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Biomedical subjects

R Haddad

Publications and source records attributed to R Haddad.

At least 37 records · Page 2Linked to original sources

Screening for high utilizing somatizing patients using a prediction rule derived from the management information system of an HMO: a preliminary study.

BACKGROUND: Somatization is a common, costly problem with great morbidity, but there has been no effective screening method to identify these patients and target them for treatment. OBJECTIVES: We tested a hypothesis that we could identify high utilizing somatizing patients from a management information system (MIS) by total number of visits and what we termed "somatization potential," the percentage of visits for which ICD-9 primary diagnosis codes represented disorders in the musculoskeletal, nervous, or gastrointestinal systems or ill-defined complaints. METHODS: We identified 883 high users from the MIS of a large staff model HMO as those having six or more visits during the year studied (65th percentile). A physician rater, without knowledge of hypotheses and predictors, then reviewed the medical records of these patients and identified somatizing patients (n = 122) and nonsomatizing patients (n = 761). In two-thirds of the population (the derivation set), we used logistic regression to refine our hypothesis and identify predictors of somatization available from the MIS: demographic data, all medical encounters, and primary diagnoses made by usual care physicians (ICD-9 codes). We then tested our prediction model in the remaining one-third of the population (the validation set) to validate its usefulness. RESULTS: The derivation set contained the following significant correlates of somatization: gender, total number of visits, and percent of visits with somatization potential. The c-statistic, equivalent to the area under the ROC curve, was 0.90. In the validation set, the explanatory power was less with a still impressive c-statistic of 0.78. A predicted probability of 0.04 identified almost all somatizers, whereas a predicted probability of 0.40 identified about half of all somatizers but produced few false positives. CONCLUSIONS: We have developed and validated a prediction model from the MIS that helps to distinguish chronic somatizing patients from other high utilizing patients. Our method requires corroboration but carries the promise of providing clinicians and health plan directors with an inexpensive, simple approach for identifying the common somatizing patient and, in turn, targeting them for treatment. The screener does not require clinicians' time.

Adult↗

[Photodynamic therapy of nasal basal cell carcinoma].

Photodynamic therapy (PDT) is a noninvasive modality used topically for several skin cancers. We evaluated the effects of PDT on basal cell carcinoma (BCC) of the nose, using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source (Versa-Light). The advantages of this light source are synergistic, hyperthermia and fewer side effects. A paste of 20% ALA was applied topically to biopsy-proven BCC of the nose. Lesions were covered with occlusive light-shielding dressing and after 18 hours they were submitted to 10 minutes of exposure to the light. Initial evaluation was made after 21 days and every 3 months thereafter. Patients who did not respond after 2 treatments were referred for surgery. Mean follow-up in 31 patients was 19 months (range 6-36). There were no significant side-effects. There was complete response in 24/27 (88.9%), in whom there was recurrence in 2/27 (7.4%).

Administration, Topical↗

Effects of intravenous gamma immunoglobulins treatment on severe peritonitis in rats.

BACKGROUND: Generalized purulent peritonitis is characterized by an early exposure of the immune system to a large number of bacterial antigens. The hypothesis that intravenous IgG treatment may improve the outcome of severe experimental peritonitis was studied. METHODS: Peritonitis was induced in rats by cecal ligation and perforation. Continuous intravenous fluid infusion, broad-spectrum antibiotics, and twenty-four hours treated forty rats after the induction of the disease they were re-operated and the perforated cecum was excised. Twenty of these animals received in addition specific rat IgG in two intravenous infusions (0.4 gr./kg), two and twenty four hours after the induction of peritonitis. RESULTS: Elevated WBC counts and mild metabolic acidosis was found one day after the induction of peritonitis. IgG treatment was associated with lower WBC counts in the following days and with higher pH than in the control group (p < 0.05 for both parameters). All peritoneal cultures and 90% of blood cultures were positive 24 hours after the initial operation. These rates decreased in the following days and in the IgG treatment rats the peritoneal cavity and blood were sterile earlier than in the control animals (p < 0.05). Serum IgG was depleted in the control animals within 48 hours after the induction of peritonitis, while in the IgG treated animals its levels were remarkably elevated. IgG administration significantly improved the survival, which was 70% in the IgG treatment rats as compared to 40% in the control rats. CONCLUSION: These results indicate that intravenous IgG has beneficial effects on severe experimental peritonitis.

Animals↗

Radioimmunoguided surgery for recurrent colorectal cancer manifested by isolated CEA elevation.

BACKGROUND: Carcinoembryonic antigen (CEA) is a sensitive marker for detecting recurrent colorectal carcinoma. An asymptomatic rise of CEA can precede by several months the detection of recurrent cancer by standard imaging modalities. Yet, surgeons are hesitant to operate solely on the basis of an observed increase in CEA. We investigated the ability of radioimmunoguided surgery to enhance the surgeon's capability of detecting intraabdominal disease in these patients. METHODS: Nineteen patients who underwent radioimmunoguided surgery for suspected tumor recurrence based solely on elevated CEA were included in the study. They underwent colonoscopy and CT of the abdomen and chest, all of which were negative. They then underwent scintigraphy scan with an anti-CEA monoclonal antibody (MoAb) labeled with (99m)Tc or Indium I-111. All patients were injected with the CC49 MoAb (an anti-TAG-72 tumor-associated glycoprotein) labeled with (125)I three weeks before surgery. During surgery, traditional exploration was followed by survey with a gamma-detecting probe. RESULTS: Traditional surgical exploration identified 26 recurrent tumors: 7 hepatic, 8 pelvic, 6 retroperitoneal, 3 colonic, 1 splenic, and 1 anastomotic. Radioimmunoguided surgical exploration confirmed all recurrent tumors and identified additional tumor sites in seven patients that resulted in changing the surgical plan. CEA scans correlated with intraabdominal findings in seven patients. Abdominal pathology did not correlate completely with the scans in three patients, and CEA scan results were undetermined in two patients. CONCLUSION: Patients with elevated CEA and no other findings should be operated upon without delay, and radioimmunoguided surgery should be used to enhance the surgeon's knowledge of the extent of disease.

Adult↗

Restriction landmark genomic scanning of mouse liver tumors for gene amplification: overexpression of cyclin A2.

SV40 T/t antigen-induced liver tumors from transgenic mice were analyzed by Restriction Landmark Genomic Scanning (RLGS). Using NotI as the restriction landmark, RLGS targets CpG islands found in gene-rich regions of the genome. Since many RLGS landmarks are mapped, the candidate gene approach can be used to help determine which genes are altered in tumors. RLGS analysis revealed one tumor-specific amplification mapping close to CcnA2 (cyclin A2) and Fgf2 (fibroblast growth factor 2). Southern analysis confirmed that both oncogenes are amplified in this tumor and in a second, independent liver tumor. Whereas Fgf2 RNA is undetectable in tumors, CcnA2 RNA and cyclin A2 protein was overexpressed in 25 and 50% of tumors, respectively. Combining RLGS with the candidate gene approach indicates that cyclin A2 amplification and overexpression is a likely selected event in transgenic mouse liver tumors. Our results also indicate that our mouse model for liver tumorigenesis in mice accurately recapitulates events observed in human hepatocellular carcinoma.

Age Factors↗

Identification of lymph node metastases in recurrent colorectal cancer.

Lymph node metastases are an important prognostic prediction factor in patients with recurrent colorectal cancer, particularly those with liver metastasis. Fifty-six patients with recurrent colorectal cancer were operated by us using the RIGS (radioimmunoguided surgery) technology. Patients were injected with 1 mg monoclonal antibody (MoAb) CC49 labeled with 2 mCi 125I. In surgery, traditional exploration was followed by survey with a gamma-detecting probe. Sixty of 151 patients enrolled in the Neo2-14 Phase III study for recurrent colorectal cancer were diagnosed with liver metastases based on preoperative CT. In 17/56 patients (30%), RIGS identified at least one tumor site confirmed by pathology (H&E). This resulted in 16 major changes in surgical plan. RIGS performance varied between lymphatic and non-lymphatic tissue, with positive predictive value (PPV) of 100% and negative predictive value (NPV) of 94% for non-lymphoid tissue, compared to PPV of 46.5% and NPV of 100% for the lymphoid tissue. Thirty-five out of 60 patients were considered resectable after traditional evaluation. RIGS identified occult tumor in 10 of these patients (28.5%). 7/10 occult patients expired (70%), while only 7/25 of the non-occult patients expired (28%) (P = 0.046). In localizing patients, no RIGS activity in lymph nodes signifies no tumor, while H&E confirmation is needed for decisions based on RIGS activity in the lymph nodes. RIGS provides important staging information, identifying patients for whom surgery may be done with curative intent.

Adenocarcinoma↗

The effects of somatostatin and octreotide on experimental and human acute pancreatitis.

The role of somatostatin and octreotide for AP has been studied for two decades, yet the data still remain inconclusive. The inconsistencies of the results of experimental studies and clinical trials may stem from the fact that the optimal therapeutic modality has not been determined. Furthermore, although they are similar in structure and physiologic activities, the mechanisms of action and effects of somatostatin and octreotide in AP may be different. Because the data are sparse, most reports, primarily those in the English literature, on the efficacy of somatostatin and octreotide in the management of AP were reviewed. Included are both nonrandomized and prospective, double-blind, clinical trials and studies on the effects of these agents on various experimental models of the disease. The results of the studies on somatostatin and octreotide are presented and discussed separately, with specific reference to the experimental and treatment details. The main focus of the review is the effect of subcutaneous and intravenous administration of octreotide. Analysis of the data suggests that somatostatin could not be recommended for AP and that the efficacy of subcutaneous administration of octreotide is also questionable. Theoretically, intravenous octreotide may be more appropriate for this condition, but recent results with this therapeutic method are limited and contradictory. Studies that would delineate the optimal therapeutical modality and the patient population most likely to respond to the treatment are prerequisite for large-scale clinical trials on the effects of octreotide on human pancreatitis.

Acute Disease↗

The hand in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa is still a difficult challenge for surgeons and doctors. Hand retractions are different from burns. The medical team must have a good knowledge of the disease. Surgery must be performed with the collaboration of every member of the team, as well as the family. In young children, complete correction of the retractions is possible. On the other hand, when retractions are present for a long time in children and adolescents, surgery is purely functional. Static and dynamic splints delay recurrences, but their prolonged use presents psychological obstacles in adolescents and adults.

Anesthesia↗

Photodynamic therapy of murine colon cancer and melanoma using systemic aminolevulinic acid as a photosensitizer.

BACKGROUND: Side effects of conventional photosensitizers, such as hematoporphyrins, are a limiting factor in the use of photodynamic therapy (PDT). We evaluated the effect of PDT on mice colon carcinoma and melanoma using systemic 5-aminolevulinic acid (ALA). METHODS IN VITRO STUDIES: CT26 colon carcinoma and B16 melanoma cells were incubated with ALA for 48 h. Subsequently, cells were subjected to photoradiation at 40, 60 and 100 J/cm2 and viability was assessed. In vivo studies: Balb/C mice were injected subcutaneously with 2x10(5) CT26 colon cancer cells and C57/Bl mice were injected subcutaneously with 2x10(5) melanoma cells. ALA 60 mg/kg was injected intra-peritoneally when tumors were visible. After 24 h mice were subjected to photoradiation (100 J/cm2). RESULTS IN VITRO STUDIES: There was a significant decrease in the viability of treated cells as compared with non-treated tumor cells and with treated splenocytes (p<0.001). In vivo studies: PDT induced necrosis of both tumors. PDT also significantly prolonged the survival of the treated mice (p<0.05). CONCLUSIONS: Photodynamic therapy using systemic ALA as a photosensitizer was effective in treating mice colon cancer and melanoma in both in-vitro and in-vivo studies. Further pre-clinical and clinical studies are being conducted now.

Aminolevulinic Acid↗

[Photodynamic therapy for dysphagia due to esophageal carcinoma].

Surgery is the mainstay in the treatment of esophageal carcinoma and is effective for palliation of dysphagia. Patients unfit for surgery are difficult therapeutic problems. We evaluated photodynamic therapy for palliation of dysphagia in this condition. Patients were given 5-aminolevulinic acid, 60 mg/kg, orally and 24 hour later gastroscopy was performed during which red light illumination (100 j/cm2 for 600 seconds) was administered. This was repeated 48 hours later. The degree of dysphagia was recorded before and 14 days after treatment. 8 patients with an advanced non-resectable tumor, or who were unfit for surgery, were thus treated. 4 had squamous cell carcinoma of the mid-esophagus and 4 had adenocarcinoma of the lower esophagus. There was mild, self-limited photosensitivity in all. Liver and renal function tests and blood count were not affected by the treatment. Dysphagia was improved in all except 1 patient. A patient with early stage disease continued to eat a normal diet. We believe that photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a non-laser light source is feasible and safe in advanced esophageal cancer. It is an effective modality for relief of dysphagia in that condition.

Adenocarcinoma↗

Photodynamic therapy of cancer of the esophagus using systemic aminolevulinic acid and a non laser light source: a phase I/II study.

BACKGROUND: Surgery is the mainstay for the treatment of carcinoma of the esophagus and is also considered to be effective for palliation of dysphagia. Patients who are unfit for surgery represent a difficult therapeutic problem. The goal of the present study was to evaluate the effects of photodynamic therapy by using systemic administration of 5-aminolevulinic acid and a non laser light source on carcinoma of the esophagus. METHODS: Patients were given 60 mg/kg 5-aminolevulinic acid orally. Twenty-four hours later gastroscopy was performed. After initial localization of the tumor with the use of white light, the light source was switched to the red light band at 100 J/cm2 for 600 seconds. Gastroscopy was repeated at 48 hours and 7 days after the treatment. The degree of dysphagia was recorded before and 14 days after treatment. RESULTS: Five patients with advanced nonresectable tumors or who were unfit for surgery were treated. Two patients had squamous cell carcinoma of the mid-esophagus and three had adenocarcinoma of the distal esophagus. Mild self-limiting photosensitivity was noted in all patients. Liver and renal function tests as well as hemoglobin level and white blood cell count were not affected by the treatment. Improvement of dysphagia was observed in four patients who had pretreatment dysphagia. The patient with the early stage of disease continued to eat a normal diet. CONCLUSIONS: Photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a non laser light source is feasible and safe in advanced-stage esophageal cancer. It can be an effective modality for the relief of dysphagia in these patients.

Adenocarcinoma↗

Localization of monoclonal antibody CC49 in colonic metastasis from renal cell carcinoma.

We report a rare case of solitary metastasis from renal cell carcinoma which manifested as a primary colonic tumour 5 years after nephrectomy. A monoclonal antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery, was found to localize in the tumour. Pathological examination revealed metastasis of renal cell carcinoma in the colon. Immunohistochemistry with CC49 showed moderate staining of the colonic mucosa around the metastasis with no reaction in the tumour itself. Based on this case and other published studies, we conclude that TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and expressed in normal colonic mucosa adjacent to another tumour as a result of stimulations, such as cytokine release, in response to this tumour.

Aged↗

Octreotide ameliorates glucose intolerance following acute experimental pancreatitis.

The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.

Acute Disease↗