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At least 73 records · Page 4Linked to original sources
PubMed1992

Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines.

Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno-chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4-epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1991

False-positive radionuclide arthroscintigraphy with a porous-coated total hip prosthesis.

The evaluation of a painful hip prosthesis for suspected loosening frequently requires a multi-modality approach. Radionuclide arthroscintigraphy is a valuable adjunct to contrast arthrography, demonstrating greater sensitivity than contrast arthrography in detecting loosening of the femoral component of the prosthesis. Despite its reliability in the evaluation of cemented hip prostheses, the value of arthroscintigraphy in patients with uncemented or porous-coated prostheses is undetermined. The case of a false-positive radionuclide arthroscintigram in a patient with an uncemented prosthesis is reported. The literature is briefly examined, and the potential implications regarding interpretation of arthroscintigraphy in patients with porous-coated prostheses are discussed.

False Positive Reactions↗
PubMed1991

Fluvoxamine and alcoholism.

There has been much recent interest in the pharmacological manipulation of alcohol intake and alcohol seeking behaviour. An effective drug treatment could form an important part of a multi-modal treatment programme and could make controlled drinking more of a reality. In animal models the serotonin reuptake inhibitors, including fluvoxamine, have been consistently shown to reduce alcohol consumption, even in alcohol-preferring rat strains. Clinical studies have shown that these specific serotonin reuptake inhibitors may also be useful in significantly reducing the alcohol intake of a group of early stage problem drinkers. Although there are many possible mechanisms, the most likely mechanism to explain this mode of action of these specific serotonin antidepressants is that the serotonin enhancement they produce reduces the positive reinforcement properties of alcohol and thereby produces an anti-craving effect. These studies now need to be replicated, with particular attention being given to those patients who fulfil the criteria of the alcohol dependence syndrome. Such an ongoing study with fluvoxamine will be described.

Alcohol Drinking↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed1991

Differential diagnosis and treatment of conversion disorder and Guillain-Barre syndrome.

Three cases are presented which illustrate the possible difficulties in differentiating between the diagnoses of Guillain-Barre Syndrome and conversion disorder. Accepted criteria are specified for each condition, as well as some associated features often characteristic of similar cases. Supportive interdisciplinary treatment for Guillain-Barre Syndrome is reviewed, and an interdisciplinary multi-modal approach to treatment of conversion disorder is described.

Adolescent↗
PubMed2026

The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV.

HIV persistence within anatomical reservoirs remains the primary barrier to achieving an HIV cure. While antiretroviral therapy effectively suppresses plasma viremia, it does not eliminate integrated proviral genomes that persist in long-lived cellular compartments. The central nervous system (CNS) is a clinically important HIV reservoir, characterized by immune privilege and the persistence of tissue-resident infection despite effective antiretroviral therapy (ART). Evidence from postmortem studies reveals that HIV DNA, RNA, and even intact replication-competent proviruses remain detectable in brain tissue from virally suppressed people with HIV. Evidence derived primarily from in situ approaches and viable-cell studies supports myeloid-lineage reservoirs, particularly microglia and CNS-associated macrophages, as key cellular sources of persistence, while the extent and biological relevance of astrocyte infection remains debated. These reservoirs exhibit transcriptional activity and are associated with chronic neuroinflammation, which may contribute to HIV-associated neurocognitive disorders, despite systemic viral suppression. Here, we synthesize recent findings from autopsy brain studies, including work enabled by major biorepositories, such as the National NeuroHIV Tissue Consortium and rapid-autopsy programs, including the Last Gift, both of which are essential for studying HIV reservoirs in the CNS. We summarize methodologies for detecting and characterizing HIV in brain tissue, highlight heterogeneous patterns of regional distribution and compartmentalization, and review emerging links between CNS persistence and neuroinflammation. We conclude with priorities for harmonized tissue processing, multi-modal single-cell and spatial profiling, and coordinated cross-cohort analyses to clarify the contribution of CNS reservoirs to neuroHIV pathogenesis and systemic rebound.

Humans↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed1991

Chemotherapy for retinoblastoma: where do we go from here? A review of published literature and meeting abstracts, including discussions during the Vth International Symposium on Retinoblastoma, October 1990.

The history of the application of chemotherapy in the management of retinoblastoma (RB) may conveniently be divided into three eras: initial enthusiasm (from early 1950s to mid 1970s), realism (from late 1970s to mid 1980s) and possibility (from mid 1980s to the future). Available data from each of these eras are reviewed in the clinical categories of: intraocular RB, micrometastatic RB and overt dissemination. The latter is further sub-classified into: orbital invasion, central nervous system involvement and systemic metastases. Experimental models are described with particular emphasis on future directions. Early reports led to initial optimism subsequently dampened by a more critical approach. Recent results with increasingly effective chemotherapeutic regimens offer the possibility of a valid contribution in each of the above clinical settings. A multi-modality approach is recommended optimizing a combination of the most active drugs with continuing refinements of other techniques. In selected patients with intraocular, and particularly bilateral RB, visual outcome may be enhanced by the combined use of non-surgical modalities. Adjuvant treatment of presumed micrometastases needs to be studied within risk categories defined by prognostic factors. Invasion of the ocular coats and/or of the optic nerve are the most relevant factors but there are continued difficulties in defining the extent of involvement and eligibility criteria for such a strategy. Overt dissemination has recently been demonstrated to be curable in each of the three subgroups above. Intensive regimens incorporating cyclophosphamide, vincristine, cisplatinum, etoposide and possibly doxorubicin, plus intrathecal agents in combination with radiation therapy and, in some instances supplemented by bone marrow transplantation have produced promising results. Multi-institutional collaboration has been encouraged by the recently formed International Committee for the Staging and Management of Retinoblastoma, opening the way for prospective clinical trials. At the same time both laboratory and clinical experimental studies are being pursued and may produce further improvements in currently available strategies.

Drug Therapy↗
PubMed1976

Changes in cell age cohort composition of tumors and normal tissues by radiation and chemotherapy.

The cell cycle is now known to be important in normal and tumor tissue and to be altered by a variety of states and therapies. The fact that there is considerable normal variation in cell ages or age cohorts present in both normal and tumor tissues has only recently been widely appreciated. These differ in normal, malignant, young and adult tissues. They are also greatly perturbed by radiation or chemotherapeutic injury. How to combine multi-modality therapy to optimize tumor control using available agents while sparing normal tissues is a problem for the future of cancer therapy and radiation oncology.

Animals↗
PubMed1975

Philadelphia's community based drug abuse program: broader medical and social concepts.

The rehabilitation of drug dependent people has undergone drastic changes since first attempts were made to curb the abuse of illegal drugs. The isolated law-enforcement model proved to be of no use in this area. So, too, the medical model, the psychological model and the public health model proved disappointingly low in their results. During the last ten years, a so-called "metabolic replacement model" has had its upsurge, creating a controversy still under discussion. The Drug Abuse Rehabilitation Programs of the West Philadelphia Community Mental Health Consortium, Inc. have been in the forefront with its treatment models. Established in 1968 as a purely methadone maintenance program, it has evolved into becoming a model, applying community mental health principles. This paper will explore this model further, describing the mechanics of its changes. From a municipal hospital-based methadone dispensing station, the program has developed into a multi-modality project. Three decentralized drug-free outpatient services are located in the midst of the community where the drug abuse problem is more accute. Outreach is emphasized and case-funding is applied. A possibly unique river-front motel was just acquired for the development of a community-based treatment modality. The 94 rooms were converted into a first-floor alcoholism program which also has a "highway safety program" and an intermediate care facility for alcoholics. The second floor of this facility contains outpatient services for the treatment of drug addicts, including a methadone maintenance program, counselling, family therapy and group therapy. The place where most of the emphasis has been placed is the Work Rehabilitation Center (a novel approach whereby patients will spend up to six hours in "partial hospitalization"). Clients will be tested for vocational aptitude and four workshops will be developed on the premises - carpentry, automotive, electricity and clerical. A huge cafeteria with a semi-automatic kitchen will allow further training in cooking and kitchen aids. The third floor of this renovated motel will include highly sophisticated clinical research area where computer utilization is already giving us very meaningful data. Clinical research is rapidly developing, and new drugs for the rehabilitation of drug addicts will be used. Further comments on the usefulness of methadone as a tool will be included in this paper and general comments as to the outcome of treatment further explored.

Alcoholism↗
PubMed1991

[Effect of plasmapheresis with substitution by dextran solutions on hemostatic parameters in patients with ischemic heart disease].

Plasmapheresis on a continuous blood flow fractionator to remove 1,200-2,000 ml plasma and substitute for the same values of dextran solutions was employed in the multi-modality treatment of 25 patients with Functional Classes II-IV exertional angina and myocardial infarction. Plasma and thrombocyte hemostatic parameters were examined just before and 24 and 48 hours after plasmapheresis. The analysis of the baseline data revealed that hemostatic changes were directly related to the severity of a disease in the patients and there was a correlation between the increased platelet aggregability and the elevated levels of fibrin-monomeric complexes. Plasmapheresis along with substitution of removed plasma for dextran solutions was accompanied by a profound hypocoagulative effect, as evidenced by plasma and thrombocyte hemostatic parameters. In addition, in patients with baseline high values of platelet aggregability plasmapheresis resulted in its decrease, whereas in those with baseline low values, it led to its increase.

Adult↗
PubMed1991

[Clinical experience of expandable metallic stent placement for malignant biliary obstruction].

Expandable metallic stents of modified Gianturco design were used in nine cases of malignant biliary obstruction. Stents were placed through a percutaneous transhepatic approach without any severe complications. Initial patency was obtained seven of nine patients. Of these seven patients, recurrent jaundice was observed in three within four weeks. One patient had recurrent stenosis after four months due to ingrowth of the tumor. Although the expandable metallic stent offers several theoretical advantages over currently available stents, a disadvantage is that tumors may grow through the spaces between the legs of the wire or grow over the stent. We found that multi-modal treatment combined with radiation therapy was indispensable to maintain the patency of the stent in malignant biliary obstruction.

Aged↗
PubMed1991

Relationship between apo[a] isoforms and Lp[a] density in subjects with different apo[a] phenotype: a study before and after a fatty meal.

Plasma Lp[a] levels and apo[a] isoform distribution among lipoproteins isolated by density gradient ultracentrifugation were studied in subjects with one-band or two-band apo[a] phenotypes as assessed by gradient gel electrophoresis before and after an oral fat load. There were no significant differences in the ultracentrifugal profile between fasting plasma and postprandial plasma that was freed of triglyceride-rich particles (TRP). One-band phenotypes exhibited a single symmetrical peak in the density gradient, whereas two-band phenotypes exhibited a multi-modal distribution. Low molecular weight apo[a] isoforms were preferentially associated with low density Lp[a] whereas high molecular weight apo[a] isoforms were found with high density Lp[a] particles. Feeding a high fat meal caused no significant increase in the total plasma level of Lp[a]. However, the isolated TRP contained the apoB-100-apo[a] complex in a quantity that represented only about 1% of its total amount in the fasting plasma. In all cases the apo[a] isoforms present in TRP were also present in the fasting plasma; however, in the two-band apo[a] phenotypes the ratio of the slow over the fast migrating band was in all cases about eightfold higher in TRP than in the fasting plasma. These observations indicate that postprandially a small percentage of apoB-100-apo[a] associates with TRP and suggest that this complex may derive from de novo synthesis rather than from a pre-existing Lp[a] plasma pool. The liver would be the source of the complex due to the presence in the latter of apoB-100.

Adult↗
PubMed1991

[Hemopurification in the management of ARDS complicating multiple organ failure].

In the field of critical care medicine, it has been claimed that ARDS often develops as a part of multiple organ failure (MOF). Since multi-modality therapy is necessary in the management of MOF, it is also mandatory even in the management of ARDS. Among the various therapeutic approaches for patients with MOF, hemopurification is one of the most effective therapeutic tools. Various hemopurification methods such as hemodialysis, peritoneal dialysis, hemoadsorption, hemofiltration and plasma exchange have been applied in the management of MOR. However, our recent experiences suggest that continuous hemofiltration (CHF) and/or continuous hemodiafiltration (CHDF) are safest, most easily performed and effective hemopurification in the management of ARDS/MOF. The efficacy of hemopurification in the management of ARDS is summarized as follows. 1) Removal of humoral mediators and causative substances of ARDS following insults such as sepsis and trauma. 2) Treatment of pulmonary interstitial permeability edema which has been claimed to be one of the most important pathological conditions in ARDS. 3) Removal of excess water given as carrier in IVH solution and accumulating in the body. 4) Immunomodulation which has also been considered to be necessary in the treatment or prevention of ARDS.

Hemofiltration↗
PubMed1978

Update of naltrexone treatment.

To summarize, then, our work with naltrexone in a multi-modality treatment program indicates that it appeals to about 5-10 percent of narcotic addicts--those who conciously want to obtain drug-free status. It does significantly attentuate the effect of narcotics to the extent that they lose their reinforcing properties, and it has minimal side effects. Although we treated a self-selected population, it is noteworthy that about 10 percent of those who remained on naltrexone for more than a week were still opiate free 6 months after cessation of treatment. For some it appeared to be a turning point in their lives. It was the first time in years that they could live in their neighborhood and not be either intoxicated or occupied with the pursuit of narcotics. Our behavioral studies have identified a number of conditioned psychophysiological responses associated with the self-injection ritual. So far, although we have succeeded in extinguishing some of these responses, this has not resulted in an improved clinical outcome. We are currently working on more comprehensive behavioral treatments, but the clinical significance of these conditioned responses is uncertain at present.

Adult↗
PubMedDate not supplied

C. parvum clinical protocols: prototypes and summary results in U. S. trials with Wellcome Coparvax.

Clinical investigations utilizing Wellcome C. parvum in cancer therapy number more than one hundred in multiple institutions. Multiple diseases in various stages are being attacked by multi-modality therapy, making the role of immunotherapy very difficult to assess. Fundamental laboratory observations have suggested ways of weaving non-specific with specific immunotherapy, and these with chemotherapy and radiation to yield maximum therapeutic benefit. Current protocols include examples of the critical interactions as well as instructive information on dosing, timing and adjunctive symptomatic therapies. Several protocols will be reviewed, especially where promising clinical results are expected. Important differences between systemic and regional administration are observed.

Clinical Trials as Topic↗
PubMed1979

Influence of varied stimuli on development of motor patterns in the premature infant.

The premature infant is at risk for both mortality and morbidity. His writhing contributes to weight loss, and his extrauterine environment does not contain the multi-modality patterned afferent stimuli that impinge upon the developing brain in utero. Sound is the most effective modality to achieve concurrent decrement in motility along with enhancement of cortical activity. It was anticipated that subjects exposed to 5 minutes of patterned sound 6 times a day would, by 36 weeks gestation, evidence: (a) less gross motor activity, (b) the normal predominance of upper over lower limb activity, and (c) beginning laterality. The sample consisted of 80 males and 73 females whose gestational age at birth was 26--33 weeks. By random assignment 52 subjects were exposed to the routine ambient noise of the isolette and nursery, 50 to a tape recording of their mother's voice, and 51 to an orchestral arrangement of Brahm's Lullaby. Limb activity was measured just prior to discharge by accelerometers worn unilaterally for a 24-hour period on the ankle and wrist prior to transfer to the alternate side for an additional 24 hours. No statistically significant differences were demonstrated among the limb patterns of the 3 groups. Large intragroup variation in gross activity precluded demonstration of between-group differences. The majority of subjects evidenced predominance of upper limb activity and laterality.

Acoustic Stimulation↗