Medical versus surgical management of diverticulitis in patients under age 40

BACKGROUND: Diverticulitis in patients under age 40 is a distinct entity. We compared the medical versus surgical management of diverticulitis for complications and outcomes in these patients. METHODS: A retrospective review was performed for treatment, hospitalizations, complications, and outpatient visits. Complications included readmission, recurrent symptoms after antibiotic therapy, and postoperative problems. RESULTS: Twenty-nine patients had a radiographic or surgical diagnosis of diverticulitis (18 surgical, 11 medical). Medically managed patients had significantly more emergency department visits (4.7 +/- 6.6 versus 0.3 +/- 0.6, P < or =0.01), and readmissions (7 versus 4, P < or =0.02). Three surgical patients (17%) had a total of 6 complications as compared with 6 medical patients (55%) with 25 complications (chi square, P < or =0.05). All medically treated patients had recurrent symptoms, and 6 required surgery. CONCLUSION: Medically managed patients had significantly more emergency department visits and complications than those managed surgically. Surgery is the indicated treatment for the first episode of diverticulitis in patients under age 40.     

Aip3p/Bud6p, a yeast actin-interacting protein that is involved in morphogenesis and the selection of bipolar budding sites

A search for Saccharomyces cerevisiae proteins that interact with actin in the two-hybrid system and a screen for mutants that affect the bipolar budding pattern identified the same gene, AIP3/BUD6. This gene is not essential for mitotic growth but is necessary for normal morphogenesis. MATa/alpha daughter cells lacking Aip3p place their first buds normally at their distal poles but choose random sites for budding in subsequent cell cycles. This suggests that actin and associated proteins are involved in placing the bipolar positional marker at the division site but not at the distal tip of the daughter cell. In addition, although aip3 mutant cells are not obviously defective in the initial polarization of the cytoskeleton at the time of bud emergence, they appear to lose cytoskeletal polarity as the bud enlarges, resulting in the formation of cells that are larger and rounder than normal. aip3 mutant cells also show inefficient nuclear migration and nuclear division, defects in the organization of the secretory system, and abnormal septation, all defects that presumably reflect the involvement of Aip3p in the organization and/or function of the actin cytoskeleton. The sequence of Aip3p is novel but contains a predicted coiled-coil domain near its C terminus that may mediate the observed homo-oligomerization of the protein. Aip3p shows a distinctive localization pattern that correlates well with its likely sites of action: it appears at the presumptive bud site prior to bud emergence, remains near the tips of small bund, and forms a ring (or pair of rings) in the mother-bud neck that is detectable early in the cell cycle but becomes more prominent prior to cytokinesis. Surprisingly, the localization of Aip3p does not appear to require either polarized actin or the septin proteins of the neck filaments.     

Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features

OBJECTIVE: To determine whether the 2 periodic febrile syndromes familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are distinct diseases. METHODS: Clinical manifestations of the diseases were analyzed by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels were studied in 70 patients with FMF using nephelometry or ELISA and compared with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the chromosome 16 polymorphic locus RT70, currently used for refined localization of the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients) using polymerase chain reaction amplification and gel electrophoresis. RESULTS: The main clinical features distinguishing FMF from HIDS were lymphadenectomy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%), significantly lower than the prevalence reported for HIDS. We found no evidence for genetic linkage between HIDS and the chromosome 16 marker RT70. CONCLUSION: HIDS and FMF are different entities, clinically, immunologically, and genetically.     

Radical fringe positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb

Vertebrate limb outgrowth requires a structure called the apical ectodermal ridge, formation of which follows the previous establishment of the dorsoventral limb axis. Radical fringe is expressed in the dorsal ectoderm before the ridge appears, and is repressed by Engrailed-1, which is expressed in the ventral ectoderm. Misexpression of these genes indicates that a ridge is formed wherever there is a boundary between cells expressing and not expressing Radical fringe. Thus, as in Drosophila, Radical fringe positions the ridge at the dorsoventral limb boundary.     

Stage I corpus cancer: is teletherapy necessary?

OBJECTIVE: Our aim was to evaluate the perioperative morbidity after hysterectomy and lymphadenectomy as primary treatment of endometrial cancer and to analyze the recurrence and survival of patients classified as having surgical stage I disease who did not receive adjunctive teletherapy. STUDY DESIGN: Over a 10-year interval 444 patients underwent extensive surgical staging for corpus cancer. Perioperative events were recorded prospectively. Outcome events were updated after the last year of study. RESULTS: After patients with high-risk histologic types of cancer were excluded, 396 patients were evaluable. The risk of extrauterine disease, detected in 21.8% of patients, increased with increasing lack of tumor differentiation. The associated surgical morbidity, including blood loss (mean 336 ml), surgical site infection (3.5%), thromboembolic events (1.5%), and urinary injury (0.6%), and deaths (0.6%) did not differ from those in reports of women undergoing lesser operative procedures. Late complications, including lymphocyst (1.2%), leg edema (1.8%), and hernia (2.9%), were infrequent. Recurrence and survival analysis indicated a calculated 5-year survival of 97% of all patients with surgical stage I disease. There was a significant survival difference related to grade and stage for women in whom disease was confined to the uterus. Overall survival in patients with stage IA (100%) was significantly different (p < 0.0001) from that of patients with stage IB (97%) and stage IC (93%). All recurrences included a distal component. CONCLUSION: Extensive surgical staging including lymphadenectomy can be performed safely. Our results suggest that the risk of pelvic recurrence is not increased and the risk of survival is not compromised in those women not receiving adjunctive teletherapy.     

Effects of specimen collection, processing, and storage conditions on stability of human immunodeficiency virus type 1 RNA levels in plasma

To define the optimal blood collection parameters for plasma human immunodeficiency virus type 1 (HIV-1) viral load testing, plasma HIV-1 RNA levels were quantitated with the NASBA HIV-1 RNA QT System from blood specimens that were collected, processed, and stored under a variety of conditions that might have affected HIV-1 RNA stability. We determined that when whole blood was processed within 2 h of specimen collection the levels of HIV-1 RNA detected in EDTA-, heparin-, and acid citrate dextrose (ACD)-anticoagulated plasma samples were comparable. The levels of HIV-1 RNA in serum specimens (mean = 4.126 log units) were significantly lower (P < 0.01) than the levels in corresponding plasma samples (mean = 4.501 log units). One cycle of freeze-thaw (-70 degrees C) did not significantly reduce the level of HIV-1 RNA detected in EDTA-, heparin-, or ACD-anticoagulated plasmas. The EDTA-anticoagulated plasmas showed the smallest decrease in HIV-1 RNA copies (0.050 log units). HIV-1 RNA levels decreased over a 6-month time period in serum as well as in EDTA-, ACD-, and heparin-anticoagulated plasmas stored at -70 degrees C. However, the only significant decreases were for serum (mean decrease = 0.317 log units) and heparin-anticoagulated samples (mean decrease = 0.384 log units). A comparison of the levels of HIV-1 RNA in cell-free plasma collected in VACUTAINER EDTA Plasma Preparation Tubes and in standard VACUTAINER EDTA tubes determined that HIV-1 RNA levels were stable for up to 30 h after collection when stored at either room temperature (mean standard deviation [SD] = +/- 0.101 log units) or at 4 degrees C (mean SD = +/- 0.102 log units) as cell-free plasma or as EDTA-anticoagulated whole blood (mean SD = +/- 0.109 log units). These data indicate that EDTA-anticoagulated plasma is the most suitable and stable matrix for HIV-1 RNA quantitation.     

Effects of aerobic exercise training and yoga on the baroreflex in healthy elderly persons

It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training. The effects of aerobic exercise training and yoga, a non-aerobic control intervention, on the baroreflex of elderly persons was determined. Baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF; 0.15-0.35 Hz, reflecting parasympathetic activity) and mid-frequency (MF; 0.05-0.15 Hz, reflecting sympathetic activity as well), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. Twenty-six (10 women) sedentary, healthy, normotensive elderly (mean 68 years, range 62-81 years) subjects were studied. Fourteen (4 women) of the sedentary elderly subjects completed 6 weeks of aerobic training, while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate decreased following yoga (69 +/- 8 vs. 61 +/- 7 min-1, P < 0.05) but not aerobic training (66 +/- 8 vs. 63 +/- 9 min-1, P = 0.29). VO2 max increased by 11% following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No significant change in alpha MF (6.5 +/- 3.5 vs. 6.2 +/- 3.0 ms mmHg-1, P = 0.69) or alpha HF (8.5 +/- 4.7 vs. 8.9 +/- 3.5 ms mmHg-1, P = 0.65) occurred after aerobic training. Following yoga, alpha HF (8.0 +/- 3.6 vs. 11.5 +/- 5.2 ms mmHg-1, P < 0.01) but not alpha MF (6.5 +/- 3.0 vs. 7.6 +/- 2.8 ms mmHg-1, P = 0.29) increased. Short-duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects. alpha HF but not alpha MF increased following yoga, suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable.     

New tumor markers of testis cancer

Microtubules are filamentous polar polymers with plus and minus ends. This polarity plays a crucial role in a variety of cellular functions such as chromosome movement and organelle transport. To examine the relationship between the growth polarity of microtubules and guanine nucleotide dependence, we polymerized microtubules from axonemes of sea urchin sperm flagella either with GTP or with GTP and GDP, and observed individual microtubules by dark-field microscopy. Tubulin concentrations were adjusted in each case to grow microtubules from only one end of each axoneme. The growth polarity of microtubules was determined using N-ethylmaleimide-modified tubulin (NEM-tubulin). In the presence of GTP only and at low tubulin concentrations, microtubules grew from the plus ends of axonemes. Surprisingly, in the presence of GTP and GDP, microtubules grew from the minus ends, even at high tubulin concentrations. To confirm these results, we used a perfusion chamber to monitor the growth polarity of microtubules from the same axoneme under different conditions. Exchanging a solution containing only GTP for one containing GTP and GDP elicited a switch in the growth polarity of microtubules from the plus ends to the minus ends. These results suggest that GDP directly affects microtubule polymerization and inverts microtubule growth polarity, probably by inhibiting microtubule growth at the plus ends.     

Characterization of a temperature-sensitive yeast vacuolar ATPase mutant with defects in actin distribution and bud morphology

The 27-kDa E subunit, encoded by the VMA4 gene, is a peripheral membrane subunit of the yeast vacuolar H+-ATPase. We have randomly mutagenized the VMA4 gene in order to examine the structure and function of the 27-kDa subunit. Cells lacking a functional VMA4 gene are unable to grow at pH > 7 or in elevated concentrations of CaCl2. Plasmid-borne, mutagenized vma4 genes were screened for failure to complement these phenotypes. Mutants producing Vma4 proteins detectable by immunoblot were selected; one (vma4-1(ts)) is temperature conditional, exhibiting the Vma- phenotype only at elevated temperature (37 degreesC). Sequencing revealed that a single point mutation, D145G, was responsible for the phenotypes of the vma4-1(ts) allele. The unassembled 27-kDa subunit made in the vma4-1(ts) cells is rapidly degraded, particularly at 37 degreesC, but can be protected from degradation by prior assembly into the V-ATPase complex. In purified vacuolar vesicles from the mutant cells, the peripheral subunits are localized to the vacuolar membrane at decreased levels and a comparably decreased level of ATPase activity (14% of the activity in wild-type vesicles) is observed. When vma4-1(ts) mutant cells are shifted to pH 7.5 medium at 37 degrees C, the cells become enlarged and exhibit multiple large buds, elongated buds, and other abnormal morphologies, together with delocalization of actin and chitin, within 4 h. These phenotypes suggest connections between the vacuolar ATPase, bud morphology, and cytokinesis that had not been recognized previously.     

Role of the Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins

Dicarbonyl compounds such as glyoxal and methylglyoxal are reactive dicarbonyl intermediates in the nonenzymatic browning and cross-linking of proteins during the Maillard reaction. We describe here the quantification of glyoxal and methylglyoxal-derived imidazolium cross-links in tissue proteins. The imidazolium salt cross-links, glyoxal-lysine dimer (GOLD) and methylglyoxal-lysine dimer (MOLD), were measured by liquid chromatography/mass spectrometry and were present in lens protein at concentrations of 0. 02-0.2 and 0.1-0.8 mmol/mol of lysine, respectively. The lens concentrations of GOLD and MOLD correlated significantly with one another and also increased with lens age. GOLD and MOLD were present at significantly higher concentrations than the fluorescent cross-links pentosidine and dityrosine, identifying them as major Maillard reaction cross-links in lens proteins. Like the N-carboxy-alkyllysines Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine, these cross-links were also detected at lower concentrations in human skin collagen and increased with age in collagen. The presence of GOLD and MOLD in tissue proteins implicates methylglyoxal and glyoxal, either free or protein-bound, as important precursors of protein cross-links formed during Maillard reactions in vivo during aging and in disease.