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Biomedical subjects

R L Friedman

Publications and source records attributed to R L Friedman.

At least 19 recordsLinked to original sources
PubMed2001

Laparoscopic cholecystectomy in the new millennium.

BACKGROUND: Laparoscopic cholecystectomy has become the gold standard for the treatment of symptomatic cholelithiasis. Many authors-including investigators at our institution, who reported one of the initial experiences with laparoscopic cholecystectomy in July 1992-have documented a definite learning curve associated with this procedure. We present a follow-up study of our experience with laparoscopic cholecystectomy and compare these data to an earlier study of the initial experience with laparoscopic cholecystectomy at the Beth Israel Medical Center. METHODS: We retrospectively reviewed 300 consecutive patients from March 1998 through March 1999. The patient population was epidemiologically similar to that of the original study with regard to age, sex, and American Society of Anesthesia (ASA) classification. However, whereas the initial population included only patients with chronic disease, in our study 13.7% of the patients had been admitted through the emergency room with acute stone disease of the biliary tract. RESULTS: We found a 5.7% conversion rate, a 1% rate of major complication, and a 5.7% rate of minor complication rates, as compared to the initial study's rates of 12%, 4%, and 10%, respectively. Whereas none of the patients in the original study left the hospital on the day of surgery and only 49% were discharged within 1 day, in our group, 29 patients (10%) underwent ambulatory procedures and an additional 186 patients (62%) were discharged on the 1st post-operative day. The average duration of the operation was 90 min, which did not represent a statistical improvement over the time of 93 min reported in the earlier study. CONCLUSIONS: Since 1992, both the conversion rate and length of stay have declined at our hospital, but operative time has remained essentially the same. These findings probably reflect a bimodal learning curve, the increase in the number of cholangiograms and additional intraoperative procedures now performed, the greater severity of gallbladder disease currently treated with laparoscopic cholecystectomy, and increases in the number of attending physicians as well as the level of residents who perform this procedure.

Adolescent↗
PubMed2001

Subcellular localization of the Iitracellular survival-enhancing Eis protein of Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within human macrophages. It is not clear how M. tuberculosis avoids the destructive action of macrophages, but this ability is fundamental in the pathogenicity of tuberculosis. A gene previously identified in M. tuberculosis, designated eis, was found to enhance intracellular survival of Mycobacterium smegmatis in the human macrophage-like cell line U-937 (J. Wei et al., J. Bacteriol. 182:377-384, 2000). When eis was introduced into M. smegmatis on a multicopy vector, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the appearance of a unique 42-kDa protein band corresponding to the predicted molecular weight of the eis gene product. This band was electroeluted from the gel with a purity of >90% and subjected to N-terminal amino acid sequencing, which demonstrated that the 42-kDa band was indeed the protein product of eis. The Eis protein produced by M. tuberculosis H37Ra had an identical N-terminal amino acid sequence. A synthetic polypeptide corresponding to a carboxyl-terminal region of the deduced eis protein sequence was used to generate affinity-purified rabbit polyclonal antibodies that reacted with the 42-kDa protein in Western blot analysis. Hydropathy profile analysis showed the Eis protein to be predominantly hydrophilic with a potential hydrophobic amino terminus. Phase separation of M. tuberculosis H37Ra lysates by the nonionic detergent Triton X-114 revealed the Eis protein in both the aqueous and detergent phases. After fractionation of M. tuberculosis by differential centrifugation, Eis protein appeared mainly in the cytoplasmic fraction but also in the membrane, cell wall, and culture supernatant fractions as well. Forty percent of the sera from pulmonary tuberculosis patients tested for anti-Eis antibody gave positive reactions in Western blot analysis. Although the function of Eis remains unknown, evidence presented here suggests it associates with the cell surface and is released into the culture medium. It is produced during human tuberculosis infection and therefore may be an important M. tuberculosis immunogen.

Acetyltransferases↗
PubMed2000

The Bvg accessory factor (Baf) enhances pertussis toxin expression in Escherichia coli and is essential for Bordetella pertussis viability.

Pertussis toxin expression in the Gram-negative respiratory pathogen, Bordetella pertussis, is regulated by the BvgAS two-component system. Previous studies suggested that an additional gene encoding a Bvg accessory factor (Baf) was required, along with BvgAS, for expression of a ptx-lacZ fusion in Escherichia coli grown in rich medium. However, other studies showed that BvgAS is sufficient for ptx-lacZ expression in minimal medium. Here we show that Baf acts with BvgAS to further increase ptx-lacZ expression in E. coli grown in minimal media and this is concomitant with a two-fold increase in BvgA protein levels. Gene replacement experiments show that baf is essential for viability of B. pertussis, suggesting that Baf affects the expression of other genes in addition to ptx.

Bacterial Proteins↗
PubMed2000

Mechanisms of systemic hypertension during acute elevation of intraabdominal pressure.

INTRODUCTION: In previous studies we described mechanisms by which acute elevation of the intraabdominal pressure (IAP) induces intracranial hypertension (ICHTN). Here we sought to define the role of ICHTN in mediating systemic hypertension (HTN) during CO(2) pneumoperitoneum (PNP). METHODS: Six large animals (swine) were hyperventilated to buffer hypercarbia. Intracranial pressure (ICP) was monitored with a Camino intraparenchymal ICP monitoring system. A Foley catheter was introduced intracranially via a separate burr hole. At phase 1, changes in ICP, central venous pressure (CVP), and mean arterial pressure (MAP) were recorded during periods of CO(2) PNP at IAP levels of 15, 20, 25, and 30 mm Hg. At phase 2, ICHTN was produced directly by inflating the intracranial balloon to the same ICP levels that had been measured in phase 1 for each degree of IAP. CVP and MAP were recorded. Repeated measures analysis of variance was applied. RESULTS: At phase 1, the mean DeltaCVP, DeltaICP, and DeltaMAP increased relative to the degree of IAP (P = 0.0001, 0.0004, and 0.024, respectively). At phase 2, the increments in DeltaMAP were significant (P = 0.024) and in the same direction and amplitude as at phase 1. CONCLUSIONS: In this study, increasing the IAP with CO(2) PNP with a consequent increase of ICP and direct manipulation of the ICP produced a comparable systemic HTN. We believe that this further supports our hypothesis: Elevated IAP produces an immediate increase in the CVP, which impairs venous drainage from the central nervous system (CNS), increases the ICP, and initiates a CNS-mediated response and systemic HTN.

Abdomen↗
PubMed2000

The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma.

BACKGROUND: This study examined the impact of secondary cytoreductive surgery on survival of patients with recurrent epithelial ovarian carcinoma. METHODS: One hundred six patients with a disease free interval (DFI) > 6 months after primary treatment underwent secondary cytoreductive surgery. Multivariate analysis determined which variables influenced the cytoreductive outcome and survival. RESULTS: Eighty-seven patients (82.1%) underwent removal of all visible tumor. The median and estimated 5-year survival for the entire cohort after recurrence was 35.9 months and 28%, respectively. The probability of complete cytoreduction was influenced by the largest size of recurrent tumor (< 10 cm ¿90.0% vs. > 10 cm ¿66.7%; P = 0.003), use of salvage chemotherapy before secondary surgery (chemotherapy given ¿64.3% vs. chemotherapy not given ¿93.8%; P = 0.001), and preoperative Gynecologic Oncology Group performance status (0 ¿100%, 1 ¿91.4%, 2 ¿82.4%, and 3 ¿47.4%; P = 0.001). Survival was influenced by the DFI after primary treatment (6-12 months ¿median, 25.0 months vs. 13-36 months ¿median, 44.4 months vs. > 36 months ¿median, 56.8 months; P = 0.005), the completeness of cytoreduction (visibly disease free ¿median, 44.4 months vs. any residual disease ¿median, 19.3 months; P = 0.007), the use of salvage chemotherapy before secondary surgery (chemotherapy given ¿median, 24.9 months vs. chemotherapy not given ¿median, 48.4 months; P = 0.005), and the largest size of recurrent tumor (< 10 cm ¿median, 37.3 months vs. > 10 cm ¿median, 35.6 months; P = 0.04). CONCLUSIONS: Complete cytoreduction is possible for the majority of patients with recurrent epithelial ovarian carcinoma and maximizes survival if undertaken before salvage chemotherapy. The authors believe a randomized trial should be initiated to confirm these findings.

Adult↗
PubMed2000

Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages.

Intracellular survival plays a central role in the pathogenesis of Mycobacterium tuberculosis. To identify M. tuberculosis genes required for intracellular survival within macrophages, an M. tuberculosis H37Rv plasmid library was constructed by using the shuttle vector pOLYG. This plasmid library was electroporated into Mycobacterium smegmatis 1-2c, and the transformants were used to infect the human macrophage-like cell line U-937. Because M. smegmatis does not readily survive within macrophages, any increased intracellular survival is likely due to cloned M. tuberculosis H37Rv DNA. After six sequential passages of M. smegmatis transformants through U-937 cells, one clone (p69) was enriched more than 70% as determined by both restriction enzyme and PCR analyses. p69 demonstrated significantly enhanced survival compared to that of the vector control, ranging from 2.4- to 5.3-fold at both 24 and 48 h after infection. DNA sequence analysis revealed three open reading frames (ORFs) in the insert of p69. ORF2 (1.2 kb) was the only one which contained a putative promoter region and a ribosome-binding site. Deletion analysis of the p69 insert DNA showed that disruption of ORF2 resulted in complete loss of the enhanced intracellular survival phenotype. This gene was named the enhanced intracellular survival (eis) gene. By using an internal region of eis as a probe for Southern analysis, eis was found in the genomic DNA of various M. tuberculosis strains and of Mycobacterium bovis BCG but not in that of M. smegmatis or 10 other nonpathogenic mycobacterial species. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis showed that all M. smegmatis eis-containing constructs expressed a unique protein of 42 kDa, the predicted size of Eis. The expression of this 42-kDa protein directly correlated to the enhanced survival of M. smegmatis p69 in U-937 cells. These results suggest a possible role for eis and its protein product in the intracellular survival of M. tuberculosis.

Amino Acid Sequence↗
PubMed1998

Identification of Btr-regulated genes using a titration assay. Search for a role for this transcriptional regulator in the growth and virulence of Bordetella pertussis.

Bordetella pertussis is the causative agent of the respiratory disease pertussis or whopoping cough. Btr, an oxygen-responsive transcriptional regulator of B. pertussis, is homologous to the FNR protein of E. coli. Using a murine respiratory model, we observed in the present study that Btr is important in growth and survival of B. pertussis in vivo. A titration assay was developed that identified genes containing Btr binding sites including B. pertussis sodB and btr, E. coli aspA and a new B. pertussis gene, brg1. The brg1 gene encodes a protein similar to the LysR family of transcriptional regulators and its expression is activated threefold by Btr under anaerobic growth conditions but unaffected by Btr aerobically. The nucleotide sequence flanking brg1 encodes proteins with similarity to various metabolic enzymes. Putative overlapping promoters and a Btr binding site (FNR box) were identified in the DNA sequence between brg1 and the adjacent genes. These intervening sequences may represent sites for regulation by Btr and Brg1.

Amino Acid Sequence↗
PubMed1998

Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study.

OBJECTIVE: Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer, relatively few undergo complete cytoreduction. This study was initiated to prospectively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact on survival. METHODS: Between 1990 and 1996, 163 consecutive patients underwent primary cytoreduction. The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy. A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction (logistic regression) and survival (Cox proportional hazards model). RESULTS: One hundred thirty-nine patients (85.3%) underwent removal of all visible tumor, 22 (13.5%) had cytoreduction to </=1 cm residual disease, and 2 (1.2%) had unresected bulky disease. The median and estimated 5-year survival for the entire cohort was 54 months and 48%, respectively. The probability of achieving complete cytoreduction was influenced independently by the preoperative Gynecologic Oncology Group performance status (0-1 vs 2-3, P = 0.04), the number of mesenteric and intestinal serosal implants (</=75 vs >75 implants, P = 0.005), and stage (IIIC vs IV, P = 0.006). The probability of survival was independently influenced by age (</=61 vs >61 years, P = 0.003), volume of ascites (</=1 vs >1 liter, P = 0.01), stage (IIIC vs IV, P = 0.04), histology (clear cell and mucinous vs all other, P = 0.03), and the completeness of cytoreductive operation (complete vs incomplete cytoreduction, P = 0.02). CONCLUSIONS: Complete cytoreduction is possible for the majority of patients and improves survival, even compared to operations with minimal (</=1 cm) residual disease. Unless their medical condition prohibits anesthesia and surgery, patients with advanced epithelial ovarian cancer should undergo primary cytoreductive surgery with the intention of complete tumor removal.

Carcinoma↗
PubMed1998

Effects of hyperventilation and hypoventilation on PaCO2 and intracranial pressure during acute elevations of intraabdominal pressure with CO2 pneumoperitoneum: large animal observations.

BACKGROUND: The side effects of acute elevations in intraabdominal pressure (IAP) are related to a multifactorial etiology. Previous studies have reported that acute elevations in IAP produce an immediate increase in intracranial pressure (ICP). This study was designed to analyze the reasons for increased ICP during acute elevations of IAP and to determine the combined effects of IAP and changes in ventilation indices on ICP and hemodynamic indices. STUDY DESIGN: Five pigs were studied. A subarachnoid screw was placed for ICP monitoring. The jugular vein, femoral vein, and femoral artery were cannulated. Mean arterial pressure (MAP), central venous pressure (CVP), ICP, and arterial pressure of carbon dioxide (PaCO2) were monitored before and after carbon dioxide pneumoperitoneum was established at 0, 10, and 20 mmHg of IAP Effects of hyperventilation and hypoventilation were recorded and compared with baseline ventilation. Cavography was performed to evaluate the morphology of the inferior vena cava (IVC) at different levels of IAP. Multiple regression and Student's t-test were used to examine the effects of IAP and ventilation on dependent variables. RESULTS: The IVC showed a progressive narrowing at the level of the diaphragm as IAP was increased. There was a simultaneous increase in CVP, MAP, and ICP. The mean changes in ICP with hypoventilation were significantly larger than with hyperventilation. CONCLUSIONS: Acutely increased IAP displaces the diaphragm cranially, narrowing the IVC and increasing intrathoracic pressure. This increases CVP and increases ICP by venous stasis and increased pressure in the sagittal sinus with decreased resorption of cerebrospinal fluid. Hemodynamic changes are directly related to the rise in ICP. Hypoventilation and hypercarbia significantly increase ICP when compared with hyperventilation and hypocarbia. Hyperventilation does not significantly decrease ICP during acute elevations of IAP.

Abdomen↗
PubMed1997

Second-look laparotomy for ovarian cancer provides reliable prognostic information and improves survival.

From 1990 to 1995, 120 consecutive patients with stage IIIC and IV ovarian carcinoma underwent surgical cytoreduction to < or = 1-cm residual disease followed by platinum-based chemotherapy. At the conclusion of chemotherapy all patients who were clinically disease free and whose CA-125 was < 35 were offered a second-look operation that obtained at least 100 tissue specimens. Of 107 patients who qualified for second look, 78 underwent the procedure. Forty-three (55.1%) had negative pathology, 20 (25.6%) were microscopically positive, and 15 (19.2%) had gross disease. Patients with positive findings received individualized salvage therapy. Patient age (P = 0.01) and the number of implants at primary surgery (P = 0.004) correlated with second-look results. Twelve (27.9%) of the patients with negative pathology have recurred. Eleven of these patients had metastatic disease > or = 10 cm at primary surgery (P = 0.003). Patients refusing second look had a median survival of 39.1 months. Approximately 60% of patients who underwent second look remain alive. Stepwise logistic regression selected two covariates significantly affecting survival: the number of implants at primary surgery (P = 0.0130) and performance of a second look (P = 0.0103). Using the protocol described in a population of optimally resected patients with advanced-stage ovarian cancer, second-look laparotomy can impact positively on survival. Patients with > 10-cm metastatic disease at primary surgery and negative second-look findings should be the focus of future protocols for consolidation chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Laparoscopic or open splenectomy for hematologic disease: which approach is superior?

BACKGROUND: This study was undertaken to compare safety, outcome, and costs of laparoscopic (LS) and open splenectomy (OS) for a variety of hematologic diseases. STUDY DESIGN: The records of 137 patients who underwent splenectomy (63 LS and 74 OS) at a large private teaching hospital between March 1991 and April 1996 were reviewed retrospectively. Diagnosis, age, gender, operative time, blood loss, splenic weight, time to resumption of oral diet, postoperative hospital stay, morbidity, mortality, and costs (direct and operative) were analyzed by multivariate statistical analysis. RESULTS: Laparoscopic splenectomy patients had significantly shorter hospitalization and time to resumption of an oral diet (p < 0.01); although operative costs were higher, total direct costs were not. Idiopathic thrombocytopenic purpura patients had earlier resumption of an oral diet after LS, shorter postoperative stay, and comparable OR time. Five patients (7%) were converted, with outcomes similar to OS except for greater operative time and cost. Grade II complications occurred in three LS and four OS patients; Grade III in three OS patients; and Grade IV in two OS patients. There were two major complications of LS and eight of OS, with two deaths. Multivariate analysis showed that operative time and time to resumption of oral intake were significantly related to age, diagnosis, operative technique, and splenic weight. Duration of postoperative hospitalization was related to operative technique, splenic weight, and major complications. Costs (direct and operative) were related to age, splenic weight, and major complications, but not to operative technique. CONCLUSIONS: LS results are influenced by splenic weight, disease, and age. Splenic weight appears to be the crucial determinant of operative time and length of hospitalization. LS is a superior treatment for patients with idiopathic thrombocytopenic purpura and patients with small spleens.

Adolescent↗
PubMed1996

In vivo and in vitro analysis of Bordetella pertussis catalase and Fe-superoxide dismutase mutants.

Bordetella pertussis produces a catalase and a Fe-superoxide dismutase. The importance of these enzymes in virulence was investigated, in vitro as well as in vivo, by using mutants deficient in their production. The catalase-deficient mutant survived within polymorphonuclear leukocytes, killed J774A.1 macrophages through apoptosis, and behaved as the parental strain in a murine respiratory infection model. These results suggest no direct role for catalase in B. pertussis virulence. The absence of expression of Fe-superoxide dismutase had profound effects on the bacterium including a reduced ability to express adenylate cyclase-hemolysin and pertactin, two factors important for B. pertussis pathogenesis. The Fe-superoxide dismutase-deficient mutant also had decreased abilities to colonize and persist in the murine respiratory infection model.

Adenylate Cyclase Toxin↗
PubMed1996

Laparoscopic splenectomy for ITP. The gold standard.

BACKGROUND: A comparison of safety, efficacy, and cost of laparoscopic splenectomy (LS) vs open splenectomy (OS) for idiopathic thrombocytopenic purpura (ITP) was performed. METHODS: The records of 49 consecutive patients who underwent splenectomy for ITP (31 LS and 18 OS) at a large metropolitan teaching hospital between 3/91 and 8/95 were reviewed. Morbidity, mortality, hospital stay, operative time, blood loss, time to oral fluid intake, direct costs, and operating room (OR) costs were analyzed. RESULTS: Age, sex, comorbidity, and spleen size were similar in both groups. LS was successful in 94% of patients in whom it was attempted. Operative times showed a learning curve for LS, with average times for the last ten cases (94 +/- 35 min) significantly shorter than for the first ten (p = 0.01) and also shorter than for OS (103 +/- 45 min). Postsurgical hospital stay was 2.9 +/- 1.3 days for LS and 6.9 +/- 3. 0 days for OS (p < 0.001). Patients tolerated an oral diet 1.2 +/- 0. 5 days after LS and 3.2 + 0.7 days after OS (p < 0.001). Direct hospital cost was $5,509 +/- 3,636 for LS and $9,031 +/- 12,752 for OS. In the LS group, six patients (21%) had accessory spleens identified and removed, compared with two patients (11%) in the OS group. Platelet counts did not respond in two (7%) patients in the LS group, but no accessory spleens were identified by nuclear scan. One major complication occurred in the LS group. There were no cases of splenosis or mortality in either group. CONCLUSIONS: LS is a safe and effective treatment for ITP, with significantly shorter postoperative hospital stay than OS.

Adolescent↗
PubMed1996

Routine cholangiography reduces sequelae of common bile duct injuries.

BACKGROUND: An effort was made to determine whether a policy of routine cholangiography affects the incidence, morbidity, and cost of bile duct injuries. METHODS: A retrospective review of consecutive 3,242 laparoscopic cholecystectomies was performed. Most patients had routine intraoperative cholangiography. RESULTS: There were 12 bile duct injuries (0.37%). All injuries were Bismuth levels 1 and 2. Eleven of 12 injuries were recognized intraoperatively. Ten were repaired primarily and one required hepaticojejunostomy. All repairs were successful. Average hospital charges were $26,669. One of 12 patients had delayed recognition of a bile duct injury and underwent primary repair over a T-tube on postoperative day 7. Hospital charges were $43,957. CONCLUSION: Routine cholangiography did not appear to decrease the absolute incidence of bile duct injuries compared to previously published reports. Injury severity, morbidity, late sequelae, and costs were reduced by a policy of routine cholangiography.

Cholangiography↗
PubMed1996

Resident education in laparoscopic cholecystectomy.

BACKGROUND: Resident education in laparoscopic cholecystectomy (LC) was studied in a retrospective analysis of consecutive cases performed at two academic institutions with different educational approaches. METHODS: Each procedure was performed by a resident as operating surgeon under the direct guidance of one of a small, constant group of LC-certified attendings acting as first assistant. In group I (n = 48), residents acquired LC skills by graded exposure and surgical responsibility similar to their training in other general surgical procedures. In group II (n = 48) residents were additionally certified via an intensive course (including didactic and animal model experience) prior to assuming responsibility as surgeon. RESULTS: Results were similar in each group. No technical errors were identified. Blood transfusion was not required related to surgery. Conversion to an open procedure occurred in 10% and 8% in groups I and II, respectively. The rate of complications was 4% for group I and 8% for group II. A longer operating time was noted in group I and may be attributed to nonoperative reasons. CONCLUSIONS: Education in LC via graded experience throughout residency achieves results similar to that found with the addition of an intensive course. This additional training may not be necessary for surgical residents.

Acute Disease↗
PubMed1996

Laparoscopic transabdominal preperitoneal hernioplasty: results of 1000 consecutive cases.

From October 1992 until September 1995, 859 patients with 1000 inguinal hernias underwent a transabdominal preperitoneal mesh repair (TAPP) in the First Department of Surgery of the Diakonie-Hospital Rotenburg/Wümme, Germany. One hundred and seventeen of these repairs were for recurrences after previous open hernia surgery. There were 76 (7.6%) peri- and postoperative complications, but most of them were minor without necessity for surgical intervention. There were no implant infections or any adverse reaction of the mesh. During the postoperative follow-up period, which ranged from 2-36 months, 11 early recurrences were observed after TAPP, but none were in the recurrent hernia group. Our results support other studies and randomized trials reported in the literature and demonstrate that TAPP is an effective and safe operative procedure especially for the repair of recurrent groin hernias.

Adolescent↗