Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.     

Kr-81m ventilation imaging: clinical utility in suspected pulmonary embolism

The results of Kr-81m/Tc-99m ventilation-perfusion (VP) lung scintigraphy were correlated with the results of pulmonary angiography for 74 patients suspected of having pulmonary embolism (PE). Among patients having a diagnostic scan, the sensitivity and specificity of scintigraphy were 91% and 94%, respectively. Also, 157 consecutive cases of Kr-81m/Tc-99m VP lung scintigraphy were reviewed, and the frequency of an indeterminate scan was found to be 22%. A similar frequency was found for VP scintigraphy with xenon-133. Of eight patients who had indeterminate scans due to the presence of a single VP mismatch, four were demonstrated to have PE by angiography. Kr-81m is an excellent agent for VP scanning in cases of suspected PE, offering accuracy in diagnosis as well as favorable physical properties.     

Should patients with a pre-operative prostatespecific antigen greater than 15ng/ml be offered radical prostatectomy?

Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml. Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed. Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106). Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative lymph node frozen section.     

Circulating concentrations of chemokines in cord blood, neonates, and adults

Chemokines are critical for the movement of leukocytes. Chemotaxis is deficient in neonates, particularly those delivered prematurely, and this likely contributes to their increased vulnerability to sepsis. The concentrations of circulating chemokines in neonates have not been reported, nor is it known whether low chemokine concentrations contribute to their defective chemotaxis. We hypothesized that serum concentrations of chemokines 1) would be lower in preterm than term neonates, and 2) would be lower in preterm and term neonates than adults. Samples were obtained from preterm and term neonates with normal neutrophil and eosinophil counts, umbilical cord blood samples from pregnancies without clinical evidence of intra-amniotic infection, and healthy adult volunteers. The concentrations of epithelial neutrophil activating peptide-78, growth-related oncogene-alpha, eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 alpha were measured using specific ELISA. Serum concentrations from preterm infants were either similar to or higher than those measured in term neonates and adults. We conclude that the chemotactic defect observed in premature neonates is not the result of diminished circulating concentrations of any of the specific chemokines we measured.     

Ranitidine and omeprazole as adjuvant therapy to pancrelipase to improve fat absorption in patients with cystic fibrosis

BACKGROUND: Inadequate treatment of pancreatic insufficiency in patients with cystic fibrosis (CF) causes malabsorption of nutrients with significant sequelae. The objective of this study was to measure the effect of acid suppressant therapy on fat absorption in patients with CF who received a pH-sensitive, enteric-coated microtablet enzyme product. METHODS: A double-blind, placebo-controlled crossover study of 12 children and 10 adults with pancreatic insufficient CF was performed. All subjects were receiving pancrelipase therapy (Pancrease MT10 and MT16; Ortho-McNeil, Springhouse, PA, U.S.A.) and for the study also received either placebo or ranitidine (Zantac; Glaxo-Wellcome, Research Triangle Park, NC U.S.A.) 5 mg/kg or 10 mg/kg daily. The adult subjects also received omeprazole therapy (Prilosec; AstraZeneca/Merck, Wilmington, DE, U.S.A.), 20 mg daily, as adjuvant therapy to pancreatic enzymes. Serial 3-day fat-balance studies were performed in the Clinical Research Center. The data were analyzed using individual paired t tests that compared each treatment with placebo and two repeated-measures, general linear model F tests. RESULTS: The linear model for all subjects showed no overall adjuvant drug effect on fat absorption, P = 0.32. A second linear model F test analysis of adult subjects, comparing all four drug treatments (placebo, ranitidine 5 and 10 mg/kg daily and omeprazole), also showed no difference in fat absorption, P = 0.15. Paired t test subgroup analysis of the adults showed an improvement of 4.97% (P = 0.003) in mean fat absorption comparing low-dose ranitidine to placebo. All other t test analyses showed no significant change in fat absorption between placebo and acid suppressant treatment. There was marked intersubject and intrasubject variability in fat absorption. CONCLUSIONS: No overall significant improvement in fat absorption could be demonstrated with adjuvant therapy. Fat absorption measured by 3-day fat-balance studies varied greatly even when comparing the same subject for placebo and baseline treatments, despite identical dietary fat and enzyme intakes. The large variability limited our ability to test for a difference in fat absorption and has significant implication for the use of this test, considered the gold standard, for determining enzyme dosage adequacy.     

Comparison of steatocrit and fat absorption in persons with cystic fibrosis

BACKGROUND: Exocrine pancreatic insufficiency is a common problem in persons with cystic fibrosis causing malabsorption and poor growth. The 72-hour fecal fat study is the best qualitative measure of fat malabsorption used in clinical practice. This test has several drawbacks, which include cost and logistics. The steatocrit has been proposed as a rapid method to assess fat malabsorption. OBJECTIVES: The objective of this study was to determine whether the steatocrit is an accurate estimation of fat malabsorption in persons with cystic fibrosis. METHODS: Forty-nine stool samples for steatocrit processing were obtained from 72-hour fecal fat collections performed on twenty-seven persons with cystic fibrosis. Stools were weighed and homogenized with sand and water. The emulsified specimen was pipetted into heparinized capillary tubes and centrifuged for 15 minutes. The length of the fatty layer was compared to the length of the solid layer plus the fatty layer in each tube to determine the steatocrit value. Four steatocrit mixtures were evaluated: (1) standard steatocrit, (2) dilute steatocrit, (3) acid steatocrit, (4) dilute acid steatocrit. Steatocrit values were compared with the coefficient of fat absorption determined from the 72-hour fecal fat collection. RESULTS: The correlation coefficient of the steatocrit and the coefficient of fat absorption ranged from -.045 to -.491. Only the coefficient of fat absorption and the acid steatocrit had a significant correlation ( = 0.033). CONCLUSION: The steatocrit is an imprecise measure of fat absorption and not clinically useful in estimating steatorrhea.     

Flexed sitting maneuver for complete lumbar myelography in patients with severe spinal stenosis and apparent block

A new technique has been designed to improve myelography examinations of the entire lumbar spinal canal in patients with severe spinal stenosis using a single needle puncture. When a high-grade obstruction to the caudal flow of contrast material is encountered, the patient is placed in a flexed sitting position for 1 minute. This technique was performed in eight patients with severe lumbar spinal stenosis. It successfully helped depict the lower lumbosacral canal below an apparently complete block in four patients and resulted in improved visualization of the lower sac in four patients with partial block.     

The double puncture: an effective percutaneous technique for removing complex, multiple renal calculi

Percutaneous nephrostolithotomy, which can require a double puncture, is presently the method of choice in our institution for the removal of renal stones. Patients that underwent this procedure were evaluated to identify the possible reasons for the double puncture. Of 200 patients evaluated, 14 needed a second tract. The three variables that determined whether a second puncture was needed, in order of importance, were number and size of the stones, with second tracts needed in patients with multiple stones and staghorn calculi; anatomical variations of the renal collecting system itself, with bifid systems the most significant anatomic variation; and the dexterity of the radiologist in performing the puncture and the ability of the urologist to extract the stone. Second tracts were needed more frequently in patients who presented with stones in both the lower and middle poles of the collecting systems.     

Experience with the Amplatz retrievable vena caval filter. Work in progress

The Amplatz retrievable vena caval filter was designed in an attempt to decrease complications associated with the placement of Mobin-Uddin or Kimray-Greenfield filters. The design allows percutaneous retrieval, thus expanding application of the filter to situations requiring temporary prophylaxis against pulmonary embolism. Filters have been placed in 16 patients, nine (56%) for prophylactic purposes. All filters were easily inserted percutaneously. Complications occurred in three patients; these included complete thrombosis of the inferior vena cava below the filter, misplacement of one filter into the pericaval retroperitoneal tissue, and development of thrombus cranial to the filter. With the current introduction system, the possibility of filter misplacement has been essentially eliminated. No patient experienced symptoms suggestive of pulmonary embolism after filter insertion. One filter retrieval has been performed, with no complications.