Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge.

A controlled trial was performed to compare enteral feeding with either an amino acid based feed or a whole protein feed as sole treatment for active Crohn's disease. Twenty four patients were studied (nine with ileal, 11 with ileocolonic, and four with colonic disease). Both feeds proved effective; nine of 13 patients randomised to receive the amino acid based feed were in clinical remission within three weeks as defined by a simple activity index compared with eight of 11 treated with the whole protein feed. Patients in clinical remission were then crossed over onto the other feed. None of the six patients who were changed to the whole protein feed relapsed over the subsequent three week period compared with three of seven patients who were changed to the amino acid based feed. In responders the median serum C reactive protein concentration fell from 21 mg/l (range 9-82) on entry to 6 mg/l (range 3-19) at six weeks. Seven patients relapsed within eight months of starting solid food (mean 3.7 months), while nine were still in remission (follow up period 3-9 months, median six months). Detailed studies of staged reintroduction of food and permitted food additives were carried out over a four year period in a patient with extensive stricturing small bowel Crohn's disease who had been brought into remission by open treatment with enteral feeding. Carrageenan, other permitted emulsifiers, bread, meat, potatoes, oranges, refined sugar, dairy produce, flour, and rice were all reintroduced without any objective ill effect, but green vegetables provoked a clinical and biochemical relapse within one week of introduction. Remission was rapidly achieved by switching back to the enteral feed but reintroduction of the low residue diet that had been previously tolerated produced a brisk relapse. Clinical and biochemical remission was again achieved by a return to the enteral feed but relapse again occurred with reintroduction of the low residue diet. These studies confirm the therapeutic effect of enteral feeding in Crohn's disease. This effect does not seem to be due to avoidance of whole protein, but the very low residue of chemically defined enteral feeds may be important, particularly in patients with intestinal strictures.     

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas

Oral Diseases (2010) 16 , 774–780 Summary: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. Methods: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. Results: Strong correlation among the expression of ErbB family receptors was found (ErbB1–ErbB2 P = 0.008, ErbB1‐ErbB4 P = 0.018, EbB2‐ErbB3 P = 0.001, ErbB2‐ErbB4 P = 0.006, ErbB3‐ErbB4 P = 0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). Conclusions: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1‐ErbB2, ErbB1‐ErbB4, ErbB2‐ErbB3, ErbB2‐ErbB4, and ErbB3‐ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.     

Similar patterns of V kappa gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstrom's macroglobulinemia, and myeloma

To compare V kappa gene usage and the amount of somatic mutation in rearranged Ig genes from patients with lymphoproliferative disorders, we have polymerase chain reaction-amplified and sequenced a total of 26 V kappa genes from a total of 55 cases. Six sequences were obtained both from six cases of prolymphocytic leukemia (PLL) and from nine cases of hairy cell leukemia (HCL). Seven sequences were obtained both from 11 cases of Waldenstrom's macroglobulinemia (WM) and 29 cases of multiple myeloma (MM). Eleven different germline genes have been used in this series, indicating a wide but nonrandom usage of germline Ig gene rearrangements in these disorders. Comparison of the nucleotide sequences of V kappa genes obtained from B-cell malignancies with germline V kappa genes shows that somatic mutation is rare in PLL and HCL and common in WM and MM. Analysis of the pattern of mutations suggests that WM and MM are derived from B cells that have been selected by antigen at a relatively late stage of differentiation.     

Epidemiologic characteristics of blood donors with antibody to human immunodeficiency virus

From March 1985 through July 1986, blood donors who were positive for antibody to human immunodeficiency virus (HIV) were evaluated at three major blood centers in the United States. Of 818,629 donations, 450 (0.05%) were HIV antibody-positive. The seroprevalence decreased from 0.07 to 0.04 percent during the study period, due perhaps to a decline in repeat donors. HIV-seropositive donors tended to be 20 to 29 years old (52%) and male (88%). HIV seroprevalence among white donors (2/10,000 donations) was less than that among Hispanic (9/10,000; p less than 0.0001) and black donors (31/10,000; p less than 0.0001). Of 152 seropositive men interviewed, 77 percent reported sexual contact with men; of this latter group, 53 percent were bisexual. Fifteen (44%) of 34 seropositive women had apparently acquired infection from heterosexual contact, and an equal number denied having any known risk factors for HIV infection. Educational efforts must address women and bisexual men who do not perceive themselves to be at risk for HIV infection and should be specifically designed for the mores of different racial and ethnic groups.     

Halo vest effect on balance

OBJECTIVE: To determine the effect of a halo vest, a cervical orthosis, on clinically relevant balance parameters. DESIGN: Subjects performed unipedal stance (with eyes open and closed, on both firm and soft surfaces) and functional reach, with and without the application of a halo vest. SUBJECTS: A convenience sample of 12 healthy young subjects, with an equal number of men and women. OUTCOME MEASURES: Seconds for unipedal stance (maximum 45); inches for functional reach. RESULTS: Both unipedal stance times and functional reach (mean +/- standard deviation) were significantly decreased with the halo vest as compared to without it (29.1+/-5.8 vs. 32.8+/-6.4 seconds, p = .002; 12.9+/-1.4 vs. 15.1+/-2.1 inches, p<.01). CONCLUSION: A halo vest causes an acute impairment in balance in the healthy young. It is likely that the impairment would be greater in older or injured patients, thus increasing their risk for a fall, which could have devastating consequences.     

Gastric Acidity and Iron Absorption

achlorhydria has been recognized as an associated feature of iron deficiency anaemia for many years (Faber, 1909; Witts, 1930). There has, however, been little agreement as to the part played by gastric acid in the absorption of iron from the intestinal tract. Early workers produced evidence that iron absorption was greater in the presence of normal gastric acidity than in cases of achlorhydria (Minot and Heath, 1932; Heilmeyer and Plotner, 1936; Barer and Fowler, 1937). Others found that this was not the case (Moore, Arrowsmith, Welch and Minnich, 1939; Grace, Doig and Wolff, 1954; Pirzio-Biroli, Bothwell and Finch, 1958). More recently Goldberg, Lochhead and Dagg (1963) and Cook, Brown and Valberg (1964) have shown that in some circumstances iron is better absorbed by subjects with normal gastric acid than in those with a histamine fast achlorhydria.
In the present investigation quantitative studies of both iron absorption and of gastric acid production have been made in patients with iron deficiency anaemia and additional observations have been made in normal subjects. The relationship between iron absorption and gastric secretory capacity is examined.     

Diagnostic specificity of immunoglobulin M (IgM) response in differentiation Legionnaires' disease from psittacosis.

Specific IgM and IgG antibody responses to Legionella pneumophila (LDB) and Chlamydia psittaci (PSI) in serum specimens from 22 cases of Legionnaires' Disease (LD) were examined by micro-immunofluorescence (IF) tests to explore the diagnostic significance of the IgM antibody response. Serial samples from 5 patients with LD showed greater than or equal to 4-fold changes in IgG antibody against LDB and PSI. All 5 patients possessed IgM antibodies against LDB but not against PSI. In single convalescent serum samples from 17 additional cases, 16 exhibited IgG and 15 showed IgM antibodies against LDB; all 17 exhibited IgG but not IgM antibodies against PSI. The IgM antibody response appears more specific than the corresponding IgG response in the serodiagnosis of LD, and may be valuable in differentiating LDB infections from those due to PSI.     

Idiotype as a tumor-specific marker in childhood B cell acute lymphoblastic leukemia

Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.     

Measures of the inflammatory response in cryptogenic fibrosing alveolitis

Cryptogenic fibrosing alveolitis (CFA) is characterized by interstitial fibrosis and parenchymal inflammation. Eleven patients with CFA (10 proved by lung biopsy) were followed over 2 yr using clinical symptoms, radiographic change, and pulmonary function tests to adjust their treatment. Lung lavage, positron camera (PET) measurements of regional extravascular lung density (Dev), pulmonary blood volume (Vb), and the metabolic rate for 18F-deoxyglucose (MRglc), clearance of 99mTc-diethylenetriaminepentacetate (99mTc-DTPA) aerosol, and lung uptake of 67Ga were measured initially and at the end of the first year to give a profile of the inflammatory response. Compared with normal subjects, there was an increased percentage of neutrophils and eosinophils in the lung lavage, increased Dev (p less than 0.002) with no significant difference in Vb, increased MRglc (p less than 0.02), 99mTc-DTPA clearance (p less than 0.002), and 67Ga uptake (p less than 0.02). The smallest increases in Dev were seen in the two patients with most destruction shown by lung biopsy. There were inverse correlations between Dev and both FVC and TLC, but a direct correlation between Vb and transfer factor. 99mTc-DTPA clearance changed concordantly with clinical status and radiographic and respiratory function changes during the first year. If glucose utilization (MRglc) remained in the normal range between the initial and first yearly assessment, the patient improved or remained stable during the second year as shown by clinical status and radiographic and respiratory function measurements. If it rose or remained high, the patient's condition deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)     

FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells

FLT3 ligand is a hematopoietic growth factor that plays a key role in growth of primitive hematopoietic cells. FLT3 receptor mRNA is found in early hematopoietic progenitors and in human myeloid leukemia blasts. Much less is known about the surface expression of FLT3 receptor on human hematopoietic cells. Using human 125I-FLT3 ligand, we have identified and characterized surface FLT3 receptors on normal and malignant human hematopoietic cells and cell lines. Our results showed that surface display of FLT3 receptor was greatest in fresh myeloid leukemia blast cells and myeloid leukemia cell lines. Erythroleukemic and megakaryocytic leukemia cell lines (n = 5) bound little to no 125I- FLT3 ligand. Scatchard analysis of 125I-FLT3 ligand binding data shows that three myeloid leukemia cell lines, ML-1, AML-193, and HL-60, as well as normal human marrow mononuclear cells, exhibit high affinity FLT3 receptors. Crosslinking of 125I-FLT3 ligand to FLT3 receptors on the surface of ML-1 myeloid leukemia cells indicates that the FLT3 ligand. The rates of FLT3 ligand internalization and degradation were determined by binding 125I-FLT3 ligand to ML-1 cells and acid stripping to distinguish surface bound from internalized ligand. Internalized 125I-FLT3 ligand was detected within 5 minutes after binding to ML-1 cells. In addition, we evaluated the effect of FLT3 ligand on megakaryocytic colony growth and nuclear endoreduplication, alone or in the presence of thrombopoietin. FLT3 ligand did not promote colony forming unit megakaryocyte (CFU-Meg) colony growth or megakaryocyte nuclear maturation, nor did FLT3 ligand augment the effects of thrombopoietin on these measures of megakaryopoiesis. These data indicate that the FLT3 receptor shares several characteristics with the c-kit receptor including dimerization and rapid internalization. However, the more restricted cellular distribution of the FLT3 receptor may target the effects of FLT3 ligand to primitive hematopoietic cells and to myeloid and lymphoid progenitor cells, in contrast to the pleiotropic effects of the c-kit receptor ligand, stem cell factor.