

BACKGROUND: Botulinum toxin is a neuromuscular blocking agent produced by the bacterium Clostridium botulinum. It has been used as a therapeutic agent in ophthalmology for over 18 years. OBJECTIVE: To present the cosmetic use of botulinum toxin in oculoplastic surgery. METHODS: We present our experience with botulinum toxin as a cosmetic agent. RESULTS: Botulinum toxin was successful in treating hyperfunctional lines of the face and neck. CONCLUSIONS: Botulinum toxin is a safe and effective method of treating dynamic lines of the face and neck.

Botulinum Toxins, Type A↗
PubMed1997

Percutaneous management of a bladder-drained pancreas transplant pseudocyst by a transcystic approach.

BACKGROUND: We describe a 35-year-old male type 1 diabetic who underwent a cadaveric combined kidney-bladder-drained pancreas transplant with a duodenocystostomy for exocrine drainage who developed a large pelvic pseudocyst associated with a dilated pancreatic duct and an elevated serum amylase level. METHODS: Due to the risk of surgical revision and the possibility of creating a cutaneous fistula with conventional percutaneous drainage, a pseudocyst-to-bladder drainage was performed. After the procedure, the catheter was capped to allow drainage of the pancreatic secretions into the bladder. RESULTS: After drainage, the patient's serum amylase and lipase normalized along with resolution of the pseudocyst. The tube was removed after 19 weeks with no evidence of a recurrent pseudocyst and a normal serum amylase level. CONCLUSION: The percutaneous pseudocyst-cystostomy obviated the need for surgical revision of the exocrine gland drainage and thus eliminated the morbidity and the potential risk of graft loss associated with such surgery.

Adult↗
PubMed1997

MPc2, a new murine homolog of the Drosophila polycomb protein is a member of the mouse polycomb transcriptional repressor complex.

The evolutionarily conserved polycomb and trithorax-group genes are required to maintain stable expression patterns of homeotic genes and other target genes throughout development. Here, we report the cloning and characterization of a novel mouse polycomb homolog, MPc2, in addition to the previously described M33 polycomb gene. Co-immunoprecipitations and subnuclear co-localization studies show that MPc2 interacts with the mouse polycomb-group oncoprotein Bmi1 and is a new member of the mouse polycomb multiprotein complex. Gal4DB-MPc2 or -M33 fusion proteins mediate a five- to tenfold repression of stably integrated reporter constructs carrying GAL4 binding sites, demonstrating that these proteins are transcriptional repressors. The MPc2 gene is localized on chromosome 11, in close proximity to the classical mouse mutations tail short (Ts) and rabo torcido (Rbt). Ts and Rbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of phenotypes observed in mice with mutated polycomb or trithorax-group genes, suggesting that MPc2 is a candidate gene for Ts and Rbt.

Amino Acid Sequence↗
PubMed1997

Ecological constraints and the evolution of hormone-behavior interrelationships.

Vertebrates show a diverse array of social behaviors. Equally complex are the mechanisms by which these behavioral patterns are regulated by hormones and the effects of behavioral interactions on hormone secretion. Nonetheless, comparative field and laboratory experiments indicate that general underlying themes, including mechanisms, may exist. For example, comparative studies in birds reveal that testosterone activates a type of aggression, territorial behavior, in those species that are territorial only during the breeding season. Territoriality at other times appears to be independent of sex steroid control, although qualitatively and quantitatively the behavior appears identical. Similarly, formation of pair bonds appears to be complex. In some populations such bonds are sexual, whereas in others they appear to be alliances possibly for joint defense of a territory. In cooperative groups of birds, pair bonds and alliances may exist simultaneously. Testosterone appears to be important for activation of the courtship behavior that leads to formations to sexual pair bonds. However, many investigations indicate that pair bonds in nonsexual contexts are not regulated by testosterone. Hormonal mechanisms underlying the establishment of alliances (if any) remain unknown. Clearly, these complex behavioral patterns due to seasonal changes and variation in context pose important questions for control mechanisms. One obvious question is, why this diversity in control mechanisms? It appears that there are evolutionary "costs" to high circulating levels of testosterone. They can be energetic costs or may involve increased predation risk or reduced survival after wounding. In males that express parental behavior, high circulating testosterone levels interfere with parental care, resulting in reduced reproductive success. Thus, regulation of testosterone secretion must balance the need to compete with other males as well as provide parental care. High circulating levels of testosterone for prolonged periods are also known to suppress the immune system. This latter effect may have profound implications for the development of androgen-dependent secondary sex characteristics that have evolved through sexual selection. There are several ways to avoid potential "costs" of hormone secretion at inappropriate times. A hormone may be metabolized at its target cell to another form that then binds to a different receptor (e.g., aromatization of testosterone to estradiol). Also receptors may be downregulated in tissues that would otherwise respond inappropriately in a specific life history state. On the other hand, multiple hormone mechanisms may have evolved to activate behavioral traits at the right time and in the correct context. When a behavioral trait is expressed throughout the life cycle, hormones may potentially deactivate behavior for short periods. With detailed investigations of organisms in their natural environment we can determine the potential ecological costs underlying hormone-behavior interactions that, in turn, shed light on their evolution. These data also indicate a number of problems for hormonal control mechanisms, but also indicate trends, alternatives, and hopefully in the future a more complete understanding of common mechanisms underlying behavioral endocrinology at the cell and molecular level. Only then will we be able to predict when and where specific mechanisms of hormone-behavior interactions operate and how they evolved.

Animals↗
PubMed1997

Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin.

Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945) and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds.

Adult↗
PubMed1997

Natural spillover of a distinctly Canidae-associated biotype of rabies virus into an expanded wildlife host range in southern Africa.

Rabies enzootics in southern Africa are associated with two genetically distinct groups of viruses, thought to be adapted to two different sets of host species. The virus groups are referred to as the canid biotype (infecting carnivores of the family Canidae) and the viverrid biotype (infecting carnivores of the subfamily Viverrinae). Cross- or spillover infections of one biotype into the host range of the other are thought to occur from time to time. However, very little is known about this phenomenon and its role in the epidemiology of rabies in southern Africa. We have investigated spillover by monoclonal antibody and nucleic acid sequence analysis of a wide range of virus isolates. Although the inverse had been documented, this report constitutes the first evidence of spillover of canid biotype viruses into viverrid hosts. Our genetic analysis was focused specifically on the G-L intergenic region of the virus genome, thought to be a remnant or pseudogene and it was indicated that, with respect to this region of the genome, spillover does not influence the phylogeny of virus isolates.

Animals↗
PubMed1997

Hereditary demyelinating neuropathy of infancy. A genetically complex syndrome.

Nine cases are described of a demyelinating peripheral neuropathy that had an onset in infancy. The clinical features conformed to those of type III hereditary motor and sensory neuropathy or Dejerine-Sottas disease. All showed a severe neurological deficit and had profoundly reduced nerve conduction velocities. Amongst these cases we identified four novel point mutations in the peripheral myelin protein 22 (PMP22) gene. These were Ser72Trp, Ser76lle and Leu80Pro. The Ser72Trp mutation was dominantly inherited by a mother and son, both severely affected. Two novel mutations in the gene for P0 myelin protein were also detected. These were Ile134Thr in exon 3, and a complex rearrangement in exon 4. The remaining three patients had presumed autosomal recessive inheritance. In these, no abnormality for the PMP22 and P0 genes was detected and a mutation at another locus or loci seems probable. On nerve biopsy the final two cases were shown to be examples of hereditary neuropathy with focally folded myelin sheaths. One showed both bulbar and diaphragmatic involvement. It is concluded that hereditary demyelinating neuropathy of infancy is genetically heterogeneous. Mutational screening for the PMP22 and P0 genes and nerve biopsy are therefore merited in patients with a childhood demyelinating neuropathy that is more severe than usual and in whom a chromosome 17 duplication is not present.

Adolescent↗