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Biomedical subjects

W Lang

Publications and source records attributed to W Lang.

At least 163 records · Page 9Linked to original sources
PubMed1995

A phase II controlled study of a combination of the immune modulator, lentinan, with didanosine (ddI) in HIV patients with CD4 cells of 200-500/mm3.

This study was carried out to assess the safety and efficacy of a combination of lentinan, an immune modulator, and didanosine (ddI) in a controlled study in HIV positive patients with CD4 levels of 200-500 cells/mm3. Didanosine was administered to HIV patients at doses of 400 mg/day (po) for six weeks (bid), then 2 mg of lentinan i.v. was added per week for 24-80 weeks. A control group (20%) received ddI only. A total of 107 patients were enrolled at three sites, and 88 patients started the ddI/lentinan phase. The combination caused significant increases in CD4 levels up to 38 weeks, whereas ddI alone was significant at the 5% level at 14 weeks. Based on these data, lentinan qualifies as a participant in future multi-drug studies in HIV.

Adjuvants, Immunologic↗
PubMed1994

A positron emission tomography study of oculomotor imagery.

Focal increases of regional cerebral blood flow (rCBF) were measured by positron emission tomography in order to study the anatomo-functional analogies between imagined and executed saccadic eye movements. Oculomotor imagery was performed in the absence of overt eye movements. Compared with a control state the two conditions were associated with normalized rCBF increases in the median cingulate gyrus, and the supplementary and frontal eye fields of both hemispheres. Therefore in the human brain execution and mental imagery of eye movement appear to be functionally linked and mediated by a common network of frontal structures.

Adult↗
PubMed1994

Changes in AIDS survival time in two San Francisco cohorts of homosexual men, 1983 to 1993.

BACKGROUND: During the first decade since the recognition of the acquired immunodeficiency syndrome (AIDS), new therapies have been introduced and the frequency of clinical manifestations has changed. The impact of these changes on AIDS survival, however, has not been well characterized. DESIGN: A prospective cohort study of the outcomes of human immunodeficiency virus (HIV) infection. SETTING: Homosexual and bisexual men residing in San Francisco, Calif, recruited in 1983 and 1984 for two prospective studies and followed up for more than 9 years with clinical examinations. PARTICIPANTS: A total of 761 HIV-positive homosexual and bisexual men. MAIN OUTCOME MEASURES: Survival time from a CD4 lymphocyte count at 0.20 x 10(9)/L (200/microL) and from a clinical AIDS diagnosis to death. RESULTS: Median survival time from a CD4 lymphocyte count at 0.20 x 10(9)/L increased from 28.4 months in the October 1983 to November 1986 period to 40.1 months in the November 1986 to November 1988 period and is estimated at 38.1 months in the November 1988 to February 1993 period. Patients diagnosed with Pneumocystis carinii pneumonia (PCP) accounted for most of this increase with a gain in median survival time of 9.7 months (P = .0009), compared with a nonsignificant decline in the survival time of those patients without a PCP diagnosis. Multivariate analysis showed that rate of CD4 lymphocyte loss (P < .001) and receipt of both PCP prophylaxis and antiretroviral therapy (P = .04) were significantly associated with longer survival time, whereas antiretroviral therapy alone was not (P = .81). Time to death from a clinical AIDS diagnosis was 14.7 months in the 1983 to 1986 period, 19.1 months in the 1986 to 1988 period, and an estimated 15.7 months in the 1988 to 1993 period. CONCLUSIONS: Survival time from a CD4 lymphocyte count at 0.20 x 10(9)/L has improved significantly by about 1 year; yet survival time using the 1987 AIDS case definition has shown small improvement. The largest increase in survival time from a CD4 lymphocyte count at 0.20 x 10(9)/L was in patients diagnosed with PCP, suggesting that PCP prophylaxis and treatment were more important factors in longer survival time than antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Tactile mental imagery in sighted persons and in patients suffering from peripheral blindness early in life.

Patterns of cortical activity as measured by scalp-recorded event-related slow negative DC potential shifts were recorded in 9 early blind and 23 sighted normals while they imagined the feel of textures with the fingertips of one hand. All sighted subjects reported to have concomitant visual imagery as well. Hence, it was not surprising to observe occipital negative shifts, previously described as a sign of occipital visual cortex involvement in visual mental imagery. Though having never had visual perception, the blind, too, had occipital negativities. Their absolute amplitudes were smaller than in the sighted, not only occipitally but also and more pronounced at other areas, particularly frontally where amplitudes were even positive. On the hypothesis that the smaller overall amplitudes in the blind could obscure topographical differences between groups, the relative distribution of negativity across the scalp was assessed, using normalized data. Such normalized parameters significantly differed between groups, indicating that the occipital potentials of the blind were relatively more negative as related to the other scalp areas, than were the occipital potentials of the sighted as related to the other scalp areas. This occipital finding might indicate a participation of the blind's visually deprived occipital cortex in tactile imagery. Second, parietal DC potentials were maximal over the hemisphere contralateral to the imaging hand, possibly indicating involvement of the contralateral parietal association cortex in tactile imagery. Reasons why this was true only for the sighted, are discussed.

Adolescent↗
PubMed1994

[Follow-up of vena cava filters with color Doppler ultrasound].

In 49 patients, colour-coded Duplex sonography was performed after implantation of a Greenfield caval filter. A plain film radiograph of the abdomen was taken additionally. The examination could be assessed free of artifacts in the longitudinal and transverse section in a total of 41 patients (84%). The procedure facilitates not only a diagnosis of thrombotic changes in the vena cava but can also display the topographical position of the filter and the venous flow. Caval thrombosis was verified in 5 patients. In 7 cases there was a decentral position of the filter apex with tilting. The penetration of filter struts through the vein wall eluded sonographic diagnosis as did morphological changes to the filter (e.g. filter fracture). In combination with the plain film radiograph, colour-coded Duplex sonography can replace cavography or computed tomography in the investigation of position and venous flow.

Adult↗
PubMed1994

Functional localization of motor processes in the primary and supplementary motor areas.

Aspects of human brain activity were measured when subjects performed self-initiated voluntary movements, responded to external cues, or either executed or imagined performing sequential movements. Biophysical modeling of movement-related magnetic and electric fields of the brain succeeded in localizing focal activity in primary and supplementary motor areas, describing the temporal course of focal activation, and analyzing effects of type and consequences of movements on motor preparation. Positron emission tomography was used to test functional specializations of primary and supplementary areas by systematic variations of motor sequence tasks. Studies on functional brain imaging have been employed not only to contribute towards the understanding of brain physiology but also to investigate pathophysiology of movement disorders, principles of functional reorganization following brain lesions, and drug-induced changes of movement-related brain activity.

Brain↗
PubMed1994

The mechanism of transcription termination by RNA polymerase I.

Eukaryotic ribosomal gene transcription units are bordered at their 3' ends by short DNA sequences which specify site-specific termination by RNA polymerase I (polI). PolI terminators from yeast through to mammals appear to follow similar rules: they contain a site for a sequence-specific DNA-binding protein; they function only in one orientation; 3' ends are formed upstream of the binding site; and 5' flanking sequences influence the position and efficiency of 3' end formation. Recent progress in understanding the mechanism of RNA chain elongation by other polymerases suggests a model for polI termination in which termination is seen as one of the several outcomes possible when a polymerase encounters a pause site.

Animals↗
PubMed1994

Monoclonal antibodies directed against tick-borne encephalitis virus with neutralizing activity in vivo.

Monoclonal antibodies (MoAbs) were raised against the tick-borne encephalitis (TBE) virus, strain K23. The reactivities of 14 selected MoAbs were characterized by ELISA, Western blot analysis, haemagglutination inhibition, immunoprecipitation, in vivo protection and in vitro neutralization tests. All MoAbs reacted only with the glycoprotein E. The binding epitope of one MoAb could be delimited by a synthetic peptide to amino acids 306-339 representing one immunodominant loop structure of the glycoprotein E. The MoAbs exhibited individual reactivities against 13 different TBE virus isolates in ELISA and immunoblot test ranging from type-specific reactions to a broad reactivity with all isolates. Four MoAbs also showed a cross-reaction with other flaviviruses like West Nile virus and/or Yellow fever virus in immunoblot analysis. By competition ELISA the MoAbs could be divided into five different reaction patterns. Four MoAbs showed neutralizing activity with titers in the range 1:140 to 1:5,000 in an in vitro assay. These neutralizing activities could be confirmed by an in vivo mouse challenge model. The MoAbs are useful for diagnostic purposes and for differentiation of TBE virus strains and other flaviviruses.

Amino Acid Sequence↗
PubMed1994

[Cava filter for prevention of lung embolism: is implantation still justified?].

During a period of 11 years operative placement of a Greenfield vena caval filter was planned in 132 patients. The clinical records of these patients were reviewed retrospectively. Main indications for filter placement were pulmonary embolism in patients with deep venous thrombosis in spite of anticoagulation therapy (45%) and patients with contraindications for anticoagulation (40%). Insertion was successful in 117 patients with a failure rate of 14.6% (21 of 143 procedures). Follow-up data were obtained of all 117 patients with inserted filter (6 of them with 2 filters). Physical examination was performed in 67 of 74 patients alive after a mean postoperative period of 57 months (median: 52.5/range: 1-128). In addition, plain abdominal X-ray was available of all patients. CT scans of the abdomen or venacavography studies were obtained in 60 patients. Major complications as recurrent pulmonary embolism (8%), caval thrombosis (13%), penetrations of struts through the caval wall (33%), tilting of filters (25%), migration (5%) and filter fracture (two cases) were observed. In conclusion, indication should be restricted to certain cases with failure of surgical intervention or drug therapy (thrombectomy, lysis, anticoagulation).

Adult↗
PubMed1994

A phase I study of curdlan sulfate--an HIV inhibitor. Tolerance, pharmacokinetics and effects on coagulation and on CD4 lymphocytes.

Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which has anti-HIV activity in vitro, and inhibits attachment of the virus to T-cells. After two weeks of exposure of virus and cells to CRDS, there is complete inhibition of virus replication. CRDS is also active against cytomegalovirus. The favorable toxicological profile of CRDS in animals suggested clinical trials. In this study, doses of 0.014, 0.14, 0.42, 1.42, 2.84 and 4.26 mg/Kg (hereinafter referred to as 1, 10, 30, 100, 200 and 300 mg/body, respectively, for convenience) were administered to three HIV-positive patients at each dose level for four hours intravenously. Activated partial thromboplastin times (APTT) were measured hourly. Unexpectedly, single doses of CRDS produced marked, dose-related, increases in CD4 lymphocytes in HIV-infected patients. There were no clinical side effects seen at any dose tested. All laboratory parameters were normal except for prolongation of APTT in the 200 and 300 mg dose group. Two patients in the 300 mg dose group had a doubling of the APTT during the four hour infusion, which was the termination point of the trial according to the protocol. The half-life of CRDS was estimated to be 2 to 3 hours from the APTT data and from the blood level assays (not shown). CRDS was well tolerated in the study with the APTT levels being a convenient monitoring basis for dosing. Marked increases in CD4 levels were seen at higher doses, which, if confirmed and extended, may have therapeutic implications. CRDS is considered safe for multiple dosing with monitoring of APTT.

Adult↗
PubMed1993

[Necrotizing hepatitis with a fatal outcome after carbimazole therapy].

A 74-year-old woman developed weakness, lack of appetite and abdominal swelling 7 months after starting treatment with carbimazole (10 mg/d for 10 weeks) and, subsequently, radioiodine for hyperthyroidism. Physical examination revealed generalized oedema and ascites. Computed tomography showed a liver of normal size but infiltrated by nodules up to 4 cm in diameter. Erythrocyte sedimentation rate was raised and there were abnormal concentrations of haemoglobin, total proteins, liver enzymes and creatinine, as well as decreased platelet and white cell counts. Thyroid function was normal. Viral and autoimmune diseases were largely excluded. Liver biopsy showed a severe, highly active hepatitis with parenchymal necroses, large-drop fatty infiltration and intralobular granuloma-like inflammatory reactions, as well as lympho-histiocytic inflammation of the portal areas. The most likely cause was the carbimazole treatment. In addition to symptomatic treatment she received prednisone (1 mg/kg), because an allergic diathesis could not be excluded. But she died of hepatic failure 6 weeks after admission.

Aged↗
PubMed1993

Popliteal arteriovenous fistula after corrective upper tibial osteotomy.

Injuries to the popliteal artery or vein are rare complications of knee arthroscopy or osteosynthesis at the distal femur or the proximal tibia. We report a case of iatrogenic arteriovenous fistula after proximal tibial osteotomy for varus deformity. A 71-year-old woman complained of pain and swelling of the foot 9 weeks after a corrective barrel-vault osteotomy of the left tibia. Angiography demonstrated an arteriovenous fistula between the popliteal vessels due to osteotomy of the tibial head. The fistula was separated and popliteal vessels closed by continuous suture and a small saphenous vein patch.

Aged↗
PubMed1993

Pharmacokinetic-metabolic studies with 14C-aloe emodin after oral administration to male and female rats.

After oral administration of 4.5 mg/kg 14C-aloe emodin (AE) to rats 20-30% of the dose was excreted in urine and the rest in feces. AE was quickly metabolized to rhein, to an unknown metabolite and to conjugates of all three. In the plasma about 10% of 14C-activity was identified as free AE. Maximum plasma values were reached 1.5-3 h p.a. with 248 (male) and 441 (female) ng equivalents AE/ml. Maximum concentrations in plasma were about 3 times higher than those in ovaries and 10 times higher than those in testes. Only liver, kidney and intestinal tract showed higher concentrations than plasma. Terminal half-life (for radioactivity) in blood was about 50 h.

Absorption↗
PubMed1993

An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease.

Dehydroepiandrosterone (DHEA) is a naturally occurring adrenal steroid reported to have immunomodulatory and antiviral activity in cellular and animal models as well as modest in vitro antiretroviral activity against human immunodeficiency virus (HIV). A phase I dose-escalation study was performed to evaluate the safety and pharmacokinetics of DHEA in subjects with symptomatic HIV disease and an absolute CD4 lymphocyte count between 250 and 600 cells/microliters. Thirty-one subjects were evaluated and monitored for safety and tolerance. The oral drug was administered three times daily in doses ranging from 750 mg/day to 2,250 mg/day for 16 weeks. Some immunological and virological parameters were monitored as well. The drug was well tolerated and no dose-limiting side effects were noted. Dose proportionality was evidenced neither by the serum DHEA nor by DHEA-S time-concentration curves for the three dosing groups. However, the study cohort appeared to consist of two subpopulations with markedly different bioavailability for a given DHEA dose. No sustained improvements in CD4 counts nor decreases in serum p24 antigen or beta-2 microglobulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at week 8 compared with baseline in all dosing groups. DHEA was well tolerated by patients with mild symptomatic HIV disease; evaluation of this agent for efficacy in HIV disease would require randomized, controlled trials.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels.

OBJECTIVE: To identify and characterize individuals with long-term HIV-1 infection who have experienced little or no progressive CD4+ T-cell loss during follow-up. PATIENTS AND METHODS: The rate of CD4+ T-cell loss (CD4 slope) was determined for each of the 290 participants in the San Francisco Men's Health Study who were seropositive at study entry in 1984. The study population was stratified, by CD4 slope, into 10 groups of 29 individuals and each group was characterized using a variety of cross-sectional and longitudinal laboratory measurements. RESULTS: Approximately 10% of the HIV-1-infected men experienced no net CD4+ T-cell loss during 78 months of follow-up. Compared with all other seropositive subjects, these 'non-progressors' were the extreme cases in a relatively continuous distribution of CD4 slopes, rather than a discrete subpopulation. Although they had no net cell loss, their mean CD4+ cell count was approximately 400 x 10(6)/l lower and their mean CD8+ cell count approximately 250 x 10(6)/l higher than seronegative subjects, suggesting early changes followed by stabilization. The CD4 slope was associated with the levels of beta 2-microglobulin, neopterin, p24 antibody, erythrocyte sedimentation rate, viral burden, and the proportion of HIV-1 isolates with tropism for the MT-2 T-cell line. Multivariate cluster analysis of these laboratory markers did not distinguish the non-progressors as a distinct subgroup. CONCLUSIONS: These findings support both a biphasic natural history and the suggestion that the broad range in HIV disease progression rates may be the result of several independent factors interacting in a variety of combinations. Recent changes in laboratory markers, known to predict both CD4+ cell loss and AIDS, suggest that non-progressors are undergoing slow HIV disease progression.

Acquired Immunodeficiency Syndrome↗