Abstract  An elderly man with ischaemic heart and peripheral vascular disease presented with a 3-month history of increasingly severe postprandial epigastric pain, nausea, vomiting, diarrhoea and weight loss, associated with gastroscopic evidence of superficial antral ulceration and discoloration. The patient died shortly after admission to hospital. Autopsy showed evidence of mesenteric vascular disease and ischaemic bowel. The literature on chronic mesenteric ischaemia is briefly reviewed, and the role of arteriography is discussed.

Abstract  Between January 1983 and August 1998, a total of 18 patients (14 men, 4 women; median age 58 years, range 36-75 years) with primary adenocarcinoma of the duodenum underwent surgical therapy. Main clinical symptoms were upper abdominal pain (61%), weight loss (44%) and anaemia (38%). The tumors were resectable in 10 patients (56%), and eight Whipple operations and two segmental duodenectomies were performed. Tumor classification according to the TNM system was pT2 (n = 2), pT3 (n = 6) and pT4 (n = 2). In eight patients, local lymph nodes were tumor positive (pN1), and in two patients synchronous liver metastases were excised. The UICC stage of the resected tumors was: stage I (n = 1), stage II (n = 1), stage III (n = 6) and stage IV (n = 2). In irresectable cases (n = 8), the patients underwent palliative (n = 6) or explorative (n = 2) operations. With no operative mortality, overall morbidity was 22% (4/18). Patients' survival was 90%, 66.7% and 53.3%, respectively, at 1, 3 and 5 years after resection. None of the patients with irresectable tumors survived longer than 25 months. Survival was significantly better for the resection group (P = 0.0027). Due to the often unspecific symptoms, the diagnosis of duodenal adenocarcinoma is frequently established at advanced tumor stages, resulting in a low resectability rate. Radical surgical resection of the tumors, however, is able to provide a more favorable prognosis for duodenal carcinoma than for other periampullary tumors.

Abstract  Estrogen receptor (ER)-negative breast cancer cells display extensive methylation of the ER gene CpG island and elevated DNA methyltransferase (DMT) expression compared to ER-positive cells. The present study demonstrates that DMT protein levels tightly correlate with S phase fraction in ER-positive cells, whereas ER-negative cells express DMT throughout the cell cycle. In addition, levels of p21CIP1, which disrupts DMT binding to PCNA, are inversely correlated with DMT levels. Therefore increased DMT expression in ER-negative cells is not simply due to elevated S-phase fraction, but rather to more complex changes that allow cells to escape normal cell cycle-dependent controls on DMT expression. Because ER-negative breast tumors often have activated growth factor pathways, the impact of these pathways on DMT expression was examined in ER-positive cells. Stable transfection with fibroblast growth factors (FGFs) 1 and 4 led to increased DMT expression that could not be accounted for by a shift in S phase fraction. Elevated DMT protein expression in FGF-transfectants was accompanied by a significant decrease in p21, again suggesting a reciprocal relationship between these two proteins. However, acquisition of an estrogen-independent phenotype, even in conjunction with elevated DMT levels, was not sufficient to promote ER gene silencing via methylation. These results indicate that multiple steps are required for de novo methylation of the ER CpG island.

Abstract  OBJECTIVE: To obtain in vivo bacterial colonization profiles on endotracheal tubes at different sites in the neonatal airway in an attempt to better characterize one potential element of chondritis.

DESIGN: A case series in which cultures were obtained from calculated segments of 33 endotracheal tubes immediately following extubation. This allowed for sampling at specific levels of the airway corresponding to the trachea, the subglottis, and the oropharynx. Data collected included gender, race, duration of intubation, use of antibiotic therapy, comorbidities, gestational age at birth and extubation, crown-rump length, weight, radiographic distance from tube tip to carina, and culture results.

SETTING: Newborn intensive care unit at a tertiary care medical center.

PATIENTS: Twenty-nine neonates intubated for longer than 24 hours (range, 24 hours to 15 days).

MAIN OUTCOME MEASURES: Bacterial and fungal cultures obtained from 3 endotracheal tube segments for each extubation.

RESULTS: A statistically significant difference (P < .05) was found in colonization rates between patients intubated for less than 4 days and those intubated for longer periods. No significant difference was noted in bacterial profile between the 3 sites.

CONCLUSIONS: Data demonstrate that bacterial colonization of an indwelling object in the neonatal airway increases with the duration of intubation. Furthermore, 4 days seems to represent a critical period in the formation of such colonization (possibly in the form of a biofilm). These bacteria may contribute to the chondritis known to precede the development of subglottic stenosis. Further studies are indicated to suggest ways to interrupt this process and reduce the incidence of airway injury.

Abstract  The interval from the beginning of the Q wave to the origin of the T wave (Q-oTc interval) and total and ionized serum calcium levels were measured in 27 full-term and 77 premature infants. The correlation between Q-oTc and total and ionized calcium levels was significant in both full-term and normal premature infants. No correlation was found in a group of critically ill premature infants, most of whom had evidence of CNS involvement. Constant infusion of calcium gluconate in a number of infants belonging to the latter group produced a significant shortening of the Q-oTc interval. It is speculated that the lack of correlation of Q-oTc interval and total or ionized calcium levels in sick premature infants could be explained on the basis of a dysfunction in cardiac sympathetics or alternatively by marked variations in serum catecholamines.

Abstract  Myocardial infarction has been found to be a significantly frequent cause of unexpected sudden death in Black males in Pretoria and its vicinity. A study of 758 autopsies performed for unexplained sudden death in Blacks revealed 39 fatal infarcts in 511 males but only 1 in 247 females. The condition became evident in the third decade, rose sharply in the fourth and declined gradually thereafter.

Abstract  Sixty-four instances of histologically documented ossifying and/or cementifying fibromas were evaluated. Adequate radiographs were available in 43 of the cases. Most of these benign fibro-osseous neoplasms occurred in women, with a predilection for the third and fourth decades. Six distinct radiographic patterns could be identified: (1) radiolucent, superimposed over teeth or residing in edentulous regions (28%); (2) radiolucent with opaque foci, lying in edentulous areas or superimposed over teeth (42%); (3) radiolucent, interposed between contiguous teeth (5%); (4) radiolucent with opaque foci, interposed between contiguous teeth (9%); (5) multilocular expansile (7%); and (6) aggressively expansile with opacification (9%). All lesions exhibited well-defined margins. Root resorption was a feature in 11% of the sample, and root divergence occurred in 17% of the cases.

Abstract  The gene for yeast cytochrome c oxidase subunit V, COX5, has been isolated from a Saccharomyces cerevisiae DNA library by complementation of a cytochrome c oxidase subunit V mutant, JM28. One complementing plasmid, YEp13-511, with a DNA insert of 4.8 kilobase pairs, has been characterized in detail. This plasmid restores respiratory competency in JM28, results in increased cytochrome c oxidase activity and a new form of subunit V in JM28 mitochondria, and is capable of selecting mRNA for subunit V. These results indicate that YEp13-511 carries the COX5 gene and that the subunit V encoded by this plasmid gene is capable of entering the mitochondrion and assembling into a functional holocytochrome c oxidase.

Abstract  Bacterial lipopolysaccharides (LPS) greatly increase cGMP levels in rat fetal liver cells without affecting the concentration of cAMP. This elevation is due to the Lipid A moiety of the LPS molecule, is time and dose dependent, and is markedly potentiated by small amounts of serum. Because of the magnitude of the serum potentiation, a series of experiments was undertaken to further characterize this effect. Although serum was not absolutely necessary for a cGMP response, small amounts increased the cGMP potency of LPS more than 100-fold. Under these same conditions, serum did not greatly affect the ability of nitroprusside to raise cGMP levels or of epinephrine to raise cAMP levels. The effect of serum on the cGMP response was dose dependent and was produced with as little as 1 microliter (0.1% v/v) per culture. Absorption with limulus lysate, heating to 56 degrees C for 30 min, or extensive dialysis did not significantly alter the cGMP enhancing effect of serum. However, albumin and IgG were both inactive at all concentrations tested. Thus, serum produces a large dose dependent enhancement of the LPS induced cGMP response that appears to be selective, i.e. it is not a non-specific protein effect and there is no similar potentiation of nitroprusside stimulated cGMP levels. Furthermore, the cGMP effect of serum is probably not related to substances that opsonize bacteria and is due to a component or components of serum large enough not to be dialyzable.

Abstract  The mechanism of environmental pollution promoting gastric cancer incidence and difficulty of treatment is not fully understood. In the present article, perfluorodecanoic acid (PFDA), a common persistent environmental pollutant, was used to treat the gastric cell lines and mice to test its genotoxicity. The γ-H2AX immunoblot and plasmid fragment PCR results showed that PFDA had a promotion effect on the DNA double-strand breaks (DSBs) in human and mouse cells. Subsequent results showed that PFDA significantly altered the sensitivity of cells to chemotherapy. Microarray data showed that the expressions of some important DNA repair genes were changed. Further investigation discovered that PFDA inhibition of DNA repair was mediated by X-ray repair cross complementing 4 (XRCC4). The cells deficient in XRCC4 generally exhibited reduced proliferation and premature aging in culture; however, our results indicated that PFDA induced p53 inhibition rescued cells from the apoptosis that was triggered by nonhomologous end-joining (NHEJ) inactivation, and overexpression of p53 expression in PFDA-treated cells enhanced their apoptosis. Finally, T-cell specific factor 4 was suggested by the results as an upstream regulator of XRCC4. This article revealed for the first time that perfluorinated chemicals affect chemotherapeutic sensitivity and the NHEJ pathway, and p53 reduction rescues cells from death.

Abstract  We present a case in which an island extended inferior epigastric artery musculocutaneous flap, used to resurface an amputation stump, retained sensation. The reasons for this are discussed.

Abstract  A new case of X/autosome translocation in a male patient is described. Azoospermia and Klinefelter like stigmata can be explained as a consequence of the balanced translocation, or by disturbed X-chromosomal inactivation during spermiogenesis.

Abstract  In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.

Abstract  PURPOSE: Invasive breast carcinoma is the most common cancer in women as in non-ovariectomised pet dogs, which are already identified as a valuable spontaneous preclinical model for that disease. Geographical and time trends suggest that environmental factors may play an important role in the etiology and pathogenesis of breast cancer. Persistent organic pollutants (POPs) fit perfectly with these trends and are known to interact with hormonal receptors implicated in breast cancer subtyping. The aim of this innovating study was to evaluate the interest of the companion dog model in assessing chemical exposure and breast cancer associations, in order to identify common etiological features with the human disease in a context of comparative oncology.

METHODS: We monitored a hundred of molecules belonging to a large panel of POPs (dioxins, dioxin-like and non dioxin-like polychlorobisphenyls, organochlorine pesticides, brominated flame retardants, perfluorinated alkylated substances) in companion dogs diagnosed for mammary adenocarcinoma (n = 54) and non cancer controls (n = 47).

RESULTS: All targeted chemical families were able to be detected in canine samples. We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer.

CONCLUSIONS: Similarities observed in the spontaneous dog model are very helpful to progress in interpretation of human breast cancer-environment relationships. This study provides a new insight focusing on this discrete but recurrent signature.

Abstract  Ultrastructural studies were performed on blood samples from five neonates with Down's syndrome and transient abnormal myelopoiesis (TAM). Three methods of fixation were employed to detect diaminobenzidine (DAB) reactivity. The first method used glutaraldehyde solution, while the second and third methods used tannic acid-glutaraldehyde mixtures. Before fixation by the second method, specimens were washed in order to eliminate plasma, and before fixation by the third were diluted to lessen the effects of plasma protein. The latter two methods were more sensitive than the first for detection of DAB reactivity, while the third also resulted in better preservation of morphology than did the second. Even the first method was able to detect DAB reactivity in cells of megakaryocyte-platelet series in appropriate sections. Although the majority of blasts appeared with light microscopy to be undifferentiated, their ultrastructural morphology and ultrastructural cytochemistry were in fact found to be quite heterogeneous, consisting of cells of the megakaryocyte-platelet and granulocytic series, including basophils, and erythroid precursors. This finding supported the view that TAM was the result of unstable hematopoiesis rather than true leukemia.