bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal craniocervical necrotizing fasciitis in an immunocompetent patient: A case report and literature review
Authors: Henrich Douglas E. , Smith Timothy L. , Shockley William W.
Published: February 2007

Background. Craniocervical necrotizing fasciitis (CCNF) is a rapidly progressive, severe bacterial infection of the superficial fascial planes of the head and neck. Group A beta–hemolytic Streptococcus, staphylococcus aureus, and obligate anaerobic bacteria are common pathogens. The disease usually results from a dental source or facial trauma. Extensive fascial necrosis and severe systemic toxicity are common manifestations of CCNF. Recently the lay press has referred to necrotizing fasciitis in several articles about “flesh eating” bacteria, which have resulted in several deaths.

Methods. We report the first case of a fatality in an otherwise immunocompetent patient. The patient was a 66‐year‐old black man with no identifiable source of infection and no history or evidence of immunocompromising disorders.

Results. Despite aggressive surgical debridement and broad‐spectrum antibiotic coverage, he died 30 hours after admission from multisystem organ failure secondary to overwhelming sepsis.

Conclusion. Treatment consists of early recognition of CCNF combined with aggressive surgical debridement and drainage of the involved necrotic fascia and tissue along with broad‐spectrum intravenous antibiotic coverage. Although 11 other fatal cases of CCNF have been previously reported, all had an underlying medical problem which created an immunocompromised state, usually diabetes mellitus or chronic alcoholism. We present a case report and literature review along with a discussion of the related anatomy. © 1995 Jons Wiley & Sons, Inc.
Outcome analysis of Zenker's diverticulectomy and cricopharyngeal myotomy
Authors: Witterick Ian J. , Gullane Patrick J. , Yeung Eugene
Published: February 2007

Background. The optimal management of Zenker's diverticula is controversial in part because of the method of categorizing treatment success or failure. Subjective and objective radiologic tests have been used to evaluate the various treatment modalities. There seems to be poor correlation between subjective and objective findings, and we tested this hypothesis in a group of patients undergoing one form of therapy (diverticulectomy and cricopharyngeal myotomy [CPM]).

Methods. Eighteen consecutive patients underwent Zenker's diverticulectomy and CPM. Postoperative symptoms and abnormalities detected by barium esophagrams were evaluated after a mean follow‐up of 30.3 months (range, 7–74 months).

Results. Three of 18 patients (17%) complained of dysphagia (2 occasional and not bothersome; 1 bothersome and affecting dietary intake). Postoperative static contrast esophagrams were interpreted without knowledge of the subjective symptoms. Small diverticula were identified in 8 patients (44%). There was poor correlation between symptoms and objective radiographic abnormalities with agreement of 56% and a kappa statistic of 0.23.

Conclusions. Objective radiographic abnormalities are far more common than subjective complaints following diverticulectomy and CPM. Postoperative static contrast radiography is not routinely required and may be misleading because of the poor correlation between symptoms and radiographic findings. The value of dynamic videofluoroscopy needs to be evaluated. © 1995 Jons Wiley & Sons, Inc.
Paget's sarcoma of the mandible
Authors: Gleich Lyon L. , Eberle Robert C. , Shaha Ashok R. , Solomon Marshall
Published: February 2007

Background. Sarcomatous change occurs in less than 1% of patients with Paget's disease. It has been reported in only 9 patients in the mandible, and has been uniformly fatal. Comparison of Paget's sarcoma of the mandible to osteosarcoma of the mandible and to osteosarcoma in other locations was made to attempt to explain and improve the outcome of patients with these tumors.

Methods. Two 78‐year‐old women with Paget's sarcoma of the mandible treated with radical resection are reported. The literature is reviewed to compare the clinical presentation and prognosis of patients with mandibular Paget's sarcoma to patients with osteosarcoma in non‐Pagetoid mandibles and with osteosarcoma outside of the head and neck.

Results. Both patients died within 2 years of lung metastases. The patients with mandibular Paget's sarcoma were markedly older, with an average age of 65.6 years, compared to 32.5 years for mandibular osteosarcoma. Paget's sarcoma of the mandible was uniformly rapidly fatal; in non‐Pagetoid mandibles the 5‐year survival is 40%. There have been reports of only 7 patients who have survived with Paget's sarcoma in other locations. In osteosarcoma of the extremities 5‐year disease‐free survival exceeds 75% with multimodality therapy.

Conclusions. Paget's sarcoma of the mandible is a rare tumor which affects elderly patients. It progresses rapidly and has a much poorer prognosis than osteosarcoma occurring in a non‐Pagetoid mandible. The prognosis may be improved with early detection and treatment with multimodality therapy. © 1995 Jons Wiley & Sons, Inc.
Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth
Authors: Woolgar Julia A. , Scott John
Published: February 2007

Background. Cervical lymph node metastasis has a major influence on survival in oral cancer. However, the factors influencing its occurrence are uncertain. Our aim was to improve the prognostic efficiency of the histologic assessment of the primary tumor in predicting metastasis in an individual patient.

Methods. The relationship between selected clinical and histologic features of the primary tumor of tongue/floor of the mouth and the actual metastatic status was investigated in 45 patients. Invasive cell grading was supplemented by histologic measurements of tumor size and assessments of vascular and perineural invasion.

Results. Ten histologic features showed significant differences in relation to metastasis. A logistic regression model with two predictor variables (total histologic malignancy score and vascular invasion) classified correctly 39 (87%) of the 45 cases.

Conclusions. Histologic assessment of tumor size and malignancy grade are useful in predicting metastasis. Vascular and perineural invasion are important predictors and should be included in multifactorial malignancy grading schemes. Application of the prognostic index to the biopsy specimen would aid in treatment planning. © 1995 Jons Wiley & Sons, Inc.
Management of penetrating laryngotracheal injuries
Authors: Grewal Harsh , Rao Prakashchandra M. , Mukerji Sanjay , Ivatury Rao R.
Published: February 2007

Background. Penetrating Iaryngotracheal injuries are uncommon; however, these injuries are associated with significant morbidity and mortality. In an attempt to define the management of penetrating laryngotracheal injuries, we reviewed our experience with these injuries.

Methods. We retrospectively analyzed the records of all patients admitted to a Level I trauma center who required operative management for penetrating laryngotracheal injuries. During the period of this study all patients with penetrating neck injuries were managed according to a protocol of selective exploration.

Results. Of fifty‐seven patients with penetrating laryngotracheal injury 32 patients sustained gunshot wounds and 25 had stab wounds. The injuries were to the larynx in 24 (42%) and trachea in 33 (58%). Forty‐six (81%) had isolated airway injuries and 11 (19%) had combined airway and digestive‐tract injuries. Emergent airway management in 32 (56%) patients included: tracheostomy (15), endotracheal intubation (14), and cricothyroidotomy (3). Respiratory distress and subcutaneous crepitus were the commonest clinical findings. Diagnostic evaluation included: Iaryngoscopy/tracheoscopy (17), esophagoscopy (12), contrast esophagography (9), angiography (8), and bronchoscopy (3). Repair of laryngotracheal and esophageal injury was performed in the majority of patients. Selected patients with milder Iaryngotracheal injury did not have tracheostomy performed, with no increase in morbidity or mortality. There were 2 (3.5%) early deaths from associated major vascular injury.

Conclusion. Mortality can be minimized by aggressive airway control. Endotracheal intubation can be accomplished safely in selected patients with penetrating laryngotracheal injuries. Digestive‐tract injuries can often clinically occult and contribute significantly to morbidity and mortality; therefore, early evaluation of the esophagus is vital. Simple repair of Iaryngotracheal and digestive‐tract injuries can be performed safely with good results. In patients with minor injuries, tracheostomy does not appear to be mandatory. © 1995 Jons Wiley & Sons, Inc.
Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two‐fold hippocampus enlargement
Authors: Almgren Malin , Persson Ann‐Sophie , Fenghua Chen , Witgen Brent M. , Schalling Martin , Nyengaard Jens R. , Lavebratt Catharina
Published: February 2007

The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker‐like voltage‐gated potassium channel Kv1.1 brain, which results in a malfunctioning protein. A key question in elucidating the mechanism behind the unique brain overgrowth is whether it is caused by an increase in cell number. By applying stereological techniques, we found that the number of both neurons and astrocytes, as well as structure volume, was increased approximately two‐fold within dentate gyrus (DG), CA2/3, and hilus of 12‐week‐old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth and the second week of life. To investigate the hyperplasia, cell proliferation was studied within the subgranular zone of the DG using BrdU and Ki67. There was a three‐fold increase in proliferation in mceph/mceph mice compared to wild type mice at an age before onset of epileptic symptoms (3 weeks), and these new mceph/mceph neurons showed increased migration and had a 6‐week survival rate as the new neurons in wild type DG. Also when seizures were frequent in mceph/mceph (9 weeks old), the proliferation rate was three‐fold higher than in wild type. The number of TUNEL‐positive cells in hippocampus was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks of age. This phenotype is a result, at least in DG, from increased proliferation, neurogenesis, and enhanced general hippocampal cell survival. © 2007 Wiley‐Liss, Inc.
Comparison of the performance of flow‐routing algorithms used in GIS‐based hydrologic analysis
Authors: Wilson John P. , Lam Christine S. , Deng Yongxin
Published: February 2007

Flow direction and specific catchment area were calculated for different flow‐routing algorithms using TAPES‐G and TauDEM. A fuzzy classification was used along with eight topo–climatic attributes to delineate six landscape classes from a 10‐m USGS DEM. A series of maps and tabular outputs were produced to compare flow‐routing predictions in different parts of the study area in the Santa Monica Mountains of southern California. The matched pair t‐test was used to compare the performance of pairs of specific catchment area grids across six user‐defined fuzzy landscape classes. The results show that (1) the ‘source’ cells predicted with the D∞, DEMON, and FD8 algorithms were confined to hilltops; (2) two single flow‐routing algorithms (Rho8, D8) produced poor results; and (3) the choice of flow‐routing algorithm has potentially important consequences for the calculation of upslope contributing areas, sediment transport capacity, topographic wetness, and several other topographic indices. Copyright © 2007 John Wiley & Sons, Ltd.
Association of immunoescape mechanisms with Epstein‐Barr virus infection in nasopharyngeal carcinoma
Authors: Ogino Takeshi , Moriai Shigetaka , Ishida Yoshiya , Ishii Hideyuki , Katayama Akihiro , Miyokawa Naoyuki , Harabuchi Yasuaki , Ferrone Soldano
Published: February 2007

We have investigated the association of immunoescape mechanisms in nasopharyngeal carcinoma (NPC) lesions with Epstein‐Barr virus (EBV) infection and clinical course of the disease. Tumor biopsy specimens obtained from 36 Japanese NPC patients were examined for antigen processing machinery component and HLA class I antigen expression, CD8+T cell infiltration, and Fas, Fas ligand (FasL) and IL‐10 expression using immunohistochemical staining. The results were correlated with the histopathological characteristics of the lesions, the clinical course of the disease and EBV infection. LMP2, TAP1, tapasin and HLA class I antigens were downregulated in more than 65% of the lesions tested, while FasL, Fas and IL‐10 were expressed in at least 60% of the lesions. Statistical analysis showed that (i) HLA class I antigen expression was significantly correlated with LMP2 and tapasin expression (r= 0.39 and 0.45, respectively); (ii) CD8+T cell infiltration into tumor lesions was significantly correlated with HLA class I antigen, LMP2 and Fas expression (r= 0.34, 0.49 and 0.44, respectively); (iii) LMP2 and FasL expression was significantly correlated with IL‐10 expression (r= 0.49 and 0.52, respectively); (iv) IL‐10 expression was significantly associated with EBERs and EBV oncoprotein LMP1 expression (p= 0.00078 and 0.015, respectively) and (v) FasL overexpression was significantly associated with reduced patients' survival (p= 0.033). Multivariate analysis identified FasL overexpression as an independent unfavorable prognostic marker. These results suggest that NPC cells may utilize multiple immunoescape mechanisms, including dysfunction of HLA class I antigens and Fas/FasL apoptosis pathways. Furthermore, FasL expression appears to be associated with IL‐10 upregulation in EBV positive NPC cells. © 2007 Wiley‐Liss, Inc.
Detection of mutated BRAFV600E variant in circulating DNA of stage III–IV melanoma patients
Authors: Daniotti Maria , Vallacchi Viviana , Rivoltini Licia , Patuzzo Roberto , Santinami Mario , Arienti Flavio , Cutolo Gianluca , Pierotti Marco A. , Parmiani Giorgio , Rodolfo Monica
Published: February 2007

BRAFV600E is the most represented somatic point mutation in cutaneous melanoma, thus providing a unique molecular marker for this disease. The development of efficient methods for its detection in free circulating DNA of patients may lead to the improvement of diagnostic and prognostic tools. With this aim, we evaluated whether BRAFV600E represents a detectable marker in the plasma/serum from melanoma patients in a pilot study. Circulating cell‐free DNA was extracted from the serum or plasma of 15 healthy donors and 41 melanoma patients at different clinical stages and obtained either presurgery or after surgery during follow‐up. Quantitative analysis showed higher levels of circulating free DNA in patients compared to controls, with the highest levels detected in samples obtained presurgery and at stage IV. Four different PCR methods were compared for their capacity to amplify a few copies of BRAFV600E in wild‐type DNA. BRAFV600E was detectable in circulating DNA of 12 patients and in none of the controls; only 1 PCR method reproducibly amplified BRAFV600E. Positive samples were obtained from 8/13 patients at stage IV and from 4/24 patients at stage III, but not in 4 patients at stage I–II; half of the positives were obtained presurgery and half at follow‐up. Correspondence between circulating DNA and related tumors were examined for 20 patients, and a correlation was found for stage IV patients. In conclusion, this method can be utilized for monitoring the disease in stage IV melanoma patients but it appears unsatisfactory for the early detection of melanoma. © 2007 Wiley‐Liss, Inc.
Depletion of CD4+CD25+ human regulatory T cells in vivo: Kinetics of Treg depletion and alterations in immune functions in vivo and in vitro
Authors: Mahnke Karsten , Schönfeld Kurt , Fondel Sabine , Ring Sabine , Karakhanova Svetlana , Wiedemeyer Katharina , Bedke Tanja , Johnson Theron Scott , Storn Volker , Schallenberg Sonja , Enk Alexander Herrmann
Published: February 2007

The aim of this study was to investigate whether depletion of CD4+CD25+ regulatory T cells (Treg) from melanoma patients affects immune responses against tumors. By application of recombinant IL‐2‐diphteria toxin fusion protein, also known as ONTAK, we were able to significantly reduce the frequency of Treg in peripheral blood, whereas other cell populations remained unaffected. The reduction of Treg started immediately after the first bolus of ONTAK with a dose of 5 μg ONTAK per kg bodyweight and lasted for 13 days with subsequent recovery thereafter. Successive ONTAK treatments further reduced the number of circulating Treg. Using the contact sensitizer DCP we show that all patients developed vast eczema after Treg depletion, whereas no or only mild eczematous reactions were detectable before ONTAK treatment. Corresponding induction of DCP‐specific CD4+ and CD8+ T cells were detectable. Moreover, after immunization of ONTAK treated patients with tumor antigen peptides, MelanA/MART‐1 and gp100, significant induction of peptide specific CD8+ T cells could be observed in 90% of the patients treated. These cells displayed effector functions, as they were able to lyse peptide‐pulsed target cells and secreted IFNγ upon restimulation. In aggregate, our data indicate that ONTAK depletes Treg in vivo significantly, resulting in enhanced immune functions and substantial development of antigen‐specific CD8+ T cells in vaccinated individuals. © 2007 Wiley‐Liss, Inc.
Systemic efficacy of oncolytic adenoviruses in imagable orthotopic models of hormone refractory metastatic breast cancer
Authors: Ranki Tuuli , Särkioja Merja , Hakkarainen Tanja , Smitten Karl von , Kanerva Anna , Hemminki Akseli
Published: February 2007

Conditionally replicating oncolytic adenoviruses represent a promising developmental strategy for the treatment of cancer refractory to current treatments, such as hormone refractory metastatic breast cancer. In clinical cancer trials, adenoviral agents have been well tolerated, but gene transfer has been insufficient for clinical benefit. One of the main reasons may be the deficiency of the primary adenovirus receptor, and therefore viral capsid modifications have been employed. Another obstacle to systemic delivery is rapid clearance of virus by hepatic Kupffer cells and subsequent inadequate bioavailability. In this study, we compared several capsid‐modified oncolytic adenoviruses for the treatment of breast cancer with and without Kupffer cell inactivation. Replication deficient capsid‐modified viruses were analyzed for their gene transfer efficacy in vitro in breast cancer cell lines and clinical samples and in vivo in orthotopic models of breast cancer. The effect of Kupffer cell depleting agents on gene transfer efficacy in vivo was evaluated. An aggressive lung metastatic model was developed to study the effect of capsid‐modified oncolytic adenoviruses on survival. Capsid‐modified viruses displayed increased gene transfer and cancer cell killing in vitro and resulted in increased survival in an orthotopic model of lung metastatic breast cancer in mice. Biodistribution of viruses was favorable, tumor burden and treatment response could be monitored repeatedly. Kuppfer cell inactivation led to enhanced systemic gene delivery, but did not increase the survival of mice. These results facilitate clinical translation of oncolytic adenoviruses for the treatment of hormone refractory metastatic breast cancer. © 2007 Wiley‐Liss, Inc.
Human papillomavirus 16 and head and neck squamous cell carcinoma
Authors: Furniss C. Sloane , McClean Michael D. , Smith Judith F. , Bryan Janine , Nelson Heather H. , Peters Edwards S. , Posner Marshall R. , Clark John R. , Eisen Ellen A. , Kelsey Karl T.
Published: February 2007

Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case–control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA. HPV16 seropositivity was associated with 1.5‐ and 6‐fold risks for tumors of the oral cavity and pharynx, respectively. There was a dose response trend for HPV16 titer and increasing risk of HNSCC (p < 0.0001) and HPV16 tumor DNA (p < 0.0001). In cases, HPV16 DNA and seropositivity were significantly associated with sexual activity; odds ratios (ORs) of 12.8 and 3.7 were observed for more than 10 oral sexual partners and ORs of 4.5 and 3.2 were associated with a high number of lifetime sexual partners, respectively. Finally, HPV16 seropositivity and HPV16 tumor DNA were associated with hazard ratios of 0.4 and 0.5, respectively, indicating better survival for HPV positive individuals. HPV16 seropositivity was associated with risk for HNSCC, with greatest risk for pharyngeal cancer. We observed dose response relationships between serology titer and both risk for HNSCC and HPV16 tumor DNA. In cases, HPV16 tumor DNA and positive serology were associated with sexual history and improved disease free survival. © 2007 Wiley‐Liss, Inc.
Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) composite biomaterials for bone tissue regeneration: In vitro performance assessed by osteoblast proliferation, osteoclast adhesion and resorption, and macrophage proinflammatory response
Authors: Cool S. M. , Kenny B. , Wu A. , Nurcombe V. , Trau M. , Cassady A. I. , Grøndahl L.
Published: February 2007

The efficacy of composite materials for bone tissue engineering is dependent on the materials' ability to support bone regeneration whilst inducing a minimal inflammatory response. In this study we examined the in vitro osteogenic and inflammatory properties of poly(3‐hydroxybutyrate‐co‐3‐valerate) (PHBV) with various calcium phosphate‐reinforcing phases: nano‐sized hydroxyapatite (HA); submicron‐sized calcined hydroxyapatite (cHA); and submicron‐sized β‐tricalcium phosphate (β‐TCP), using bioassays of cultured osteoblasts, osteoclasts, and macrophages. Our study showed that the addition of a nano‐sized reinforcing phase to PHBV, whilst improving osteogenic properties, also reduces the proinflammatory response. Proinflammatory responses of RAW264.7/ELAM‐eGFP macrophages to PHBV were shown to be markedly reduced by the introduction of a reinforcing phase, with HA/PHBV composites having the lowest inflammatory response. Osteoclasts, whilst able to attach to all the materials, failed to form functional actin rings or resorption pits on any of the materials under investigation. Cultures of osteoblasts (MC3T3‐E1) readily attached and mineralised on all the materials, with HA/PHBV inducing the highest levels of mineralization. The improved biological performance of HA/PHBV composites when compared with cHA/PHBV and β‐TCP/PHBV composites is most likely a result of the nano‐sized reinforcing phase of HA/PHBV and the greater surface presentation of mineral in these composites. Our results provide a new strategy for improving the suitability of PHBV‐based materials for bone tissue regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Vascularization and cellularization of collagen scaffolds incorporated with two different collagen‐targeting human basic fibroblast growth factors
Authors: Zhao Wenxue , Chen Bing , Li Xiaodong , Lin Hang , Sun Wenjie , Zhao Yanhong , Wang Bin , Zhao Yannan , Han Qianqian , Dai Jianwu
Published: February 2007

To develop a collagen‐based wound targeting repair system, we introduced two collagen‐binding domains (CBDs) into the human basic fibroblast growth factor (bFGF). Three expression vectors were constructed: the first one (named V‐bFGF) contained bFGF and the CBD WREPSFCALS derived from von Willeband's factor (vWF); the second (named C‐bFGF) contained bFGF and the CBD TKKTLRT derived from collagenase; the third (named bFGF) was bFGF as a control. The recombinant proteins of V‐bFGF and C‐bFGF were demonstrated to retain both growth factor activity and collagen‐binding activity. We found that C‐bFGF possessed higher collagen‐binding ability than V‐bFGF. The targeted repair systems consisting of collagen scaffolds and CBD‐bFGFs were assembled in vitro and then implanted subcutaneously. Results showed that C‐bFGF promoted vascularization at the implanted sites more effectively than V‐bFGF. Histological analysis showed more cells migrated into collagen scaffolds incorporated with C‐bFGF than those with V‐bFGF. These data suggested that the higher collagen‐binding ability the CBD‐bFGF possessed, the more significant vascularization, and cellularization were observed. In summary, CBD‐bFGF/collagen system could be used as a targeted repair system with beneficial effects of the restriction of bFGF diffusion, the prolonging of bFGF activity, and the targeted promotion of vascularization and cellularization. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Thrombotic thrombocytopenic purpura: Report of fourteen cases—occurrence during pregnancy and response to plasma exchange
Authors: Caggiano Vincent , Fernando Leonor P. , Schneider Jack M. , Haesslein Hanns C. , Watson‐Williams Edward J.
Published: February 2007

Thrombotic thrombocytopenic purpura (TTP), a syndrome of diverse etiology probably related to factors regulating platelet‐vessel wall interaction, is predominantly a disorder of women. We report our experience with 14 patients in an 11‐year period. Thirteen were female and aged between 25–69 years. Four were postmenopausal, and of the nine premenopausal women three were pregnant, one was immediately postpartum, and three were taking estrogennine premenopausal women three were pregnant, one was immediately postpartum, and three were taking estrogen‐containing oral contraceptives. A review of the literature confirms the two to one female/male preponderance and that TTP is reported in 56 women who are pregnant or recently postpartum. While this association with possible hormonal events has been noted, it has previously received little comment. We stress the similarity between TTP and some occurrences of preeclamptic toxemia, and that this may suggest not only a common etiology but that therapeutic attempts should be similar.

While no single therapeutic modality is universally successful, our experience is that plasma exchange is the most effective, with five of seven patients so‐treated obtaining prolonged remission; four of five patients responded to splenectomy and corticosteroids, but one died of infection postoperatively. Five patients, including two treated exclusively with antiplatelet aggregating agents, died without achieving remission. The frequency of successful therapy is not changed by the concurrent pregnancy, but the fetal loss is high. There does seem to be an increased risk of recurrence of TTP in a subsequent pregnancy, and this might be considered when counseling premenopausal patients who have achieved remission of TTP.
A trial of immunotherapy in aplastic anemia and pure red cell aplasia
Authors: Young Neal S. , Klein Harvey G. , Griffith Patricia , Nienhuis Arthur W.
Published: February 2007

Immunotherapy, consisting of lymphocyte depletion or plasmapheresis in combination with cyclophosphamide and prednisone, was employed in three patients with refractory pure red cell aplasia and six patients with aplastic anemia of various etiologies. All three patients with pure red cell aplasia responded to plasmapheresis. One patient with atypical aplastic anemia showed partial recovery following lymphocyte depletion; the other five patients showed no evidence of a clinical response. The effect of patients' sera or bone marrow on formation of myeloid or erythroid colonies by bone marrow from normal individuals was determined in vitro. A decline in serum inhibition of erythroid colony formation was observed in the patients with pure red cell aplasia following treatment. Any changes in serum inhibition were less marked or unrelated to treatment outcome in the patients with aplastic anemia, although the single patient who responded to lymphocyte depletion exhibited reversal of coculture bone marrow inhibition. Our experience suggests that in vitro assay methods may not adequately predict the response of patients with aplastic anemia to this form of immunotherapy, and furthermore clinical improvement was too sporadic for this treatment to be recommended. Plasmapheresis may be a useful adjunct in patients with pure red cell aplasia, but remissions may not be dramatic or sustained.
Intensive plasma exchange in small and critically ill pediatric patients: Techniques and clinical outcome
Authors: Fosburg Martin , Dolan Mary , Propper Richard , Wolfe Lawrence , Kevy Sherwin
Published: February 2007

Standard apheresis techniques require modification of use in children, particularly those with serious concurrent medical problems, as they are prone to apheresis‐induced disturbances of volume, metabolism, and coagulation. We report 112 plasma exchanges (TPE) on 11 children, 9 of whom weighed less than 20 kg and 7 of whom were critically ill. All were treated on continuous flow apparatus; seven on centrifugal systems (CS), two on a membrane filtration system (MFS), and two on both. Perturbations of blood and red blood cell (RBC) volume were prevented by priming the extracorporeal circuits with a red cell saline mixture having an hematocrit equal to or greater than the patient's hematocrit. Priming volume and minimal flow rates were 170 ml and 40 cc/min (MFS) and 350 ml and 10 cc/min (CS). TPE dose varied from 1.3 to 3 plasma volumes. Immunoglobulins fell by the following amounts: IgG 43.7%, IgA 36.7%, and IgM 41% per plasma volume. Platelets fell by 20–90% (CS) and 5–7% (MFS). Vascular access was obtained by various means including Thomas shunts, dialysis catheters, and standard 16–19 gauge butterflies and angiocaths. Bleeding in patients with coagulopathies was prevented by using repeated small boluses of heparin to maintain a clotting time of 2.5–3 minutes. Morbidity from TPE was limited to citrate toxicity (2 patients) and transient pulmonary edema (1 patient).

Treatment outcome was successful in 8 out of 11 patients. We have shown that if PEX is otherwise indicated, it should not be withheld solely for patient size or the complexity of concurrent medical problems.
Comparison of filtration to continuous‐flow centrifugation for plasma exchange
Authors: Wood Lucille , Bond Rodney , Jacobs Peter
Published: February 2007

The Asahi Plasmaflo Hollow Nylon Fibre Filtration System (n = 13) was directly compared to the NCI‐IBM 2990 Continuous‐Flow Blood Fraction Separator (n = 10) for plasma exchange. The systems were equally efficient in achieving plasma separation. There were significant differences favouring filtration for clearance of fibrinogen (P < 0.05), and the fourth component of complement (P < 0.01). Greater loss of urea (P < 0.05) was found after plasma exchange, using the cell separator. The flow characteristics were markedly different. In a standardised 4‐L plasma exchange, filtration took place at 35 ml/minute, with a procedure time of 109 ± 45 minutes in contrast to centrifugation at a plasma flow collection rate of 19 ml/minute, requiring 208 ± 17 minutes. This time advantage for the former procedure was offset by 195 minutes required to regenerate the hollow nylon fibre unit and a further 90 minutes required for cleaning under strictly controlled aseptic techniques prior to reuse. Each filter was regenerated at least twice and reused without infection, but there was incremental loss of filtration efficiency demonstrated by decreasing clearance of an intravascular marker dye. In two of the 13 procedures using the Plasmaflo system, serious reactions necessitated termination of the procedure; this did not occur using the cell separator. Restriction of the number of times that the filter unit could be regenerated without loss of efficiency, the prolonged time required for regeneration and cleaning, coupled with the need for artifical vascular access to meet high blood flow rates required, limit the usefulness of this technique for plasma exchange.
Plasmapheresis versus lymphoplasmapheresis in rheumatoid arthritis: Immunologic comparisons and literature review
Authors: Wallace Daniel J. , Medici Michael A. , Nichols Sherri , Klinenberg James R. , Brck Miriam , Gatti Richard , Goidfinger Dennis
Published: February 2007

Eight patients with Functional Class III. seropositive, erosive rheumatoid arthritis unresponsive to remittive drugs each underwent nine aphereses over 3 weeks. Four had a 40‐ml/kg plasma exchange and four others had a 40‐ml/ kg plasma exchange plus a mean 5.67 × 109 lymphocyte depletion. Both groups appeared to improve clinically. T and B cell counts and OK T4 and OK T8 ratios decreased in the lymphoplasmapheresis group. Phytohemagglutinin stimulation decreased in lymphoplasmapheresis and increased in plasmapheresis patients with significant comparisons (p = 0.02). These findings confirm and extend previous work. Plasmapheresis and lymphoplasmapheresis appear to have fundamentally different actions on lymphocyte function.
Drug‐resistant bronchial asthma successfully treated with plasma exchange
Authors: Bambauer R. , Jutzler G. A. , Micka K. , Austgen M. , Schlimmer P. , Trendelenburg F.
Published: February 2007

Two patients suffering from allergic bronchial asthma who showed no improvement despite six and four weeks, respectively, of drug therapy were successfully treated with therapeutic plasma exchange. The first patient had no attacks over a period of five months, and the other patient had none for over one year. Although this report only deals with single observations, we believe that therapeutic plasma exchange is of particular value for patients with severe allergic bronchial asthma because it eliminates in addition to immunocomplexes other substances, including antigens, rapidly from the blood. This means that it is possible to directly intervene in the pathomechanism. However, further investigations are necessary in order to corroborate this successful therapy.
Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the poems syndrome
Authors: Silberstein L. E. , Duggan D. , Berkman E. M.
Published: February 2007

A patient with osteosclerotic myeloma and POEMS syndrome, unresponsive to pulse prednisone and melphalan therapy, was admitted to the hospital for a trial of plasma exchange therapy. The presentation included IgG lambda monoclonal gammopathy, peripheral neuropathy, hepatosplenomegaly, hyperpigmentation and thickening of the skin, edema, and tense ascites. Laboratory tests confirmed hypothyroidism, hypogonadism, and adrenal insufficiency. Six exchange procedures failed to affect the clinical course, and the patient died. Greater‐than‐one‐plasma‐volume exchanges (patient's measured plasma volume, 2,703 cc) were performed. When IgG and cholesterol removal were compared to the predicted removal, based on the volume of plasma removed, significantly less reduction in concentration than predicted was measured. IgG concentrations increased postapheresis and, at 2 weeks, three‐fourths of the removed IgG had reaccumulated. A reduced efficiency of removal of both IgG and cholesterol can be explained by postulating increased vascular permeability with free exchange of soluble substances from one compartment to another. If an abnormal product is produced by the disease and is responsible for the clinical syndrome, a more intensive schedule of plasma exchange therapy may be needed to achieve a sustained depletion of the responsible soluble substance. Alternatively, neither increased vascular permeability or the clinical manifestations are responsive to removal of a soluble substance or are caused by a soluble substance produced by the malignancy.
Acquired immunodeficiency syndrome (AIDS) ‐ apheresis and operative risks
Authors: Kiprov Dobri D. , Lippert Randolph , Sandstrom Erik , Jones Frank R. , Cohen Richard J. , Abrams Donald , Busch David F.
Published: February 2007

The removal of immune complexes, autoantibodies and suppressor factors from the circulation of patients with AIDS and AIDS related conditions by plasmapheresis and selective immunoadsorption may play a role as a therapeutic modality in these disorders. Lymphocytapheresis may also be of potential use in AIDS related conditions with presumed autoimmune basis. Perfusion of plasma over immobilized protein A columns is being evaluated as a possible immunomodulatory and antitumor therapy in patients with AIDS related Kaposi's sarcoma. Although apheresis procedures as a therapeutic modality in AIDS related conditions are still at the experimental stage, preliminary results are encouraging. The possible transmission of the disease by blood products presents a health hazard to health workers involved in the field of apheresis. Since the mode of transmission of the disease appears to be similar to hepatitis B, strict hepatitis B precautions should be enforced in every case in which AIDS suspected blood is being processed.
The effect of serial therapeutic plasmapheresis on platelet count, coagulation factors, plasma immunoglobulin, and complement levels
Authors: Wood Lucille , Jacobs Peter
Published: February 2007

One hundred therapeutic phasmaphereses were carried out at biweekly intervals in seven patients, without morbidity or mortality, using the IBM 2997 blood fraction separator. In standardised procedures, 1.5 times the calculated plasma volume was replaced with an electrolyte solution containing 4% salt‐free human albumin. Anticoagulation was achieved using a whole venous blood to acid‐citrate dextrose ratio of 11 to 1. Median flow rates, plasma collection, and procedure times were respectively 40 ml/minute, 20 ml/minute, and 3 hours. Haemoglobin and total white cell counts were not significantly affected by the procedures. In contrast, platelet count, fibrinogen, immunoglobulin levels, total haemolytic complement, as well as C3 and C4 fractions fell, and the prothrombin and partial thromboplastin times were lengthened by the exchanges. All these measurements had returned to normal within 24 hours, apart from the fibrinogen, which took between 48 and 72 hours, and the immunoglobulin level, which required 35 days to return to baseline. In a further patient, more detailed studies (n = 13) were carried out to characterise the behaviour of antithrombin III and factor VIII. Both levels were markedly reduced immediately following the procedure and, like fibrinogen, had returned to normal within 48 hours. These data indicate that in an isovolaemic plasmapheresis there was a transient but rapidly reversible effect on all the factors studied, with fibrinogen level, antithrombin III, and factor VIII returning more slowly to normal than the others, and immunoglobulin levels responding the slowest. None of these changes was associated with clinically significant haemostatic abnormalities. It is concluded that there is no need to use fresh frozen plasma as replacement fluid, thereby avoiding the risk of hepatitis, and, secondly, that although transient decrease is demonstrable in coagulation and associated factors, patients can nevertheless be safely treated once every 48 hours using an albumin and electrolyte solution unless there is a pre‐existing abnormality in the haemostatic mechanism.
Risk of AIDS‐related virus (human immunodeficiency virus) transmission through apheresis procedures
Authors: Kiprov Dobri , Simpson Denyse , Romanick‐Schmiedl Sue , Lippert Randolph , Spira Thomas , Busch David
Published: February 2007

Since exposure to blood products occurs on a daily basis during hemapheresis, the acquired immunodeficiency syndrome (AIDS) epidemic has a serious impact both for patients undergoing apheresis procedures as well as for health professionals working in the field. We studied serum samples from 110 patients who underwent therapeutic plasmapheresis for a variety of diseases not related to AIDS for the presence of antibodies to human immunodeficiency virus (HIV). Exchange fluids used in the majority of the patients were plasma protein fraction and 5% human albumin. Four patients received only fresh‐frozen plasma. Fifty‐five patients also received IV gammaglobulin. The follow‐up period exceeded 24 months. All patients who did not belong to any known high‐risk group for AIDS were negative for HIV antibodies prior to treatment and remained negative at last follow‐up. Seven patients were homosexual men. All seven were seropositive prior to plasmapheresis and remained so throughout the treatment period.

Seven health professional working in a busy haemapheresis unit were followed for 2 1/2 years. All remain HIV seronegative with normal immune function.

These data indicate that transmission of HIV is unlikely through haemapheresis procedures.
Phenytoin removal during plasma exchange
Authors: White Roger L. , Garnett William R. , Allen Jody H. , Kline Berry J. , Sharp David E.
Published: February 2007

Plasma exchange is currently being used to treat a variety of disorders including immune complex and hematologic disorders. It has been shown that the removal of plasma removes drugs bound to plasma proteins. This case documents the removal of phenytoin during plasma exchange therapy. Total and free phenytoin serum concentrations were obtained before and after each exchange. Aliquots were obtained from each pass, and total phenytoin concentrations were determined. The total phenytoin serum concentration increased during the first exchange, while the total concentration decreased as a result of the second exchange. It was determined that approximately 27.7 mg and 30.4 mg of phenytoin were removed by the first and second plasma exchanges, respectively.
Aluminium loading during therapeutic plasma exchange
Authors: Monteagudo Felix , Wood Lucille , Jacobs Peter , Folb Peter , Cassidy Michael
Published: February 2007

Graphite furnace atomic absorption spectroscopy was used to demonstrate a fivefold increase in the median plasma aluminium levels of four patients undergoing therapeutic plasmapheresis. This plasma aluminium loading resulted from contamination of albumin incorporated in the replacement fluids and took place during its preparation, with albumin aluminium levels of 646, 669, and 715 μg/liter present in three representative samples. Aluminium overload may result in the development of encephalopathy and osteomalacia in patients with renal impairment, indicating the need to monitor aluminium levels in the albumin‐containing replacement fluids to avoid this potential hazard.
Leukocytapheresis in inclusion body myositis
Authors: Dau Peter C.
Published: February 2007

A patient with inclusion body myositis was treated with a course of 22 leukocytaphereses combined with prednisone and azathioprine therapy. He improved clinically during an induction phase of frequent cytapheresis, which reduced the circulating levels of T lymphocytes and monocytes and decreased the ratio of the T4+ to T8+ lymphocyte subsets. During subsequent maintenance cytapheresis there was partial recovery of the T4+ population without recovery of T8+ lymphocytes, and the patient lost most of his clinical improvement. In contrast to T lymphocytes and monocytes, there was no persistent reduction in circulating Blymphocyte levels during the course of therapy. T8+ lymphocyte populations may regenerate more slowly than T4+ lymphocytes following depletion with leukocyatpheresis combined with prednisone and azathioprine therapy. A loss of of T8+ suppressor relative to T4+ helper‐cell function could lead to an intensification of autoimmune conditions.
The effect of plateletpheresis on the fenwal CS‐3000 on donor platelet counts
Authors: Kalish Robert I. , Chambers Linda A. , Linden Jeanne V.
Published: February 2007

To evaluate the risk of significant plateletpheresis‐induced thrombocytopenia in normal volunteer donors undergoing plateletpheresis less frequently than every 56 days and to help understand factors influencing platelet yield in these donors, pre‐ and postapheresis platelet counts (×103/μl) and platelet yields were analyzed from 916 plateletpheresis procedures (Fenwal CS‐3000) on 607 donors (405 men, 202 women). The mean preaphresis platelet count was 265 ± 59 (SD) (range 155‐650) (men 256 ± 55 [170‐444]; women 284 ± 65 [155‐650]; P < .001, t‐test). After an average platelet yield of 4.08 × 1011, the mean postplatelet count was 185 ± 46 (range 72‐420) (men 184 ± 42 [80‐345]; women 194 ± 52 [72‐500]; P < 0.1). The percent decrease in platelet count (mean 29.4 ± 13, range −28.1‐65.5) had positive correlations with platelet yield (P < .01, r = 0.10), predonation platelet count (P < .001, r = 0.29), and age (P < .01, r = .10) and a negative correlation with weight (P < .001, r = 0.18) Both the percent decrease and platelet yield were significantly higher in women than in men (P < .001, t‐test), and platelet yield was best predicted by preapheresis platelet count in both sexes (r = 0.65). The effects of plateletpheresis on donor platelet count thus vary widely among donors. Although a decrease of greater than 50% was not a rare event (5.9% of all procedures), in only three instances (0.3%) was the actual postapheresis platelet count below 100 (72, 94, 95). Thus, plateletpheresis in normal donors appears unlikely to produce clinically significant thrombocytopenia immediately after apheresis.
Multiple use of plasmafilters
Authors: Lai Kar Neng , Lai Fernand Mac‐Moune , Lam Christopher W. K. , Kung Jean L. S.
Published: February 2007

The practice of multiple use of membrane plasmafilters was examined in six patients receiving intermittent or regular plasmapheresis treatment. The plasmafilters were cleaned by flushing and ultrafiltration using positive pressure in the blood and filtrate compartments of the plasmafilter. Twenty‐six plasmafilters were studied and the membrane permeability characteristics were examined during 56 plasmapheresis treatments with reused plasmafilters. The clearances of nitrogen urea and creatinine, and the sieving coefficients of albumin and immunoglobulins remained unchanged with the reuse of plasmafilters. The practice is safe, efficient, and can contribute to cost containment in plasmapheresis treatment.
New application of the autotrans: Autologous support of the organ donor and salvage of the donor's red blood cells for the transfusion support of organ recipients
Authors: Valbonesi Mauro , Ferrari Mauro , Zia Susanna , Piri Carlo , Fella Mauro , Pittaluga Pierantonlo , Zat Carla , Concaro Alessandro , Fontana Iris , Destefano Francesco , Ciappina Gian Franco , Canale Marcello
Published: February 2007

Organ donation is usually limited to solid tissues; paradoxically, organ donors undergoing expiant are often transfused in preparation for or during surgery. This practice increases the requirement for blood and adds immunological and infectious risks for both recipients and donors of grafts. We have investigated the possibility of supporting an expiant with intraoperative blood salvage and, in the case of a cadaver donor, at the end of the operation, salvaging blood for potential use in the graft recipient. This preliminary report describes the technique and the results obtained in two procedures. The volume of red cells with a hematocrit of 55% obtained from the two donors was 2,090 and 1.180 ml, respectively. These components were employed for the transfusion support of the organ recipients.