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Biomedical subjects

S Saad

Publications and source records attributed to S Saad.

At least 19 recordsLinked to original sources

Securing the appendiceal stump in laparoscopic appendectomy: evidence for routine stapling?

BACKGROUND: This metaanalysis aimed to compare endoscopic linear stapling and loop ligatures used to secure the base of the appendix. METHODS: Randomized controlled trials on appendix stump closure during laparoscopic appendectomy were systematically searched and critically appraised. The results in terms of complication rates, operating time, and hospital stay were pooled by standard metaanalytic techniques. RESULTS: Data on 427 patients from four studies were included. The operative time was 9 min longer when loops were used (p = 0.04). Superficial wound infections (odds ratio [OR], 0.21; 95% confidence interval (CI), 0.06-0.71; p = 0.01) and postoperative ileus (OR, 0.36; 95% CI, 0.14-0.89; p = 0.03) were significantly less frequent when the appendix stump was secured with staples instead of loops. Of 10 intraoperative ruptures of the appendix, 7 occurred in loop-treated patients (p = 0.46). Hospital stay and frequency of postoperative intraabdominal abscess also were comparable in loop-treated and staple-treated patients. CONCLUSIONS: The clinical evidence on stump closure methods in laparoscopic appendectomy favors the routine use of endoscopic staplers.

Appendectomy↗

Laparoscopy for abdominal emergencies: evidence-based guidelines of the European Association for Endoscopic Surgery.

BACKGROUND: Emergency laparoscopic exploration can be used to identify the causative pathology of acute abdominal pain. Laparoscopic surgery also allows treatment of many intraabdominal disorders. This report was prepared to describe the effectiveness of laparoscopic surgery compared to laparotomy or nonoperative treatment. METHODS: A panel of European experts in abdominal and gynecological surgery was assembled and participated in a consensus conference using Delphi methods. The aim was to develop evidence-based recommendations for the most common diseases that may cause acute abdominal pain. RECOMMENDATIONS: Laparoscopic surgery was found to be clearly superior for patients with a presumable diagnosis of perforated peptic ulcer, acute cholecystitis, appendicitis, or pelvic inflammatory disease. In the emergency setting, laparoscopy is of unclear or limited value if adhesive bowel obstruction, acute diverticulitis, nonbiliary pancreatitis, hernia incarceration, or mesenteric ischemia are suspected. In stable patients with acute abdominal pain, noninvasive diagnostics should be fully exhausted before considering explorative surgery. However, diagnostic laparoscopy may be useful if no diagnosis can be found by conventional diagnostics. More clinical data are needed on the use of laparoscopy after blunt or penetrating trauma of the abdomen. CONCLUSIONS: Due to diagnostic and therapeutic advantages, laparoscopic surgery is useful for the majority of conditions underlying acute abdominal pain, but noninvasive diagnostic aids should be exhausted first. Depending on symptom severity, laparoscopy should be advocated if routine diagnostic procedures have failed to yield results.

Abdomen↗

In vitro models for oral malodor.

A model is a representation of some real phenomena and contains aspects or elements of the real system to be modeled. The model reflects (or duplicates) the type of behavior (or mechanisms) seen in the real system. The main characteristic of any model is the mapping of elements or parameters found in the system being studied (e.g. tongue dorsum biofilm in situ) on to the model being devised (e.g. laboratory perfusion biofilm). Such parameters include correct physico-chemical (abiotic) conditions as well as biotic conditions that occur in both model and reality. The main purpose of a model is to provide information that better explains the processes observed or thought to occur in the real system. Such models can be abstract (mental, conceptual, theoretical, mathematical or computational) or 'physical', e.g. in the form of a real disaggregated in vitro system or laboratory model. A wide range of different model systems have been used in oral biofilm research. These will be briefly reviewed with special emphasis on those models that have contributed most to knowledge in breath odor research. The different model systems used in breath odor research are compared. Finally, the requirements for developing an overall 'bad breath model' from considering the processes as a whole (real oral cavity, substrates in saliva, biotransformation by tongue microflora, odor gases in the breath) and extending this to the detection of malodor by the human nose will be outlined and discussed.

Biofilms↗

Use of n-butanol as an odorant to standardize the organoleptic scale of breath odour judges.

OBJECTIVE: The alcohol n-butanol has been recommended for use as a standard odorant by various groups for the training or standardization of breath odour judges and sensory evaluation panels. The objective of this study is to assess the use of n-butanol as a suitable odorant for organoleptic training of breath judges. METHODS: One judge with full smell acuity was trained in the method of organoleptic assessment using odorant solutions of main chemical classes (acids, amines, indole and sulphides) with the exception of alcohols. The subject was proficient in scoring odorant solutions, standard gas mixtures and human breath using the Rosenberg 0-5 organoleptic scale. A wide range of n-butanol solutions were prepared from 0 to 90 000 ppm and dispensed as replicate 12-ml volumes in Universal bottles (24 ml) leaving a headspace of 12 ml. Sets of odorants were prepared, labelled by code, randomized and presented to the judge in a completely blind fashion. The judge scored each concentration. This process was repeated on 32 occasions over a period of 12 weeks. Mean values of data for each determination for each concentration series were plotted against the log concentrations of odorant. Linear regression slope analysis was used to measure slope, the 95% CI of slope and the scatter of points (R2 value). Headspace concentrations of odorant were determined using gas chromatography (GC) analysis. RESULTS: The n-butanol regression slope gave a high R(2) value (0.971) and low scatter. However, the data did not correspond to other published work using an ASTM method where the range of recommended butanol concentrations was insufficient at both the high and low ends to determine the top and threshold. Moreover, headspace analysis using GC confirmed the published gas concentrations to be in error by a factor of 100. It was also observed that high concentrations of odorants were irritant causing desensitization if used for prolonged periods. CONCLUSION: The published method had erroneous headspace calculations listed and n-butanol could not be recommended as a training odorant because of its irritancy.

1-Butanol↗

Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure.

Postprandial hyperglycemia is implicated as a risk factor predisposing to vascular complications. This study was designed to assess recurrent short-term increases in glucose on markers of renal fibrogenesis. Human renal cortical fibroblasts were exposed to fluctuating short-term (2 h) increases to 15 mM d-glucose, three times a day over 72 h, on a background of 5 mM d-glucose. To determine whether observed changes were due to fluctuating osmolality, identical experiments were undertaken with cells exposed to l-glucose. Parallel experiments were performed in cells exposed to 5 mM d-glucose and constant exposure to either 15 or 7.5 mM d-glucose. Fluctuating d-glucose increased extracellular matrix, as measured by proline incorporation (P < 0.05), collagen IV (P < 0.005), and fibronectin production (P < 0.001), in association with increased tissue inhibitor of matrix metalloproteinase (MMP) (P < 0.05). Sustained exposure to 15 mM d-glucose increased fibronectin (P < 0.001), in association with increased MMP-2 (P = 0.01) and MMP-9 activity (P < 0.05), suggestive of a protective effect on collagen matrix accumulation. Transforming growth factor-beta(1) (TGF-beta(1)) mRNA was increased after short-term (90 min) exposure to 15 mM glucose (P < 0.05) and after 24-h exposure to 7.5 mM ? (P < 0.05). Normalization of TGF-beta(1) secretion occurred within 48 h of constant exposure to an elevated glucose. Fluctuating l-glucose also induced TGF-beta(1) mRNA and a profibrotic profile, however, to a lesser extent than observed with exposure to fluctuating d-glucose. The results suggest that exposure to fluctuating glucose concentrations increases renal interstitial fibrosis compared with stable elevations in d-glucose. The effects are, in part, due to the inherent osmotic changes.

Blood Glucose↗

Effect of progesterone receptor a predominance on breast cancer cell migration into bone marrow fibroblasts.

Women exposed to exogenous progesterone have increased breast cancer risk, but the mechanisms of progesterone involvement in breast cancer development are unknown. In human breast and endometrium, progesterone receptor (PR) isoform expression is disrupted in premalignant lesions and predominance of one isoform, usually PRA, in invasive cancers is associated with poorer prognosis. Disrupted PR isoform expression results in disrupted progestin regulation of cell morphology, including rounded morphology and decreased adherence of cells to tissue culture flasks. The purpose of this study was to test the hypothesis that predominance of PRA affects the interaction of breast cancer cells with a physiologically relevant stromal tissue, bone marrow stroma. T-47D breast cancer cells demonstrated the ability to migrate into bone marrow fibroblasts and this was inhibited by progestin treatment. The antiprogestin RU38486 abrogated the progestin effect on migration, demonstrating that it was PR-mediated. In cells expressing a predominance of PRA, after induction of a stably integrated inducible PRA construct, the ability of progestin to inhibit breast cancer cell migration was lost. A number of integrins were progestin regulated in T-47D cells, but there was no difference in the progestin effect in cells with PRA predominance, nor were the levels of focal adhesion proteins altered in these cells. This suggested that the lack of inhibition by progestin of breast cancer cell migration in cells with PRA predominance was not mediated by PRA effects on the membrane components of the adherens junctions. In summary, this study has shown that PRA predominance has a striking functional effect on breast cancer cell migration into stromal layers. PRA predominance may render breast cancer cells relatively resistant to the inhibitory effects of progestins and one consequence of this may be increased invasion of stroma. If borne out in vivo, these findings suggest that tumours with PRA predominance may be predisposed to cancer progression and this may signal a poorer prognosis in patients.

Bone Marrow Neoplasms↗

[The technique of laparoscopic-thoracoscopic esophageal resection for esophageal cancer--first experiences].

Esophageal resection for carcinoma is still associated with high mortality and morbidity. Minimally invasive techniques are regarded to reduce operative trauma. However, to date only few studies on minimally invasive esophageal resection have been published. We describe in detail the technique of combined laparoscopic and thoracoscopic esophageal resection with gastric-pull-up and conventional open cervical anastomosis for esophageal squamous carcinoma. Prone positioning of the patient with bilateral lung ventilation was used during the thoracoscopic part of the operation. Our first experiences in 5 patients confirm the feasibility of the technique. We did not observe any surgical related adverse incidences and found the typically advantages of minimally invasive surgery, such as early mobility, less pain and a comfortable cosmetic result in our patients. Although the number of procedures is to low to decide the value of minimally invasive surgery for esophageal cancer, we think it could be a promising technology to reduce mortality and morbidity for esophageal resection.

Carcinoma, Squamous Cell↗

Study on the organoleptic intensity scale for measuring oral malodor.

The 0-5 organoleptic scale is used widely in breath research and in trials to measure the efficacy of anti-odor agents. However, the precise relationship between odor scores and gas concentrations of target odorants is unknown. The purpose of this study was to relate mean organoleptic scores from odor judges (n = 7) for pure odorants (n = 8) representative of those found in oral malodor. Judges used a common 0-5 scale to report the odor intensity of sample sets in random order of concentration. Regression analysis of data showed that odor score was proportional to the log concentration of odorant, and comparison of slopes showed H(2)S to be the most significant in terms of odor power. Detection thresholds (mol.dm(-3)) were: Skatole (7.2 x 10(-13)) < methylmercaptan (1.0 x 10(-11)) < trimethylamine (1.8 x 10(-11)) < isovalerate (1.8 x 10(-11)) < butyrate (2.3 x 10(-10)) < hydrogen sulphide (6.4 x 10(-10)) < putrescine (9.1 x 10(-10)) < dimethyl disulphide (5.9 x 10(-8)). The study demonstrates the exponential nature of the olfactory response and shows that any single compound's contribution to malodor depends on odor power and threshold in addition to concentration.

Butyrates↗

High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase.

The mitogen-activated protein (MAP) kinases contribute to altered cell growth and function in a variety of disease states. However, their role in the endothelial complications of diabetes mellitus remains unclear. Human endothelial cells were exposed for 72 h to 5 mM (control) or 25 mM (high) glucose or 5 mM glucose plus 20 mM mannitol (osmotic control). The roles of p38 and p42/44 MAP kinases in the high glucose-induced growth effects were determined by assessment of phosphorylated MAP kinases and their downstream activators by Western blot and by pharmacological inhibition of these MAP kinases. Results were expressed as a percentage (means +/- SE) of control. High glucose increased the activity of total and phosphorylated p38 MAP kinase (P < 0.001) and p42/44 MAP kinase (P < 0.001). Coexposure of p38 MAP kinase blocker with high glucose reversed the antiproliferative but not the hypertrophic effects associated with high-glucose conditions. Transforming growth factor (TGF)-beta1 increased the levels of phosphorylated p38 MAP kinase, and p38 MAP kinase blockade reversed the antiproliferative effects of this cytokine. The high glucose-induced increase in phosphorylated p38 MAP kinase was reversed in the presence of TGF-beta1 neutralizing antibody. Although hyperosmolarity also induced antiproliferation (P < 0.0001) and cell hypertrophy (P < 0.05), there was no change in p38 activity, and therefore inhibition of p38 MAP kinase had no influence on these growth responses. Blockade of p42/44 MAP kinase had no effect on the changes in endothelial cell growth induced by either high glucose or hyperosmolarity. High glucose increased p42/44 and p38 MAP kinase activity in human endothelial cells, but only p38 MAP kinase mediated the antiproliferative growth response through the effects of autocrine TGF-beta1. High glucose-induced endothelial cell hypertrophy was independent of activation of the MAP kinases studied. In addition, these effects were independent of any increase in osmolarity associated with high-glucose exposure.

Cell Division↗

Extension of ischemic tolerance of porcine livers by cold preservation including postconditioning with gaseous oxygen.

BACKGROUND: Transplantation of organs from nonheartbeating donors was recommended to reduce organ shortage. In vitro experiments with rat livers have shown that the warm ischemic tolerance of the liver may be extended by persufflation with gaseous oxygen during cold storage. The qualification of this method for procurement of livers harvested after cardiac arrest was tested in an in vivo approach with pigs. METHODS: Livers from 15 donor pigs were explanted, heparinized, flushed with and stored in University of Wisconsin solution for 4 hr at 4 degrees C, and then implanted into 15 recipients. The organs were dissected immediately after cardiac arrest (group 1) or after 60 min of warm ischemia (groups 2 and 3). Group 2 livers received 75,000 IU of superoxide dismutase together with the flush solution and were persufflated with gaseous oxygen via the venous vascular system during cold storage. Main end point was survival after 5 days. Additionally, metabolic, functional and inflammatory criteria were measured in the blood. RESULTS: All animals of the groups 1 and 2 survived, all animals of group 3 died within 3 hr after reperfusion. In all groups the blood parameters reflected significant damage of the livers. However, the ischemic damage was comparable in the groups 1 and 2 whereas the livers of group 3 exhibited significantly higher levels of aspartate alanine aminotransferase and lactate dehydrogenase, and a significantly elongated partial thromboplastin time 1 hr after reperfusion (P=0.016). CONCLUSIONS: Venous systemic oxygen persufflation in combination with antioxidative medication is a promising new method of resuscitating ischemically altered livers from nonheartbeating donors for successful transplantation.

Animals↗

The clinical impact of warmed insufflation carbon dioxide gas for laparoscopic cholecystectomy.

BACKGROUND: Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain. METHODS: In a randomized controlled trial with 20 patients undergoing laparoscopic cholecystectomy, the effect of insufflation using carbon dioxide gas warmed to 37 degrees C (group W) was compared with insufflation using room-temperature cold (21 degrees C) gas (group C). Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery. Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics. RESULTS: There were no significant group-specific differences during the operation, neither in body temperature (group W: 36.1 +/- 0.4 degrees C vs group C: 35.7 +/- 0.6 degrees C) nor in intra-abdominal temperature (group W: 35.9 +/- 0.3 degrees C vs group C: 35.6 +/- 0. 6 degrees C). Postoperatively, the two groups did not differ in pain susceptibility and need of analgesics. CONCLUSION: The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect.

Aged↗

Induction of matrix metalloproteinases MMP-1 and MMP-2 by co-culture of breast cancer cells and bone marrow fibroblasts.

Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Antibodies to the adhesion molecules CD44, E-cadherin, ICAM- 1, and integrin chains alpha2, alpha3, alpha4, alpha5, alpha6, alpha v, beta1, beta3 and beta7 failed to inhibit breast cancer cell migration through bone marrow fibroblasts. Inhibitors of matrix metalloproteases, 1, 10-phenanthroline, Ro-9790, TIMP-1 and TIMP-2 were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts. Modulation of MMP production by cell-cell contact or soluble factors suggests a mechanism by which breast cancer cells can enhance their ability to invade the bone marrow microenvironment.

Bone Marrow Cells↗

The homogeneity assumption in differential prediction analysis: does it really matter?

In simulation studies, the F test for differences in regression slopes has tended to distort nominal Type I and II error rates when the 2 subgroup error variances exceeded a 1.50:1 ratio. This study examines the frequency and extent that this ratio is violated within data sets relevant to applied psychology. The General Aptitude Test Battery (GATB) validity study database contained ability data and overall job performance ratings. The Project A military database contained both ability and personality data, along with job performance factor scores and an overall job performance rating. Results suggest that subgroup (White-Black, male-female) error variances are often homogeneous enough to support F test results from past empirical work. Enough heterogeneity was found, however, to urge applied psychologists investigating differential prediction to explore their data and consider the possibility of alternative statistical tests.

Adult↗

Preoperative high dose methylprednisolone improves patients outcome after abdominal surgery.

OBJECTIVE: To assess the effect of preoperative high dose methylprednisolone on stress response and outcome. DESIGN: Randomised, placebo-controlled, double-blind study. SETTING: University hospital, Germany. SUBJECTS: 20 patients listed for abdominal surgery of whom 10 had major intra-abdominal interventions and 10 had incisional hernias repaired. INTERVENTIONS: Methylprednisolone 30 mg/kg (100 ml) was given by slow intravenous infusion 90-60 minutes before operation. The control group received the same volume of sodium chloride. MAIN OUTCOME MEASURES: Speed of convalescence, degree of fatigue, amount of pain, consumption of analgesics, breathing capacity, and hospital stay, as well as humoral and cellular mediators of the stress response. RESULTS: Methylprednisolone significantly improved criteria of postoperative recovery, fatigue by 47%, (day 1), convalescence by about 45% (days 1-3), and breathing capacity (FEV1) between 47% and 29% (days 5, 7) (p < 0.05, ANOVA), and led to a significant reduction of median hospital stay of 4.5 days. C-reactive protein concentration was significantly decreased (by 46% on day 3) and T-cell activation was suppressed (day 1). CONCLUSION: Outcome of the patients after conventional abdominal surgery is substantially improved by preoperative high dose methylprednisolone. This effect is more pronounced in patients having major operations.

Adult↗

Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.

A population-based study of hemophilia B mutations was conducted in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall (micro), male (v), and female (u) mutation rates for hemophilia B. The values obtained per gamete per generation and the 95% confidence intervals are micro;=7.73 (6. 29-9.12&parr0;x10-6; v=18.8 (14.5-22.9&parr0;x10-6; and u=2.18 (1. 44-3.16&parr0;x10-6. The ratio of male-to-female mutation rates is 8. 64, with a 95% confidence interval of 5.46-14.5. The higher male rate was not caused by a much higher rate of transition at CpG sites in the male. Attempts to detect evidence of gonadal mosaicism for hemophilia B mutation in suitable families did not detect any instances of ovarian mosaicism in any of 47 available opportunities. This suggests that the risk of a noncarrier mother manifesting as a gonadal mosaic by transmitting the mutation to a second child should be <0.062.

CpG Islands↗

Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen.

BACKGROUND: In order to reduce the shortage of viable donor livers for organ transplantation, a method has been developed that allows even predamaged livers from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine livers were harvested 45 min after cardiac arrest of the nonheparinized donor, preflushed with heparinized saline solution, and subsequently rinsed with University of Wisconsin solution, to which superoxide dismutase was added as an oxygen free radical scavenger. Thereafter, the livers were persufflated with gaseous oxygen via the venous vascular system while immersed in University of Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic transplantation, all of the livers conditioned with gaseous oxygen were able to support life-sustaining function during the whole observation period of 7 days post transplantation, while no survival of the recipients could be obtained without the described treatment. CONCLUSIONS: The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.

Animals↗

Endischemic oxygen persufflation to improve viability of marginally preserved donor livers.

The quality of cold-stored donor livers slowly declines beyond approximately 12 h, although these organs may still be used for clinical transplantation. The aim of the present study was to improve the energetic status and viability of long-term-preserved livers by short-term gaseous oxygen insufflation prior to implantation of the organ using a technique that has already been shown to promote aerobic energy metabolism during hypothermia. Livers from ten male Wistar rats were isolated, rinsed blood-free. Five livers (group 1) were stored for 48 h at 4 degrees C in UW preservation solution, and five livers (group 2) were isolated and stored in the same manner for 47 h, and were then, during the last 60 min of the preservation period, connected to a persufflation device and gaseous oxygen was introduced into the organ via the inferior caval vein, with the liver still immersed in cold UW solution. This technique of endischemic gaseous oxygenation resulted in a significant normalization of vascular resistance upon isolated reperfusion in vitro and a reduction in hepatic efflux of alanine aminotransferase as well as glutamate dehydrogenase, which led to improved recovery of the reperfused grafts of group 2 as evidenced by an elevated energy charge potential at the end of the reperfusion period. In conclusion, the technique described seemed effective in enhancing the preoperative viability of marginal donor grafts.

Animals↗