Search PubMed⌕ Search

Biomedical subjects

J Mills

Publications and source records attributed to J Mills.

At least 163 records · Page 9Linked to original sources
PubMed1990

Comparative study of 5% permethrin cream and 1% lindane lotion for the treatment of scabies.

A multicenter, randomized, investigator-blind controlled trial was conducted to compare the safety and efficacy of a single, whole-body application of 5% permethrin cream with that of 1% lindane lotion for the treatment of scabies in 467 patients. At 14 +/- 3 days after treatment, the mean active lesion count decreased from pretreatment levels of 85 (range, 4 to 600) in both treatment groups to 14 (range, 0 to 133) in the permethrin group and to 15 lesions (range, 0 to 500) in the lindane group. At 28 +/- 7 days after treatment, complete resolution had occurred in 181 (91%) of 199 patients treated with permethrin and in 176 (86%) of 205 patients given lindane. Pruritus due to scabies persisted at 28 +/- 7 days in 14% of the permethrin group and in 25% of the lindane group. The most frequent adverse effects were new or increased pruritus and mild, transient burning or stinging; the latter was slightly more frequent following permethrin treatment and appeared to be related to severity of infestation. Because of a lower potential for neurologic toxicity, permethrin may be preferable to lindane for the treatment of scabies particularly in children.

Adolescent↗
PubMed1989

Comparison of the human immunodeficiency virus type 1 and 2 proteases by hybrid gene construction and trans-complementation.

To determine the cleavage specificity of the proteases of the type 1 and 2 human immunodeficiency viruses (HIV-1, HIV-2), we interchanged this domain of the polymerase (pol) genes and analyzed the maturation programs of the chimeric polyproteins in an Escherichia coli expression system. In both cases, release of reverse transcriptase and integrase was observed, together with the respective 10-kDa protease form resulting from autocatalysis, although the maturation proceeded less efficiently compared to the homologous system. In further experiments, the ability of both HIV-1 and HIV-2 proteases to release in vivo gag p24 from an in-frame fusion of the full length gag and protease precursors was analyzed. In either case, p24 was released, albeit with greater efficiency in the heterologous gene construction. In vitro mixed lysate experiments with the HIV-1 gag precursor furthermore demonstrate that both enzymes respond to the aspartyl proteinase inhibitor pepstatin A. Taken together, these results illustrate that although different cleavage recognition sequences exist for HIV-1 and -2, they are amenable to the proteases of both viruses, but additionally that subtle differences in the mode of action of both enzymes are observable.

Catalysis↗
PubMed1989

Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). An uncontrolled trial.

STUDY OBJECTIVE: To determine whether trisodium phosphonoformate (foscarnet) is efficacious in treating severe mucocutaneous disease due to acyclovir-resistant herpes simplex virus type-2 (HSV-2) infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Open-labeled drug administration to patients with AIDS and severe ulcerative disease due to acyclovir-resistant HSV-2 infection. SETTING: Medical floors of acute care hospital. PATIENTS: Four patients with AIDS who developed progressive ulcerative mucocutaneous lesions of the genitals, perineum, perianal region, or finger due to acyclovir-resistant, thymidine-kinase (TK)-negative strains of HSV-2. INTERVENTION: Foscarnet, 60 mg/kg body weight intravenously every 8 hours (with reduced dosage for renal impairment), for 12 to 50 days. MEASUREMENT AND MAIN RESULTS: All patients receiving foscarnet had dramatic improvement in their clinical findings with marked clearing of mucocutaneous lesions and eradication of HSV from mucosal surfaces. CONCLUSION: Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions.

STUDY OBJECTIVE: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. SETTING: County hospital and AIDS clinic. PATIENTS: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. INTERVENTION: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. MEASUREMENTS AND MAIN RESULTS: Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). CONCLUSIONS: A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.

Acetylation↗
PubMed1989

Incidence of acute mountain sickness at intermediate altitude.

The incidence of acute mountain sickness was determined by questionnaire in 454 individuals who attended week-long continuing medical education programs at ski resorts in the Rocky Mountains with base elevations of about 2000 m. As a control group, 96 individuals who attended continuing medical education programs at sea level in San Francisco completed similar questionnaires. Study subjects were classified as having acute mountain sickness when they reported three or more of the five possible cardinal symptoms: headache, insomnia, dyspnea, anorexia, and fatigue. Only symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. Acute mountain sickness-like symptoms occurred in 25% of subjects at 2000 m compared with 5% of subjects at sea level. The incidence of acute mountain sickness at 2000 m was greatest among subjects who had come from lower altitudes. Half of the subjects with symptoms took medication. The duration of symptoms was short, with 90% of all symptoms that were reported occurring in the first 72 hours. Acute mountain sickness is common at intermediate altitudes, and it is frequently severe enough to prompt self-medication.

Adult↗
PubMed1989

Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes.

To test the value of dexamethasone acetate for ameliorating acute mountain sickness (AMS), we conducted a double-blind, randomized study that compared the effects of 4 mg of dexamethasone acetate or a placebo (given every six hours for six doses beginning at the time of exposure) at 2700 and 2050 m. Study subjects, who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains, were classified as having AMS when they reported three or more of the five usual symptoms (headache, insomnia, dyspnea, anorexia, and/or fatigue) on a single day. All symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. At 2700 m, there was a 50% decrease in the mean AMS symptom score in the dexamethasone group (0.94 +/- 1.11 vs 1.84 +/- 1.44 [mean +/- SD]) and the incidence of AMS was 20% of that in the control group (3/38 vs 14/35). At 2050 m, there was no difference between dexamethasone and a placebo in the mean AMS symptom score (1.52 +/- 1.50 vs 1.24 +/- 1.33) and the incidence of AMS (5/25 vs 4/25). Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 m.

Adult↗
PubMed1989

Comparative assessment of antiretrovirals in human monocyte-macrophages and lymphoid cell lines acutely and chronically infected with the human immunodeficiency virus.

We compared the efficacy of 3 antiretrovirals in cultured human peripheral blood monocyte-derived macrophages and lymphoid cells infected with the human immunodeficiency virus (HIV). Zidovudine (greater than 0.01 micrograms/ml) or foscarnet (greater than or equal to 100 micrograms/ml) consistently inhibited HIV replication (p24 antigen production) in acutely infected macrophages by more than 90%; alpha interferon (1,000 units/ml) inhibited HIV replication by 88-99%. Drug efficacy was equal in lymphoid cells and monocyte-derived macrophages. However, these antiretrovirals even in high concentration only minimally inhibited chronic, established HIV infection: while zidovudine (0.01 micrograms/ml) inhibited infection by over 90% in acutely infected macrophages and lymphoid cells, 50 micrograms/ml of this antiretroviral produced only 19-55% inhibition of HIV replication in chronically infected cells. Slot-blot analysis of HIV RNA was concordant with the p24 antigen data. Acutely infected macrophages are as susceptible to the inhibitory effects of antiretrovirals as lymphoid cells; however, chronically infected macrophages (which probably constitute the main in vivo reservoir for HIV) are several orders of magnitude more resistant.

Antiviral Agents↗
PubMed1989

Acyclovir-resistant, foscarnet-sensitive oral herpes simplex type 2 lesion in a patient with AIDS.

We report the case of an immunocompromised patient with AIDS in whom developed a perioral and several intraoral HSV 2 lesions that persisted for more than 1 year. The virus was resistant to acyclovir but was sensitive to foscarnet. Viral isolates were thymidine kinase negative. The lesions resolved with intravenous foscarnet therapy given over a 15-week period, and when last seen, 8 months after foscarnet was discontinued, the patient had not had a recurrence.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effects of selective depletion of L3T4+ T-lymphocytes on herpes simplex virus encephalitis.

The L3T4 surface molecule defines a subset of murine lymphocytes which are homologous to CD4+ lymphocytes in humans, and are functionally characterized as "helper/inducer" cells. To determine the role of helper/inducer lymphocytes in the host defense against herpes simplex virus type 1 (HSV-1) encephalitis, we utilized a monoclonal antibody to selectively deplete L3T4+ lymphocytes from BALB/c mice prior to experimental HSV infection. Susceptibility to HSV was only minimally increased by the depletion of L3T4+ cells, although mice receiving anti-L3T4 were profoundly immunosuppressed; splenic lymphocytes did not respond to stimulation by virus antigen in vitro, and L3T4+ lymphocyte-depleted mice failed to produce antibodies to HSV-1. However, mice receiving anti-L3T4 had a prolonged increase in natural killer cell activity following HSV infection as compared to controls. These data demonstrate that L3T4+ lymphocytes contribute minimally to host resistance to acute neural HSV infection, even though elimination of these lymphocytes markedly inhibits the genesis of immune responses.

Animals↗
PubMed1989

The independent action of radiation and cisplatin on the survival or recovery of human normal or tumour cells in vitro or in vivo.

Recovery from radiation- or cisplatin-induced lethal damage has been studied in euoxic normal human foetal lung fibroblasts (HFL cells) that remain viable for at least 20 days in plateau-phase culture. After a 1 hour treatment with cisplatin the half-time of recovery was about 2 days. By contrast recovery after radiation was more rapid with half-times of approximately 10 h. There was no further measurable recovery after 2 days. With either agent the recovery ratios (RR) were dose-dependent but recovery (following treatment with equitoxic doses of the two agents) was appreciably greater after cisplatin (RR approximately 123 after 40 microM for 1 h) than after radiation (RR approximately 15 after 900 cGy). When radiation (900 cGy) was combined with cisplatin (40 microM for 1 h) the cell survival, measured at 5 days or later times after the treatments, was not significantly less than that predicted by the additive, independent effects of both agents (calculated as the product of their respective effects on cell survival) irrespective of whether cisplatin was given 1 h before, during or for 1 h immediately after radiation. In euoxic, exponentially growing HFL or HeLa cells there was no evidence that combinations of cisplatin and radiation gave more than additive toxic effects in the protocols tested. The combined effects of cisplatin or carboplatin and whole-body irradiation given 45 min later, on human melanoma cells (assessed by their colony-forming abilities in vitro) growing in thymectomised mice, were essentially the same as that predicted by the additive, independent effects of the two agents.

Animals↗
PubMed1989

Diagnosis of coronary artery disease using thallium imaging: tomographic versus planar imaging.

Coronary artery disease was evaluated with tomographic and planar thallium imaging in 31 subjects who had undergone coronary angiography for assessment of chest pain syndrome. Coronary arteriography revealed significant coronary artery disease in 17; and 14 had normal coronary arteries. The sensitivity and specificity for planar imaging was 71% and 79%, and that for tomography, 94% and 79% respectively. The sensitivity and specificity figures for individual coronary artery lesion detection for planar imaging were 87/83 for LAD, 33/100 for LCX and 50/86 for RCA respectively, and for tomography the figures were 87/87 for LAD, 33/95 for LCX and 90/76 for RCA respectively. The use of coronary arteriography as a gold standard was considered by assessing its interobserver variability, which was 16%. The interobserver variability for thallium imaging was 8% and 3% respectively for tomographic and planar acquisitions.

Adult↗
PubMed1989

Effects of L3T4+ lymphocyte depletion on acute murine cytomegalovirus infection.

We examined the role of T lymphocytes bearing the L3T4 phenotype in acute murine cytomegalovirus (MCMV) infection. In vivo administration of rat IgG2b monoclonal antibody (MAb) GK 1.5 was used to deplete mice of L3T4+ lymphocytes during acute MCMV infection. Unlike the saline-treated controls that resolved their infections, mice receiving the MAb developed persistent and high levels of virus in the salivary gland, lung and spleen. The production of antibody to MCMV was delayed and the titres achieved were markedly less than in the controls. Despite the higher levels of virus replication, there was no increase in mortality seen in animals treated with the MAb. Following intraperitoneal challenge with MCMV, depletion of L3T4+ lymphocytes was protective, increasing the dose of MCMV required to produce death. These data indicate that T lymphocytes of the L3T4 phenotype influence the degree of MCMV replication during acute infection and may contribute to mortality following intraperitoneal virus challenge.

Acute Disease↗
PubMed1989

Isolation and characterization of a multipotent clone of human embryonal carcinoma cells.

Histopathological studies suggest that the stem cells of human teratomas may be classified into two major categories: nullipotent stem cells, and multipotent stem cells, capable both of self-renewal and differentiation into a wide range of somatic and extraembryonic cell types. We have isolated a multipotent stem cell clone from the human teratoma cell line GCT 27, and compared its properties to a nullipotent clone derived from the same strain. The multipotent clone GCT 27 X-1 gave rise to colonies of mixed cell morphology in vitro. Analysis of cell surface, cytostructural and extracellular matrix markers in GCT 27 X-1 cells showed that the stem cells of this line were very similar in phenotype to nullipotent cells. The two cell clones were predominantly hypotriploid, and contained several marker chromosomes in common. GCT 27 X-1 was feeder-cell-dependent for continuous growth in vitro; removal of the feeder layer resulted in differentiation of the stem cells into a variety of cell types, some with characteristics of extraembryonic endoderm, others showing neuronal properties. When transplanted into nude mice, GCT 27 X-1 cells gave rise to teratocarcinomas containing embryonal carcinoma stem cells, and many other cell types: yolk sac carcinoma cells; cells producing alphafetoprotein or human chorionic gonadotrophin; glandular, columnar, cuboidal, and squamous epithelium; primitive mesenchyme and cartilage; neuroectodermal cells. Nullipotent GCT 27 C-1 cells could form colonies in the absence of feeder layers, but multipotent GCT 27 X-1 cells could not. While a range of known growth factors and related substances failed to substitute for feeder layers in supporting the growth of GCT 27 X-1 stem cells, supernatants from yolk sac carcinoma cell line GCT 44 could partially replace the feeder cell requirement. Thus, the results revealed a basic difference in growth control between these multipotent and nullipotent human embryonal carcinoma cells, and suggested a possible paracrine regulatory pathway between multipotent stem cells and yolk sac carcinoma cells.

Animals↗
PubMed1989

Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized (no new retinal lesions and stable old lesions [7 patients]) or improved (decreased retinal opacification [2 patients]). All eight patients with CMV in urine or blood upon entry into the study had negative urine and blood cultures at the end of induction. After induction therapy, seven patients continued maintenance foscarnet therapy, 60 mg/kg as a single daily infusion, 5 days/week. In six patients, retinal lesions increased in size after 2 to 32 weeks of maintenance therapy. One was invaluable because a retinal detachment developed. Only 9 of 42 blood and urine cultures obtained during maintenance foscarnet therapy yielded CMV, compared with 7 of 14 obtained prior to the initiation of foscarnet induction therapy (P = 0.04). Foscarnet toxicity was mild and infrequent: elevation in serum creatinine by 0.5 to 1.3 mg/dl over the base line (two patients), muscle twitching (three patients), hemoglobin decrease by 1 mg/dl (two patients), nausea (two patients), absolute neutrophil count decrease by 50% (one patient), rise in serum phosphorus to greater than 5.5 mg/dl (four patients), and proteinuria (two patients). Intermittently administered intravenous foscarnet appears to be an effective, relatively nontoxic therapy for CMV retinitis. Additional studies to determine the optimal dosage for maintenance therapy are needed, as are comparative trials with ganciclovir.

Acquired Immunodeficiency Syndrome↗