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J Jacobson

Publications and source records attributed to J Jacobson.

At least 19 recordsLinked to original sources
PubMed2025

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n&#x2009;=&#x2009;1,196 reported ever use, n&#x2009;=&#x2009;4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p&#x2009;<&#x2009;5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p&#x2009;>&#x2009;0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans↗
PubMed2004

Fetal lung dysplasia: clinical outcome based on a new classification system.

OBJECTIVE: To evaluate the clinical application of a new classification system of fetal lung anomalies. METHODS: Forty fetal diagnoses of lung lesions were analyzed according to our proposed classification system in which each lung component is considered using two-dimensional ultrasound and color and power Doppler technology. Medical files, natural history and neonatal follow-up were recorded. RESULTS: Type I dysplasia: Four cases of agenesis of the lung were diagnosed, three with right lung agenesis and one with left lung agenesis. Three of the four patients elected to undergo termination of pregnancy (TOP). The surviving fetus was diagnosed with scimitar syndrome and postnatal embolization of the aberrant vessel was performed. Type II dysplasia: One case of normal lung with abnormal systemic feeding artery was diagnosed with normal neonatal outcome. Type III dysplasia: Abnormal lung with abnormal vascularity was found in 14 cases, presenting in most cases as echogenic lung masses. Seven were supradiaphragmatic, six subdiaphragmatic and one case was of undetermined position. All 14 fetuses showed an aberrant systemic artery emerging from the aorta. Abnormal venous drainage could be identified in only five (36%) of the fetuses: three had prominent azygos vein, one showed drainage to the inferior vena cava and one had multiple intrapulmonary veins forming a huge arteriovenous (A-V) shunt. Two cases in this group underwent TOP, the case with A-V shunt following development of hydrops, and one on maternal request. The remaining 12 fetuses (86%) survived and were alive and well at the time of writing; only one of them needed immediate postnatal embolization of the bilateral aberrant feeding arteries. Type IV dysplasia: Abnormal lung with no vascular abnormality was diagnosed in 20 fetuses. In this group there was one case of intrauterine fetal death, two patients underwent TOP, one complicated with hydrops and one on maternal request. The survival rate in this group was 85%. Only two cases needed immediate surgical repair. Type V miscellaneous dysplasia: One fetus demonstrated echogenic lung with split notochord syndrome and survived. CONCLUSIONS: Congenital bronchopulmonary and related vascular anomalies can be categorized using the new classification system. This new approach enabled prenatal evaluation of each lung component and facilitated cogent management of the fetus with congenital lung dysplasia.

Blood Vessels↗
PubMed2004

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women with complaints of sexual dysfunction.

Androgen insufficiency has been associated with decreased libido and arousal in postmenopausal women, but rarely has been evaluated in healthy premenopausal women. In all, 32 healthy premenopausal women were enrolled in this study, 18 with one or more complaints of sexual dysfunction and 14 without. Assays of ovarian and adrenal androgens were measured before and after ACTH stimulation. The women with complaints of sexual dysfunction had significantly lower adrenal androgens than did the control women. There were no differences in the basal ovarian androgens or cortisol levels. After ACTH, both groups stimulated cortisol as well as adrenal and ovarian androgens. In conclusion, premenopausal women with complaints of sexual dysfunction had lower adrenal androgen precursors and testosterone than age-matched control women without such complaints. Further study is required to determine how lower adrenal androgens contribute to female sexual dysfunction.

Adrenal Glands↗
PubMed2004

Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20-49 years with no complaints of sexual dysfunction.

Androgen insufficiency is a recognized cause of sexual dysfunction in men and women. Age-related decrements in adrenal and gonadal androgen levels also occur naturally in both sexes. At present, it is unclear if a woman's low serum androgen level is a reflection of the expected normal age-related decline or indicative of an underlying androgen-deficient state. We studied premenopausal women with no complaints of sexual dysfunction to help define a normal female androgen profile. In all, 60 healthy, normally menstruating women, ages 20-49 y, were studied. The Abbreviated Sexual Function Questionnaire was administered along with a detailed interview. Radioimmunoassay measurements of morning serum testosterone (T), free testosterone (fT), dehydroepiandrosterone-sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were measured during days 8-15 of the menstrual cycle. In women 20-49 y old without complaints of sexual dysfunction, serum androgen levels exhibit a progressive stepwise decline. Comparing values obtained in women age 20-29 y to those obtained in women 40-49 y, specific hormone decrements were DHEAS 195.6-140.4 microg/dl, serum T 51.5-33.7 ng/dl, fT 1.51-1.03 pg/ml. SHBG did not change significantly in women in this age group. The FAI reflected the age-related decrease in female androgen levels. The framework for the development of a female androgen profile in women with no complaints of sexual dysfunction has been established, and an age-related decrease in testosterone and its adrenal precursor, DHEAS, has been demonstrated. The FAI mirrors these decreases and its usefulness in clinical practice is confirmed. A precipitous decline in all androgens occurs after the decade of the 20s, yet SHBG does not show a significant change throughout the premenopausal years.

Adult↗
PubMed2004

Membrane formation mechanism of cross-linked polyurea microcapsules by phase separation method.

This research was conducted to clarify the membrane formation mechanism of cross-linked polyurea microcapsules by phase separation method, especially the role of polymeric surfactant, such as poly(ethylene-alt-maleic anhydride) (poly(E-MA)) at the interface of O/W emulsion. It was found that poly(E-MA) was necessary for the formation of cross-linked polyurea membrane. The addition of sodium dodecyl sulphate (SDS) prohibited the membrane formation reaction at the interface, even in the case of poly(E-MA) concentration enough for polymeric microcapsule formation. From the results in this study, poly(E-MA) was found to be adsorbed on the O/W emulsion and provide the reaction site for the membrane formation of polymeric microcapsules.

Capsules↗
PubMed2003

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (P<0.001) and free testosterone (P<0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (P<0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

Aging↗
PubMed2002

Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial.

Yohimbine has had questionable effects in men with organic erectile dysfunction. We conducted this study to better define the population of men responsive to yohimbine, because tobacco was thought to affect a regimen of yohimbine more than other risk factors. We measured nocturnal penile tumescence with the RigiScan monitor, hormone profiles, answers to the Florida Sexual Health Questionnaire, and clinical responses at baseline and after two different doses of yohimbine in 18 nonsmoking men with erectile dysfunction. Of the 18 men, nine (50%) were successful in completing intercourse in more than 75% of attempts. The yohimbine responders were men with less severe erectile dysfunction as manifested by improved increased rigidity on RigiScan testing, higher Florida Sexual Health Questionnaire scores, and slightly higher levels of serum testosterone. Yohimbine is an effective therapy to treat organic erectile dysfunction in some men with erectile dysfunction.

Adrenergic alpha-Antagonists↗
PubMed2001

Pelvic instability after bone graft harvesting from posterior iliac crest: report of nine patients.

OBJECTIVE: To report the imaging findings in nine patients who developed pelvic instability after bone graft harvest from the posterior aspect of the iliac crest. DESIGN AND PATIENTS: A retrospective study was performed of the imaging studies of nine patients who developed pelvic pain after autologous bone graft was harvested from the posterior aspect of the ilium for spinal arthrodesis. Plain films, bone scans, and CT and MR examinations of the pelvis were reviewed. Pertinent aspects of the clinical history of these patients were noted, including age, gender and clinical symptoms. RESULTS: The age of the patients ranged from 52 to 77 years (average 69 years) and all were women. The bone graft had been derived from the posterior aspect of the iliac crest about the sacroiliac joint. All patients subsequently developed subluxation of the pubic symphysis. Eight patients had additional insufficiency fractures of the iliac crest adjacent to the bone graft donor site, and five patients also revealed subluxation of the sacroiliac joint. Two had insufficiency fractures of the sacrum and one had an additional fracture of the pubic ramus. CONCLUSIONS: Pelvic instability is a potential complication of bone graft harvesting from the posterior aspect of the iliac crest. The pelvic instability is manifested by insufficiency fractures of the ilium and subluxation of the sacroiliac joints and pubic symphysis.

Aged↗
PubMed2001

Prospective randomized neurocognitive and S-100 study of hypothermic circulatory arrest, retrograde brain perfusion, and antegrade brain perfusion for aortic arch operations.

BACKGROUND: To determine the optimal method of brain protection during deep hypothermic circulatory arrest (DHCA) for arch repair. METHODS: Of 139 potential aortic arch repairs (denominator), we randomized 30 patients to either DHCA alone (n = 10), DHCA plus retrograde brain perfusion (RBP) (n = 10), or antegrade perfusion (ANTE) (n = 10); a further 5 coronary bypass (CAB) patients were controls. Fifty-one neurocognitive subscores were obtained for each patient at each of four intervals: preoperatively, 3 to 6 days postoperatively, 2 to 3 weeks postoperatively, and 6 months postoperatively. Intraoperative and postoperative S-100 blood levels and electroencephalograms were also obtained. RESULTS: For the denominator, the 30-day and hospital survival rate was 97.8% (136 of 139) and the stroke rate 2.8% (4 of 139). For the randomized patients, the survival rate was 100% and no patient suffered a stroke or seizure. Circulatory arrest (CA) times were not different (DHCA: RBP:ANTE) for 11 total arch repairs (including 6 elephant trunk; mean, 41.4 minutes; standard deviation, 15). Hemiarch repairs (n = 17) were quickest with DHCA (mean 10.0 minutes; standard deviation, 3.6; p = 0.011) and longest with ANTE (mean 23.8 minutes; standard deviation, 10.28; p = 0.004). Of the patients, 96% had clinical neurocognitive impairment at 3 to 6 days, but by 2 to 3 weeks only 9% had a residual new deficit (1 DHCA, 1 RBP, 1 ANTE), and by 6 months these 3 patients had recovered. Comparison of postoperative mean scores showed the DHCA group did better than RBP patients in 5 of 7 significantly different (p < 0.05) scores and versus 9 of 9 ANTE patients. There were no S-100 level differences between CA groups, but levels were significantly higher versus the CAB controls, particularly at the end of bypass (p < 0.0001); however, these may have been influenced by other variables such as greater pump time, cardiotomy use, and postoperative autotransfusion. Circulatory arrest (p = 0.01) and pump time (p = 0.057) correlated with peak S-100 levels. CONCLUSIONS: The results of hypothermic arrest have improved; however, there is no neurocognitive advantage with RBP or ANTE. Nevertheless, retrograde brain perfusion may, in a larger study, potentially reduce the risk of strokes related to embolic material. S-100 levels may be artificial. In patients with severe atheroma or high risk for embolic strokes, we use a combination of retrograde and antegrade perfusion on a selective basis.

Aged↗
PubMed2001

Standard-dose therapy for multiple myeloma: The Southwest Oncology Group experience.

We summarize the Southwest Oncology Group (SWOG) experience with standard therapy for multiple myeloma by reviewing and updating data from seven consecutive SWOG trials. Some modest progress has been made since the introduction of melphalan and prednisone (MP) for induction therapy, using regimens that involve vincristine and doxorubicin, and which save alkylating agents for possible later high-dose therapy. For maintenance, it appears that prednisone plays a useful role. We demonstrate the use of the data collected in these trials with a proposed new staging system.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Antiretroviral hepatotoxicity in human immunodeficiency virus-infected patients.

BACKGROUND: Drug hepatotoxicity is a potentially serious adverse reaction of antiretroviral therapy in human immunodeficiency virus-infected patients. The impact of this problem in the routine treatment of patients with human immunodeficiency virus infection is poorly defined. OBJECTIVES: Our aim was to determine what clinical features are associated with hepatotoxicity in human immunodeficiency virus-infected patients receiving antiretroviral therapy. METHODS: Consecutive patients in a primary care-based human immunodeficiency virus clinic were evaluated for hepatotoxicity. Clinic records were used to obtain patient characteristics, as well as independent variables including CD4+ count, coexisting hepatitis C and current alcohol use. RESULTS: Sixty-five patients taking antiretroviral therapy were evaluated. Twenty-four were identified to have antiretroviral hepatotoxicity. An age over 40 years (P=0.019), an absolute CD4+ count of less than 310 cells/mL (P=0.002) and coexisting hepatitis C infection (P=0.035) were significantly associated with hepatotoxicity. Patients older than 40 years had a sevenfold increased risk (risk ratio, 6.9; 95% confidence interval, 1.7-27.3) and those with an absolute CD4+ count of less than 310 cells/mL had a tenfold increased risk (risk ratio, 10.2; 95% confidence interval, 2.5-41.9) for antiretroviral hepatotoxicity, in comparison with those who were younger or who had a greater absolute CD4+ count. Of the eight patients documented to have coexisting hepatitis C infection, six (75%) were in the antiretroviral hepatotoxicity group. CONCLUSIONS: An age older than 40 years and an absolute CD4+ count of less than 310 cells/mL were significantly associated with antiretroviral-induced hepatotoxicity. The majority of our patients with chronic hepatitis C had hepatotoxicity from antiretroviral therapy.

Adult↗
PubMed2001

Diet and breast cancer surveillance behaviors among Harlem women.

The consumption of green, yellow, and other vegetables, fruits and fruit juices may be protective against breast cancer, and, alongside regular breast cancer screening, may contribute to ethnic and racial differences in breast cancer rates. The purpose of this study is to assess the dietary and sociodemographic predictors of surveillance among Harlem women, using a population-based household survey. One half of the Harlem women in this sample consumed no or one fruit or vegetable per day. Logistic regression analyses revealed that women who consumed more fruits and vegetables had received more recent mammography, and that women who were unemployed were less likely to receive recent breast cancer screening than were those who worked full- or part-time. The high response rate and the representativeness of the sample are study strengths. Owing to the small sample size for women between 40-65, the ages for which screening mammography and clinical breast exam are recommended, subgroup analyses were limited. Therefore, additional study of age-adjusted dietary patterns and screening among African American women is suggested.

Adolescent↗
PubMed2001

Pharmacokinetics and pharmacodynamics of thalidomide in HIV patients treated for oral aphthous ulcers: ACTG protocol 251. AIDS Clinical Trials Group.

Thalidomide has increasing clinical benefits, including the healing of aphthous ulcers in patients with HIV. Unfortunately, pharmacological information addressing the pharmacokinetics (PK) of this compound in HIV patients is limited. Concern exists as to whether thalidomide may alter its own metabolism owing to in vitro data previously reported. Furthermore, no information is available defining the relationship between drug exposure and clinical response. This study evaluated the PK and pharmacodynamics (PD) of thalidomide in patients enrolled in AIDS Clinical Trials Group Protocol 251. Study patients had HIV infection and oral aphthous ulcers of at least 2 weeks'duration. Pharmacologic studies were completed in those subjects randomized to receive active thalidomide at a dose of 200 mg daily for the 4-week study period. PK studies involving serial sampling were carried out in 7 subjects following multiple dosing during study weeks 1 and 4. In addition, trough measurements were done in 20 subjects during each of the 4 study weeks to explore the relationship between time-averaged trough values and extent of clinical response. All samples were analyzed using a validated HPLC method, and parameters were determined using noncompartmental PK analysis. Thalidomide oral clearance averaged 0.14 +/- 0.08 and 0.12 +/- 0.05 l/h/kg on weeks 1 and 4 (p = 0.72), while the terminal elimination half-life averaged 5.7 +/- 1.5 and 7.3 +/- 1.7 hours (p = 0.12). The median time-averaged trough value for subjects deemed complete responders was 0.60, while the median value for noncomplete responders was 0.54. Adjusting for baseline CD4 count and initial index ulcer area, no significant effects were observed of increased thalidomide levels on response. In summary, this study provides steady-state PK data in HIV patients managed with thalidomide and suggests negligible effect of chronic dosing on drug clearance (comparing results from weeks 1 and 4). Furthermore, variable trough measurements between patients do not directly influence the effectiveness of thalidomide for oral aphthous ulcers.

Adult↗
PubMed2000

Dendritic cells, infected with vesicular stomatitis virus-pseudotyped HIV-1, present viral antigens to CD4+ and CD8+ T cells from HIV-1-infected individuals.

Nonreplicating vectors are being considered in HIV-1 vaccine design. However, nonreplicating viruses are typically weak immunogens, leading to efforts to target the vaccine to mature dendritic cells (DCs). We have studied a single-cycle form of HIV-1, prepared by pseudotyping envelope-defective HIV-1 plasmids with the envelope from vesicular stomatitis virus (VSV) G protein (VSV-G), to which most humans lack preexisting immunity. The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4. A majority of the cells reverse transcribed the HIV-1 RNA, and a minority expressed gag protein. The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls. Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated. Macrophages were much less efficient in expanding HIV-1-responsive T cells, and bulk mononuclear cells responded weakly to VSV/HIV-1. CD4(+) T cells from at least half of the donors showed strong responses to VSV/HIV-1-infected DCs. Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added. Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.

Adult↗