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At least 253 records · Page 14Linked to original sources
PubMed1999

Characterization of a generic monoclonal antibody harvesting system for adsorption of DNA by depth filters and various membranes.

The physical parameters governing adsorption of DNA by various positively charged depth filters and membranes have been assessed. Buffers that reduced or neutralised the depth filter or membrane charge, and those that impeded hydrophobic interactions were shown to affect their operational capacity, demonstrating that DNA was adsorbed by a combination of electrostatic and hydrophobic interactions. The adsorption profile of DNA by a Sartobind Q anion exchange membrane showed immediate breakthrough, irrespective of challenge DNA concentration or flow rate, and in this case adsorption was by electrostatic interactions only. The production-scale removal of DNA from harvest broths containing therapeutic protein by partitioning of cells and debris from protein in sequential centrifugation and filtration steps, and the concentration of DNA in process supernatant were assessed. Centrifugation reduced the quantity of DNA in the process material from 79.8 micrograms ml-1 to 9.3 micrograms ml-1 whereas the concentration of DNA in the supernatant of pre- and post-filtration samples had only marginally reduced DNA content: from 6.3 to 6.0 micrograms ml-1 respectively. DNA was concentrated to 27.3 micrograms ml-1 along with monoclonal antibody in the ultrafiltration step. Similar effects were observed in the harvest step for a second antibody.

Adsorption↗
PubMed2006

[MALT-lymphoma].

Gastric lymphoma is most frequently an extranodal marginal zone-B-cell-lymphoma of mucosa-associated lymphoid tissue (MALT). The diagnosis is established by biopsy of the tumor. Computed-tomography, endosonography and recently capsule-endoscopy are used for staging. It is a relative new finding that MALT-lymphomas of the stomach are induced by Helicobacter pylori. A side-effect-poor breakthrough has been achieved by eradication of this bacterium with antibiotics. Refractory cases are amenable to radiotherapy, chemotherapy or surgical resection. The rarer aggressive lymphomas of the stomach are treated primarily by chemotherapy and radiotherapy. For both entities a further improvement may be achieved in ongoing prospective clinical trials by addition of the monoclonal antibody rituximab, which targets CD20 on lymphoma cells.

Biomarkers, Tumor↗
PubMed1987

Molecular epidemiology of live, attenuated varicella virus vaccine in children with leukemia and in normal adults.

Restriction endonuclease analysis of varicella-zoster virus (VZV) DNA has been used in unraveling the complex epidemiology of VZV infections in individuals immunized with a live, attenuated varicella virus vaccine. Early rashes appearing within the first six weeks after vaccination are invariably due to vaccine virus. True breakthrough infections with wild-type VZV also occur in vaccinees. Five cases of zoster have been seen in leukemic children vaccinated while in remission. One case appeared 22 months after vaccination in the same general area as the inoculation. The virus isolated was vaccine derived. A second case of zoster appeared in a dermatome unrelated to the sites of vaccination approximately 19 months after apparently natural varicella. This virus was wild type. Vaccine virus can therefore establish latency and can later reactivate as herpes zoster.

Adult↗
PubMed2003

Beyond echoplaylia: promoting language in children with autism.

The article was written to support the use of play as a medium to extend and enrich the communicative exchanges and, more specifically, the symbolic language of children on the autistic spectrum. The first argument in support of such use of play lies within the features of autistic communication, and particularly the extreme challenges encountered in imaginative play and narrative thought. The second argument on behalf of play lies within the selection of specific intervention strategies, which are discussed subsequently. Finally, the article presents a case illustration of how adult facilitated dramatic peer play led to a breakthrough in a range of symbolic behaviours in a 9-year-old girl with autism, who up to that point had not progressed beyond a semi-communicative use of echolalia, best described as 'situation association'.

Autistic Disorder↗
PubMed2003

Monitoring the emergence of hepatitis B virus polymerase gene variants during lamivudine therapy in human immunodeficiency virus coinfected patients: performance of CLIP sequencing and line probe assay.

Sera from 12 patients infected with human immunodeficiency virus and hepatitis B virus (HBV), on lamivudine as part of an antiretroviral therapy, were retrospectively analysed for the presence of HBV polymerase mutations by the line probe assay, INNO-LiPA HBV DR, and by the direct sequencing assay, TRUGENE HBV genotyping kit. Results at codons 180, 204 and 207 were compared for 44 samples. Full concordance was observed for 81.4% of the 129 analysed codons. Discordance involved only mixed populations: LiPA detected additional species in 19 codons and TRUGENE in five. Viral breakthrough occurred in seven patients, 12-33 months after lamivudine initiation. In five cases with close sampling available, both assays detected mutations before the rise in viral load, although earlier by LiPA for three patients. The time interval between the first mutant detection and viral escape ranged from 2 to 22 months. Mutations were detected in four of the five remaining patients: 1) at therapy initiation in a primary non-responder; 2) after 37 months, but replication became undetectable after tenofovir introduction; 3) transiently at 6 months by LiPA but treatment was ceased thereafter; 4) after 23 months but replication levels remained low during a 5-year follow-up. Interestingly, TRUGENE sequencing identified on late samples from three patients a variant carrying rtV173L plus rtL180M plus M204V mutations, having the in vitro characteristics of 'vaccine escape' mutants. Both assays appear to be valuable tools for the early detection of mutated HBV strains. The detection of genotypic therapeutic decision-making, although clinical or other virological factors may determine the rapidity of the viral breakthrough.

Acquired Immunodeficiency Syndrome↗
PubMed1982

The global eradication of smallpox.

On May 8, 1980, the 33rd World Health Assembly declared the world free of smallpox. This followed approximately 2 1/2 years after the last documented naturally occurring case of smallpox was diagnosed in a hospital worker in Merca, Somalia. A major breakthrough for the eventual control of this disease was the discovery of an effective vaccine by Edward Jenner in 1796. In 1966 the World Health Assembly voted a special budget to eliminate smallpox from the world. At that time, smallpox was endemic in more than 30 countries. Mass vaccination programs were successful in many Western countries; however, a different approach was taken in developing countries. This approach was known as surveillance and containment. Surveillance was aided by extensive house-to-house searches and rewards offered for persons reporting smallpox cases. Containment measures included ring vaccination and isolation of cases and contacts. Hospitals played a major role in transmission in a number of smallpox outbreaks. The World Health Organization is currently supporting several control programs and has not singled out another disease for eradication. The lessons learned from the smallpox campaign can be readily applied to other public health programs.

Cross Infection↗
PubMed1998

"Breakthrough" during interferon therapy for chronic hepatitis C. Overview on the diagnosis, possible aetiology and recommendations for management.

A relapse of serum aminotransferase levels after complete normalisation during alpha interferon therapy for chronic hepatitis C is diagnosed as Breakthrough. Its prevalence ranges between 14% and 21% of the responders, with no significant differences between the alpha interferons. Hepatitis C virus genotype and interferon dose do not seem to represent predisposing factors. The development of neutralising antibodies to interferon is associated with Breakthrough in about half of the patients; other aetiologic factors such as down-regulation of interferon receptors or development of virus resistance to interferon may be implicated in the remaining cases. The therapeutic switch from recombinant to lymphoblastoid alpha interferon has been demonstrated to be a successful strategy to overcome Breakthrough and to restore a complete response.

Antibody Formation↗
PubMed1996

Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial.

The efficacy of low-dose fluconazole (200 mg orally administered thrice weekly) as primary prophylaxis for cryptococcal infection was prospectively assessed in a multicenter trial involving 218 patients who were infected with human immunodeficiency virus (HIV) and who had CD4 cell counts of < or = 100/mm3. The median CD4 cell count at baseline was 39/mm3, 58% of the patients had an AIDS-defining illness or infection prior to enrollment. Cryptococcal meningitis occurred in 0.4% (1) of the 218 patients. The breakthrough isolate was susceptible to fluconazole, and the fluconazole kinetic study demonstrated adequate drug absorption and serum fluconazole levels; noncompliance could not be excluded in this case. Mucocutaneous and/or esophageal candidiasis developed in 18% (40) of the patients. Noncompliance with fluconazole therapy was the only variable independently associated with breakthrough candidiasis in the study patients (P = .00002). Thus, fluconazole (200 mg thrice weekly) given to HIV-infected patients with CD4 cell counts of < or = 100/mm3 was efficacious as primary prophylaxis for cryptococcosis, with notably lower costs and increased convenience for patients in comparison with daily administration of the drug.

AIDS-Related Opportunistic Infections↗
PubMed2005

Effects of ionic strength on lysozyme uptake rates in cation exchangers. I: Uptake in SP Sepharose FF.

Fluorescence scanning confocal microscopy was used in parallel with batch uptake and breakthrough measurements of transport rates to study the effect of ionic strength on the uptake of lysozyme into SP Sepharose FF. In all cases the adsorption isotherms were near-rectangular. As described previously, the intraparticle profiles changed from slow-moving self-sharpening fronts at low salt concentration, to fast-moving diffuse profiles at high salt concentration, and batch uptake rates correspondingly increased with increasing salt concentration. Shrinking core and homogeneous diffusion frameworks were used successfully to obtain effective diffusivities for the low salt and high salt conditions, respectively. The prediction of column breakthrough was generally good using these frameworks, except for low-salt uptake results. In those cases, the compressibility of the stationary phase coupled with the shrinking core behavior appears to reduce the mass transfer rates at particle-particle contacts, leading to shallower breakthrough curves. In contrast, the fast uptake rates at high ionic strength appear to reduce the importance of mass transfer limitations at the particle contacts, but the confocal results do show a flow rate dependence on the uptake profiles, suggesting that external mass transfer becomes more limiting at high ionic strength. These results show that the complexity of behavior observable at the microscopic scale is directly manifested at the column scale and provides a phenomenological basis to interpret and predict column breakthrough. In addition, the results provide heuristics for the optimization of chromatographic conditions.

Cation Exchange Resins↗
PubMed1998

Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart.

BACKGROUND: The activation patterns that underlie the irregular electrical activity during atrial fibrillation (AF) have traditionally been described as disorganized or random. Recent studies, based predominantly on statistical methods, have provided evidence that AF is spatially organized. The objective of this study was to demonstrate the presence of spatial and temporal periodicity during AF. METHODS AND RESULTS: We used a combination of high-resolution video imaging, ECG recordings, and spectral analysis to identify sequential wave fronts with temporal periodicity and similar spatial patterns of propagation during 20 episodes of AF in 6 Langendorff-perfused sheep hearts. Spectral analysis of AF demonstrated multiple narrow-band peaks with a single dominant peak in all cases (mean, 9.4+/-2.6 Hz; cycle length, 112+/-26 ms). Evidence of spatiotemporal periodicity was found in 12 of 20 optical recordings of the right atrium (RA) and in all (n=19) recordings of the left atrium (LA). The cycle length of spatiotemporal periodic waves correlated with the dominant frequency of their respective optical pseudo-ECGs (LA: R2=0.99, slope=0.94 [95% CI, 0.88 to 0.99]; RA: R2=0.97, slope=0.92 [95% CI, 0.80 to 1.03]). The dominant frequency of the LA pseudo-ECG alone correlated with the global bipolar atrial EG (R2=0.76, slope=0.75 [95% CI, 0.52 to 0.99]). In specific examples, sources of periodic activity were seen as rotors in the epicardial sheet or as periodic breakthroughs that most likely represented transmural pectinate muscle reentry. However, in the majority of cases, periodic waves were seen to enter the mapping area from the edge of the field of view. CONCLUSIONS: Reentry in anatomically or functionally determined circuits forms the basis of spatiotemporal periodic activity during AF. The cycle length of sources in the LA determines the dominant peak in the frequency spectra in this experimental model of AF.

Animals↗
PubMed2000

Strategy for the treatment of arteriovenous malformations.

The treatment of arteriovenous malformations (AVMs) is still a challenging problem in the neurosurgical field. The deep-seated AVMs are a definite indication for radiosurgery for the small AVMs and with pre-embolisation for the large AVMs. The superficial AVMs are a good indication for surgery. In the case of small AVMs, surgery alone is a viable option; however, in the case of large AVMs, pre-operative embolisation is essential for prevention of NPPB (normal perfusion pressure breakthrough). Embolisation alone cannot be used, except for a small AVM in the non-eloquent cortex. Preoperative embolisation makes surgery easy; however, it causes the surrounding cortex to infarct. Hyperperfusion may occur after the direct removal of high-flow large AVMs, therefore postoperative management will be difficult in these cases. In eloquent cortex minimally invasive surgery is more reliable with respect to the morbidity produced. Therefore in cases of small AVMs in the functional cortex, direct surgery is the only choice. In cases of high-flow large AVMs, surgery and postoperative management are risky because of NPPB. Therefore pre-operative embolisation followed by surgery is a better choice. In high-flow AVMs, local blood circulation is not decreased by temporary clipping of the feeding arteries. So we recommend temporary clipping of all feeding arteries, even away from the nidus where it is easier to control bleeding.

Adolescent↗
PubMed2004

Bridging the gap: the Virtual Chemotherapy Unit.

Due to the complexity of pediatric chemotherapy administration, systems promoting safety must be utilized. Computerized order entry has been proven to reduce errors in the ordering of chemotherapeutic agents. A task force (the Breakthrough Committee) at The Children's Hospital of Philadelphia (CHOP) evaluated systems and identified the need to streamline the chemotherapy admission process from the outpatient clinic to the inpatient unit. In the outpatient setting chemotherapy orders were handwritten, whereas inpatient orders were computerized. Patients due for chemotherapy admissions were unable to start chemotherapy until they were physically admitted to an inpatient bed. In many cases, patients would not start receiving chemotherapy until late in the evening or even overnight. The Breakthrough Committee created the Virtual Chemotherapy Unit (Virtual Unit), which standardizes the ordering and documentation for all chemotherapy admissions. As per its name, the Virtual Unit is not an actual hospital unit but merely a location in the computer system where the patient is admitted prior to having a bed on the inpatient unit. Patients are now able to start chemotherapy infusions in the outpatient setting early in the day, rather than waiting until arrival to the inpatient unit. The nurses in the outpatient clinic are able to document chemotherapy administration online, giving the inpatient staff the ability to view the medications that were given. The Virtual Unit bridges the gap in chemotherapy ordering and documentation by utilizing 1 online episode per patient admission. Oncology nurses at CHOP played a fundamental role in the creation of the Virtual Unit. Nurses identified situations with potential for error in the ordering and administration of chemotherapy. These scenarios were analyzed and used in creating a safer system.

Antineoplastic Agents↗
PubMedDate not supplied

A comparison of papaveretum-promethazine with morphine-ondansetron for patient-controlled analgesia.

BACKGROUND: Patient-controlled analgesia (PCA) with intravenous morphine is commonplace. Antiemetics are often added to reduce side-effects. In our institution an unusual combination of papaveretum-promethazine is in use. AIMS: We set out to compare this combination with a more commonly used one (morphine-ondansetron) by auditing the records of our pain-control team assessing analgesia and control of side-effects. METHODS: The records of two groups of 100 consecutive patients were studied. Pain scores were recorded 24 hours post-operatively on a scale of zero to ten. Also recorded were sedation scores, pruritus, emesis, and usage of breakthrough analgesia. The groups contained the work of a variety of anaesthetists and surgeons, though the majority were orthopaedic cases. All results were recorded by one pain-control nurse, using the same question, over a nine-month period. RESULTS: Sedation scores were identical, while side-effects were few and similar in both groups. The use of breakthrough analgesia was also similar. However, the median pain-score of zero in the papaveretum group was significantly lower than that of two in the morphine group, (p < 0.001, Mann-Whitney U). CONCLUSION: Papaveretum-promethazine appeared to be effective for PCA. This combination is also much less expensive than morphine-ondansetron. A previously described synergistic interaction between promethazine and opiates may be a factor in its success. Further evaluation of these drugs in PCA is warranted.

Analgesia, Patient-Controlled↗
PubMed1983

[Adsorption characteristics of organic solvent vapors on the fixed bed of activated carbon].

Many different sizes of activated carbon fixed beds are widely used for adsorption of organic solvent vapors and hazardous gases, such as air cleaners, gas masks and gas sampling tubes, but only limited information is available for the comprehensive relationship between adsorption characteristics of the fixed bed and practical factors; the amount of activated carbon, the gas flow rate, the vapor concentration and bed diameter. The authors investigated experimentally the effect of these factors on the adsorption zone length, the effective adsorption capacity and the breakthrough time. The following results were obtained; The adsorption zone length was approximately independent of the amounts of activated carbon packed in a column of a definite diameter. Therefore, the effective adsorption capacity increased with the increasing activated carbon amount, and the breakthrough time was nearly proportional to it. The adsorption zone length increased and the effective adsorption capacity reduced with the increasing gas flow rate. The adsorption zone length was little affected by the vapor concentration, but the effective adsorption capacity increased with the increasing concentration. In case of the same amount of activated carbon, the adsorption zone length, the effective adsorption capacity and the breakthrough time reduced with the increasing bed diameter.

Adsorption↗
PubMed1996

Doctors and the health industry: a case study of transcutaneous oxygen monitoring in neonatal intensive care.

This case study presents an industry perspective on medical innovation. Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen monitoring was rapidly adopted for routine use in neonatal intensive care. But plagued by technical problems, it was within a decade being replaced by pulse oximetry, a still more recent technology. Its use in efforts to prevent retinopathy of prematurity, an eye disease of preterm newborns often leading to blindness, proved disappointing. The project included interviews with executives and design engineers of companies marketing the device, with investigators who had pioneered the technology, and with senior practicing neonatologists. The findings, reflecting complexity and uncertainty, are relevant to issues concerning health care in the United States and other developed nations. They centre on the key role and ultimate responsibility of the medical profession, with a need for greater attention to the scientific training of health care workers, as perceived by members of the medical device industry. The views of senior investigators are integrated into the picture, with discussion of major challenges faced by the medical community.

Blood Gas Monitoring, Transcutaneous↗
PubMed1997

Site accessibility and the pH dependence of the saturation capacity of a highly cross-linked matrix. Immobilized metal affinity chromatography of bovine serum albumin on chelating Superose.

Immobilized metal ion affinity chromatography has shown promise for isolating desired proteins from a mixture based on their affinity for chelated metal ions. Using frontal analysis, the pH dependence of the saturation capacity of chelating Superose matrix for bovine serum albumin (BSA) is examined over a broad pH range. A significant increase in the capacity was observed near the elution pH of BSA (pH 4.5) from a Cu-imminodiacetic acid column. The results of several experiments indicated that this apparently abnormal variation may reflect the low degree of accessibility of a large portion of copper sites inside chelating Superose. In a broader sense, these results suggest that during frontal analysis, the assumption of column saturation based on a plateau in the exit concentration that is almost at the same level as the input concentration could be misleading for highly cross-linked matrices and relatively large sized proteins. That is, the relatively less accessible copper sites may become difficult to be reached due to high levels of protein adsorption in the more accessible regions and thus give the appearance of a plateau in the breakthrough curve prior to complete column saturation. This is likely to be the case at high pH where BSA demonstrates very high affinity for immobilized copper or at high input concentrations where the equilibrium coverage is expected to be high. The results demonstrate that the estimated saturation capacity could be significantly smaller than the actual capacity.

Binding Sites↗
PubMed2004

Answering a century old riddle: brachydactyly type A1.

In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.

Animals↗
PubMedDate not supplied

The break-even point: when medical advances are less important than improving the fidelity with which they are delivered.

Society invests billions of dollars in the development of new drugs and technologies but comparatively little in the fidelity of health care, that is, improving systems to ensure the delivery of care to all patients in need. Using mathematical arguments and a nomogram, we demonstrate that technological advances must yield dramatic, often unrealistic increases in efficacy to do more good than could be accomplished by improving fidelity. In 2 examples (the development of anti-platelet agents and statins), we show that enhanced efficacy failed to achieve the health gains that would have occurred by delivering older agents to all eligible patients. Society's huge investment in technological innovations that only modestly improve efficacy, by consuming resources needed for improved delivery of care, may cost more lives than it saves. The misalignment of priorities is driven partly by the commercial interests of industry and by the public's appetite for technological breakthroughs, but health outcomes ultimately suffer. Health, economic, and moral arguments make the case for spending less on technological advances and more on improving systems for delivering care.

Biotechnology↗