Search PubMed⌕ Search

Biomedical subjects

K Henry

Publications and source records attributed to K Henry.

At least 55 records · Page 3Linked to original sources
PubMed1998

Concentration-controlled zidovudine therapy.

BACKGROUND: Heterogeneity in the response to antiretroviral therapy has been attributed to pharmacologic, immunologic, and virologic differences between patients. Currently available antiretroviral agents used for the treatment of human immunodeficiency virus (HIV) infection in adults are administered in standard fixed doses. The active moiety of nucleoside anti-HIV drugs is the intracellular anabolite. Therefore the heterogeneity in response to nucleoside agents may arise as a result of pharmacologic variability at both the systemic and cellular level. OBJECTIVES: To determine whether a novel concentration-controlled zidovudine regimen could improve anti-HIV response compared with the standard fixed-dose approach. DESIGN: At the Outpatient Clinic of the General Clinical Research Center at the University of Minnesota, 20 persons with HIV infection received an oral regimen of zidovudine designed to achieve a target concentration in plasma of 0.7 mumol/L and the 500 mg/day standard dose in a randomized, crossover 24-week study. RESULTS: The concentration-controlled regimen achieved overall higher systemic concentrations with reduced interpatient variability: steady-state average zidovudine plasma concentrations were 0.76 mumol/L (coefficient of variation, 12%) versus 0.62 mumol/L (coefficient of variation, 32%) for the standard regimen. There was no difference in safety and tolerance between regimens. Intracellular zidovudine triphosphate concentrations averaged 160 fmol/10(6) peripheral blood mononuclear cells (PBMCs) with concentration-controlled versus 92 fmol/10(6) PBMCs for standard therapy. The percentage change from baseline in CD4 cells was a 22% increase for the concentration-controlled regimen versus a 7% decrease with standard therapy. CONCLUSIONS: These data indicate that pharmacologic variability affects antiretroviral response. Furthermore, these findings provide a framework to characterize the pharmacologic determinants of effect and quantitate their contribution to the heterogeneity in clinical response to optimize therapeutic benefit.

Adult↗
PubMed1997

Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection.

In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by >/=3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.

Adult↗
PubMed1997

Skin involvement in Kikuchi's disease: an immunocytochemical and immunofluorescence study.

Kikuchi's disease (KD) is a benign self-limiting febrile illness usually affecting young women, which is manifested clinically by fever and cervical lymphadenopathy. Skin involvement in KD is very rare and is evident clinically in the form of skin rashes and nodules. We describe one such case of KD in a 33-year-old Bulgarian woman who presented with cervical and axillary lymphadenopathy and who developed a transient facial rash. Biopsy of axillary lymph nodes showed the characteristic features of KD with infiltration of the lymph node paracortex by apoptotic plasmacytoid monocytes. Biopsies of the facial skin showed two features: (1) dermal infiltration by apoptotic plasmacytoid monocytes; (2) on immunofluorescence studies of frozen sections prepared from involved and uninvolved facial skin, deposition of immunoglobulins and complement at the dermoepidermal junction and in the walls of dermal blood vessels. Such immunofluorescence findings in the skin of patients with KD have never been described. These findings suggest the presence of an autoimmune reaction as a component of KD.

Adult↗
PubMed1997

Delayed presentation to clinics for sexually transmitted diseases by symptomatic patients. A potential contributor to continuing STD morbidity.

OBJECTIVE: To determine the proportion of symptomatic patients attending public sexually transmitted disease (STD) clinics who fail to seek care within 7 days of the onset of STD symptoms and their self-reported reasons for delays in obtaining care. DESIGN: Interviewers administered 23-item questionnaire to a cross section of STD clinic clients between April and September 1995. SETTING: Five urban STD clinics in the United States (Birmingham, AL; St Paul, MN; San Francisco CA; Seattle, WA; and Raleigh, NC). RESULTS: Of 1,621 patients with genitourinary symptoms, over one third (35% of men, 37% of women) presented to STD clinics only after 1 week or more of symptoms. Men with genital warts (73%) or with nongonococcal urethritis (23.1%) or symptomatic men who were recent contacts to sex partners with STDs were significantly more likely to delay clinic attendance more than a week than men with gonorrhea (6.5%, p < 0.001 for each). Overall 43.8% of women receiving specific clinical diagnoses other than genital warts delayed clinic attendance for more than 1 week. When asked why they delayed clinic attendance, respondents were most likely to respond that they had hoped their symptoms would "go away" (48.5% of men and 49.4% of women who waited a week or more before seeking care). CONCLUSION: A substantial proportion of patients with genitourinary symptoms attending public STD clinics delay seeking care for a week or more, increasing their likelihood of complications and of transmission of infection to others. Interventions to promote more timely clinic attendance may help reduce STD morbidity in the United States.

Adolescent↗
PubMed1997

Patients attending STD clinics in an evolving health care environment. Demographics, insurance coverage, preferences for STD services, and STD morbidity.

OBJECTIVES: To characterize client demographics, sexually transmitted diseases (STD) morbidity, insurance status, reasons for attending public STD clinics, and future preferences for source of STD services. DESIGN: Cross-sectional study of 2,490 clients attending five urban STD clinics for new problems with interviewer-administered 23-item questionnaire and chart review to obtain clinical and laboratory STD diagnoses. RESULTS: Participants were young (51% < 25 years of age), minority (64% nonwhite), poor (43% < or = $10,000/year), and largely uninsured (59% uninsured, 27% private insurance, and 14% Medicaid). Half had previously visited the STD clinic, and 81% had used other providers for non-STD services in the prior 3 years. STD symptoms were cited as the reason for the visit by 63%. The most common factors associated with seeking care at these STD clinics were walk-in services, costs, and confidentiality concerns. STD morbidity was high; 66% of clients were diagnosed with one or more STD. Most (68%) clients preferred to be treated at the STD clinic in the future if they could go anywhere for STD services. CONCLUSIONS: STD clinics see young, minority, poor, and uninsured clients with high STD rates. Even with unlimited future choice, two thirds of the clients surveyed would still prefer to be treated at STD clinics. This study indicates the continuing need for publicly funded, categorical STD clinics in urban areas with high STD morbidity and the importance of easily accessible, confidential, expert STD services from the private sector and managed care organizations.

Adult↗
PubMed1997

Pharmacokinetics of hyperimmune anti-human immunodeficiency virus immunoglobulin in persons with AIDS.

Hyperimmune anti-human immunodeficiency virus immunoglobulin (HIVIG) is an intravenous immunoglobulin prepared from HIV-infected asymptomatic donors with a CD4 cell count greater than 400 cells/microl and a high titer of antibody to HIV-1 p24 protein. Twelve persons with AIDS received four doses of HMG (two at 50 mg/kg of body weight and then two at 200 mg/kg) every 28 days. Pharmacokinetics were evaluated by measurement of anti-p24 antibody. HIVIG was well tolerated, and all participants completed the study. Three subjects who were not receiving Pneumocystis carinii pneumonia (PCP) prophylaxis developed PCP. The mean value for HIVIG clearance was 3.02 ml/kg/day at 50 mg/kg and 3.65 ml/kg/day at 200 mg/kg (P = 0.027); the mean trough antibody titers (reciprocal units) were 1,442 and 4,428, respectively. This study indicates that high titers of anti-p24 antibody can be maintained with a monthly administration schedule of HIVIG and that short-term safety is acceptable. Comparisons to evaluate the therapeutic potential of HIVIG are justified.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The relationship between tumor necrosis factor and human immunodeficiency virus gene expression in lymphoid tissue.

In tissue culture models of chronic human immunodeficiency virus type 1 (HIV-1) infection, cytokines such as tumor necrosis factor alpha (TNF-alpha) activate viral gene expression. We sought evidence that TNF-alpha might similarly regulate viral gene expression in vivo in the major lymphoid tissue (LT) reservoir. We used in situ hybridization, quantitative image analysis, and double-label techniques to compare cytokine and HIV-1 RNA levels in sections of tonsil and lymph node tissues obtained from individuals in early and later stages of HIV-1 infection. The levels of TNF-alpha gene expression in LT from HIV-1-infected an uninfected individuals were indistinguishable, and we found no correlation between TNF-alpha gene expression in LT and the level of HIV-1 gene expression in LT. There is thus little evidence that in vivo TNF-alpha significantly influences HIV production in LT.

Gene Expression↗
PubMed1997

HIV/AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Antiretroviral therapy for HIV infection. Heartening successes mixed with continuing challenges.

Probably nothing in the field of medicine has changed as rapidly over the last decade as antiretroviral (ARV) therapy for HIV infection. New insights into pathogenesis, new tests for measuring virus levels in plasma, and availability of powerful new drugs have combined to transform the care of persons with HIV infection into a field infused with real hope. However, ARV therapy remains complex, expensive, and not universally effective or available. This article focuses on a general approach to the use of ARV agents.

Anti-HIV Agents↗
PubMed1996

Quantitative image analysis of HIV-1 infection in lymphoid tissue.

Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy. A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productively infected cells. Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment.

Adult↗
PubMed1996

Outpatient biopsies of the palatine tonsil: access to lymphoid tissue for assessment of human immunodeficiency virus RNA titers.

OBJECTIVES: Our objective was to assess the feasibility of using tonsillar lymphoid biopsy specimens obtained on an outpatient basis to quantitate a patient's lymphoid human immunodeficiency virus (HIV) RNA titers. DESIGN: A pilot cohort study was performed. PATIENTS: We evaluated ten HIV-seropositive patients who ranged in age from 26 to 48 years and had CD4+ cell counts ranging from 110 to 833 at enrollment. MAIN OUTCOME MEASURES: The main outcome measures were tolerance and safety of outpatient tonsil biopsies and quantitation of HIV RNA titers in tonsillar lymphoid biopsy specimens, plasma, and peripheral blood mononuclear cells determined by a new method of HIV RNA signal amplification with branched DNA probes. RESULTS: Outpatient tonsil biopsies were well tolerated and were performed without complications. Nine of 10 tonsil biopsies from the HIV-seropositive patients examined were positive for significant concentrations of HIV RNA, ranging from 106 to 101 HIV RNA equivalents per gram of tissue. All of the HIV RNA-positive tonsillar lymphoid specimens had HIV RNA titers that were 101 to 104 times greater than those recovered from plasma (per milliliter) of the same patient obtained at the time of biopsy. CONCLUSIONS: Sufficient tonsillar tissue can be obtained in an outpatient clinic setting to quantitate lymphoid HIV titers by the new branched-DNA signal amplification method with relative ease and without complication. The biopsy method described here affords ready access to the lymphoreticular system, which may help to advance our understanding of the pathogenesis of myriad immune diseases without the need for excisional node biopsies.

Adult↗
PubMed1996

Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises.

STUDY GOAL: To compare the efficacy and safety of single 1 g oral azithromycin with doxycycline, 100 mg twice daily for seven days for treatment of uncomplicated urogenital chlamydial infection. STUDY DESIGN: Randomised, unblinded, comparative trial, involving 597 patients demonstrating clinical evidence of genital chlamydia and a positive non-culture assay for Chlamydia trachomatis. RESULTS: Among the azithromycin- and doxycycline-treated patients 61% and 60%, respectively, were asymptomatic within one week after the first dose. At two weeks, these figures increased to 86% and 83%, respectively. Bacteriological eradication, based on a negative assay, occurred in 338 (97%) of 347 azithromycin-treated patients and 161 (99%) of 163 doxycycline-treated patients. CONCLUSION: Treatment of uncomplicated chlamydial cervicitis and urethritis with single 1 g oral azithromycin is equivalent to standard therapy with doxycycline. Drug-related adverse events were approximately twice as common as previously reported for both drugs.

Adolescent↗