Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.     

Parathyroid hormone-related protein in patients with primary breast cancer and eucalcemia

Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia in breast cancer and other malignancies. We studied circulating PTHrP levels with three different immunoassays directed against different parts of the PTHrP molecule in 48 patients with breast cancer and eucalcemia. The methods used were: (a) a RIA with antibodies directed toward the midregion (63-78); (b) an immunofluorometric assay with two antibodies against 1-34 and 38-67; and (c) an immunoradiometric assay with antibodies against 1-40 and 1-72. Although most patients had PTHrP levels indistinguishable from normal when measured by all three methods, four patients had increased serum levels in the IFMA. PTHrP was detected by immunohistochemistry in tumors from nearly all patients. One patient with elevated PTHrP in plasma measured by IFMA showed intense staining of tumor by immunohistochemistry; the tumor was histologically graded as III (severe) and was the largest of all tumors in this patient group. The IFMA can identify increased serum PTHrP in some patients with breast cancer who are not hypercalcemic. This assay may be especially useful in screening patients for this tumor during a relative early phase of the disease.     

Effect of bonding agents on adhesion of composite resin following CO2 laser etching of dental enamel

This paper looks at the process of setting up a Head Injury Register whose aims are: (1) to identify reliably and rapidly patients who have sustained a head injury so that service can be offered to them; and (2) to obtain epidemiological data to identify needs and inform future service planning and development. The register records all cases of head injury in patients aged 16-65, regardless of severity, which present to hospital services in Oxfordshire whether or not admitted as inpatients. It was set up as part of a research project into the value of providing an early follow-up service for head injury patients. The paper highlights the difficulty of identifying these patients reliably. It details the administrative and technological problems encountered, together with some of their solutions.     

S100B, a neurotropic protein that modulates neuronal protein phosphorylation, is upregulated during lesion-induced collateral sprouting and reactive synaptogenesis

Using light and electron microscopic immunocytochemistry, we examined the expression of the Ca2+-binding protein S100B in the dentate gyrus of adult rats during lesion-induced sprouting and reactive synaptogenesis. Nine days following unilateral lesioning of the entorhinal cortex, S100B was upregulated in cells primarily in the outer part of the molecular layer of the ipsilateral dentate gyrus. When examined with electron microscopy, numerous astrocytes and synapses containing S100B were identified. These data show that during lesion-induced sprouting and reactive synaptogenesis, S100B is upregulated in astrocytes and can be found in pre- and post-synaptic compartments where it might influence neuronal protein phosphorylation.     

Separation of discontinuous adventitious sounds from vesicular sounds using a wavelet-based filter

The separation of pathological discontinuous adventitious sounds (DAS) from vesicular sounds (VS) is of great importance to the analysis of lung sounds, since DAS are related to certain pulmonary pathologies. An automated way of revealing the diagnostic character of DAS by isolating them from VS, based on their nonstationarity, is presented in this paper. The proposed algorithm combines multiresolution analysis with hard thresholding in order to compose a wavelet transform-based stationary-nonstationary filter (WTST-NST). Applying the WTST-NST filter to fine/coarse crackles and squawks, selected from three lung sound databases, the coherent structure of DAS is revealed and they are separated from VS. When compared to other separation tools, the WTST-NST filter performed more accurately, objectively, and with lower computational cost. Due to its simple implementation it can easily be used in clinical medicine.     

Porcine aortic wall flexibility. Fresh vs Denacol fixed vs glutaraldehyde fixed

It has been postulated that, in theory, stentless bioprosthetic heart valves provide improved hemodynamics and durability over their stented counterparts. A number of glutaraldehyde modified porcine stentless valves are currently either on the market or in clinical trials. Polyepoxy compound as an alternative cross-linking reagent to glutaraldehyde for bioprostheses has been reported to mitigate calcification. The present study was to investigate the effect of the fixation methods on porcine aortic wall flexibility. Ring specimens were selected from three groups of porcine roots: fresh, low pressure glutaraldehyde fixed, and low pressure Denacol (polyepoxy compound) fixed. Pulled between two rods on a tensile tester, a ring specimen's load-deformation relationship was recorded and analyzed to numerically compute the tissue modulus at low strains. The results showed that the Young's moduli were 0.113 +/- 0.036, 0.494 +/- 0.113, and 1.320 +/- 0.292 MPa (mean +/- SD, n = 10) for the fresh, Denacol fixed, and glutaraldehyde fixed aortic walls, respectively. The Denacol fixed aortic wall was more flexible than the glutaraldehyde fixed one. It was also found that the Denacol fixed aortic wall maintained most of the natural residual strains, while the glutaraldehyde fixed aortic wall did not.     

Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects

The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.     

Paradoxical reactions in children associated with midazolam use during endoscopy

All 2,617 children who received midazolam and meperidine for a variety of endoscopic procedures were monitored for the development of adverse behavioral problems. Thirty-six (1.4%) of the children (ages 1-17 years) experienced a paradoxical behavioral reaction, which consisted of inconsolable crying, combativeness, disorientation, dysphoria, tachycardia, agitation, and restlessness. The reaction occurred at a mean of 17 minutes after the administration of midazolam. Following treatment with flumazenil, the reaction dissipated within a mean of 14 minutes. Three of the 36 patients underwent additional endoscopic procedures utilizing only meperidine. No similar reaction was observed in these patients. Awareness of the reaction and prompt administration of flumazenil decreased the duration of the reaction.     

Intrinsic signals in the unique domain target p56(lck) to the plasma membrane independently of CD4

In T lymphocytes, the Src-family protein tyrosine kinase p56(lck) (Lck) is mostly associated with the cytoplasmic face of the plasma membrane. To determine how this distribution is achieved, we analyzed the location of Lck in lymphoid and in transfected nonlymphoid cells by immunofluorescence. We found that in T cells Lck was targeted correctly, independently of the cell surface proteins CD4 and CD8 with which it interacts. Similarly, in transfected NIH-3T3 fibroblasts, Lck was localized at the plasma membrane, indicating that T cell-specific proteins are not required for targeting. Some variation in subcellular distribution was observed when Lck was expressed in HeLa and MDCK cells. In these cells, Lck associated with both the plasma membrane and the Golgi apparatus, while subsequent expression of CD4 resulted in the loss of Golgi-associated staining. Together, these data indicate that Lck contains intrinsic signals for targeting to the plasma membrane. Furthermore, delivery to this site may be achieved via association with exocytic transport vesicles. A mutant Lck molecule in which the palmitoylation site at cysteine 5 was changed to lysine (LC2) localized to the plasma membrane and the Golgi region in NIH3T3 cells. However, the localization of a mutant in which the palmitoylation site at cysteine 3 was changed to serine (LC1) was indistinguishable from wild-type Lck. Chimeras composed of only the unique domain of Lck linked to either c-Src or the green fluorescent protein similarly localized to the plasma membrane of NIH-3T3 cells. Thus, the targeting of Lck appears to be determined primarily by its unique domain and may be influenced by the use of different palmitoylation sites.     

Results of conventional and hysteroscopic surgery

Müllerian anomalies usually come to medical attention when they become problematic and require treatment. Most of these complications require surgical correction. The most commonly presenting anomaly is the double uterus which can be the source of recurrent abortion and preterm deliveries. The Strassman, Jones and Tompkins metroplasties have been shown to greatly improve the rate of successful deliveries in these patients. Hysteroscopic metroplasty, using either scissors, resectoscope or laser is now the recommended treatment for most septate uteri due to its relative simplicity, low morbidity and excellent reproductive outcome.