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Biomedical subjects

J Jacobs

Publications and source records attributed to J Jacobs.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1997

Rice burning and asthma hospitalizations, Butte County, California, 1983-1992.

We investigated the association between rice burning and daily asthma hospitalizations in Butte County, California, from 1983 to 1992. Eighty-two percent of planted rice was burned, with a mean of 555 acres burned on days when burning was permitted. For 60% of the days during this period, no rice burning occurred. Peak burning occurred in fall and spring but was not correlated with criteria pollutants. Asthma admissions averaged 0.65/day and peaked in March. In the basic Poisson model with daily asthma hospitalizations as the outcome of interest, burn acreage showed a small but statistically significant elevation of risk for hospitalization per acre of rice burned [relative risk (RR) = 1.0001; 95% confidence interval (CI), 1. 00004-1.0002], after adjusting for maximum daily temperature, seasonal factors, and yearly population. In this model, burn acreage showed a dose-response effect as acreage burned increased. Days with the greatest acreage burned (>499 acres) had the largest risk of hospitalization (RR = 1.23; CI, 1.09-1.39), and days with moderate burning (between 100 and 499 acres) had a slightly lower risk of admission (RR = 1.2; CI, 1.05-1.37). Elevations of air pollutants were not associated with days of increased rice burning; however, rice burn acreage was shown to have a small but statistically significant effect on asthma morbidity in Butte County. This evidence suggests that further limitations on the daily amount of rice straw permitted to be burned should be considered to reduce pulmonary morbidity related to asthma.

Adolescent↗
PubMed1997

Immunotoxicity of medical devices. Symposium overview.

Determination of the ability of a medical device to interact with the immune system currently involves assessment of the immunogenic potential and biocompatibility of the device or an extract of the device. However, implants are often in the body for extended periods of time and/or are placed by a surgical procedure that in and of itself will generate an acute inflammatory response. This symposium discussed studies that have been performed to evaluate the immunogenicity of various devices consisting of several different compositions (i.e., silicone, metals, and latex) in contact with different anatomical sites, the ability of a device to modulate an inflammatory response generated by a surgical procedure or trauma, and the response of the body to a material left in place for extended periods of time. This symposium brought together scientists from many different disciplines to begin to identify and fill in the gaps in this area.

Animals↗
PubMed1997

Aspirin reduces the incidence of second eye NAION: a retrospective study.

The objective of this study was to determine if aspirin reduces the incidence of second eye involvement after nonarteritic anterior ischemic optic neuropathy (NAION) in one eye. Records were reviewed of 131 patients who sustained unilateral NAION. Of these, the 33 patients who sustained second eye NAION were compared to those followed for a minimum of 2 years without sustaining a second eye NAION (67). Thirty-one of the 131 patients were excluded because of inadequate follow-up. Except for diabetes (relative risk [RR] 1.43, p = 0.05), the incidence of second eye NAION was independent of gender, age, cup/disk, hypertension, anemia, and migraine. The degree of visual acuity or field dysfunction in the first eye correlated poorly with the acuity (r = 0.28) and field (r = 0.33) loss in the second eye. Aspirin (65-1,300 mg) taken two or more times per week decreased the incidence (17.5% vs. 53.5%) and relative risk (RR = 0.44, p = 0.0002) of second eye AION regardless of the usual risk factors. Even after eliminating those patients who had bilateral disease when first referred, ASA still reduced the incidence of second eye involvement (35% vs. 13%, RR = 0.74, p = 0.01). Aspirin may be an effective means of reducing second eye NAION.

Aged↗
PubMed1996

Evolution of the Radiation Therapy Oncology Group clinical trials for head and neck cancer.

During the past 25 years, the Radiation Therapy Oncology Group (RTOG) has played a major role in head and neck cancer clinical research. The major research themes for recent and currently active trials have been: (a) combined modality therapy, (b) altered fractionation radiotherapy, (c) hypoxic cell sensitizers, (d) organ preservation, (e) chemoprevention, and (f) clinical/laboratory correlations. For advanced operable disease, the RTOG showed improved local-regional control with postoperative radiotherapy as compared to preoperative radiotherapy for carcinoma of the supraglottic larynx and hypopharynx. This established the use of surgery followed by postoperative radiotherapy as the standard treatment in subsequent RTOG and Intergroup trials for operable disease. For advanced inoperable disease, the RTOG demonstrated the feasibility of testing altered fractionation radiotherapy in a multiinstitutional clinical trials setting. A Phase III trial comparing hyperfractionation and accelerated fractionation to conventional fractionation is now in progress. Phase I/II combined modality studies established the efficacy of concurrent high-dose cisplatin and radiotherapy in the treatment of advanced disease and provided the basis for further testing in Phase III trials for nasopharyngeal carcinoma, larynx preservation, and high-risk advanced operable disease. Analysis of the extensive RTOG Head and Neck Cancer database established the incidence of second malignancies and their adverse impact on patients whose initial tumors were cured by radiotherapy, and provided the basis for chemoprevention trials. Recursive partitioning analysis identified 6 distinct prognostically homogeneous patient groups based on pretreatment tumor or patient characteristics and/or treatment variables. Retrospective analysis identified tumor p105 antigen density as an independent prognostic indicator in patients irradiated for head and neck cancer. Future trials will continue to focus on the reduction of morbidity and mortality, and improvement of the quality of life of head and neck cancer patients through innovative radiotherapy delivery, multimodality approaches, use of chemical and biological modifiers, and other novel therapies, identification of clinical and biological prognostic indicators, and prevention or diminution of acute morbidity and late complications of the disease and its treatment.

Antineoplastic Agents↗
PubMed1996

Comparison of four laboratory tests for diagnosis of Clostridium difficile-associated diarrhea.

Four different laboratory tests for diagnosis of Clostridium difficile-associated diarrhea were compared to determine the optimal one for management of patients with hospital-acquired diarrhea. Stool samples from 231 patients with diarrhea were tested by the following methods: culture for Clostridium difficile with subsequent determination of exotoxin production, with a toxigenic Clostridium difficile positive (TCP) result considered truly positive; enzyme immunoassay (EIA); latex agglutination test; and an immunobinding blot assay. The rates of positive results were as follows: EIA 5.5%, TCP 7.3%, latex agglutination 16.7%, and immunobinding blot assay 26.1%. Compared to the TCP results, the sensitivity and specificity were, respectively, 61 and 98% for EIA, 47 and 85% for latex agglutination, and 60 and 76% for the immunobinding blot assay. Samples from patients with > or = 6 stools/day were TCP and EIA positive in 27 and 17% of cases, respectively, whereas in patients with < 6 stools/day, these percentages decreased to 2 and 3%, respectively (p < 0.001). In hospitalized patients with > or = 6 stools/day, EIA appears to be the optimal test for diagnosis of Clostridium difficile-associated diarrhea, with a 73% positive predictive value and a 97% negative predictive value. However, in patients with < 6 stools/day, the prevalence of Clostridium difficile is low, and laboratory detection of this organism remains problematic.

Anti-Bacterial Agents↗
PubMed1996

Lung abscess in patients with AIDS.

We identified 31 patients with human immunodeficiency virus (HIV) infection and lung abscess. All patients had advanced HIV disease, and the mean CD4 cell count was 17/mm3 (range, 2-50/mm3). Twenty-two patients (71%) had previous opportunistic infections, and 24 (77%) had previous pulmonary infections. Symptoms at the time of presentation included fever (90% of patients), cough (87%), dyspnea (35%), pleuritic chest pain (26%), and hemoptysis (10%). The microbiological etiology was established for 28 patients, and the pathogens recovered were bacteria (65%), Pneumocystis carinii (6%), fungi (3%), and mixed microorganisms (16%). The pathogens included Pseudomonas aeruginosa (11), Streptococcus pneumoniae (6), P. carinii (5), Klebsiella pneumoniae (5), Staphylococcus aureus (4), Aspergillus species (3), viridans streptococcus (2), Haemophilus influenzae (1), Streptococcus milleri (1), Proteus mirabilis (1), and Cryptococcus neoformans (1). Mycobacterium tuberculosis was not isolated; two patients for whom a microbiological etiology was not established responded to antituberculous therapy. Patients were treated for 2-12 weeks; 25% of the patients received > 4 weeks of therapy. The outcome was poor: 36% of the patients had recurrences, and 19% died. In patients with AIDS, lung abscess is associated with advanced HIV infection, is due to a broad spectrum of pathogens, responds poorly to antibiotics, and has a poor prognosis.

AIDS-Related Opportunistic Infections↗