Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

Although iron, vltamm B₁₂, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients Durmg a l0-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vltamin B₁₂, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developmg these deficiencies decreases over time Hemoglobin and hematocrit levels were slgnificantly decreased at all postoperative intervals in comparison to preoperative values Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased signifiantly compared to the preceding interval Folate levels were significantly increased compared to preoperative levels at all time intervals Iron and vltamin B₁₂ levels were lower than preoperative measurements and remained relatively stable postoperatively Half of the low hemoglobin levels were not associated with iron deficiency Taking multivltamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B₁₂ deficiency Oral supplementation of iron and vitamin B₁₂ corrected defiaencies in 43% and 81% of cases, respectively Folate deficiency was almost always corrected with multivitamins alone No patient had symptoms that could be attributed to either vitamin B₁₂ or folate deficiency Conversely, many patients had symptoms of iron deficiency and anenua Lack of symptoms of vitamin B₁₂ and folate deficiency suggests that these deficiencies are not clinically important after RYGB Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB     

Lipid Levels: A Link Between Cardiovascular Disease and Osteoporosis?

Epidemiological observations support a positive relationship between cardiovascular diseases (CVD) and osteoporosis, where cholesterol has been indicated to be a possible link. Only a few studies have investigated the relation between lipids and BMD, but the association remains unclear. We studied the relationship between serum lipids and BMD of the calcaneus. A cross‐sectional population‐based study was performed, based on data from the Longitudinal Aging Study Amsterdam, including 620 men and 635 women, 65–88 yr of age. BMD was measured by quantitative ultrasound (QUS), velocity of sound (VOS; m/s), and broadband ultrasound attenuation (BUA; dB/MHz). Models were adjusted for age, body mass index, physical activity, smoking, alcohol, diabetes mellitus, hypertension, testosterone, and 25‐hydroxyvitamin D. No association was found between total cholesterol (TC) and QUS. Men and women in the highest quartile of high‐density lipoprotein cholesterol (HDL‐c) had a significantly lower QUS (men—VOS: β = ?20.8, p = 0.00; BUA: β = ?5.2, p = 0.02; women—VOS: β = ?18.6, p = 0.00) compared with men and women in the lowest quartile. An even stronger positive association was seen between TC/HDL‐c ratio and QUS (men—VOS: β = 21.8, p = 0.00; BUA: β = 5.5, p = 0.01; women—VOS: β = 19.2, p = 0.00; BUA: β = 3.6, p = 0.05). Our analysis shows that the lipid profile that is favorable in the prevention of CVD (i.e., high levels of HDL‐c and low TC/HDL‐c ratio) is unfavorable for QUS. These results indicate that HDL‐c levels do not explain the association between osteoporosis and CVD.     

Dynamic radioulnar convergence after Darrach operation,soft tissue stabilizing operations of the distal ulna and ulnar head prosthesis implantation--an experimental biomechanical study

The most common method of treating the arthrotic distal radioulnar joint (DRUJ) is resection of the entire ulnar head (Darrach procedure). Complications related to instability of the distal forearm resulting from loss of the ulnar head are usually manifested by pain and weak grip strength and have remained the drawbacks of this procedure. In an attempt to mechanically stabilize the distal forearm, an endoprosthesis was developed to replace the ulnar head after Darrach resection. The purpose of this study was to: 1) evaluate the dynamic effects of the Darrach procedure on radioulnar convergence; and 2) evaluate the mechanical efficacy of two soft tissue stabilizing techniques (Pronator quadratus advancement flap and ECU/FCU tenodesis) for the unstable distal ulnar stump and 3) the stability after the implantation of an ulnar head endoprosthesis following a Darrach resection on radioulnar convergence. With a dynamic PC-controled forearm simulator the rotation of 7 fresh-frozen cadaver upper extremities was actively and passively performed while loading relevant muscles. Resultant total forearm torque and the 3-dimensional kinematics of the ulna, radius and third metacarpal were recorded simultaneously. The implantation of the ulnar head endoprosthesis effectively restored the stability of the DRUJ. There were significantly better results after the implantation of the prosthesis compared with the Darrach and the soft tissue stabilization procedures. This study provides laboratory validity to the option of implanting an ulnar head endoprosthesis as an attempt to stabilize the distal forearm after Darrach resection in lieu of performing soft tissue stabilization techniques.     

The effect of macrophage-colony stimulating factor and other humoral factors (interleukin-1, -3, -6, and -11, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor) on human osteoclast formation from circulating cells

Macrophage-colony stimulating factor (M-CSF) is an essential requirement for human osteoclast formation, but its effect on the proliferation and differentiation of circulating osteoclast precursor cells is unknown. Other growth factors and cytokines are also known to support/stimulate osteoclast formation from mouse marrow precursors, but it is not certain whether these factors similarly influence human osteoclast formation. In this study, human monocytes were cocultured with osteoblast-like UMR-106 cells on coverslips and dentine slices for up to 21 days in the presence of 1,25 dihydroxyvitamin D(3) (10(-7) mol/L), dexamethasone (10(-8) mol/L), and various concentrations of either M-CSF or other humoral factors (interleukin [IL]-1beta, IL-3, IL-6, and IL-11; tumor necrosis factor-alpha [TNF-alpha]; and granulocyte macrophage [GM]-CSF). The effect on osteoclast formation was assessed by tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor staining and lacunar bone resorption. The results of time-course and proliferation studies showed that M-CSF stimulated both the proliferative and differentiation stages of human osteoclast formation from circulating osteoclast precursors in a dose-dependent manner. A high concentration of M-CSF (100 ng/mL) did not inhibit osteoclast formation. IL-3 and GM-CSF were also capable of stimulating human osteoclast formation, although these growth factors were much less potent than M-CSF. IL-3- and GM-CSF-stimulated osteoclast formation was inhibited by an antibody specific for human M-CSF. Osteoclast formation and lacunar resorption was not seen when either TNF-alpha, IL-1beta, IL-6 (+ soluble IL-6 receptor), or IL-11 was substituted for M-CSF during coculture. These results confirm that M-CSF is essential for human osteoclast formation from circulating mononuclear precursors, and also shows that IL-3 and GM-CSF may support osteoclast differentiation via the stimulation of M-CSF production by human monocytes.     

Immunohistochemical localization of membrane and alpha-granule proteins in human megakaryocytes: application to plastic-embedded bone marrow biopsy specimens

Using a new technique for antigen localization, we have demonstrated platelet proteins in megakaryocytes in plastic-embedded biopsy specimens of normal human bone marrow. In a series of 25 specimens, megakaryocytes showed labeling with antibodies to the integral membrane glycoproteins IIIa, IIb, and the IIb-IIIa complex; granule membrane protein 140; and five alpha-granule matrix proteins: thrombospondin, factor VIII-related antigen, beta-thromboglobulin, platelet factor 4, and fibrinogen. The antibodies to the membrane glycoproteins IIIa, IIb, and IIb-IIIa produced diffuse cytoplasmic staining and heavier staining on the plasma membrane, whereas the antibodies to the alpha-granule matrix proteins produced a distinct granular staining within the cytoplasm. Staining for granule membrane protein 140 was also granular in distribution. Rare mononuclear cells consistent with megakaryocyte precursors were labeled with these markers. Other enzyme histochemical and lectin-binding studies showed that the enzyme alpha-naphthyl acetate esterase, the lectin Ulex europaeus I, and the periodic-acid Schiff reaction were consistent, but not specific, markers of megakaryocytes. This immunohistochemical technique should facilitate the examination of qualitative and quantitative changes in megakaryocytes in a variety of physiologic and pathologic processes.     

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