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J Lipman

Publications and source records attributed to J Lipman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.

Somatic mutations in DNA mismatch repair genes have been observed in sporadic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the development of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determined accurately. We have analyzed 66 sporadic colorectal tumors for the expression of hMLH1 by immunohistochemistry and identified 4 tumors that do not express hMLH1. These four colorectal tumors, a colon tumor cell line (SW48) and an endometrial tumor cell line (AN3CA), did not express hMLH1, despite the absence of mutations in its coding sequence. Cytosine methylation of the hMLH1 promoter region was found in these four colorectal tumors, whereas cytosine methylation of the hMLH1 promoter region was absent in adjacent normal tissue or in nine tumors that expressed hMLH1. In addition, cytosine methylation of the hMLH1 promoter region was observed in the SW48 and AN3CA cell lines that do not express hMLH1 but not in four tumor cell lines known to express hMLH1 mRNA. Our data indicate that DNA methylation is likely to be a common mode of mismatch repair gene inactivation in sporadic tumors.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Intermittent bolus dosing of ceftazidime in critically ill patients.

Ceftazidime is frequently used in critically ill patients, particularly for the treatment of Pseudomonas aeruginosa infections. The recommended dosing regimen is based on pharmacokinetic data obtained in healthy volunteers and may not be appropriate in the critically ill. We administered ceftazidime in the maximum recommended dose (2 g i.v. every 8 h) to ten critically ill patients with normal plasma creatinine. Eighteen arterial blood samples were taken from each patient over the first 8 h for measurement of ceftazidime concentrations and subsequent compartmental pharmacokinetic analysis. An additional trough sample was taken from each patient on day 3. Although mean pharmacokinetic variables did not differ from previously reported data in normal volunteers there was wide variability in plasma drug concentrations. Three of our patients had plasma ceftazidime concentrations less than the MIC for P. aeruginosa (8 mg/L) and nine had concentrations less than 5 x MIC, which has been recommended to ensure efficacy. On day 3 trough ceftazidime concentrations were less than the MIC in four out of the seven patients in whom measurements were made and less than 5 x MIC in the remaining three. There was no clinical predictor of which patients would have low plasma concentrations. Our results show that plasma concentrations of ceftazidime are very variable when the recommended intermittent bolus dosing regimen is used and may result in inadequate plasma concentrations of drug in critical infections. This may result in treatment failure and the emergence of antibiotic resistance. A loading dose followed by continuous infusion should overcome these problems but this awaits in-vivo evaluation.

Adult↗
PubMed1997

Gastric intramucosal pH and blood lactate in severe sepsis.

We prospectively investigated the effect of conventional resuscitation on gastric intramucosal pH and lactate over 5 days in a group of patients with newly diagnosed severe sepsis. Lactate and gastric intramucosal pH were measured on entry into the study, as soon as resuscitation end points were met, eight hourly for 48 h and daily for 5 days. Sixteen of 18 patients had a low gastric intramucosal pH (mean (SD) 7.17 (0.12)) at the time of diagnosis of severe sepsis. At no time did gastric intramucosal pH or lactate distinguish between shocked and nonshocked patients. Lactate distinguished survivors from nonsurvivors over time (p = 0.02). Gastric intramucosal pH did not distinguish survivors from nonsurvivors over time (p = 0.72). At 48 h lactate was lower in survivors (p < 0.01) and gastric intramucosal pH higher in survivors (p < 0.05). Receiver operating characteristic curves at this time indicate that lactate is a better predictor of survival. It is likely, based on the inability of gastric intramucosal pH to distinguish survivors from nonsurvivors until 48 h, that it is not possible to use this measurement to guide resuscitation in patients who are severely ill and who have gastric intramucosal acidosis.

Adult↗
PubMed1997

Measurements of glomerular filtration in the intensive care unit are only a rough guide to renal function.

An estimate of glomerular filtration rate (GFR) is important in intensive care units (ICUs) to individualize drug dosages, and for the early detection of acute renal failure (ARF). Creatinine clearance or calculations based on plasma creatinine are the most widely used indicators of GFR, but may be very inaccurate in critically ill patients. We have assessed the accuracy of predictions of GFR by creatinine clearance and plasma creatinine in critically ill patients with variable creatinine kinetics. This is a retrospective record review set in a 24-bed multidisciplinary ICU. Eighteen patient records (9 normal renal function, 9 with ARF-250 patient days) were evaluated. Creatinine clearance measured daily over an 8-hour period, plasma creatinine, creatinine production and 8-hourly urine output were recorded for each day of ICU stay. The discrepancy between measured creatinine clearance and creatinine clearance predicted by the Cockcraft-Gault equation was determined. The coefficient of variation (CV) for each of the contributing variables and the final inherent error for the estimation of GFR were determined. The difference between measured and predicted creatinine clearance was large (predicted GFR may be from 60 ml/min above to 70 ml/min below measured creatinine clearance). The mean CV for creatinine production was 28% and for 8-hourly urine output it was 34%. The estimation of GFR from creatinine clearance can be made at +/- 52% of the calculated value, whereas the estimation of GFR by Cockcraft-Gault is accurate at +/- 37% of the calculated value. Unstable creatinine kinetics from variable urine output and creatinine production in critically ill patients make accurate estimation of GFR impossible. While prediction methods have fewer inherent sources of error, plasma creatinine may be influenced by factors other than renal function. The use of prediction equations is as inaccurate as measured clearance in unstable ICU patients.

Acute Kidney Injury↗
PubMed1997

Severe soft-tissue infections--a diagnostic challenge. The need for early recognition and aggressive therapy.

OBJECTIVES: This article was written to highlight the difficulty in diagnosing necrotising fasciitis (NF) and in differentiating it from other severe soft-tissue infections, and to stress the need for early aggressive therapy in all severe soft-tissue infections. METHOD: Four cases of severe soft-tissue infection admitted to Baragwanath Hospital Intensive Care Unit between January 1993 and March 1996 are reported, presenting the relevant clinical features. RESULTS: The clinical diagnosis of NF when used alone was found to be unreliable and the diagnosis appeared to be made late in the course of the disease. Late diagnosis makes intensive care (largely supportive therapy) of limited value. CONCLUSION: Astute clinical awareness and prompt therapy for severe soft-tissue infections are needed to enable the early diagnosis of these syndromes and thus prevent their serious sequelae. This should include a thorough knowledge of these conditions and predisposing risk factors. For comparative purposes specific defining clinical criteria are required. Even with full intensive care support, severe soft-tissue infections are associated with a significant mortality rate.

Adult↗
PubMed1996

Poor discriminatory performance of the Pediatric Risk of Mortality (PRISM) score in a South African intensive care unit.

OBJECTIVE: The use of the Pediatric Risk of Mortality (PRISM) score or other scoring systems in the intensive care unit (ICU) is of great importance for evaluating the efficacy and efficiency of a particular ICU. However, the PRISM score was developed and validated in the United States and subsequently validated in Europe, but has not been evaluated in a less affluent society. In general, scoring systems should be used only in populations similar to the reference population in which the prediction model was developed. We set out to determine the applicability of the PRISM score at Baragwanath Hospital, South Africa. DESIGN: Prospective, descriptive study. SETTING: Twenty-four-bed multidisciplinary ICU. PATIENTS: We analyzed 1,528 consecutive pediatric admissions from January 1989 to June 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM scores, Therapeutic Intervention Scoring System scores, demographic, and clinical data collected prospectively were entered and stored by means of a commercial software package at the time of admission of each patient. The prediction of actual mortality by PRISM scoring was evaluated by the Hosmer and Lemeshow goodness-of-fit test (chi2[8 degrees of freedom]). Receiver operating characteristic curves were constructed and compared with those curves from pediatric ICU populations in the United States and Europe. Individual receiver operating characteristic curves were constructed for surgical and nonsurgical patients, age categories, and diagnostic categories. Compared with European and American ICU populations, our patients were younger, were mostly nonsurgical emergency admissions, stayed longer in the ICU, and were more severely ill with a higher admission PRISM score and overall mortality rate. Respiratory and septic diagnoses predominated, with very few surgical cases admitted. The Hosmer and Lemeshow goodness-of-fit test showed a significant failure of the PRISM scoring system to accurately predict mortality over a wide range of expected mortality rates (chi2[8 degrees of freedom] = 465, p = 0). Similarly, receiver operating characteristic analysis indicated a poor predictive power (Az = 0.73 +/- 0.01 [SEM]), with an area under the curve significantly less than that for the PRISM reference population (p = 0). PRISM showed equally poor discriminatory function at all age groups and diagnostic categories. CONCLUSIONS: The PRISM score needs to be recalibrated or recalculated for our patient population in view of the high discrepancy and poor discriminatory function shown. Part of the inaccuracy may derive from different demographic characteristics of our ICU population and a different pattern of diseases. It appears that PRISM is not population independent.

Child↗
PubMed1996

Acute stridor as a presentation of bilateral abductor vocal cord paralysis.

We report the case of a 48-year-old woman, referred to the Intensive Care Unit with community-acquired pneumonia, who was noted to have stridor of acute onset. Subsequent indirect laryngoscopy revealed bilateral abductor vocal cord paralysis, secondary to unsuspected carcinoma of the oesophagus, requiring immediate tracheostomy. We highlight the importance of visualisation of the vocal cords in cases of stridor of uncertain aetiology.

Carcinoma, Squamous Cell↗
PubMed1996

Predictors of mortality in severe malaria: a two year experience in a non-endemic area.

Management of severe malaria is an increasing problem worldwide. This paper reviews the pathophysiology and management documenting two years' experience of admissions of severe malaria to an ICU in a non-endemic area. Clinical and laboratory features of severe malaria were analysed for predictors of mortality Twenty-eight patients had clinical or laboratory features compatible with the WHO criteria for severe malaria and, despite treatment with intravenous quinine and supportive ICU care, mortality was 28.5% (8/28). The three pregnant patients died with 100% foetal mortality and the four paediatric patients survived. Of the non-survivors, 8/8 developed ARDS (defined by worst ALI score > 2.5), 7/8 developed shock requiring inotropic support and 7/8 developed acute renal failure requiring CVVHD. Admission haemoglobin, platelet count, parasite count, and lowest Glasgow Coma Score in the first 24 hours were shown not to be predictors of mortality.

Acute Kidney Injury↗
PubMed1996

A guideline for competency of the critical care nurse.

BACKGROUND: To maintain a high standard of quality nursing care the individual critical care nurse s competencies should be determined objectively. Few international guidelines describe the qualities required by critical care nurses to function effectively in a critical care unit. These guidelines often focus only on the education and training of critical care nurses. OBJECTIVE: To formulate and describe guidelines for the competency requirements of registered critical care nurses. METHOD: A focus group interview, a qualitative research method, was conducted as an open conversation in which each participant could ask questions, comment, or respond to comments. Interaction among the respondents was encouraged to stimulate in-depth discussion. The study was conducted within the framework of South African critical care nursing. RESULTS: The four main categories that were identified are as follows: professional competence, cognitive competence, interpersonal skills, and critical care patterns of interaction. These are described in detail along with a formulated guideline for critical care nurse competency requirements. CONCLUSION: This study describes an attempt to formulate objective guidelines for critical care nurses competency requirements.

Adult↗
PubMed1996

High-dose adrenaline with low systemic vascular resistance and symmetrical peripheral gangrene.

Symmetrical peripheral gangrene (SPG) is an uncommon syndrome consisting of distal ischaemic damage in two or more extremities, without large-vessel obstruction. We describe its development in the presence of a high cardiac and low systemic vascular resistance in a patient who was on high-dose adrenaline. With palpable radial and popliteal pulses the patient's hands and feet became dusky. This progressed to SPG. A sudden increase in serum lactate to high levels, noted in this case, may mark the onset of SPG.

Adult↗
PubMed1996

Development and validation of a critical care patient classification system.

OBJECTIVE: To describe the research methodology used in development and validation of a scientific patient classification instrument for South African critical care patients. METHOD: This is a contextual, exploratory, and descriptive study. A two-phase validating model was used as a research method. In the development phase a literature review was carried out (domain identification), a provisional instrument developed (item generation), and a peer group discussion conducted (item formation). In the quantification phase 16 experts determined if both the items of the instrument and the entire instrument were content valid. The study was conducted within the framework of South African critical care nursing. RESULTS: In the peer group discussion the instrument was debated until consensus was reached. In the quantification phase, both the items of the instrument and the entire instrument were rated as content valid. CONCLUSIONS: Established patient classification systems can be successfully adapted and validated for local use.

Critical Illness↗