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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
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↗
PubMed1996

Metal on metal total hip replacement workshop consensus document.

The objective of this workshop was to provide a forum to discuss the reintroduction of metal on metal bearings for clinical use in total hip arthroplasty. Approximately 100 researchers clinicians, and industry representatives presented the state of the art interpretation of the metal on metal total hip replacement's past performance, and the clinical, tribologic, and biologic considerations of all metal bearings. Based on the scientific presentations at the symposium, the extant literature, the clinical experience of the panelists, and the current regulatory, legal, and economic environment, consensus statements were developed.

Alloys↗
PubMed1996

Tumor suppressor p53 gene mutation in squamous cell carcinoma of the larynx.

Using polymerase chain reaction (PCR)-SSCP (single-strand conformation polymorphism) and PCR-DNA sequencing analysis, we screened 61 cases of laryngeal squamous cell carcinoma for mutations in exons 5-8 of the p53 gene. Mutations were found in 31.3% (19 of 61) of the laryngeal cancers. Seventeen of 19 (84.2%) cases showing p53 gene mutations were stage III and IV, which suggests that p53 gene mutation is a rather late event in tumor development and is involved in the progression of laryngeal squamous cell carcinoma. A high frequency of G:C to T:A transversion (50%, seven of 14), especially G to T (35.7%, five of 14), was noted in laryngeal carcinoma samples in our study. This finding may point toward an environmental carcinogen (such as tobacco smoke) as an important agent in the genesis of laryngeal squamous cell carcinoma. Most of the p53 gene mutations (18 of 19) found in our studies could change the protein and thus may cause an inactivation of the p53 tumor suppressor gene, strongly suggesting that p53 gene mutation plays a crucial role in the progression of laryngeal carcinoma.

Biomarkers, Tumor↗
PubMed1996

Serious mushroom poisonings in California requiring hospital admission, 1990 through 1994.

Hunting and consuming wild mushrooms is an increasingly popular avocation, as well as a means of subsistence for certain groups in the United States. Consuming wild mushrooms is relatively safe for persons with the necessary expert knowledge. Each year, however, tragic deaths or illnesses occur when unsuspecting persons ingest toxic mushrooms. We conjectured that there may be vulnerable subgroups that should be targeted for public service announcements and education about mushrooms. Therefore, we reviewed California's hospital discharge database from 1990 through 1994 to ascertain demographic characteristics and outcomes of "serious" mushroom exposures requiring a hospital admission. Children younger than 5 years have a higher rate of hospital admission for "serious" poisonings. Therefore, parents should be reminded of the need for supervising children in areas with wild mushrooms. We did not find evidence that poisoning rates differed significantly between ethnic or racial groups, but this finding may be limited by a failure of these groups to seek care after becoming ill. We discuss briefly the symptoms and treatment of cases of possibly lethal ingestion of amatoxin-containing species of mushrooms.

Adolescent↗
PubMed1995

Suppression of tumor growth in vivo by local and systemic 90K level increase.

Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.

Animals↗
PubMed1995

Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.

T cell-specific transcription factor (TCF-1) and lymphoid enhancer factor 1 (LEF-1) have been implicated exclusively in the regulation of T cell-specific genes. The only adult tissue other than thymus known to express these factors is spleen and lymph node, which contain low levels of LEF-1 and no TCF-1. We noticed that genes involved in hair-specific gene expression possess LEF-1/TCF-1 consensus motifs located in similar positions relative to their TATA box. We show that of the two factors only LEF-1 is expressed in hair follicles; it can be cloned in both splice forms from human skin keratinocytes and it can bind to these sites in the hair promoters. We show that LEF-1 mRNA is present in pluripotent ectoderm, and it is up-regulated in a highly restricted pattern just before the formation of underlying mesenchymal condensates and commitment of overlying ectodermal cells to invaginate and become hair follicles. New waves of ectodermal LEF-1 spots appear concomitant with new waves of follicle morphogenesis. To test whether LEF-1 patterning might be functionally important for hair patterning and morphogenesis, we used transgenic technology to alter the patterning and timing of LEF-1 over the surface ectoderm. Striking abnormalities arose in the positioning and orientation of hair follicles, leaving a marked disruption of this normally uniform patterning. This provides the first direct evidence that ectodermal cues are critical in establishing these developmental processes, which at later stages are known to be influenced by underlying mesenchyme. Remarkably, elevated LEF-1 in the lip furrow epithelium of developing transgenic animals triggered these cells to invaginate, sometimes leading to the inappropriate adoption of hair follicle and tooth cell fates. Collectively, our findings demonstrate that ectodermal expression of LEF-1 plays a central role in gene expression, pattern formation, and other developmental processes involving epithelial-mesenchymal associations.

Alternative Splicing↗
PubMed1995

Effect of phosphorus supply on mineral balance at high calcium intakes in very low birth weight infants.

To evaluate the effect of varying phosphorus intake with constant high calcium intake (430 micrograms/kJ, or 180 mg/100 kcal), we randomly assigned 35 appropriate-for-gestational-age healthy male infants (birth weight, 715-1510 g) on day 21 postnatally to either standard-phosphorus (215 micrograms/kJ, or 90 mg/100 kcal), moderate-phosphorus (254 micrograms/kJ, or 106 mg/100 kcal), or high-phosphorus intake (287 micrograms/kJ, or 120 mg/100 kcal). Three-day mineral balances were determined after 7 d of the study diets. Weight and head circumference gain and intake of energy and vitamin D were not different for all groups. Calcium retentions were sufficient to meet intrauterine accretion in all groups. Phosphorus calculated to be available for soft tissue was significantly higher in the moderate- and high-phosphorus groups, and was sufficient to support soft tissue phosphorus accretion in these two groups. Total absorbed phosphorus and phosphorus tubular reabsorption were each affected by phosphorus intake. We conclude that very low birth weight infants fed high calcium may require greater phosphorus intake than that provided by formulas containing a ratio of calcium to phosphorus of 2:1. We suggest that the optimal mass ratio of calcium to phosphorus for formula for very low birth weight infants is from 1.6:1 to 1.8:1.

Calcium, Dietary↗
PubMed1995

Prevalence of Cyclospora species and other enteric pathogens among children less than 5 years of age in Nepal.

Stools from 124 Nepalese children aged 6 to 60 months with diarrhea were examined for organisms of the coccidian genus Cyclospora and for other enteric pathogens. Enterotoxigenic Escherichia coli, Giardia Lamblia, Campylobacter species, Cyclospora species, and Cryptosporidium species were the most common pathogens identified. Cyclospora species were detected in none of 74 children < 18 months of age compared with 6 (12%) of 50 children > or = 18 months of age (P = 0.004).

Animals↗
PubMed1995

Paradoxical insulin-induced increase in gluconeogenesis in response to prolonged hypoglycemia in conscious dogs.

The aim of this study was to determine the effects of differing insulin concentrations on the gluconeogenic response to equivalent prolonged hypoglycemia. Insulin was infused intraportally, for 3 h, into normal 18-h fasted conscious dogs at 2 (lower, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during high dose to maintain the hypoglycemic plateau (50 +/- 1 mg/dl) equivalent to lower. Epinephrine (806 +/- 180 vs. 2,589 +/- 260 pg/ml), norepinephrine (303 +/- 55 vs. 535 +/- 60 pg/ml), cortisol (5.8 +/- 1.2 vs. 12.1 +/- 1.5 micrograms/dl), and pancreatic polypeptide (598 +/- 250 vs. 1,198 +/- 150 pg/ml) were all increased (P < 0.05) in the presence of high-dose insulin. Net hepatic glucose production increased significantly from 2.2 +/- 0.3 to 3.8 +/- 0.5 mg.kg-1.min-1 (P < 0.05) during high-dose infusion but remained at basal levels (2.3 +/- 0.4 mg.kg-1.min-1) during lower-dose insulin. During the 3rd h of hypoglycemia, gluconeogenesis accounted for between 42 and 100% of glucose production during high-dose infusion but only 22-52% during lower-dose insulin. Intrahepatic gluconeogenic efficiency, however, increased similarly during both protocols. Lipolysis, as indicated by arterial blood glycerol levels, increased by a greater amount during high- compared with lower-dose insulin infusion. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. Gluconeogenesis remained similar to basal levels, but lipolysis was significantly suppressed during both series of hyperinsulinemic euglycemic studies. In summary, these data suggest that 1) the important counterregulatory processes of gluconeogenesis and lipolysis can be significantly increased during prolonged hypoglycemia despite an eightfold increase in circulating insulin levels and 2) the amplified gluconeogenic rate present during the hypoglycemic high-dose insulin infusions was caused by enhanced substrate delivery to the liver rather than an increase in intrahepatic gluconeogenic efficiency.

Animals↗
PubMed1995

Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog.

The effect of infection on hepatic uptake and disposal of a continuous (180-min) intravenous glucose infusion (8 mg.kg-1.min-1) was examined in conscious, 54-h-fasted, chronically catheterized dogs. Thirty-six hours before a study, either infection was induced by implantation of an Escherichia coli-containing (INF; 2 x 10(9) organisms/kg body wt; n = 6) fibrinogen clot, or a sterile (SH; n = 6) clot was implanted into the peritoneal cavity. Hepatic glucose metabolism was assessed using tracer ([3-3H]glucose and [U-14C]glucose) and arteriovenous difference techniques. Infection increased the basal rate of glucose appearance (45%); glucose levels were not altered. In response to glucose infusion, average blood glucose levels increased to similar levels (140 +/- 9 vs. 147 +/- 11 mg/dl in INF and SH, respectively), whereas arterial insulin levels were higher in the infected group during the last hour of the glucose infusion (77 +/- 10 vs. 41 +/- 5 microU/ml in INF vs. SH). Infection impaired net hepatic glucose uptake (0.6 +/- 0.5 and 2.7 +/- 0.7 mg.kg-1.min-1 in INF and SH; P < 0.05). The liver remained a persistent lactate consumer (4.1 +/- 1.8 mumol.kg-1.min-1), whereas the sham group became a net producer of lactate (-3.8 +/- 1.3 mumol.kg-1.min-1). Infection decreased net hepatic glycogen deposition by 53%. In conclusion, infection impairs net hepatic glucose uptake and glycogen deposition despite an exaggerated increase in insulin levels.

Animals↗