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Samir S Awad

Publications and source records attributed to Samir S Awad.

26 records · Page 2Linked to original sources

Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest.

The liver is capable of completely regenerating itself in response to injury and after partial hepatectomy. In liver of old animals, the proliferative response is dramatically reduced, the mechanism for which is unknown. The liver specific protein, C/EBPalpha, normally arrests proliferation of hepatocytes through inhibiting cyclin dependent kinases (cdks). We present evidence that aging switches the liver-specific pathway of C/EBPalpha growth arrest to repression of E2F transcription. We identified an age-specific C/EBPalpha-Rb-E2F4 complex that binds to E2F-dependent promoters and represses these genes. The C/EBPalpha-Rb-E2F4 complex occupies the c-myc promoter and blocks induction of c-myc in livers of old animals after partial hepatectomy. Our results show that the age-dependent switch from cdk inhibition to repression of E2F transcription causes a loss of proliferative response in the liver because of an inability to induce E2F target genes after partial hepatectomy providing a possible mechanism for the age-dependent loss of liver regenerative capacity.

Aging↗

Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy.

Chronic lithium therapy in patients with affective psychiatric disorders has been implicated as the cause of hypercalcemia and primary hyperparathyroidism. Our objective was to evaluate whether primary hyperparathyroidism was caused by an adenoma or four-gland hyperplasia. The medical records of 15 patients with affective psychiatric disorders who were treated with chronic lithium therapy from 1982 to 1997, all of whom were operated on for primary hyperparathyroidism, were reviewed. Data on age, symptoms, duration of lithium therapy, pre- and postoperative calcium levels, and parathyroid hormone levels were collected. Parathyroid histology for each patient was independently and blindly reviewed. The mean age was 58 +/- 10 years, the mean duration of lithium therapy 10.7 +/- 6 years, and the mean preoperative calcium level 11.7 +/- 0.5 mg/dl. All patients underwent bilateral neck exploration with selective resection of enlarged glands. Of the 15 patients, 14 (92%) had adenomas (11 single, 3 double), and 1 (8%) had four-gland hyperplasia. All patients were rendered eucalcemic, with a postoperative calcium level of 9.2 +/- 0.5 mg/dl ( p < 0.005). All patients resumed their lithium therapy, with 1 of 15 patients developing recurrent hyperparathyroidism 2 years following the first operation; this patient required reexploration, at which time an adenoma was resected. In our experience hyperparathyroidism in patients who have undergone prolonged therapy with lithium is associated with a high incidence of parathyroid adenomas versus four-gland hyperplasia. This suggests that lithium selectively stimulates growth of parathyroid adenomas in susceptible patients, who are best treated with adenoma excision rather than subtotal parathyroidectomy.

Adenoma↗

Prognostic factors for the development of gangrenous cholecystitis.

BACKGROUND: The operative morbidity and mortality for patients with gangrenous cholecystitis (GC) remains high. Our objective was to identify preoperative prognostic factors for GC in order to distinguish this subset of patients with acute cholecystitis (AC). METHODS: From 1/98 to 11/01 the medical records of patients who presented with the diagnosis of AC were reviewed. Univariate and multivariate analysis were performed on this retrospective data. RESULTS: Of 113 patients with acute cholecystitis, 45 (39.8%) had histologically confirmed gangrenous cholecystitis. Nine variables were identified that were associated with GC by univariate analysis: age > or =51 years, African-American race, white blood cell count > or =15,000, diabetes, pericholecystic fluid, asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipase. Two variables were identified by multivariate analysis: diabetes, and white blood cell count. CONCLUSIONS: Our data suggest that patients with a history of diabetes and white blood cell count >15,000 to be at an increased risk for having GC upon presentation and they should have urgent surgical intervention.

Acute Disease↗

Spider Bites Presenting with Methicillin-Resistant Staphylococcus aureus Soft Tissue Infection Require Early Aggressive Treatment.

BACKGROUND: Occasionally, spider bites result in necrotizing soft tissue infections that require aggressive surgical debridement and treatment with intravenous antibiotics. With the rise of microbial resistance in the community, management with standard gram-positive intravenous antibiotic coverage may be ineffective. Our objective was to determine the infectious organisms cultured following wide local excision of soft tissue infections caused by spider bites. We hypothesized that the majority of isolated organisms would be sensitive to penicillin based antibiotics. METHODS: From March 2000 to November 2001, the medical records were reviewed of patients who presented to a tertiary care hospital with serious soft tissue infections secondary to spider bites that required surgical treatment. For each patient, demographics, symptoms, size, time to surgical evaluation (TTSE), temperature, white blood cell (WBC) count, surgical procedure, and culture data were collected. Data are presented as mean +/- SEM. RESULTS: Thirty-eight patients presented with serious soft tissue infections secondary to spider bites that required surgical debridement and treatment with intravenous antibiotics. Twenty-nine percent (11 of 38) of these patients had failed initial outpatient therapy with penicillin-based oral antibiotics. The mean TTSE was 5.0 +/- 0.5 days (range = 2-14 days; median = 4.5 days). The most common presenting symptoms were pain and erythema surrounding the bite site. The mean temperature was 98.8 +/- 0.6 degrees F (range = 97.2-102.2 degrees F; median = 99.2 degrees F). The mean WBC count was 12.6 +/- 0.8 mm3. All patients required wide surgical debridement of the infected area. The mean size of the excised tissue was 26 +/- 4 cm2 (range = 4-120 cm2; median = 16 cm2). Every patient had cultures that grew Staphylococcus aureus. In 86.8% of patients, S. aureus was found to be methicillin-resistant (MRSA). All isolated organisms were sensitive to trimethoprim-sulfamethoxazole. CONCLUSIONS: In our experience, patients who presented with soft tissue infections as result of spider bites predominantly had methicillin-resistant S. aureus infections, corresponding to the increased incidence of MRSA reported in the community. Therefore, a more aggressive approach to the management of spider bites presenting with severe cellulitis is warranted. Routine treatment should include aggressive surgical debridement, intraoperative wound cultures, the empiric use of antibiotics with activity against MRSA, and adjustment of antimicrobial therapy based on culture and sensitivity data.

Anti-Bacterial Agents↗

Preoperative evaluation of hepatic lesions for the staging of hepatocellular and metastatic liver carcinoma using endoscopic ultrasonography.

BACKGROUND: Noninvasive imaging techniques, such as dynamic computed tomography (CT), magnetic resonance imaging and transabdominal ultrasonography are limited in their ability to detect hepatic lesions less than one cm. Intraoperative ultrasonography (IOUS) is currently the most sensitive modality for the detection of small hepatic lesions. However, IOUS is invasive requiring laparoscopy or formal laparotomy. We sought to evaluate the feasibility of using endoscopic ultrasonograhpy (EUS) for the detection and diagnosis of hepatic masses in patients with hepatocellular cancer (HCCA) and metastatic lesions (ML). We hypothesized that EUS could detect small (<1.0 cm) hepatic lesions undetectable by CT scan and could be used for biopsy of deep-seated hepatic lesions. METHODS: Consecutive patients referred for EUS with suspected liver lesions were evaluated between July 2000 and October 2001. All patients underwent EUS using an Olympus (EM30) radial echoendoscope. If liver lesions were confirmed and fine needle aspiration (FNA) was deemed necessary, a linear array scope was used and an FNA performed with a 22-gauge needle. Two passes were made for each lesion. RESULTS: 14 patients underwent evaluation with dynamic CT scans and EUS. In all 14 patients, EUS successfully identified hepatic lesions ranging in size from 0.3 cm to 14 cm (right lobe: n = 3, left lobe: n = 1, bilobar: n = 8). Moreover, EUS identified new or additional lesions in 28% (4 of 14) of the patients, all less than 0.5 cm in size (HCCA: n = 2, ML: n = 2), influencing the clinical management. In 2 of 14 patients EUS identified liver lesions, previously described as suspicious by CT scan, to be hemangiomas. Nine patients underwent EUS-guided FNA of hepatic lesions (deep seated: n = 3, superficial: n = 6). All FNA passes yielded adequate specimens (malignant: n = 8, benign: n = 1). CONCLUSIONS: Our preliminary experience suggests that EUS is a feasible preoperative staging tool for liver masses suspected to be HCCA or metastatic lesions. EUS can detect small hepatic lesions previously undetected by dynamic CT scans. Furthermore, EUS-guided FNA can confirm additional HCCA liver lesions or liver metastases, in deep-seated locations, upstaging patients and changing clinical management.

Biopsy, Needle↗

Acute respiratory failure after pleurodesis with doxycycline.

Bedside pleurodesis through a tube thoracostomy has been shown to be effective treatment of malignant pleural effusion and pneumothorax with persistent air leak. A variety of agents can be used, and each has been shown to produce rare but potentially serious complications. We report a case of sudden, severe respiratory failure in a 42-year-old man after pleurodesis with 300 mg of doxycycline. His response was consistent with an anaphylactic reaction. After intubation, mechanical ventilation and nebulizer treatments, he rapidly recovered to baseline. On the basis of this report and a review of the literature, we believe that doxycycline may not be an innocuous agent for bedside pleurodesis and that such procedures warrant a monitored setting.

Acute Disease↗

Partial liquid ventilation and positive end-expiratory pressure reduce ventilator-induced lung injury in an ovine model of acute respiratory failure.

OBJECTIVE: To examine the isolated and combined effects of positive end-expiratory pressure (PEEP) and partial liquid ventilation (PLV) on the development of ventilator-induced lung injury in an ovine model. DESIGN: Prospective controlled animal study. SETTING: University-based cardiovascular animal physiology laboratory. SUBJECTS: Thirty-eight anesthetized supine sheep weighing 22.3 +/- 2.2 kg. INTERVENTIONS: Animals were ventilated for 6 hrs (respiratory rate, 15; FIO2, 1.0, inspiratory/expiratory ratio, 1:1) with one of five pressure-controlled strategies, expressed as peak inspiratory pressure (PIP)/PEEP: low-PIP, 25/5 cm H2O (n = 8); high-PIP, 50/5 cm H2O (n = 8); high-PIP-PLV, 50/5 cm H2O-PLV (n = 8); high-PEEP, 50/20 cm H2O (n = 7); and high-PEEP-PLV, 50/20 cm H2O-PLV (n = 7). MEASUREMENTS AND MAIN RESULTS: Compared with the low-PIP control, high-PIP ventilation increased airleak, shunt, histologic evidence of lung injury, neutrophil infiltrates, and wet lung weight. Maintaining PEEP at 20 cm H2O or adding PLV reduced the development of physiologic shunt and dependent histologic injury indexes. Neither higher PEEP nor PLV reduced the high incidence of barotrauma observed in high-PIP animals. CONCLUSIONS: We conclude that application of PLV or PEEP at 20 cm H2O may improve gas exchange and afford lung protection from ventilator-induced lung injury during high-pressure mechanical ventilation in this model.

Acute Disease↗

Transperitoneal view of the PROLENE hernia system open mesh repair.

The PROLENE Hernia System (PHS), consisting of an onlay and an underlay patch with a connector, has recently been introduced as an option for tension-free open repair of inguinal hernias and is touted for the repair of both direct and indirect hernias. In theory, the underlay is placed either through the internal ring or through the transversalis fascia and is seated in the preperitoneal space. To date, there have been no views of how this underlay is seated after open repair. Our objective was to determine the position and orientation of the underlay patch after open repair. After informed consent, two patients requiring both umbilical and inguinal hernia repairs had their inguinal hernias repaired using the open technique with the PHS. In the first patient, after open inguinal repair, the umbilical hernia was reduced, a 30 degrees laparoscope was placed intraperitoneally, and the underlay patch placed in the retroperitoneal space was visualized through the translucent peritoneum. In the second patient, the umbilical hernia was initially reduced, and the laparoscope was introduced to visualize the creation of the preperitoneal space and placement of the underlay during open repair of the inguinal hernia. As per our hypothesis, we show that the preperitoneal space is successfully created during open repair with the PHS with minimal trauma. More importantly, the underlay is deployed open and contours to the shape of the abdominal wall from the native intra-abdominal pressure, covering regions at risk for future herniation.

Hernia, Inguinal↗