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Biomedical subjects

S Jacobs

Publications and source records attributed to S Jacobs.

At least 145 records · Page 8Linked to original sources
PubMed1989

An analysis of the utilisation of an intensive care unit.

We monitored the response to intensive care of 480 patients by calculating the difference in their organ failure score on the day of admission and that on the day of discharge, and related the response to hospital outcome. The patients were classified into: A) those who benefited (33%), B) those who might have benefited (28%), C) those who would never or would no longer have benefited (18%) and D) those who did not require intensive care management (21%). The criteria used were response to therapy, individually predicted outcome, hospital outcome and perceived need for intensive care. Group C patients used up 26.8% of the total intensive care unit bed days, while group D patients occupied 3.7%. We concluded that an acute terminal care unit to care for group C patients who have no hope of survival is more appropriate to the needs of our hospital than an intermediate care unit for overnight monitoring of uncomplicated postoperative and non-operative patients (group D).

Critical Care↗
PubMed1989

Lack of diurnal variation in plasma levels of androstenedione, testosterone, estrone and estradiol in postmenopausal women.

Plasma 4-en-androstenedione, testosterone, estradiol and estrone were measured during the day in six healthy postmenopausal women and in six breast cancer patients, three of whom received treatment with glucocorticoids. Blood samples were obtained at 8 a.m., 10 a.m., 12 noon, 4 p.m., 8 p.m. and 12 midnight. There was a considerable variation in plasma levels of all steroids during the day; for 4-en-androstenedione the mean within patient coefficient variation was 61.4%, for testosterone it was 28.9%, for estrone it was 17.8% and for estradiol it was 29.2%. While the plasma levels for all steroids tended to be higher in the morning than in the evening, the changes were not statistically significant (Friedman's test: P greater than 0.10). We conclude that although a moderate diurnal variation in the plasma level of these steroids may occur, it is of a moderate magnitude compared to variations due to other causes.

Androstenedione↗
PubMed1989

Accuracy of decisions to withdraw therapy in critically ill patients: clinical judgment versus a computer model.

Two clinicians and the nursing sisters working in the ICU evaluated the chance of survival of ICU patients every day. Patients were assessed either as "outcome unknown or will die." These predictions were compared with those made by computerized trend analysis of daily acute physiology and chronic health evaluation (APACHE II) scores corrected for the presence and duration of major organ system failure. The predictions were not acted upon during the study. Comparing the predictions with actual hospital outcome, the doctors and nurses had a false-positive diagnosis rate for dying of between 7.7% and 16.7%, while there were no false predictions by the computer model. The patients predicted to die by the doctors and nurses were not completely identical to those predicted by the computer. Predictions of doctors and nurses that were confirmed by the computer had a sensitivity of 20% and no false predictions of death.

Decision Making, Computer-Assisted↗
PubMed1989

Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice.

Insulin and insulin-like growth factors (IGIs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR) expressed in these cells may mediate the growth effects of these peptides. We have examined the role of this receptor on human breast cancer growth with a monoclonal antibody (alpha-IR-3) that blocks the receptor binding domain and inhibits IGF-I-induced growth. alpha-IR-3 inhibited clonal growth in vitro and blocked the mitogenic effect of exogenous IGF-I in both MCF-7 and MDA-231 breast cancer cell lines. Antibody-induced blockade of the type I SR also inhibited the estrogen-independent MDA-231 cells growing in vivo in nude mice, but growth of the estrogen-dependent MCF-7 cells was unaffected. IGIs are important growth regulators of MDA-231 breast cancer cells. Blockade of this growth stimulatory pathway may provide a new treatment strategy.

Animals↗
PubMed1989

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in patients with refractory metastatic carcinoma.

The effect of human recombinant GM-colony-stimulating factor (CSF) was evaluated in ten patients with refractory metastatic carcinoma. Initially they received an intravenous (IV) bolus injection of 5 or 25 micrograms/m2 for assessment of acute responses. Six days later, continuous IV infusions of 100 or 500 micrograms/m2 were initiated for a 14-day treatment course. All patients developed profound leukopenia within five to 30 minutes of the bolus injection. This appeared to result from increased expression of an adhesion-promoting glycoprotein (GP) on neutrophils and monocytes as judged by increased reactivity to the Mo1 monoclonal antibody (MoAb). Leukocyte counts returned to normal levels within two hours as cells were released from marrow stores. With the continuous infusion, leukocyte counts increased by 24 hours; peak values of 22,960 and 75.900/microL were achieved after ten to 14 days of treatment with the two dose levels of GM-CSF. This leukocytosis was due to an increase in virtually all cell types. At the high dose level, there was a striking increase in neutrophils (49,400/microL) and eosinophils (20,905/microL) with a sixfold increase in monocytes and two- to threefold increase in lymphocytes. Leukocyte counts declined promptly after cessation of the infusion but remained above baseline for as long as 2 weeks in some patients. These results suggest that GM-CSF may be useful as an adjuvant therapy by stimulating myelopoiesis in cancer patients.

Bone Marrow↗
PubMed1988

Effects of inhibitors of N-linked oligosaccharide processing on the biosynthesis and function of insulin and insulin-like growth factor-I receptors.

We have used specific inhibitors of oligosaccharide processing enzymes as probes to determine the involvement of oligosaccharide residues in the biosynthesis and function of insulin and insulin-like growth factor-I receptors. In a previous study (Duronio, V., Jacobs, S., and Cuatrecasas, P. (1986) J. Biol. Chem. 261, 970-975) swainsonine was used to inhibit mannosidase II, resulting in the production of receptors containing only hybrid-type oligosaccharides. These receptors had a slightly lower molecular weight and were much more sensitive to endoglycosidase H, but otherwise behaved identically to normal receptors. In this study, we used two compounds that inhibit oligosaccharide processing at earlier steps: (i) N-methyl-1-deoxynojirimycin (MedJN), which inhibits glucosidases I and II and yields glucosylated, high mannose oligosaccharides, and (ii) manno-1-deoxynojirimycin (MandJN), which inhibits mannosidase I and yields high mannose oligosaccharides. In the presence of MandJN, HepG2 cells synthesized receptors of lower molecular weight, which were cleaved into alpha and beta subunits and were able to bind hormone and autophosphorylate. These receptors were as sensitive to endoglycosidase H as receptors made in the presence of swainsonine. In the presence of MedJN, receptors of only slightly lower molecular weight than normal were synthesized and were shown to contain some glucosylated high mannose oligosaccharides. These receptors were able to bind hormone and retained hormone-sensitive autophosphorylation activity. In both cases, the incompletely processed receptors could be detected at the cell surface by cross-linking of iodinated hormone and susceptibility to trypsin digestion, although less receptor was present in cells treated with MedJN. Studies of receptor synthesis using pulse-chase labeling showed that the receptor precursors synthesized in the presence of MedJN were cleaved into alpha and beta subunits at a slower rate than normal receptors or those made in the presence of MandJN. Inhibition of oligosaccharide processing had no effect on the association of the receptor subunits into disulfide-linked oligomeric complexes.

Animals↗
PubMed1988

Predicting outcome among intensive care unit patients using computerised trend analysis of daily Apache II scores corrected for organ system failure.

Daily Apache II scores were determined prospectively on 310 consecutive adult Intensive Care Unit (ICU) patients to reflect the dynamic pathophysiological processes affecting ICU patients. Organ failure scores were derived from the Apache II scores by applying a coefficient which corresponded to the number and duration of organ failures to account for the increased mortality associated with established major organ-system failures. Computerised trend analysis of data from the first 100 patients was used to develop criteria for predicting hospital outcome of the ICU patients. The analysis took into account the absolute value of the daily scores and the rate of change relative to that of the previous day. Allowance was made for changes in scores as a result of surgery or major iatrogenic complications arising after admission to the ICU. The criteria were then tested prospectively on the next 210 consecutive ICU patients. Predictions by Apache II assessments were NOT used to influence clinical decisions during the study period. It was possible to predict with a specificity of 100% 37 out of the 72 deaths in the test group. The predictive power of daily organ failure scores was superior to those obtained from a single Apache II assessment or from daily Apache II scores by a factor of 5.3 and 1.4 respectively. The estimated long-term risk of a false prediction is 1.4% at the 95% confidence level.

Critical Care↗
PubMed1988

Audit of intensive care: a 30 month experience using the Apache II severity of disease classification system.

608 patients admitted to a general Intensive Care Unit (ICU) over a 30 month period were analyzed according to the Apache II Severity of Disease Classification System on day one of admission. Hospital outcome details were available on 583 patients in the series. The mean Apache II scores for survivors (396) and non-survivors (187) were 13 (SD 7) and 24 (SD 9), and their Risk of Death were 16 (SD 16) and 47 (SD 27) respectively (p less than 0.001 for both). The majority of deaths (75%: 141/187) in our series came from those with chronic ill health (55%: 103/187), of whom 37% (38/103) were in endstage disease, and those with "old" trauma (18%: 34/187) often with incipient sepsis transferred from other hospitals after a mean delay of 9 days. Our higher than predicted mortality (mortality ratio 1.2) in comparison with centres in the United States of America (US) may be partly explained by the high proportion of our population from these unfavourable groups, by our use of the best Glasgow Coma Scale in the first 24 h following admission, and the major differences between our patient population and that of the US upon which the Apache II was based. The presence of these large unfavourable groups indicates a change in our admission policy is warranted.

Adult↗
PubMed1988

Cost-effective eradication of an outbreak of methicillin-resistant Staphylococcus aureus in a community teaching hospital.

During an eight-month period, 25 hospitalized patients became infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) in a 464-bed acute care, medical-surgical teaching hospital. There were only five cases during the eight months prior to the outbreak period (P less than 0.0001). Initial measures, including category-specific isolation and education, did not limit the spread of the outbreak of a strain of MRSA. This prompted institution of additional measures including (1) strict isolation of all infected and colonized cases; (2) prospective microbiological surveillance to detect additional cases; (3) multiple site cultures of identified cases to determine the extent of colonization; (4) employee and environment surveillance; (5) antibiotic decolonization of patients and employees; and (6) educational efforts. The highest number of personnel carriers were noted in one of the critical care units where most of the cases occurred. The decolonization protocol was 100% effective for personnel carriers. The incidence of nosocomial cases of MRSA fell to zero in the five months following the implementation of the strategy. The cost of the entire eradication process was approximately half that of treating a single MRSA bacteremia.

Cost-Benefit Analysis↗
PubMed1988

Predicting deaths among intensive care unit patients.

Daily APACHE II assessments to reflect the dynamic pathophysiologic processes affecting ICU patients were carried out prospectively on 212 adult ICU admissions for the purpose of predicting hospital outcome. Trend analysis of daily APACHE II scores was used to develop the first set of criteria for predicting deaths among the ICU patients. The analysis took into account the absolute value of APACHE II score of each day and the rate of change relative to that of the previous day. One hundred consecutive adult ICU admissions were used to determine the criteria that were tested on the following 112 consecutive adult ICU admissions. Daily APACHE II scores identified correctly 16 of the 34 patients who died. A second set of criteria was next derived by raising the values of the original limits in order to build-in greater margins of safety without too great a loss of sensitivity. The predictive power of daily APACHE II scores using the second set of criteria was superior to that of a single APACHE II score by a factor of 4. Predictions were not used to influence clinical decision-making during this study.

Aged↗
PubMed1987

An antibody to the receptor for insulin-like growth factor I inhibits the growth of MCF-7 cells in tissue culture.

Alpha IR-3, a monoclonal antibody to the insulin-like growth factor I receptor which blocks insulin-like growth factor I binding and inhibits its activity, inhibits the binding of 125I-insulin-like growth factor I to MCF-7 cells (an estrogen dependent human breast carcinoma cell line) with an IC-50 of approximately 100 ng/ml. It also inhibits the growth of MCF-7 cells cultured in 5% calf serum with approximately the same IC-50. Inhibition of growth occurs both when cells are cultured in the presence and absence of estrogen and is more pronounced when cells are grown at a low density. These findings demonstrate a requirement for insulin-like growth factor I for optimal growth of MCF-7 cells and suggest that it is an autocrine growth factor in these cells.

Animals↗
PubMed1987

Characterization of a neuronal subtype of insulin-like growth factor I receptor.

Primary neuronal cultures from fetal rat brain were utilized to investigate the possible role of insulin-like growth factor I (IGF-I) in neuronal growth and differentiation. 125I-IGF-I binding to intact cultured neurons was specific and saturable with an apparent Kd of 7.0 +/- 1.2 nM and a Bmax of 1.8 +/- 0.3 pmol/mg protein. Binding of 125I-IGF-I to neurons was inhibited by IGF-I, followed by IGF-II and insulin. 7 S nerve growth factor, but not beta-nerve growth factor, also inhibited 125I-IGF-I binding. A similar binding site was detected on brain membranes. Affinity cross-linking of 125I-IGF-I to intact cultured neurons revealed, under reducing conditions, a major binding moiety with an Mr of 115,000 and a minor component at Mr 260,000. The former represents a neuronal type of the IGF-I receptor alpha subunit, whereas the latter probably represents an alpha dimer. The Mr = 115,000 binding component for 125I-IGF-I was also present in membranes prepared from postnatal whole brain. In contrast, the binding moiety in cultured glial cells was of Mr = 135,000, which was identical to the IGF-I receptor alpha subunit of placenta. Thus mature brain, despite its cellular heterogeneity, expresses a structural subtype of IGF-I receptor which appears to be unique to differentiated neurons. Moreover, glial and neuronal cultures secreted a polypeptide which specifically bound IGF-I; the apparent Mr of this binding protein was determined by affinity cross-linking to be approximately 35,000. The presence of neuronal IGF-I receptors and binding proteins suggested that IGF-I may exert neurotrophic effects on developing neurons. This possibility was supported by the observation that IGF-I markedly stimulated neuronal RNA synthesis.

Animals↗
PubMed1987

Gastrointestinal dysfunction among intensive care unit patients.

This study used the Acute Physiological and Chronic Health Evaluation (APACHE II) system to select two groups of ICU patients with comparable risk of hospital death to evaluate the importance of GI dysfunction, defined as failure to tolerate enteral nutrition (EN), as a prognostic factor. In our ICU, patients who have not undergone recent bowel surgery are treated by EN. Those patients who cannot tolerate EN are treated by total parenteral nutrition (TPN). One hundred and eleven patients who tolerated EN (functioning gut) and 97 TPN patients who failed to tolerate EN (GI dysfunction) were studied. The mean APACHE II scores of the two groups were 17.7 +/- 6.5 (SD) and 17.7 +/- 5.1, respectively. The observed mortality of patients with GI dysfunction (51%) was significantly higher (p less than .0005) than that of patients with a functioning gut (25%). This was associated with significantly poorer APACHE II mean BP, oxygenation, and creatinine scores among the GI dysfunction patients. Our results suggest that shock, ischemia, and hypoxemia, in addition to causing impairment of renal function, may bring about changes in the GI tract, evident clinically only as a failure to tolerate EN, which have an adverse effect on the prognosis of ICU patients so affected.

Adult↗
PubMed1987

One year's experience with the APACHE II severity of disease classification system in a general intensive care unit.

The APACHE II sickness score was applied prospectively for one year in a general intensive care unit in Saudi Arabia. Two hundred and ten patients were studied, 66 of whom died in hospital. The mean APACHE II score of survivors was 11 (SD 7.1) and of non-survivors, 25.3 (SD 8.8). The mean Risk of Death was 13.3% (SD 13.1) for the survivors and 47.2% (SD 25.8) for non-survivors. The differences in APACHE score and Risk of Death between survivors and non-survivors are highly significant (p less than 0.0005 for both). No patient survived who had a Risk of Death greater than 60% and none died with a Risk of Death less than 7%. The sensitivity of the APACHE II system in predictions of death can be improved if the scores on the day of admission and on the 3rd day are taken into account.

Adult↗
PubMed1986

Use of APACHE II severity of disease classification to identify intensive-care-unit patients who would not benefit from total parenteral nutrition.

The APACHE II severity of disease classification system was tested for its ability to identify intensive-care-unit (ICU) patients who would not benefit from treatment with total parenteral nutrition (TPN). First, the classification was validated in our patient population by testing it on 210 consecutive ICU admissions. Then a retrospective study was done on 89 ICU patients who had received TPN, to define APACHE II selection criteria. When the APACHE II system was tested prospectively on 26 ICU patients treated with TPN, it predicted correctly, with a specificity of 100%, half of the patients who died.

Adult↗