Protective effect of resveratrol on acrylamide-induced renal impairment.

BACKGROUND: Acrylamide (ACR) has a wide range of uses. It possesses a renal impairment effect. The work aimed to study the possible protecting role of resveratrol (RVS) over the ACR-mediated renal impairment in rats. The suggested underlying mechanisms participating in such protection were investigated. MATERIALS AND METHODS: Thirty Sprague-Dawley adult albino rats were divided into three groups: control, ACR, and RVS. After 4 weeks, the kidney was removed and prepared for histological, immunohistochemical, and biochemical studies. The activity of tissue oxidative (malondialdehyde [MDA]) and anti-oxidative (glutathione [GSH]) markers were assessed. RESULTS: Acrylamide induced glomerular renal affection in the form of shrinkage and distortion of the glomeruli with wrinkling of their basement membranes and widening of the urinary spaces. Degenerative tubular changes were markedly present in the proximal convoluted tubules. The necrotic tubular cells exhibited cytoplasmic vacuolation with desquamated epithelial cells within the tubular lumen. ACR increases the deposition of collagen fibres in the basement membrane of the glomerular capillaries and induced thickening of the basement membranes of the renal corpuscles and renal tubules. The administration of RVS affords high protection to the kidney. The glomeruli and renal tubules were nearly normal. The content of collagen fibres and the periodic acid Schiff reaction of the basement membrane of the renal tubules were 70% and 19% lower linked to the ACR group. The creatinine and urea levels decreased by 51% and 47%. RVS induced such a protective role through its antioxidant effect as the MDA level decreased by 45%, while the GSH level increased by 83% compared with the ACR group. CONCLUSIONS: Acrylamide causes structural and functional disorders of the kidney. It induces kidney damage through oxidative stress and apoptosis. With the use of RVS, normal kidney architecture was preserved with little structural changes. Adding, functional kidney test became normal. RVS exerts its protective effect through its anti-apoptotic and antioxidant features.

Concomitant administration of sitagliptin and rutin improves the adverse hepatic alterations in streptozotocin-induced diabetes mellitus in albino rats: an overview of the role of alpha smooth muscle actin.

BACKGROUND: Diabetes mellitus (DM), one of the commonest worldwide metabolic conditions, is believed to be associated with an imbalance between oxidants and antioxidants. Sitagliptin is an oral anti-hyperglycaemic drug that blocks dipeptidyl peptidase 4 (DPP4). Rutin is a polyphenolic natural flavonoid which has antioxidant and anti-proliferative activity. The aim of the present work is to elucidate the concomitant effect of sitagliptin and rutin on the deleterious alterations in the liver of experimentally induced diabetes in rats. MATERIALS AND METHODS: Fifty adult male albino rats, weighing 170-200 g were used. Rats were randomly divided into five groups (n = 10): group 1 (control group), the other four groups (groups II, III, IV and V) received a single i.p. injection of streptozotocin, 65 mg/kg body weight to induce diabetes; group II (diabetic), group III (diabetic and rutin administered), group IV (diabetic and sitagliptin administered), and group V (diabetic with sitagliptin and rutin concomitantly administered). Haematoxylin and eosin, Masson trichrome, periodic acid Schiff, immune-histochemistry: a-smooth muscle actin (a-SMA), histomorphometric analysis, liver enzymes and oxidants/anti-oxidants; malondialdehyde/glutathione and were done. RESULTS: Distorted hepatic architecture, dilatation, congestion of sinusoids and central veins as well as cytoplasmic vacuolations were remarkable changes in the diabetic group. There was extravasation of blood, diffuse fibrous tissue formation, increase in the mean values of liver enzymes, oxidative markers and a-SMA expression in the same group. The aforementioned changes were ameliorated in groups III and IV. Concomitant administration of sitagliptin and rutin resulted in marked enhancement of these hepatic alterations. CONCLUSIONS: Combination of sitagliptin and rutin has an ameliorating effect on the hepatic deterioration induced by diabetes, which is better than either sitagliptin or rutin alone.

Cell surface molecules and their prognostic values in assessing colorectal carcinomas.

OBJECTIVE: Carcinomas of the colon and rectum are the third leading cause of cancer-related deaths. Although advances in the surgical treatment of primary colorectal cancers have lead to improvements in patient survival at early tumor stages, treatment of more progressive cancers has not resulted in dramatic improvements in patient survival. However, the selection of patient subgroups based on their prognosis and other characteristics could result in improved outcomes from adjuvant therapies in patients with Dukes B and C carcinomas. METHODS: The authors reviewed the available data on the value of cell surface molecules in assessing the prognosis of colorectal carcinomas, paying specific attention to the evaluation of statistical analysis and multivariate procedures. RESULTS: Cell surface molecules have been identified on colorectal carcinoma cells whose expression appears to be related to malignant transformation, tumor progression, or patient prognosis. Among these cell surface molecules, various cell adhesion molecules, growth factor receptors, proteinases, and their receptors and inhibitors have been identified as potentially useful prognostic markers. CONCLUSIONS: Although data exist on the prognostic values of certain cell surface markers, the use of multivariate analysis for the identification of valuable prognostic factors remains uncommon. Using reproducible and standardized multivariate analysis procedures, new tumor markers should be carefully examined for their biologic and prognostic relevance before being considered as potentially useful in the management of colorectal cancers.

Different adhesion properties of highly and poorly metastatic HT-29 colon carcinoma cells with extracellular matrix components: role of integrin expression and cytoskeletal components.

Integrin-mediated tumour cell adhesion to extracellular matrix (ECM) components is an important step in the development of metastatic lesions. Thus, integrin expression and integrin-mediated adhesion of colon carcinoma cells to various ECM components was examined. Poorly (HT-29P) and highly (HT-29LMM) liver-metastatic colon carcinoma cells were used to study the rates of adhesion to collagen I (C I), collagen IV (C IV), laminin (LN), fibronectin (FN), or vitronectin (VN) in a static adhesion assay (10-120 min). Cells were untreated or treated with oligopeptides (RGD, GRGDS, YIGSR, RGES), anti-integrin antibodies, or colchicine, nocodazole, cycloheximide, acrylamide or cytochalasin D (to disrupt cytoskeletal structures). Both cell lines expressed similar patterns of integrin expression (alpha2, alpha3, ,alpha6, alphav, beta1, beta4, and beta5) by immunocytochemistry and immunoprecipitation. HT-29LMM cells showed significantly higher rates of adhesion to LN (P < 0.001) and FN (P < 0.001), but significantly poorer rates of adhesion to C I (P < 0.05) and C IV (P < 0.001) than HT-29P cells, respectively, adhesion to VN was insignificant. RGD and GRGDS inhibited HT-29LMM cell adhesion to FN only. Pretreatment with anti-beta, or anti-alpha2 integrin subunits suppressed adhesion to C I and C IV, and adhesion to LN was inhibited with anti-beta1 or anti-alpha6 integrin. Anti-beta1 or anti-alphav blocked adhesion to FN. Pretreatment of cells with cytochalasin D, cycloheximide or acrylamide inhibited adhesive interactions of both cell lines to the ECM components. In contrast, colchicine and nocodazole had no effect. The results demonstrate that adhesion of HT-29 cells to ECM is mediated, in part, by different integrins, depending on the substrate. Poorly and highly metastatic HT-29 cells possessed different patterns of adhesion to the various ECM substrates, but these differences were not due to different expression of integrin subunits. The results also suggested that the initial adhesion of poorly or highly metastatic HT-29 cells to ECM components requires, in part, the presence of native action and intermediate filaments, but not of microtubules. Thus the adhesion of tumour cells to ECM components may be dependent on signal transduction and assembly of microfilaments.

Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis.

OBJECTIVE: Mycoplasmal infections are associated with several acute and chronic illnesses. Some mycoplasmas can enter a variety of tissues and cells, and cause system-wide or systemic signs and symptoms. METHODS: Patients (14 female, 14 male) diagnosed with rheumatoid arthritis (RA) were investigated for mycoplasmal infections in their blood leucocytes using a forensic polymerase chain reaction (PCR) procedure. Amplification was performed with genus- and species-specific primers, and a specific radiolabelled internal probe was used for Southern hybridization with the PCR product. Patients were investigated for the presence of Mycoplasma spp., and positive cases were further tested for infections with the following species: M. fermentans, M. hominis, M. pneumoniae and M. penetrans. RESULTS: The Mycoplasma spp. sequence, which is not entirely specific for mycoplasmas, was amplified from the peripheral blood of 15/28 patients (53.6%) and specific PCR products could not be detected in 13 patients (46.4%). Significant differences (P < 0.001) were found between patients and positive healthy controls in the genus test (3/32) and in the specific tests (0/32). Moreover, the incidence of mycoplasmal infections was similar in female and male patients. Using species-specific primers, we were able to detect infections with M. fermentans (8/28), M. pneumoniae (5/28), M. hominis (6/28) and M. penetrans (1/28) in RA patients. In 36% of the patients, we observed more than one Mycoplasma species in the blood leucocytes. All multiple infections occurred as combinations of M. fermentans with other species. CONCLUSIONS: The results suggest that a high percentage of RA patients have systemic mycoplasmal infections. Systemic mycoplasmal infections may be an important cofactor in the pathogenesis of RA, and their role needs to be explored further.

Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen.

Organ-specific sites of metastastic lesions are determined in part by integrin-mediated adhesion to extracellular matrix (ECM) components. Using poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma cells we previously found different integrin-mediated adhesion to various ECM components, but similar integrin expression of both cell lines. These HT-29 cell lines were used to study adhesion to collagen I (C I) and possible intracellular signaling mechanisms that could explain different adhesive properties. HT-29LMM cells had significantly poorer rates of adhesion to C I (P < 0.05) than HT-29P cells. For examination of the integrin subunits involved in adhesion to C I, cells were treated with various anti-integrin antibodies. These results demonstrated that adhesion of HT-29 cells to C I is mediated in part by the alpha 2 beta 1 integrin. Using immunoprecipitation and Western blotting, both cell lines expressed similar patterns of integrins (alpha 2, alpha 3, alpha 6, and beta 1). Weaker signals were found for the expression of alpha v and beta 5 integrins. Although poorly and highly metastatic cells possessed different patterns of adhesion to C I, these differences were not caused by different expression of integrin subunits. For investigation of the involvement of phosphotyrosine kinases in adhesion, cells were pretreated with the Erbstatin analog, Genistein, or Herbimycin A. Genistein transiently stimulated the adhesive properties of both cell lines. In contrast, Herbimycin A had biphasic effects. At lower concentrations of Herbimycin A stimulation of adhesion was found after 30 and 90 min. However, higher concentrations inhibited adhesive properties. The stimulatory effect was more pronounced in poorly metastatic HT-29P cells. The Erbstatin analog had no effect, probably because of the lack of epidermal growth factor receptor expression in both cell lines. The results suggest that adhesion of tumor cells to ECM components may be dependent on signal transduction into the cell, and tyrosine phosphorylation appears to be involved.

Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome.

The aim of this study was to investigate the presence of different mycoplasmal species in blood samples from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection. In this study, patients with chronic fatigue syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans, Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic polymerase chain reaction. Among these mycoplasma-positive patients, infections were detected with Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% and triple infections in 22%, but only when one of the species was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.

Beta1-integrin-mediated dynamic adhesion of colon carcinoma cells to extracellular matrix under laminar flow.

To resist substantial wall shear stress exerted by blood flow metastasizing colon carcinoma cells have to form adhesive contacts with endothelial cells and subendothelial extracellular matrix (ECM). At secondary sites tumor cells have to stabilize these initial adhesive interactions to prevent detachment and recirculation. Previously we found that adhesion of colon carcinoma cells to ECM components under static conditions is mediated, in part, by various beta1-integrins. Since other malignant cells possess adhesive properties that are different under static and dynamic conditions, we analyzed human colon carcinoma cell adhesion under flow by decreasing the flow (wall shear stress, WSS) of cell suspensions and allowing cells to interact with collagen-coated surfaces in a laminar flow chamber. HT-29 colon carcinoma cells were used to study wall shear adhesion threshold (WSAT), dynamic adhesion rate (DAR) and adhesion stabilization rate (ASR). DAR was determined after a low flow period using a WSS set at 50% of WSAT. ASR was calculated 60 sec after reestablishment of high WSS. Glass slides were coated with collagen I (C I) or bovine serum albumin (BSA, negative control). In some experiments cells were pretreated with function-blocking anti-beta1 or nonspecific IgG. Rolling of cells occurred on C I- and BSA-coated surfaces at high WSS. By decreasing WSS cell sticking without definite adhesion was found, and cells stuck to BSA at WSS lower than that found for C I. Further decreasing WSS below WSAT enabled stable cell adhesion to C I, but only a few cells adhered to BSA. ASR was found to be 73% of primarily adherent cells (to C I). Pretreatment with anti-beta1 did not affect cell rolling but did inhibit cell sticking and adhesion completely, whereas nonspecific IgG was without effect. Activation of PKC using phorbol ester resulted in an increase of adhesive interactions under dynamic and static conditions, whereas its inhibition reduced adhesion. Adhesive interactions of HT-29 colon carcinoma cells with ECM-coated surfaces under laminar flow conditions occurred in various steps: (1) rolling, (2) sticking or initial adhesion, and (3) stabilization of adhesion. Under shear flow rolling of tumor cells on ECM-coated surfaces appeared to be mediated mainly by physical/mechanical and nonspecific surface-cell membrane interactions, whereas stabilized adhesion to ECM was specifically mediated by beta1-integrin binding to ECM components. PKC seems to be involved in the regulation of adhesion stabilization under static and flow conditions.

[Different integrin-induced adhesion of highly liver metastatic and little metastatic colon carcinoma cells in an extracellular matrix]. / Differente Integrin-vermittelte Adhäsion von hoch hepatisch metastasierenden und gering metastasierenden Kolon-Karzinom-Zellen an extrazellulärer Matrix.

Poorly and highly liver metastatic colon carcinoma cell lines have different integrin-mediated adhesion to extracellular matrix. Specific integrin-mediated interactions between tumor cells and extracellular matrix (ECM) in the host organs are important for organ-specific metastasis. In colon carcinoma integrin expression differs depending on the metastatic potential of the tumor. Integrin-mediated adhesion of poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma to extracellular matrix (ECM; Collagen I-C I, Collagen IV-C IV, Laminin LN, Fibronectin FN, Vitronectin VN) was investigated. HT-29LMM showed significant better adhesion to LN (45% vs. 26%; p < 0.001) and FN 20% vs. 1%; p < 0.001). No adhesion was found to VN. RGD-oligopeptides completely inhibited adhesion to FN. Using inhibition with anti-integrin-mAB it was shown, that adhesion to C I and C IV is mediated by alpha 2 beta 1-integrin, adhesion to LN by alpha 6 beta 1 and adhesion to FN by alpha v beta 1. These results have shown that adhesion of HT-29 cells is mediated by different integrins depending on ECM components. Poorly and highly metastatic cells possessed different patterns of adhesion to various substrates.

Estrogen and progesterone receptor status in breast cancer in Kuwait female population.

The levels cytosol estrogen (ERc) and progesterone (PRc) receptors were determined in 315 primary breast cancers of female Arab patients aged 23-80 years. Most of breast cancers (78%) occurred in women aged 21-50 years, and only 22% were in women aged 51-80 years. Breast cancers containing ERc and PRc concentrations in the range 5-50 fmol/mg of cytosol protein (mg c.p.) were found with similar frequency in women aged under or over 50 years (53% for ERc and 43% for PRc, respectively). On the other hand, breast cancers with ERc values of > 50 and > 100 fmol/mg c.p. were twice as frequent in women aged over 50 years as in women aged under 50 years. The frequency of breast cancers with PRc level of over 50 fmol/mg c.p. in women aged over 50 years was only half that in those aged under 50 years. In breast cancers of Kuwait Arab women the higher values of ERc (> 100 fmol/mg c.p.) and PRc (> 50 fmol/mg c.p.) were less frequent than in other populations reported in literature. The low frequency of breast cancer in postmenopausal Kuwait women is associated with low proportions of tumors with higher ERc and PRc contents. In contrast to this, data from literature indicate that in the North Western European and American populations the postmenopausal incidence rise of breast cancers is associated with increased proportions of tumors with higher ERc and PRc levels.

Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors.

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

Relations between epidermal growth factor receptor and oestrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal patients in Kuwait.

The levels of cell membrane epidermal growth factor receptor EGFR and cytosol (c) and nuclear (n), oestrogen (E) and progesterone (P) receptors (R) were determined in 132 specimens of primary breast cancers. In the tumours of postmenopausal women an inverse significant correlation was demonstrated between the concentrations of EGFR vs. ERc, ERn, and PRc while no such correlation was noted in the tumours of premenopausal women. Premenopausal and postmenopausal EGFR positive tumours (> or = 10 fmol/mg membrane protein) could be regarded as homogenous with respect to the concentration of ER and PR whose mean values were low and without being significantly different. EGFR negative tumours were heterogeneous with respect to the ER and PR concentrations. Postmenopausal EGFR negative (< 10 fmol/mg membrane protein) tumours had evidently higher mean values of ER and PR than premenopausal EGFR negative tumours, but these differences were statistically significant for oestrogen receptors only. The levels of ER and PR of premenopausal EGFR negative tumours were approximated to the corresponding levels of EGFR positive tumours.

Serial determinations of serum CEA in monitoring management of patients with colorectal carcinoma.

Serum concentrations were determined serially in two groups of patients with colorectal carcinoma: in 123 after curative resection and in 34 with residual cancer. Of the first group, in 98 serum CEA fluctuated within the normal range or with a 2-fold larger amplitude evidencing effective surgery because only 9 had recurrence; in 25 serum CEA rose persistently from a postoperative nadir indicating relapse, mostly liver metastases. Of the 34 patients with relapse, 3 had clinically and 7 CEA-directed second-look laparotomy; although 7 had operation with curative intent, only 3 remained disease-free. In the second group, there were 26 patients after palliative surgery and 8 during nonsurgical treatment. Serum CEA fluctuated within the normal range in 2 patients in remission and in 3 with progressive cancer, and rose in parallel to cancer progression in 29. Thus, serum CEA within or slightly above the normal range was 88% predictive that the patient might be free of disease or in remission; whereas elevated or rising level indicated disease progression. Accordance between serum CEA and clinical status occurred in 145 of 157 (92%) patients.

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer.

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.

Serum levels of CA 125 in patients with gastrointestinal cancers.

Serum levels of CA 125 and markers reputed as specific for cancers in relevant locations (squamous cell carcinoma, SCC, carcinoembryonic antigen, CEA, CA 19.9, alpha-fetoprotein, AFP) were determined in 107 patients with gastrointestinal (GI) carcinomas. The aim of this study was to assess their individual and combined sensitivities, and the power of CA 125 in excluding primary ovarian epithelial cancer from GI primary. Serum CA 125 levels (in U/ml) ranged from nondetectable to 400 in patients with esophageal, to 570 in those with gastric, and to 300 in patients with colorectal carcinoma. The levels for liver secondaries, pancreatic, and hepatocellular carcinoma were 480, 2,720 and 1,100 U/ml, respectively. Serum SCC antigen was elevated in all patients with esophageal cancer, CEA or CA 19.9 in 52% of patients with gastric cancer and in 63% with liver secondaries, and CEA in 95% of patients with colorectal cancer; whereas serum CA 125 above 65 U/ml was found in 25% of this subgroup, but only in those with already an elevated concentration of specific marker(s). Serum CEA or CA 19.9 was elevated in 71%, CA 125 in 59% of patients with pancreatic cancer; the latter mostly in those with already elevated CEA or CA 19.9. Serum AFP was elevated in 84% and CA 125 in 40% of patients with hepatoma; the latter mostly in those with already an elevated AFP. CA 125 values exceeding 1,000 U/ml were found in 1 patient with pancreatic cancer (2,720 U/ml) and in 2 with hepatoma (1,050 and 1,100 U/ml). These findings illustrate the nonspecificity of the CA 125 antigen, its small if any advantage compared to the specific markers, and they diminish its role as a marker for primary ovarian cancer from GI primary unless it exceeds 2,800 U/ml.

Carcinoembryonic antigen and breast carcinoma antigen (CA 15.3) in preoperative staging and postoperative monitoring of patients with carcinoma of the breast.

Serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen (CA 15.3) were determined in patients with breast carcinoma: in 129 before initial surgical or nonsurgical treatment and in 134 afterwards. Before any initial treatment, CEA was elevated in 15% of patients with Stage IV disease and CA 15.3 was high in 11% with Stage III and 48% with Stage IV. While monitoring management active disease was associated with elevated serum CEA in 66% of the patients, with elevated CA 15.3 in 73% and with at least one of the markers elevated in 86%. Both tests had high specificity (93% and 98%). The rise in serum CEA and, even more so, of serum CA 15.3 roughly paralleled the increase in bulk of the tumor: from locoregional disease through metastases to the lungs, bones, lungs with bones, and liver. Decreases in the levels of serum CEA and CA 15.3 reflected response to therapy, increases in the level of at least one marker-treatment failure, and levels fluctuating above the normal range indicated stationary disease. During follow-up, the predictive value of a negative test (levels within the normal range), suggesting that the patient might be free of disease, was 61% for CEA alone, 67% for CA 15.3 alone, and 80% for the two tests combined. We conclude that an elevated serum level of only one of the markers was useful for staging, implying advanced disease. Determination of both markers jointly was useful for monitoring the effectiveness of the therapy and for follow-up aimed at detection of relapse.

A simple and economical method for the preparation of adsorbents for the thyroid hormone uptake test.

A low-cost and simple method has been developed for the preparation of human or animal protein-based adsorbents for use in the thyroid hormone uptake test. A combination of sodium sulphate precipitation and glutaraldehyde polymerisation of pooled whole serum or purified albumin preparations was employed to yield a fine solid-phase suspension which eliminates the need for capping and rotating assay tubes. Results for 107 samples obtained by this method correlated well with those obtained by use of a commercial kit.

Clinical and laboratory evaluation of a commercial kit for measurement of serum free thyroxin ("Amerlex Free T4").

Different indexes of thyroid function were determined in conjunction with values obtained with a new commercial radioimmunoassay kit for serum free thyroxin, in 49 apparently healthy subjects, 87 pregnant women, and 142 outpatients attending the thyroid clinic. The results indicate a diagnostic success rate of 88% when free thyroxin was measured instead of estimating the so-called free thyroxin index. Furthermore, in three cases of papillary carcinoma the concentration of free thyroxin was increased, although all the other laboratory tests indicated a euthyroid state. Technically, the method is simple, rapid, and precise, and it would be of most value in the small hospital laboratory lacking the facilities of a comprehensive thyroid-function test service.

Evaluation and assessment of environmental protection alternatives for the Jeddah cement company plant.

An environmental impact assessment is conducted by utilizing monitoring, meteorological, and physical modeling data. This information serves as input to a decision analysis of the environmental protection alternatives for the cement plant in Jeddah, Saudi Arabia. Utility theory provides the methodology underlying the Evaluation and Sensivity Analysis Program (ESAP) with which the alternatives are evaluated. Recommendation include: (1) installation of electrostatic precipitators of at least 99% efficiency, (2) institution of a 1.6 km nonresidential zone given the present 60 m chimneys, and (3) substitution of low sulphur fuel for the crude oil now consumed. By illustration this study suggests the general relevance of the ESAP program to environmental assessment and management.