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B Jacobs

Publications and source records attributed to B Jacobs.

At least 37 records · Page 2Linked to original sources

Inhibition of cPLA2 translocation and leukotriene C4 secretion by fluticasone propionate in exogenously activated human eosinophils.

We examined the effect of the highly lipophilic corticosteroid, fluticasone propionate (FP), in causing (1) inhibition of nuclear translocation of cytosolic phospholipase A2 (cPLA2), and (2) blockade of leukotriene C4 (LTC4) synthesis in isolated human eosinophils in vitro. Eosinophils were isolated from peripheral blood, treated with either buffer or 10(-)10 M to 10(-)6 M FP in the presence of 10 pg/ml human recombinant interleukin-5 (rhIL-5) and activated with formyl-met-leu-phe (FMLP) + cytochalasin B (CB). At 24 h, stimulated LTC4 secretion from eosinophils was unchanged; however, when corrected for cell viability, LTC4 secretion decreased from 1,429 +/- 327 pg/10(6) cells to 762 +/- 113 pg/10(6) cells for eosinophils treated for 48 h with >/= 10(-)8 M FP (p < 0.003). FMLP/CB-stimulated translocation of cPLA2 to the nuclear envelope assessed by specific immunohistochemical staining also was blocked by FP. By contrast, membrane expression of annexin-1, which was not minimal at 30 min, was substantial at 48 h for eosinophils treated with > 10(-)10 M FP, and inhibition of LTC4 synthesis was reversed by exogenous arachidonic acid (AA). We find that FP causes a decrease in stimulated eosinophil secretion of LTC4 that is regulated by phospholipase A2 (PLA2). Inhibition of LTC4 synthesis precedes the global cytotoxic effects of FP as indicated by the simultaneous upregulation of annexin-1 expression. Inhibited stimulated secretion corresponds to inhibited translocation of cPLA2 to the nuclear envelope during cellular activation.

Administration, Topical↗

Prospective study of risk factors for Alzheimer's disease: results at 7.5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon4 genotype. METHOD: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. CONCLUSIONS: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon4 allele. Instead, increased platelet membrane fluidity and the epsilon4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.

Adult↗

Cold preservation of the porcine pancreas with histidine-tryptophan-ketoglutarate solution.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) has been used for experimental and clinical cardiac, renal, and liver transplantation. No experience exists in either experimental or clinical pancreas transplantation. METHODS: In the present study, the solution was employed to flush segmental pancreatic grafts and to autotransplant the grafts after 24, 48, and 72 hr of cold storage in a porcine model. The results were compared to those obtained from animals receiving pancreatic grafts flushed and preserved with UW (University of Wisconsin) solution. RESULTS: A total of 10 landrace pigs received a graft stored with HTK solution for 24 hr, and 6 animals received a graft stored with UW solution for 24 hr. Daily blood glucose levels were normoglycemic (i.e., blood glucose < 150 mg/dl), and glucosuria was absent in all transplant animals. Intravenous glucose tolerance tests were comparable to two unoperated controls. Seven totally pancreatectomized, nontransplant diabetic controls exhibited daily hyperglycemia, glucosuria (i.e., > 1,000 mg/dl) and highly impaired intravenous glucose tolerance tests (mean K-values of -0.52+/-0.19 vs. -1.25+/-0.46 for HTK, -1.30+/-0.81 for UW, and -1.53+/-0.81 for controls, P-value vs. diabetic <0.01). The changes in wet weight between flushing and reperfusion were +2.22+/-2.84 g for HTK and -1.40+/-2.70 g for UW stored grafts (P=0.034). After 48 hr of storage with HTK, 4/17 grafts were functioning and 1/11 recipients of grafts stored with UW were normoglycemic. All grafts stored for 72 hr in either HTK (n=3) or UW (n=3) uniformly failed to render the recipients normoglycemic. CONCLUSIONS: It is concluded that preservation of segmental pancreatic autografts for 24 hr with HTK solution provides reliable graft function, as does preservation with UW solution associated with an increase in wet weight after HTK preservation. Cold preservation with HTK and UW is feasible for 48 hr; however, the success rate is equally reduced with HTK and UW solution. Cold storage for 72 hr in either HTK or UW solution results in uniform graft failure in this model.

Adenosine↗

Is bacterial tracheitis changing? A 14-month experience in a pediatric intensive care unit.

Bacterial tracheitis is characterized by acute upper-airway obstruction and purulent secretions within the trachea. Historically, affected children were young, stridorous, and toxic-appearing and required tracheal intubation, and morbidity and mortality were significant. Staphylococcus aureus was the most common organism involved. During the 14 months of this retrospective study, 46 children were admitted to the pediatric intensive care unit because of this diagnosis, and their medical records were reviewed. Compared with those in previous reports, children in this study were older (mean +/- standard error of the mean [SEM], 69.3 +/- 6.8 months) and less toxic. Only 26 (57%) of 46 patients required tracheal intubation. Intubated patients were significantly younger than nonintubated patients (mean +/- SEM, 46.9 +/- 6.5 vs. 98.9 +/- 9.9 months). Moraxella catarrhalis was identified in 12 (27%) of 45 bacterial respiratory cultures, while influenza A virus was recovered from 18 (72%) of 25 viral respiratory cultures. There were no major complications. This series represents the largest reported cohort of patients with this condition and suggests an epidemiological change toward a less morbid condition.

Adolescent↗

Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study.

Dendritic neuropil is a sensitive indicator of the aging process and may exhibit regional cortical variations. The present study examined regional differences and age-related changes in the basilar dendrites/spines of supragranular pyramidal cells in human prefrontal (area 10) and secondary occipital (area 18) cortices. Tissue was obtained from the left hemisphere of 26 neurologically normal individuals ranging in age from 14 to 106 years (M(age) = 57 +/- 22 years; 13 males, 13 females). In tissue prepared by a modified rapid Golgi technique, ten neurons were sampled from each cortical region (N = 520) and were evaluated according to the following parameters: total dendritic length, mean segment length, dendritic segment count, dendritic spine number, and dendritic spine density. The effects of age and Brodmann areas were analyzed with a nested multiple analysis of variance design. Despite considerable interindividual variation, several clear findings emerged: 1) Dendritic systems were significantly larger in area 10 than in area 18 across the sampled life span, presumably because of the more integrative function of area 10 neurons. 2) There was a significant age effect, with a substantial decline in dendritic neuropil from the younger (< or =50 years) group to the older (>50 years) group, especially in spine measures, which decreased almost 50%. 3) Dendritic values were relatively stable after 40 years of age, suggesting that dendritic/spine degeneration in older, relatively healthy individuals may not be an inevitable consequence of the aging process. These findings underscore the importance of life-long commitment to a cognitively invigorating environment.

Adolescent↗

Sexual transmission of hepatitis B in Mwanza, Tanzania.

BACKGROUND: Hepatitis B virus (HBV) is endemic and poses a grave public health problem in Africa where it is mainly transmitted from mother to baby or during childhood. Sexual transmission has also been suggested to play a role in East Africa, but this has never been properly demonstrated. Additional preventive strategies may be proposed if sexual transmission of HBV occurred in this region where HIV and other STDs are highly prevalent. GOALS: To determine the prevalence of markers for hepatitis B virus (HBV)and other sexually transmitted diseases (STD) in routine blood samples taken from three populations in Mwanza, Tanzania, and to use the data collected to look at the association between hepatitis B and other STDs, including human immunodeficiency virus (HIV). STUDY DESIGN: Routine blood samples were collected from 1,025 patients attending a clinic for STDs, 253 voluntary blood donors from secondary schools, and 952 blood donors who gave blood in a hospital specifically for a relative who needed a blood transfusion. All samples were tested for HIV by double enzyme-linked immunosorbent assay (ELISA), and for syphilis using the Treponema pallidum hemagglutination (TPHA) and rapid plasma reagin (RPR) tests. Two markers for HBV were examined by the double ELISA method, the presence of the anti-hepatitis B core antigen (anti-HBc) and the hepatitis B surface antigen (HBsAg). RESULTS: There were high prevalences of HBV, syphilis, and HIV in relative donors and STD patients. Although HBV markers were more prevalent in men of increasing ages, syphilis and HIV markers were more prevalent in young women. Evidence of past infection with HBV (presence of anti-HBc) was associated with serologic markers of recent treponemal infection (both TPHA and RPR positive) in both sexes (men odds ratio [OR] = 1.91, P < 0.011; women OR = 2.34, P < 0.02) and with HIV in men (OR = 1.93, P < 0.003). Current infection with HBV (presence of HBsAg) was associated with recent syphilis in men (OR = 2.13, P < 0.006). In STD patients, current infection with HBV was associated with Trichomonas vaginalis in women (OR = 3.57, P < 0.002) and recent syphilis in men (OR = 3.46, P < 0.001). There was no further association between HBV markers and any other STD pathogen or any particular STD syndrome, nor was there any association between current HBV infection and HIV in both sexes. The population attributable fraction for sexual acquisition of hepatitis B is estimated at 7.2% in men and 3.0% in women, based on the association between hepatitis B and syphilis. CONCLUSIONS: These findings suggest that sexual acquisition of hepatitis B occurs at low levels in Mwanza, and that HBV can be prevented through enhancement of the current HIV/STD control activities, in addition to improved vaccination strategies.

Adolescent↗

Acute isovolaemic haemodilution: the best option for autologous blood transfusion in Africa?

The purpose of this study was to identify the best method of autologous blood transfusion to be applied in an East African hospital. One hundred and nine consecutive patients for whom major blood loss was anticipated were enrolled. Seventeen patients donated 1 unit of blood 3 days preoperatively and 92 underwent acute isovolaemic haemodilution prior to induction of anaesthesia. For the haemodiluted patients a 2:1 ratio of sterile pryogen-free saline to collected blood was used. One of the 16 patients from whom 2 units were withdrawn by haemodilution experienced hypovolaemia which was rapidly restored by additional transfusion of colloid. Of the patients who donated blood preoperatively only 23.5% were autotransfused compared to 98.9% of the haemodiluted patients. Of the latter 23.9% (22) had an intraoperative blood loss exceeding 15% of their total blood volume and 7.6% (7) lost more than 25%. Only one received homologous blood in addition. For hospitals with limited blood bank facilities and regular cancellation of surgery, the use of acute isovolaemic haemodilution is recommended. A 3:1 ratio of saline to blood is now advised when 1 unit is withdrawn and a part replacement with crystalloid when 2 units are collected.

Appointments and Schedules↗

Attitudes and beliefs about blood donation among adults in Mwanza Region, Tanzania.

A study was carried out to assess the attitudes and beliefs about blood donation among the population of Mwanza Region, Tanzania, in order to target better the voluntary blood donor recruitment and retention. A random sample of 1141 adults, 743 residents of Mwanza town and 398 from Mwanza rural areas were interviewed on aspects related to blood donation. A high proportion (26.4%) of interviewees had already given blood but only 3.8% had donated voluntarily within the last 10 years. Voluntary blood donation was correlated with secondary school attendance. We noted a positive attitude towards voluntary blood donation although the majority of people would do so only for an incentive in the form of remuneration. Respondents frequently thought that blood donation would infect them with HIV or damage their health. No correlation was found between fear to donate and self perceived risk for HIV infection. We found that a substantial number of men would accept pre-test counselling on HIV in order to "infect others" if found positive. Thus we recommend that HIV counselling should be done with extreme care and defer individuals with wrong intentions from blood donation. Donor recruitment campaigns should also focus on clearing wrong conceptions about blood donation through providing information on all aspects related to blood donation. Based on these findings, a scheme for blood donor recruitment and retention in Mwanza Region is proposed.

Adolescent↗

Evaluation of the circle of Willis with three-dimensional CT angiography in patients with suspected intracranial aneurysms.

PURPOSE: To determine the usefulness of CT angiography in the setting of suspected acute subarachnoid hemorrhage or intracranial aneurysm. METHODS: We prospectively studied 68 patients suspected of having subarachnoid hemorrhage or an intracranial aneurysm with noncontrast CT of the head followed immediately by contrast-enhanced helical CT of the circle of Willis with three-dimensional reconstruction. Twenty-seven patients with CT findings positive for subarachnoid hemorrhage or intracranial aneurysm were evaluated with digital subtraction angiography or MR angiography within 12 hours of CT angiography. Patients with negative CT/CT angiography findings were followed up with lumbar puncture. RESULTS: CT angiography showed 23 of 24 aneurysms and 2 of 2 arteriovenous malformations (sensitivity, 96%; specificity, 100%). Aneurysm size ranged from 2 to 40 mm (mean, 7.9 mm). Interobserver variability was 10%. In the 23 cases of subarachnoid hemorrhage, cisternal blood did not limit the three-dimensional reconstruction. Two patients with aneurysms on CT angiography had normal noncontrast scans. CONCLUSIONS: CT angiography of the circle of Willis is a useful technique for evaluation of suspected acute subarachnoid hemorrhage and intracranial aneurysm. It provides anatomic display of intracranial aneurysms, allowing for planning of conventional angiography and surgical approach. In selected cases, CT angiography may eliminate the need for preoperative conventional angiography.

Adolescent↗

Cuba's national AIDS program. The first decade.

There is a high incidence of infection with the human immunodeficiency virus (HIV) in many Caribbean nations. But by 1993 Cuba, with a population of greater than 10 million people, had fewer than 1,000 seropositive persons and less than 200 cases of the acquired immunodeficiency syndrome (AIDS). To investigate Cuba's approach to the AIDS epidemic, we visited Cuba, reviewed published statistics, spoke with health care officials, interviewed HIV-positive patients, and toured medical facilities. Cuba established an extensive HIV surveillance program in 1983, and more than 15 million HIV antibody tests have been done. The sexual contacts of all infected persons are closely observed. A national education program is evolving. Since 1986, all known HIV-positive patients have been placed in sanitariums, which is the most controversial aspect of Cuba's program. We review available information on AIDS in Cuba and describe that nation's attempt to prevent the spread of disease. We discuss how the political system and Cuba's relative isolation have influenced this approach. Strategies have been developed that may be of limited efficacy and would not be acceptable in most Western nations.

AIDS Serodiagnosis↗

Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy.

In 3 children who had undergone cerebral hemispherectomy (hemidecortication) between the ages of 1 year 5 months and 4 years for the alleviation of intractable epilepsy, cerebral glucose utilization was studied serially with positron emission tomography. Three to 7 months after hemispherectomy, glucose utilization in the caudate nuclei on the side of hemispherectomy had decreased to below preoperative values, presumably due to total deprivation of ipsilateral cortical input. One to 2.5 years after surgery, complete restoration of glucose metabolic activity to preoperative levels was seen in 2 patients and partial recovery was seen in 1 patient. These alterations of cerebral glucose utilization are believed to reflect microscopic anatomical reorganizational changes (e.g., collateral sprouting) that have been documented following similar lesions in several animal models. Our findings suggest that positron emission tomography may provide a sensitive measure of developmental brain plasticity in vivo.

Brain↗