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1.
Case Rep Surg ; 2023: 7443508, 2023.
Article in English | MEDLINE | ID: mdl-36687308

ABSTRACT

We describe a case of an uncommon early pancreatic cancer presentation in a patient in his 60s who had haemorrhagic shock from extensive haematochezia and required blood transfusions as well as surveillance in an intensive care unit. A splenic artery pseudoaneurysm that had been effectively embolized by angiography was seen to be actively bleeding into the colon lumen on a computerized tomography (CT) scan along with a necrotic mass of the pancreatic tail. A pancreatic mucinous adenocarcinoma was diagnosed by a transgastric biopsy. A pancreatico-colic fistula was discovered by CT scan after a colic contrast enema. A transabdominal drainage of the necrotic collection and targeted antibiotic treatment had been performed with a satisfying patient outcome. In order to assess a potential secondary surgical resection, systemic chemotherapy was planned. In conclusion, haematochezia with hemodynamic instability originated from a splenic artery pseudoaneurysm fistulising into the colon (arterio-colic fistula) and sepsis originating from a tumoral pancreatic abscess fistulising into the colon (tumoral pancreatico-colic fistula).

2.
J Hosp Infect ; 117: 172-178, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34428504

ABSTRACT

BACKGROUND: The burden of healthcare-associated infections (HAIs) and antimicrobial use in Swiss long-term care facilities (LTCFs) is currently unknown. This study assessed the prevalence of HAIs and antibiotic use among LTCF residents in Switzerland. METHODS: A point-prevalence study was undertaken in LTCFs in eastern and western Switzerland from August to October 2019 according to the 'Healthcare-associated infections in long-term care facilities' (HALT) protocol. Characteristics of residents (age, sex, wounds, dementia, indwelling catheters) and institutions (specific factors, geographic region) were assessed. LTCF residents were screened for HAIs and current antibiotic treatment. Personal and institutional factors associated with HAIs were assessed. RESULTS: In total, 1185 residents from 16 LTCFs (eight per geographic region) were screened for HAIs and antibiotic treatment. Median age was 87 years (interquartile range 79-91) and 71% were female. The prevalence of HAIs was 4.2% (west 4.3% vs east 4.2%; P=0.93), with mucocutaneous skin infections (36%) and respiratory tract infections (30%) being the most common. Independent risk factors for the presence of HAIs were presence of a chronic wound [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.0; P=0.02] and being immobile (OR 1.8, 95% CI 1.0-3.3; P=0.04). Antibiotics were given to 2.9% of residents (west 3.9% vs east 1.8%; P=0.05) on the day of the survey. The most commonly prescribed antibiotics were amoxicillin-clavulanic acid and quinolones. CONCLUSIONS: The prevalence of HAIs in Swiss LTCFs is similar to that in other European countries, whereas antibiotic consumption is lower. Further point-prevalence surveys on a broader scale are recommended to improve understanding of the burden of HAIs and antibiotic consumption in this setting.


Subject(s)
Cross Infection , Long-Term Care , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Cross Infection/epidemiology , Delivery of Health Care , Drug Utilization , Female , Humans , Prevalence , Switzerland/epidemiology
3.
J Hosp Infect ; 109: 115-122, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33422590

ABSTRACT

BACKGROUND: In Switzerland each year, influenza leads to between 112,000 and 275,000 medical consultations. Data on nosocomial influenza infection are limited. AIM: To describe nosocomial cases of seasonal influenza in south-western Switzerland. METHODS: This study was conducted during two seasonal influenza epidemics from 2016 to 2018 in 27 acute care public hospitals in south-western Switzerland. During these two time-periods, every patient hospitalized for >72 h who was positively screened by reverse transcription-polymerase chain reaction or antigen detection for influenza was included in the survey. Characteristics of patients included age, sex, and comorbidities. Included patients were followed up until discharge or death. Complications and administration of antineuraminidases and/or antibiotics were registered. FINDINGS: The median influenza vaccine coverage of healthcare workers was 40%. In all, 836 patients were included (98% with type A influenza virus in 2016-2017; 77% with type B virus in 2017-2018). Most patients (81%) had an unknown vaccine status. Overall, the incidence of nosocomial influenza was 0.5 per 100 admissions (0.35 per 1000 patient-days). The most frequent comorbidities were diabetes (20%), chronic respiratory diseases (19%), and malnutrition (17%). Fever (77%) and cough (66%) were the most frequent symptoms. Seventy-one percent of patients received antineuraminidases, 28% received antibiotics. Infectious complications such as pneumonia were reported in 9%. Overall, the all-cause mortality was 6%. CONCLUSION: The occurrence of nosocomial influenza underlines the importance of vaccinating patients and healthcare workers, rapidly recognizing community- or hospital-acquired cases, and applying adequate additional measures to prevent dissemination, including the timely administration of antineuraminidases to avoid antibiotic use (and misuse).


Subject(s)
Cross Infection , Epidemics , Influenza, Human , Cross Infection/epidemiology , Hospitals , Humans , Influenza, Human/epidemiology , Seasons , Switzerland/epidemiology
4.
J Hosp Infect ; 96(1): 69-71, 2017 May.
Article in English | MEDLINE | ID: mdl-28412178

ABSTRACT

In 2010-11, a trial conducted in nursing homes showed no benefit of meticillin-resistant Staphylococcus aureus (MRSA) universal screening and decolonization over standard precautions to reduce the prevalence of MRSA carriage. Accordingly, no routine screening was performed from 2012. A five-year follow-up shows no new evidence supporting the intervention. Recommendations issued after trial (no screening and decolonization of MRSA residents) were retained.


Subject(s)
Carrier State/epidemiology , Cross Infection/diagnosis , Mass Screening/methods , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Nursing Homes/statistics & numerical data , Staphylococcal Infections/diagnosis , Cross Infection/epidemiology , Cross Infection/prevention & control , Follow-Up Studies , Humans , Infection Control/methods , Methicillin-Resistant Staphylococcus aureus/growth & development , Prevalence , Staphylococcal Infections/epidemiology , Staphylococcal Infections/prevention & control , Switzerland/epidemiology
5.
J Chem Phys ; 139(16): 166102, 2013 Oct 28.
Article in English | MEDLINE | ID: mdl-24182089

ABSTRACT

Using the (slow-scale) linear noise approximation, we give parameter-independent bounds to the substrate and product intrinsic noise variance for the stochastic Michaelis-Menten approximation at steady state.


Subject(s)
Models, Chemical , Kinetics , Stochastic Processes
6.
Ann Oncol ; 24(3): 718-25, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23139259

ABSTRACT

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Chemoradiotherapy , DNA Mutational Analysis , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Diarrhea/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Panitumumab , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Rectal Neoplasms/genetics , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Treatment Outcome , ras Proteins/genetics
7.
Colorectal Dis ; 14(4): 463-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21689325

ABSTRACT

AIM: After an initial uncomplicated attack, sigmoid diverticulitis may recur, but the morphological characteristics of recurrent diverticulitis have not been investigated. We compared the clinical and radiological severity, the respective location and clinical outcome of the first two episodes of sigmoid diverticulitis. METHOD: We reviewed the charts of 60 patients [median age 61 (range 31-90) years] who were admitted initially for a first episode of uncomplicated left colonic diverticulitis, and who were eventually readmitted for a second episode, both being documented by abdominal computed tomography (CT) scan. RESULTS: The median delay between the two episodes was 19 (3-97) months. Six (10%) patients developed a second complicated episode of diverticulitis [Hinchey II (n = 2), CT-guided percutaneous drainage; Hinchey III (n = 3), emergency Hartmann's operation; colovesical fistula (n = 1), elective sigmoid resection]. Fifty-four (90%) patients were admitted for a second episode of uncomplicated diverticulitis. In this group, the duration of hospital stay [11 (4-22) vs 10 (1-39) days, P = 0.28], serum levels of C-reactive protein [131 (31-350) vs 112 (22-333) mm, P = 0.62] and CT scan-based severity score [3 (1-6) vs 3 (0-7) points, P = 0.07] were similar between the two episodes. In 19 out of 54 (35%) patients with simple recurrent diverticulitis, although disease severity was similar, the disease topography differed and recurrence involved another segment of the left colon. CONCLUSION: The majority of patients who develop recurrence do so in a similar mode and location. However, 10% develop complicated diverticulitis and in 35% of patients recurrent diverticulitis occurs at a different location.


Subject(s)
Diverticulitis, Colonic/diagnosis , Sigmoid Diseases/diagnosis , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/metabolism , Diverticulitis, Colonic/blood , Diverticulitis, Colonic/diagnostic imaging , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Recurrence , Retrospective Studies , Severity of Illness Index , Sigmoid Diseases/blood , Sigmoid Diseases/diagnostic imaging
8.
Ann Oncol ; 21(12): 2390-2395, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20444846

ABSTRACT

BACKGROUND: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. RESULTS: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. CONCLUSION: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Organoplatinum Compounds/administration & dosage , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease Progression , Dose-Response Relationship, Drug , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Oxaliplatin , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Survival Analysis , Treatment Outcome , Gemcitabine
9.
Ann Oncol ; 20(9): 1522-1528, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19465425

ABSTRACT

BACKGROUND: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/therapy , Esophageal Neoplasms/therapy , Neoadjuvant Therapy , Adult , Aged , Carcinoma/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Digestive System Surgical Procedures , Docetaxel , Esophageal Neoplasms/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Radiotherapy , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome
10.
Ann Oncol ; 19(4): 739-45, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18096565

ABSTRACT

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Adult , Aged , Aged, 80 and over , Analysis of Variance , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Drug Administration Schedule , ErbB Receptors/genetics , Female , Gefitinib , Humans , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Neoplasm Staging , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Quality of Life , Radiography , Risk Assessment , Risk Factors , Smoking/adverse effects , Surveys and Questionnaires , Switzerland , Treatment Outcome , ras Proteins/genetics , Gemcitabine
11.
Dermatology ; 202(4): 356-8, 2001.
Article in English | MEDLINE | ID: mdl-11455160

ABSTRACT

We present the case of a woman where the diagnosis of cold agglutinin disease could be made after we had noticed slight cutaneous manifestations during a routine examination. Leading symptoms were livedo reticularis of the thighs and a history of acrocyanosis and Raynaud's phenomenon upon cold exposure. The current knowledge about the etiology, clinical presentation and treatment of the disease is briefly discussed.


Subject(s)
Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/pathology , Cyanosis/complications , Diagnosis, Differential , Ear, External , Female , Humans , Middle Aged , Nose , Raynaud Disease/complications , Skin Diseases, Vascular/complications , Thigh
12.
Int J Cancer ; 88(1): 99-107, 2000 Oct 01.
Article in English | MEDLINE | ID: mdl-10962446

ABSTRACT

Cellular resistance to etoposide has been correlated both with reduced levels and an aberrant cytoplasmic accumulation of the drug's target, topoisomerase IIalpha (topo IIalpha). It is not known, however, whether a cytoplasmic pool of topo IIalpha is sufficient to confer drug resistance on cultured mammalian cells. In our study, we have transfected mouse fibroblasts and human 293 cells with truncated forms of human topo IIalpha fused to GFP and have examined the transformants for the subcellular localization of topo IIalpha and their resistance to etoposide. Transient transfection resulted in high-level expression of all GFP-topo IIalpha fusions tested, whereas in stably transfected cells the levels varied significantly. Transfectants expressing a central or a carboxy-terminal topo IIalpha domain (aa 428-1504, 639-1028 or 1028-1504) accumulated high levels of the fusion proteins, while only very low amounts of GFP-topo IIalpha proteins were observed in cell lines expressing constructs that retain the amino-terminus of the enzyme (aa 1-1214, aa 1-939, aa 1-611). Our results suggest that the topo IIalpha amino-terminus affects the stability of truncated forms of the enzyme in mammalian cells, perhaps due to targeted degradation. Assays that screen for cell vitality and DNA synthesis reveal no significant changes in etoposide sensitivity in transfected cells expressing high levels of cytoplasmic or nuclear localized topo II fusion proteins. Retroviral expression of a cytoplasmically anchored domain of human topo IIalpha also failed to confer drug resistance. These results suggest that a cytoplasmic pool of topo IIalpha is not sufficient to render cultured mammalian cells drug resistant.


Subject(s)
DNA Topoisomerases, Type II , DNA Topoisomerases, Type II/biosynthesis , Etoposide/pharmacology , Isoenzymes/biosynthesis , 3T3 Cells/drug effects , 3T3 Cells/enzymology , Animals , Antigens, Neoplasm , Cell Survival/drug effects , Cells, Cultured , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins , Drug Resistance , Green Fluorescent Proteins , Humans , Isoenzymes/genetics , Kidney/cytology , Kidney/drug effects , Kidney/enzymology , Luminescent Proteins/biosynthesis , Luminescent Proteins/genetics , Mice , Microscopy, Fluorescence , Peptide Fragments/biosynthesis , Peptide Fragments/genetics , Protein Structure, Tertiary , Rats , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Transfection
13.
Schweiz Med Wochenschr ; 128(46): 1808-12, 1998 Nov 14.
Article in German | MEDLINE | ID: mdl-9857387

ABSTRACT

Symptomatic or asymptomatic chronic elevation of platelet count can be observed in all forms of myeloproliferative disorders (MPD). Benefits and limitations of the traditional platelet-reducing agents, such as radioactive phosphorus, alkylating agents, hydroxyurea and interferon alpha, are well known and have been largely described. Anagrelide (Agrelin) is an additional newer drug with a selective platelet-lowering effect. We describe our own long-term experience in 6 patients with MPD who were treated with anagrelide as part of a compassionate-use protocol between April 1991 and August 1997. The median duration of therapy was 54 months (range 17 to 75 months), with an overall response rate of 100% (complete and partial response for at least 4 weeks). The initial median platelet count of 1211 x 10(9)/l (range 847 to 2050 x 10(9)/l) was reduced rapidly and lastingly to 570 x 10(9)/l (range 216 to 667 x 10(9)/l) at the time of the last control. Under treatment with anagrelide 4 of the 6 patients showed a reduction of disease-associated symptoms or complications. Adverse reactions were generally mild and transitory, and no interruption or cessation of therapy was required. Development of drug resistance or late adverse events were not observed. Treatment with anagrelide is effective, safe and in our opinion easy to administer. It also appears to be suitable for long-term administration.


Subject(s)
Myeloproliferative Disorders/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Quinazolines/therapeutic use , Thrombocytosis/drug therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myeloproliferative Disorders/blood , Platelet Aggregation Inhibitors/adverse effects , Platelet Count , Quinazolines/adverse effects , Thrombocythemia, Essential/blood , Thrombocythemia, Essential/drug therapy , Thrombocytosis/blood , Treatment Outcome
14.
Ann Oncol ; 9(1): 51-4, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9541683

ABSTRACT

BACKGROUND: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. PATIENTS AND METHODS: We examined the feasibility and safety of a CD34-selection followed by purging with anti B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophosphamide, BCNU and etoposide with retransfusion of autologous HPC's. RESULTS: A mean number of 340 x 10(8) mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2 x 10(6)/kg (range 0.6-2.2 x 10(6)/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5 x 10(9)/l and 17 days (range 13-25 days) to platelet recovery of 50 x 10(9)/l. Mean number of intravenous antibodies and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. CONCLUSIONS: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphomas.


Subject(s)
Antigens, CD34/blood , Hematopoietic Stem Cell Transplantation/adverse effects , Immunomagnetic Separation , Lymphoma, B-Cell/therapy , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Separation , Combined Modality Therapy , Dose-Response Relationship, Drug , Feasibility Studies , Humans , Immunosuppressive Agents/therapeutic use , Lymphoma, B-Cell/immunology , Transplantation, Autologous
15.
Ann Oncol ; 8(8): 785-90, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9332687

ABSTRACT

PURPOSE: To identify prognostic factors in patients with chemosensitive relapsed Hodgkin's disease treated by high-dose chemotherapy with autologous progenitor cell transplantation (HDC) and to compare the duration of treatment-free remission prior to HDC with the progression-free survival after HDC in individual patients. PATIENTS AND METHODS: Forty-five consecutive patients were analyzed retrospectively. We devised an index of pretreatment intensity (IPTI) based number of different chemo- and radiotherapy regimens given between diagnosis and HDC and on the duration of disease. RESULTS: With a median follow-up of 47 months the post-transplant event-free survival (EFS) was 44% and the overall survival (OAS) was 62% at four years. The IPTI allowed to discriminate between a low and a high-risk group with a four-year post-transplant EFS of 66% and 11% and a OAS of 87% and 28%, respectively (P = 0.0001). Of the 39 patients with sufficient follow-up after HDC, post-transplant EFS lasted on average > or = 18.5 months longer than the pretransplant treatment-free remission. CONCLUSIONS: HDC with the CBV regimen confers significant benefit to patients with chemosensitive relapsed Hodgkin's disease. The IPTI may help to select patients with a good response to HDC and to identify poor prognosis patients suitable for experimental protocols or palliative care only.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Hodgkin Disease/therapy , Adolescent , Adult , Combined Modality Therapy , Disease-Free Survival , Female , Hodgkin Disease/mortality , Humans , Male , Middle Aged , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
16.
Blood ; 88(8): 3166-75, 1996 Oct 15.
Article in English | MEDLINE | ID: mdl-8874217

ABSTRACT

The use of ex vivo expanded CD34-selected hematopoietic progenitor cells (HPCs) for autologous stem cell support or gene therapy is a major area of research and is likely to increase in the future. At present, little is known about the fate of contaminating malignant cells during ex vivo expansion of CD34-selected HPCs. We established a competitive polymerase chain reaction (PCR) titration assay to determine the number of residual lymphoma cells before and after selection and ex vivo expansion of CD34-selected HPCs in patients with t(14; 18) translocation carrying non-Hodgkin's lymphoma. Seven bone marrow (BM) and 2 mobilized peripheral blood progenitor cell samples from 8 patients without histologic BM involvement at the time of the harvest were analyzed by competitive PCR titration assay and determined to contain between < or = 10 and 4,000 lymphoma cells/ 10(6) mononuclear cells (MNCs). Immunoadsorption enriched CD34+ cells from a mean of 5% (range, 1% to 9%) to a mean of 88% (range, 76% to 94%) of MNCs and resulted in a 1 to 4 log depletion of contaminating tumor cells. Two HPC samples became PCR negative after CD34 selection, whereas 7 samples still contained < or = 10 to 200 residual lymphoma cells/10(5) MNCs. CD34-selected cells were consecutively expanded in suspension culture in the presence of stem cell factor, interleukin-1 beta (IL-1 beta), IL-3, and IL-6. The mean increase of cells was 13-fold (range, 4- to 22-fold) at day 7 and 65-fold (range, 43- to 110-fold) at day 14 of culture. Expansion resulted predominantly in myelomonocytic differentiation, whereas B-cell antigen-expressing cells became undetectable. Six of the seven PCR-positive CD34-selected samples became PCR-negative for the t(14; 18) translocation at day 7 and/or 14 of expansion. One PCR-positive and one PCR-negative CD34-selected sample were PCR-positive after ex vivo expansion, but the number of residual lymphoma cells remained at the limit of detection. We conclude that CD34-selection does not eliminate contaminating lymphoma cells in the majority of t(14; 18)+ HPC harvests. However, during ex vivo expansion of CD34-selected HPCs, residual t(14; 18)+ lymphoma cells do not proliferate and become undetectable by PCR in the majority of cases.


Subject(s)
Bone Marrow Purging/methods , Bone Marrow/pathology , Cell Separation/methods , Chromosomes, Human, Pair 14/ultrastructure , Chromosomes, Human, Pair 18/ultrastructure , Hematopoietic Stem Cells/cytology , Immunosorbent Techniques , Lymphoma, Non-Hodgkin/pathology , Neoplastic Cells, Circulating , Neoplastic Stem Cells/cytology , Translocation, Genetic , Antigens, CD34 , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cells, Cultured , Combined Modality Therapy , DNA, Neoplasm/analysis , Feasibility Studies , Flow Cytometry , Humans , Leukapheresis , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/therapy , Polymerase Chain Reaction , Reproducibility of Results
17.
Diabetes Educ ; 21(2): 117-23, 1995.
Article in English | MEDLINE | ID: mdl-7698064

ABSTRACT

This study evaluated pharmaceutical care as an adjunct to an existing, coordinated-care program at a Regional Diabetes Center. The progress of a control group receiving the standard pharmacist instruction was compared with two treatment groups receiving additional small group or individual supplementary education for a 2-month period. Outcome evaluation included assessment of individual diabetes management through blood glucose monitoring and responses on a pretest and posttest questionnaire. Patients in the treatment groups demonstrated significantly lower average weekly blood glucose levels and a decreased incidence of hyperglycemic episodes compared with the control group. Questionnaire data for both treatment groups demonstrated a significant increase in patient understanding of diabetes medications and medications for associated illnesses, an increase in knowledge about blood glucose monitoring, and a positive difference in perceptions/attitudes toward diabetes and communication with the pharmacist. This approach is consistent with the concept of pharmaceutical care in which the pharmacist helps patients avoid long-term complications and thus improve their quality of life.


Subject(s)
Ambulatory Care/organization & administration , Patient Education as Topic/organization & administration , Pharmacies/organization & administration , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Models, Organizational , Program Development , Program Evaluation , Regional Medical Programs
19.
Vasa ; 23(3): 234-43, 1994.
Article in German | MEDLINE | ID: mdl-7975869

ABSTRACT

To investigate late sequelae of deep vein thrombosis, 223 consecutive patients, 148 men, 75 women, aged 61.5 +/- 14.7 years, with phlebographically documented unilateral deep vein thrombosis were reexamined 13 years after the acute event. 29 had an isolated calf vein thrombosis, 45 a 2-level- (calf an popliteal), 72 a 3-level- (calf, popliteal and femoral), 62 a 4-level- (calf, popliteal, femoral and pelvic) thrombosis and 15 had a special location, for example an isolated popliteal or pelvic involvement. In the acute stage all patients were given full dose heparin followed by a six month period of oral anticoagulation. 144 were initially treated by thrombolytic treatment with streptokinase. Control phlebography 5-14 days after the onset of the treatment revealed no clearance in a so called negative group of 123 patients, aged 63.5 +/- 14.9 years, namely the 79 "only" anticoagulated and 44 unsuccessfully thrombolysed. In this negative group natural course of deep vein thrombosis can be studied. The positive group, comprising 100 patients, aged 59.4 +/- 13.9 years (25 with complete and 75 with partial lysis, after streptokinase), is compared with the negative group. The global incidence of postthrombotic syndrome in the natural course, 13 years after deep vein thrombosis, was 39%, 9.8% with and 29.2% without ulcer. Slight changes were noted in 25% and no change in 36%. The incidence of postthrombotic syndrome was correlated with the extent of the original thrombosis: 3.7% after isolated calf vein thrombosis vs. 55.2% after 4-level thrombosis. Moreover, the mortality after deep vein thrombosis and the frequency of recurrence in the interval and of venous symptoms were also correlated to the extent of the thrombosis. The incidence of post phlebitic syndrome in the positive group is significantly lower in patients with 3- and 4-level thrombosis (p = 0.01). Patients with complete and partial lysis also have less venous symptoms (for 3- and 4-level thrombosis p < 0.0001). Thus, the successful thrombolysis seems to be beneficial in long terms for patients with extended thrombosis. Therefore, in our hospital thrombolytic treatment is offered as an additional treatment to anticoagulation to patients with recent, less than 7 days old, 3- and 4-level-thrombosis without contraindications.


Subject(s)
Coumarins/administration & dosage , Heparin/administration & dosage , Phlebography , Streptokinase/administration & dosage , Thrombolytic Therapy , Thrombophlebitis/drug therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Survival Rate , Thrombophlebitis/diagnostic imaging , Thrombophlebitis/mortality
20.
Wien Med Wochenschr ; 144(10-11): 192-5, 1994.
Article in German | MEDLINE | ID: mdl-7856181

ABSTRACT

To evaluate the clinical and socio-economic importance of the postthrombotic syndrome (PTS), the following epidemiologic parameters are to be known: The incidence of deep vein thrombosis (DVT) in the population, the incidence of PTS after DVT, the prevalence of the PTS, the socio-medical consequences and the mortality. The DVT-incidence in the literature is about 3/1000 per year in the adult population. In our own follow-up study we found a global PTS-incidence of 40% (10% with, 30% without ulcer) 13 years after DVT. The PTS-incidence was correlated with the initial DTV-extent. The risk of PTS after 3- and 4-level DVT is significantly reduced by a successful fibrinolysis in the acute stage (p = 0.01). The mortality of patients with PTS is 3 times higher than in the population. 4% of the patients with PTS get disabled. To our knowledge an adequate study with direct assessment of the PTS-prevalence does not exist, but the PTS-prevalence can be deduced from large epidemiologic studies, such as the Basel-Study, in which the global chronic venous insufficiency is assessed. It amounts in the adult population between 0.5 to 1% for the PTS with and 3 to 5% for the PTS without ulcer.


Subject(s)
Postphlebitic Syndrome/epidemiology , Adult , Aged , Anticoagulants/therapeutic use , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Phlebography , Postphlebitic Syndrome/diagnostic imaging , Postphlebitic Syndrome/drug therapy , Recurrence , Switzerland
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