Biomedical subjects
Publications and source records attributed to S Klein.
The delayed-type hypersensitivity (DTH) response and lymphocyte-mediated angiogenesis were determined in mice bearing in vivo cultures of mammary tumor cells in diffusion chambers (DCs). Soluble tumor products which diffuse from the DCs were able to stimulate the immune system for both the DTH reaction and angiogenic activity by spleen cells.
Although more than 70 prospective randomized controlled trials have evaluated the use of nutrition support in patients with cancer, the indications for nutrition therapy in this patient population remain controversial. We reviewed the published prospective randomized controlled trials that evaluated clinically important endpoints (morbidity, mortality, and duration of hospitalization). Many trials had serious shortcomings in study design that limit the ability to draw definitive conclusions from the data. In general, the data failed to demonstrate the clinical efficacy of providing nutrition support to most patients with cancer. Therefore, the indications for using nutrition therapy should be the same as those for patients with benign disease.
Lymph node and bone marrow trephine biopsies of seventy two consecutive cases of non-Hodgkin's lymphoma occurring among black Zimbabweans were reviewed to determine bone marrow involvement. The bone marrow was involved in 23.6% of patients but the proportion of bone marrow positive cases was highest in low grade lymphomas, though these were the least common type of lymphoma encountered. Cells infiltrating the marrow showed high degree of concordance with corresponding lymph node histology. Low grade lymphomas (CLL excluded) had a predominantly diffuse pattern of marrow involvement while intermediate and high grade lymphomas had nearly equal proportions with diffuse and focal patterns. Bone-marrow involvement did not make a significant difference to the staging of non-Hodgkin's lymphoma as most cases not involving the marrow also presented with advanced disease. Mean age of patients was negatively correlated with histological grade but was not related to bone marrow involvement. Central nervous system involvement occurred mostly in the high grade lymphomas and was proportionately distributed between bone marrow positive and negative cases. 40% of non-Hodgkin's lymphoma were associated with HIV infection but HIV-associated lymphoma surprisingly very rarely infiltrated the bone marrow.
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Mammography and physical examination have a sensitivity of 85 percent for detection of carcinoma of the breast. Mammography also has a positive predictive value of 15 to 30 percent. The aim of this study was to evaluate the usefulness of scintimammography (SMM) as a screening technique for the detection of carcinoma of the breast and compare the test's sensitivity and specificity with that of mammography. We conducted SMM on 59 female patients in whom abnormal mammogram and physical examination warranted biopsy of the breast or fine needle aspiration cytology of the breast, or both. Each patient received 20 millicuries of 99mTc Sestamibi intravenously. Five and sixty minutes postinjection, planar breast images in lateral and posterior oblique views were obtained. In 23 patients with biopsy-confirmed carcinoma of the breast, the SMM result was positive. In 33 patients with benign breast lesions, no increased uptake of Sestamibi was noted in the breast. Five other patients with benign lesions of the breast had false-positive scans. There was one patient with an intraductal carcinoma and a cluster of microcalcifications on mammography without an associated mass, for whom the 99mTc Sestamibi scan was negative. In the group of patients studied, the sensitivity of SMM was 95.8 percent, specificity was 86.8 percent, positive predictive value was 82.1 percent and, most importantly, the negative predictive value for the detection of carcinoma of the breast was 97.1 percent. We conclude in this pilot study that SMM is a highly sensitive test that improves the specificity of conventional mammography for the detection of carcinoma of the breast and deserves further study as a screening technique to potentially reduce the number of mammographically "indicated" biopsies of the breast that yield negative results for carcinoma.
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The effect of overfeeding on energy metabolism was evaluated in four young adult men of normal weight. Subjects were fed a hypocaloric diet for 8 days followed by an 8-day hypercaloric diet to maximize differences in the metabolic response to the two diets. Energy intake during the hypocaloric and hypercaloric phases was 1.32 and 2.26 times resting metabolic rate (RMR), respectively. Additional calories during hypercaloric feeding were provided as 1,659 +/- 40 kcal/d carbohydrate and lipid. Total daily energy expenditure (TDEE) was measured by the doubly labeled water technique and RMR by indirect calorimetry. Nonresting energy expenditure (NREE) was calculated as the difference between TDEE and RMR. During the 8-day hypocaloric diet period, energy intake was approximately 340 kcal/d less than the measured rate of TDEE (2,384 +/- 219 kcal/d) and the subjects lost 0.8 +/- 0.3 kg body weight. During the 8-day hypercaloric diet period, TDEE increased by 425 +/- 103 kcal/d (P = .03), which dissipated 25% +/- 5% of the increased energy intake. One fourth of the increase in TDEE was caused by an increase in RMR (110 +/- 24 kcal/d, P = .02) and the remainder by an increase in NREE (316 +/- 103 kcal/d, P = .05). These results demonstrate that only a small portion of excess energy intake is dissipated by an increase in energy expenditure. NREE can be an important component of the increase in energy metabolism during overfeeding.
Candidemia in critically ill patients is a significant source of mortality. To identify perioperative risk factors accounting for patient death, we performed a retrospective study of 46 surgical patients with fungemia during the period from 1981 to 1990. Twenty patients survived (43%), and 26 died (57%). Mortality was associated with age older than 46 (p < 0.02, unpaired Student's t-test) and concomitant renal failure, hepatic failure, postoperative shock, or adult respiratory distress syndrome (p < 0.0001, p < 0.0001, and p < 0.05, respectively, chi 2 test). Survival was not influenced by the presence of diabetes, chronic obstructive pulmonary disease, gastrointestinal hemorrhage, pneumonia, alcohol consumption, steroid use, or enteral/parental nutrition. Bacterial speticemia developed in 26 patients (11 lived, 15 died) and typically preceded or was concomitant with the onset of fungal sepsis (88%). Candida albicans was the fungal species most commonly isolated from blood cultures (30 of 46). Its was cultured from other sites in addition to blood in 30 patients. Candidemia carries a higher risk of mortality in older patients and in those with multiple organ dysfunction. Other immunocompromised conditions such as diabetes and steroid use did not increase mortality. These findings suggest that the pathogenicity of Candida sepsis is not solely related to opportunistic superinfections but may reflect failure of other host defense mechanisms. Moreover, the frequent occurrence of bacterial septicemia prior to the development of Candida sepsis further emphasizes the importance of fungal surveillance cultures to detect early fungal colonization in the critically ill.
During angiogenesis capillary endothelial cells undergo a coordinated set of modifications in their interactions with extracellular matrix components. In this study we have investigated the effect of the prototypical angiogenic factor basic fibroblast growth factor (bFGF) on the expression and function of several integrins in microvascular endothelial cells. Immunoprecipitation experiments with antibodies to individual subunits indicated that microvascular cells express at their surface several integrins. These include the alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 laminin receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin receptors; the alpha 6 beta 4 basement membrane receptor; and the alpha v beta 3 and alpha v beta 5 vitronectin receptors. Treatment with bFGF caused a significant increase in the surface expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in bFGF-treated cells. Immunoprecipitation of metabolically labeled cells indicated that bFGF increases the biosynthesis of the alpha 3, alpha 5, alpha 6, beta 4, and beta 5 subunits and decreases the production of the alpha v and beta 3 subunits. These results suggest that bFGF modulates integrin expression by altering the biosynthesis of individual alpha or beta subunits. In accordance with the upregulation of several integrins observed in bFGF-treated cells, these cells adhered better to fibronectin, laminin, vitronectin, and type I collagen than did untreated cells. The largest differences in beta 1 integrin expression occurred approximately 72 h after exposure to bFGF, at a time when the expression of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly upregulated. In contrast, a shorter exposure to bFGF (24-48 h) was required for the maximal induction of plasminogen activator production in the same cells. Taken together, these results show that bFGF causes significant changes in the level of expression and function of several integrins in microvascular endothelial cells.
Stable isotope tracers and indirect calorimetry were used to evaluate the progressive alterations in lipid and glucose metabolism after 12, 18, 24, 30, 42, 54, and 72 h of fasting in six healthy male volunteers. The rates of appearance (Ra) of glycerol and palmitic acid in plasma doubled from 2.08 +/- 0.22 and 1.63 +/- 0.20 mumol.kg-1 x min-1, respectively, after 12 h to 4.36 +/- 0.36 and 3.26 +/- 0.40 mumol.kg-1 x min-1, respectively, after 72 h of fasting (P < 0.01). Of the total increase in lipid kinetics, 60% occurred between 12 and 24 h of fasting; the greatest interval change occurred between 18 and 24 h of fasting. Glucose Ra and plasma concentration decreased by approximately 25% between 12 h (11.0 +/- 0.4 mumol.kg-1 x min-1 and 5.58 +/- 0.08 mmol/l, respectively) and 72 h (8.3 +/- 0.3 mumol.kg-1 x min-1 and 4.14 +/- 0.10 mmol/l, respectively) of fasting (P < 0.01), but no statistically significant changes occurred between 18 and 24 h of fasting. Plasma insulin decreased by approximately 50% between 12 h (64.6 +/- 12.9 pmol/l) and 72 h (30.1 +/- 7.9 pmol/l) of fasting (P < 0.001). Of the total decline in plasma insulin, 70% occurred within the first 24 h of fasting. These results demonstrate that the mobilization of adipose tissue triglycerides increases markedly between 18 and 24 h of fasting in young adult men. The early alterations in lipid metabolism are associated with a decline in circulating insulin but do not seem to be regulated by changes in glucose kinetics or plasma glucose concentrations.
Basal whole body lipid kinetics were evaluated in nine endurance-trained cyclists and 10 untrained healthy controls. The rate of appearance (Ra) of glycerol (an index of whole body lipolysis), the Ra of palmitate (an index of fatty acid release), and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were determined by infusing [2H5]glycerol and [2H2]palmitate in conjunction with indirect calorimetry. All subjects were studied while they were at rest after fasting overnight. Glycerol Ra and free fatty acid Ra in the athletes (7.33 +/- 0.68 and 14.88 +/- 1.35 mumol.kg-1 x min-1, respectively) were two- to threefold higher than the values in untrained control subjects (2.53 +/- 0.15 and 7.64 +/- 0.92 mumol.kg-1 x min-1, respectively; P < 0.02). The total rate of triglyceride-fatty acid cycling was approximately four-fold higher in the athletes (16.86 +/- 2.07 mumol.kg-1 x min-1) than in the control subjects (3.91 +/- 0.36 mumol.kg-1 x min-1). Plasma concentrations of insulin and catecholamines, hormones that regulate whole body lipid kinetics, were the same in both groups. We conclude that resting basal lipid kinetics are markedly increased in athletes involved in strenuous endurance training and that this enhances the potential for increasing fatty acid oxidation rapidly at the onset of exercise.
Treatment costs for victims of gang violence have fueled the withdrawal of hospitals from trauma networks. Not included in such tallies are the medical resources that these seriously ill and medically indigent patients divert from other areas. We examined the surgical care requirements, costs incurred, and outcomes at a Level I trauma center. Local law enforcement records were matched with hospital admissions over a 1-year period to identify with hospital admissions over a 1-year period to identify casualties of gang violence. Of 191 gunshot wound admissions, 107 (56%) were gang related. The majority were males (92%); ages ranged from 14 to 50 and trauma scores from 1-16. Eighty-six were admitted during periods of minimum staffing (7:00 PM to 7:00 AM), pre-emptying the use of limited resources for other medical/surgical emergencies. Fifty-eight (54%) needed emergency surgery: laparotomy (38), thoracotomy (5), and neck/extremity (15). Forty required multiple surgical procedures, and eight patients required nine subsequent surgeries. There were two deaths. Average hospital stay ranged from 1 to 180 days; inpatient days totalled 1003, 270 of which were spent in the ICU. Total charges neared +2.0 million. Ninety-four patients (88%) were medically indigent. On discharge, 75 patients were disabled, six permanently. We conclude: 1) Gang activity caused the majority of gunshot wounds at our trauma center; 2) multiple injuries predominated, requiring extensive ICU use; 3) the combination of indigent patients and high hospital costs underestimate the financial burden as valuable resources are diverted from other areas; 4) subsequent community costs include rehabilitation and chronic care.
Laparoscopic surgical procedures are becoming simultaneously more commonplace and complex. However, carbon dioxide (CO2) pneumoperitoneum required for these procedures causes a respiratory acidosis. We undertook this study to determine if an alternate insufflating gas, such as helium, prevents this sequelae. Twenty patients undergoing elective laparoscopic cholecystectomy were randomized to receive either CO2 or helium insufflation. Intraoperative parameters, including arterial CO2 (PaCO2), end-tidal CO2, pH, bicarbonate (HCO3-), cardiac output and blood pressure were obtained before, during and at the conclusion of pneumoperitoneum. Effects of the two gases on these variables were compared. The average CO2 rose significantly from 35.7 +/- 1.0 to 50.4 +/- 3.2 (p < 0.0001), while pH decreased from 7.434 +/- 0.014 to 7.286 +/- 0.018 (p < 0.0001) in those who received CO2. No change in PaCO2 was observed in those who received He, although a small decrease in pH from 7.428 +/- 0.011 to 7.392 +/- 0.012 (p < 0.05) was observed. HCO3- decreased slightly in both groups. Increases in blood pressure and pulse rate were independent of the gas received. The cardiac output did not change. Helium insufflation for laparoscopic cholecystectomy does not produce the respiratory acidosis caused by CO2 and, therefore, merits further investigation for use, particularly in patients with underlying respiratory disease.
Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL-2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell lines. In addition, soluble IL-2R alpha molecules were demonstrated in the supernatants of three of these cultured cell lines. In primary tissues, IL-2R alpha and IL-2R beta were seen in some but not all cases. Staining was detected in Hodgkin and Reed-Sternberg and in lymphoid cells. There was a remarkable difference in the pattern of expression, in that IL-2R alpha- but not IL-2R beta-positive cells from HD patients were clustered in frozen sections. We conclude from these data that IL-2R expression might be involved in the biology of HD.
Spinal cord trauma frequently results from high energy vehicular accidents which produce multisystem trauma. Because of the priorities of resuscitation, other injuries may escape early diagnosis. This study was undertaken to examine the extent and implications of "missed injuries" associated with spinal trauma. We reviewed the charts of 24 patients (23 men, one woman) with spinal cord injuries, who presented during a consecutive 9-year period. The median age was 31 years. Two patients died. There were 13 cervical, 10 thoracic, and one lumbar injuries. Blunt trauma was responsible for injuries in 18 cases, other mechanisms were the cause in six cases. The average initial Glasgow coma score was 13 +/- 0.8 (SEM). Average revised trauma score (RTS) was 6.7 +/- 0.3 (SEM). Other injuries noted at the time of presentation included: head and neck (8), thoracic (6), extremity (2), and major vascular (1). There were 11 initially undiagnosed injuries in 10 patients (42%); six were "nonspinal" and five were "spinal," diagnosed between 1 and 30 days after admission. Average trauma scores were the same among those with and without missed injuries. Missed spinal injuries included: fractures of C5-6 (2), C4 (1), T7 (1), and L1 presenting as a progressive deficit (1). Nonspinal injuries were: pneumothorax (3), hemopneumothorax (1), paralyzed hemidiaphragm (1), and renal contusion (1). Prolonged hospital stay and/or the need for additional surgery were the most common sequelae of delayed diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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