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Biomedical subjects

Jonathan Cohen

Publications and source records attributed to Jonathan Cohen.

At least 55 records · Page 3Linked to original sources
PubMed2005

A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.

Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.

Adult↗
PubMed2005

Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning.

The incidence of Epstein-Barr virus (EBV) viraemia and lymphoproliferative disease (LPD) was studied in a consecutive cohort of 128 paediatric patients undergoing stem cell transplantation (SCT) with reduced-intensity conditioning (RIC; n = 65) or conventional-intensity conditioning (CIC; n = 68). Following CIC, six of 68 (8%) developed viraemia; all remained asymptomatic. EBV viraemia (23 of 65 patients = 35%, P < 0.001) and LPD (10 of 65 = 15%, P < 0.001) were significantly more frequent following RIC. Of the 23 RIC patients who developed viraemia, eight remained asymptomatic, five had symptomatic viraemia (fever +/- rash), and 10 patients developed LPD, two of whom died. An absolute lymphocyte count of <0.3 x 10(9)/l at the time of onset of viraemia was strongly predictive of development of LPD (P < 0.05) in this group. The incidence of viraemia was significantly higher in patients receiving serotherapy with antithymocyte globulin (ATG; 15 of 43, 35%) than Campath (12 of 73, 16.4%, P < 0.05). Primary immunodeficiency and acute graft-versus-host disease were associated with EBV viraemia in univariate analysis, but were not independent risk factors. In conclusion, EBV viraemia and LPD appear to be significantly more common in children following RIC SCT, particularly with selective depletion of recipient T cells relative to B cells following the use of ATG. This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells.

Adolescent↗
PubMed2005

Radical prostatectomy: pathology findings in 1001 cases compared with other major series and over time.

OBJECTIVE: To examine the preoperative features and pathological outcomes of clinical significance of 1001 consecutive essentially unscreened men who had a radical prostatectomy (RP) in the UK between 1988 and 2002, and their changes over time. PATIENTS AND METHODS: The details of men whose RP specimen was submitted for analysis were entered into the RP database held at the University College Hospital, London; the National Health Service and private patients of 17 surgeons were included. The age, mode of diagnosis, preoperative prostate specific antigen (PSA) level, biopsy and RP findings were compared over time. RESULTS: The mean (range) age of the men was 62 (40-76) years, the median PSA 8 (0.1-146) ng/mL and the median biopsy Gleason sum score 6; these preoperative features did not change over the study period. The diagnosis of prostate cancer was made by transurethral resection of the prostate alone in 48 men (5%). The maximum number of patients receiving neoadjuvant androgen ablation was 21 (33%) in 1996, and subsequently declined. The median (range) RP Gleason sum score was 7 (4-9). The biopsy Gleason score correlated with the prostatectomy Gleason score in 252 (47%) of 536 men, being lower in 170 (32%) and higher in 113 (21%). The median tumour volume was 2 mL (focus of invasive acini - 31 mL) and the incidence of positive intra- and extraprostatic margins was 52%. Both tumour volume and extraprostatic margin positivity declined with time. CONCLUSIONS: The preoperative features and pathological findings from this UK series are similar to those of other reported cohorts from unscreened populations. The incidence of positive extraprostatic surgical margins, tumour volume and stage decreased with time.

Adult↗
PubMed2005

Initial experience with a mechanical ventilation weaning unit.

BACKGROUND: While increasing numbers of patients require prolonged mechanical ventilation, resources for weaning are either limited (ICU beds) or inadequate (general wards). OBJECTIVES: To report on our initial experience over a 7 month period with an eight-bed mechanical ventilation weaning unit. METHODS: Sixty-nine patients requiring MV for > 10 days were admitted to the unit (nurse:patient ratio 1:4). Data collected included reason for MV, duration of hospital stay, and MVWU course. Outcome results (successful weaning and mortality) were compared to those in historic controls (patients ventilated in the general wards over a 4 month period prior to the MVWU; n = 100). RESULTS: The mean age of the patients was 68 +/- 16.6 years and hospital stay prior to MVWU admission 28.6 +/- 24.2 days (range 10-72). The main reasons for MV included acute exacerbation of chronic obstructive pulmonary disease (31%) and recent pneumonia (28%). Mean MVWU stay was 13.5 +/- 15.7 days (range 1-72 days). Thirty-four patients (49%) underwent tracheostomy. Fourteen patients required admission to the ICU due to deterioration in their status. Twenty-nine patients (42%) were successfully weaned and discharged to the wards. A further 20 patients were transferred to the chronic ventilation unit of a regional geriatric rehabilitation hospital, where 5 were subsequently weaned and 15 required prolonged ventilation. Compared to controls (matched for age and reason for mechanical ventilation), more MVWU patients underwent successful weaning (49% vs. 12%, P < 0.001) and their mortality rate (n = 12) was significantly lower (17% vs. 88%, P < 0.001). CONCLUSION: The higher level of care possible in a MVWU may result in a significantly improved rate of weaning and lower mortality. The assessment of long-term outcome in patients discharged to pulmonary rehabilitation centers requires further investigation.

Aged↗
PubMed2005

ABC in Uganda: success or subterfuge?

Since the enactment of the US President's Emergency Plan for AIDS Relief (PEPFAR) in 2003, US officials have repeatedly pointed to Uganda as an example of the effectiveness of the "ABC" (Abstain, Be faithful, use Condoms) approach to HIV prevention. Uganda is one of few African countries to have experienced a decline in national HIV prevalence, from approximately 15 percent in the early 1990s to an estimated six percent today. While scholars continue to debate the reasons for this, the US government has attributed the decline to increased abstinence, faithfulness and condom use among Ugandans, and thus has made ABC the centerpiece of its global HIV prevention strategy.

Condoms↗
PubMed2005

Successful treatment of Bouveret syndrome using holmium: YAG laser lithotripsy.

Although gallstone disease is highly prevalent, cholelithiasis causing gallstone ileus is uncommon. Consideration has been given for nonoperative strategies to resolve obstruction due to the significant age and comorbidities afflicting this population. A 94-year-old man presented with a 5-day history of abdominal distension and tenderness. CT scan revealed multiple large gallstones within the gallbladder, pneumobilia, and two ectopic gallstones (antrum of the stomach and distal ileum). The patient was taken to the operating room where an enterolithotomy and gastrotomy was performed with removal of gallstones and subsequent relief of obstruction. During the postoperative course, the patient developed symptoms of gastric outlet obstruction and underwent gastrointestinal endoscopy for diagnosis and treatment. Two large gallstones, present in the duodenum, were retracted into the stomach using a Roth net but could not be retrieved beyond the upper esophageal sphincter. A holmium: yttrium-aluminum-garnet (Holmium: YAG) laser was used for fragmentation of the stones, with subsequent successful removal. This is the first documented successful use of the holmium: YAG laser for the treatment of recurrent gallstone ileus. Physicians should remember that in a small but important subgroup of patients, endoscopy accompanied by laser lithotripsy may prove beneficial.

Aged, 80 and over↗
PubMed2005

Southern Africa: AIDS-affected children face systemic discrimination in accessing education.

In June 2005, Human Rights Watch (HRW) conducted an investigation in Kenya, South Africa and Uganda to document AIDS-affected children's experiences of inequality and neglect in the school system. HRW found, consistent with previous research, that the sickness of one or both parents due to HIV/AIDS led many children withdraw from school to perform household labour or offset lost family income. Parental death often led to abandonment, discrimination within extended and foster families, and emotional trauma that interfered with school performance.

Africa, Southern↗
PubMed2004

For the law, neuroscience changes nothing and everything.

The rapidly growing field of cognitive neuroscience holds the promise of explaining the operations of the mind in terms of the physical operations of the brain. Some suggest that our emerging understanding of the physical causes of human (mis)behaviour will have a transformative effect on the law. Others argue that new neuroscience will provide only new details and that existing legal doctrine can accommodate whatever new information neuroscience will provide. We argue that neuroscience will probably have a transformative effect on the law, despite the fact that existing legal doctrine can, in principle, accommodate whatever neuroscience will tell us. New neuroscience will change the law, not by undermining its current assumptions, but by transforming people's moral intuitions about free will and responsibility. This change in moral outlook will result not from the discovery of crucial new facts or clever new arguments, but from a new appreciation of old arguments, bolstered by vivid new illustrations provided by cognitive neuroscience. We foresee, and recommend, a shift away from punishment aimed at retribution in favour of a more progressive, consequentialist approach to the criminal law.

Brain↗
PubMed2004

Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria.

To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.

Clinical Trials as Topic↗
PubMed2004

Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.

A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (>or=0.40 endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.

APACHE↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Adult↗
PubMed2004

Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study.

OBJECTIVE: Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients. DESIGN: A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries. INTERVENTIONS: None. PATIENTS: Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period. METHODS: Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia. RESULTS: We enrolled 97 patients, mean age 64+/-15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5+/-4.0. Mean IAP was 9.8+/-4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance. CONCLUSION: Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.

Abdomen↗
PubMed2004

HLA class II polymorphisms determine responses to bacterial superantigens.

The excessive immunological response triggered by microbial superantigens has been implicated in the etiology of a wide range of human diseases but has been most clearly defined for the staphylococcal and streptococcal toxic shock syndromes. Because MHC class II presentation of superantigens to T cells is not MHC-restricted, the possibility that HLA polymorphisms could influence superantigenicity, and thus clinical susceptibility to the toxicity of individual superantigens, has received little attention. In this study, we demonstrate that binding of streptococcal and staphylococcal superantigens to HLA class II is influenced by allelic differences in class II. For the superantigen streptococcal pyrogenic exotoxin A, class II binding is dependent on DQ alpha-chain polymorphisms such that HLA-DQA1*01 alpha-chains show greater binding than DQA1*03/05 alpha-chains. The functional implications of differential binding on T cell activation were investigated in various experimental systems using human T cells and murine Vbeta8.2 transgenic cells as responders. These studies showed quantitative and qualitative differences resulting from differential HLA-DQ binding. We observed changes in T cell proliferation and cytokine production, and in the Vbeta specific changes in T cell repertoire that have hitherto been regarded as a defining feature of an individual superantigen. Our observations reveal a mechanism for the different outcomes seen following infection by toxigenic bacteria.

Amino Acid Sequence↗
PubMed2004

Renal effects of parenteral fish oil administered to heart-beating organ donors and renal-transplant recipients: a tolerance study.

BACKGROUND & AIMS: Nutrition can interfere with organ function during the different stages of transplantation. Oral fish oil supplementation to kidney transplant recipients has been found to improve renal function. The aim of the present study was to determine the safety and tolerance of intravenous administration of fish-oil emulsion to heart-beating brain-dead donors and, subsequently, to the kidney recipients, and to assess its effects on renal function. METHODS: A lipid emulsion enriched with omega-3 fatty acids (MLF 541) was given intravenously to 8 heart-beating, brain-dead organ donors for up to 4 h before organ harvesting and to the kidney recipients for 5 days postoperatively. Hemodynamic, biochemistry and hematological parameters were measured before and at the end of lipid administration in the donors and on posttransplantation days 1, 5, 30 and 180 in the recipients. Findings in the recipients were compared with a concurrent control group. RESULTS: There were no significant changes in hemodynamic or laboratory parameters during the MLF infusion in the donors or the 5 days of MLF administration in the recipients. Blood urea nitrogen and serum creatinine levels decreased over time in both the study and control recipients (P < 0.05 for both), with no significant between-group difference at any of the time points studied. CONCLUSIONS: Administration of MLF 541 is safe in organ donors and in kidney recipients. Further studies involving nutrients as pharmacological agents in organ transplantation are warranted.

Aged↗
PubMed2004

Hypophosphatemia following open heart surgery: incidence and consequences.

OBJECTIVE: Significant hypophosphatemia (SH) is common after major surgery and may be associated with considerable morbidity, including respiratory and cardiac failure. The contribution of SH to these complications after cardiac surgery is not well defined. METHODS: In this prospective study, levels of serum phosphorus and other electrolytes (potassium, magnesium and calcium) were measured in 566 consecutive patients (395 men, 182 women; mean age 65.5+/-11.1 years) undergoing elective cardiac surgery at three time points: prior to surgery, immediately on admission to the ICU, and on the first postoperative day. Preoperative (type of surgery, Bernstein-Parsonnet risk estimate), intraoperative (duration of bypass and cross-clamp, intraoperative fluid and blood product use) and postoperative data (duration of ventilation, duration of ICU and hospital stay, requirement for cardioactive drug support, development of atrial fibrillation, and mortality) were collected. Patients were divided into two groups according to the immediate postoperative phosphate level: SH, phosphate <0.48 mmol/l (mean phosphate 0.28+/-0.13 mmol/l, n = 194), and a control group (mean phosphate value 0.84+/-0.08 mmol/l, n = 372). Patients with SH received treatment with sodium or potassium phosphate (0.8 mmol/kg body weight over 6-12 h). RESULTS: SH was present in 34.3% of patients. There were no differences in the baseline characteristics between the two groups. Patients with SH received more intraoperative blood product transfusions. The postoperative course of patients with SH was characterized by prolonged ventilation (2.1+/-1.7 versus 1.1+/-0.9 days, P = 0.05), more patients requiring cardioactive drugs (12-24 h 16 versus 10.9%, P = 0.05 and >24 h 23.5 versus 13.8%, P = 0.05); and a prolonged hospital stay (7.8+/-3.4 versus 5.6+/-2.5 days, P = 0.05). CONCLUSIONS: SH was common after open-heart surgery and was associated with an increased incidence of important complications. We suggest that phosphate levels be routinely measured immediately after surgery and appropriate therapy instituted.

Aged↗
PubMed2004

The impact of tissue sampling on endoscopy efficiency.

Much of the time spent in gastrointestinal endoscopy is devoted to tissue sampling. For this reason, efforts to facilitate tissue diagnosis can greatly influence the overall efficiency of endoscopy. This overview reviews the steps involved in tissue sampling and highlights potential ways to achieve increased efficiency in tissue sampling. Both potential improvements in process and innovations in technology are considered.

Biopsy↗