Establishing a laparoscopic gastric bypass program

OBJECTIVE: To evaluate the outcomes for laparoscopic Roux-en-Y gastric bypass in a newly developed bariatric surgery program. METHODS: A prospective analysis of the initial 100 patients who underwent laparoscopic Roux-en-Y gastric bypass at a community based teaching hospital between December 2000 and October 2001 was performed. Study endpoints included operative time, early (less than 7 days) and late complication rates, hospital length of stay (LOS), time to initiation of oral diet, and percentage of excess body weight loss. RESULTS: There were 91 women and 9 men with a mean age of 39 years (range 21 to 57). Mean preoperative weight was 126.4 kg (range 92.3 kg to 214 kg), with a mean preoperative body mass index of 47.4 (range 37.3 to 75.7). Ninety (90%) patients had at least one significant medical comorbidity (median = 6 per patient). Mean operative time was 2.4 hours (range 1.0 to 6.5; 3.0 hours for the first 50 patients and 1.8 hours for the last 50 patients). Three patients required conversion to open gastric bypass, all due to equipment failure (two harmonic scalpel failures and one linear stapler malfunction). Seven patients had early complications, 3 with anastomotic hemorrhage requiring transfusion, 3 with intestinal leaks requiring reoperation, and 1 with transected nasogastric tube. Eleven patients had late complications: 5 patients with small bowel obstruction, all due to herniation through the transverse colon mesentery (these occurred early in the series, prompting a change in technique, with no subsequent occurrences), 3 with gastrojejunostomy strictures requiring endoscopic dilation, 2 superficial wound infections, and 1 port-site incisional hernia. No complications occurred in the last 40 patients. No deaths occurred. Median hospital stay was 2 days (range 1 to 37); 3 days in the first 50 cases and 1 day in the last 50 cases. The median number of days to the start of an oral diet was 1 day. Average excess body weight loss was 34% (median follow-up 4 months). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass is a technically challenging procedure that can be safely integrated into a bariatric treatment program with good results. Improved outcomes, shorter operative times, and fewer complications are associated with increased surgical experience.     

Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II)

The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8- dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo- dGTPases may be involved in the mechanisms of induction of the 8- oxoguanine lesion in DNA by the metal ions studied, especially the non- redox-active Cd(II) cation.      

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.      

Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence

The role of divalent cations in platelet adherence to deendothelialized human arteries in flowing blood was investigated in an annular perfusion chamber. Spreading of platelets on the subendothelium was impaired below 30 microM of free Ca2+ ions (Ca2+). When Ca2+ was replaced by Mg2+, adherence was unchanged in perfusates without exogenous factor VIII-von Willebrand factor (FVIII-vWF), but the ability of FVIII-vWF to support platelet adherence was lost. Binding of FVIII-vWF to the vessel wall was independent of divalent cations, but bound FVIII-vWF was only able to mediate adherence after exposure to Ca2+. Pretreatment of FVIII-vWF with the calcium chelator EGTA (10 mM) resulted in loss of the ability to facilitate platelet adherence, while the ristocetin cofactor activity remained intact. Full restoration of the ability to mediate platelet adherence could only be obtained by prolonged dialysis against Ca2+ in the millimolar range. These data indicate that divalent cations have at least two separate roles to play in supporting platelet adherence: (1) platelet spreading on the subendothelium requires Ca2+ or Mg2+; (2) FVIII-vWF should be exposed to Ca2+ to obtain its optimal biologic activity in supporting platelet adherence.     

Ovarian carcinoma: Histologic and clinical correlation of cytoplasmic estrogen and progesterone binding

Primary ovarian carcinomas from 18 patients, ages 27–79, were evaluated for the presence of estrogen- and progesterone-binding proteins. The levels of cytosolic sex steroid receptor were compared to histology, nuclear grade, and the patients' clinical course. The data suggest that nuclear grade and receptor status each correlate with the patients' clinical course. The simultaneous presence of both estrogen and progesterone receptor proteins tend to be noted in tumors with more well-differentiated nuclei. It is suggested that the determination of biochemical cytosolic receptor status may become an important addition to tumor type, nuclear grade, and staging as prognostic indicators in patients with ovarian carcinoma. Histochemical staining for estrogen-binding localization did not correlate with SDGA and DCCA receptor analysis nor with clinical parameters.     

Antibody to the mitotic spindle apparatus: immunologic characteristics and cytologic studies

A naturally occurring autoantibody directed at the mitotic spindle polar apparatus (MSA) was detected in sera from 18 patients with defined or evolving connective tissue diseases by routine indirect immunofluorescence on a tissue culture cell. This IgG antibody stained the mitotic spindle poles of dividing tissue culture and tissue section substrates, with staining most prominent on substrates of human origin. With some sera, and cell lines, interphase cells showed isolated nuclear staining. Cytoplasmic staining was not apparent in any sera on any substrate. This specificity was shown to be distinct from tubulin by double fluorescence labeling studies. Patient sera exhibiting only this specificity did not precipitate antigens in rabbit or calf thymus nuclear extracts. However, several patients with systemic lupus erythematosus exhibited anti-MSA in combination with other autoantibodies. This autoantibody may be a useful probe for spindle pole-related structures.