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J W Orr

Publications and source records attributed to J W Orr.

At least 19 recordsLinked to original sources

An evaluation of Groshong central venous catheters on a gynecologic oncology service.

One hundred ten women with gynecologic malignancies underwent 116 subclavian vein Groshong catheter insertions at the bedside under local anesthesia and intravenous sedation. Three (2.6%) additional patients had unsuccessful insertions because of an inability to access the subclavian vein or thread the guidewire. Fluoroscopy was not used. There was one delayed pneumothorax and no insertion-related infections. The 111 single-lumen catheters used primarily for the administration of chemotherapy are the subject of this report. The mean age of patients was 60 (range 13 to 89) years and their average Gynecologic Oncology Group performance score was 1.1 (range, 0 to 3). Diagnoses include 74 ovarian, 19 cervical, 13 uterine, and 5 other gynecologic malignancies. Hyperalimentation was administered in 16 (14%) patients. Grade IV neutropenia occurred in 57 (51%) patients and 44 (40%) received granulocyte colony-stimulating factor during therapy. The average lifespan of catheters was 247 (range, 37 to 703) days, and 39 (35%) women died from disease with their catheter in situ at a mean time of 288 days. Thirty-seven (33%) catheters were removed after completion of chemotherapy at an average time of 239 (range, 78 to 448) days. As of 1/1/94, 22 patients continued to use their catheters at a mean of 313 (range, 182 to 509) days. The remaining 13 (11.7%) catheters were removed due to complications (7 episodes of bacteremia, 3 tunnel infections, 2 catheter migration/thromboses, and 1 catheter laceration). Twenty episodes of fever in 17 (15.3%) patients were evaluated with blood cultures in the absence of a tunnel infection. None of the 10 culture negative cases resulted in catheter removal, whereas 7 of 10 patients with bacteremia had catheters removed. Exit site infections occurred in 23 (21%) patients and were resolved with local measures and oral antibiotics. The risk of exit site cellulitis was 3.3% per month. When compared to placement of permanent central venous access devices at our institution in the operating room or radiology suite, bedside placement of Groshong catheters resulted in a savings of $1448 and $231 per case, respectively.

Adolescent

Radical hysterectomy: does the type of incision matter?

OBJECTIVE: Our purpose was to evaluate and compare aspects of operative accessibility and perioperative outcome after radical hysterectomy and pelvic lymphadenectomy performed through a vertical, Pfannenstiel, or Maylard abdominal incision. STUDY DESIGN: During an 8-year interval, 236 patients underwent radical hysterectomy and pelvic lymphadenectomy as primary treatment for cervical cancer at the Watson Clinic. Patients were admitted under a standard perioperative protocol, and all procedures were performed by a gynecologic oncologist. All clinical data was recorded prospectively and updated regularly. RESULTS: Radical hysterectomy and pelvic lymphadenectomy was completed through a vertical (n = 113), Pfannenstiel (n = 78), or Maylard (n = 45) incision. Although lesion size and depth of stromal invasion was not different between incision types, patients with a Pfannenstiel incision were younger (p < 0.001) and weighed less than those with a vertical (p = 0.001) or Maylard (p < 0.025) incision. The Pfannenstiel was associated with a shorter operative time (Pfannenstiel vs Maylard, p < 0.05; Pfannenstiel vs vertical, p < 0.001), less blood loss (Pfannenstiel vs Maylard, p < 0.025; Pfannenstiel vs vertical, p < 0.001), a lower risk of transfusion, and a shorter hospital stay (Pfannenstiel vs Maylard, p < 0.025; Pfannenstiel vs vertical, p < 0.001). These differences persisted when controlled for patient weight and surgical experience. There was no significant difference in the total number of nodes evaluated. No patient had a positive vaginal margin. CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy can be safely performed through a vertical, Maylard, or Pfannenstiel incision. In a selected population a Pfannenstiel incision offers the potential benefit of less abdominal wall trauma without compromising surgical exposure or increasing the risk of surgical complications.

Adult

Incisional bowel herniations after operative laparoscopy: a series of nineteen cases and review of the literature.

OBJECTIVES: The objectives of this report were (1) to identify all cases of incisional bowel herniations noted after operative laparoscopy in 11 participating institutions and (2) to report the clinical details of such patients. STUDY DESIGN: A retrospective case review was performed. RESULTS: Nineteen cases of incisional bowel herniation were identified. The average age of the patients was 50.5 years. Initial laparoscopic procedures varied and included laparoscopically assisted vaginal hysterectomy (six patients), laparoscopically assisted vaginal hysterectomy with lymphadenectomy (five patients), oophorectomy (two patients), adhesiolysis (two patients), myomectomy (two patients), lymphadenectomy alone (one patient), and ovarian cystectomy (one patient). The average time to reoperation was 8.5 days. CONCLUSIONS: Incisional bowel herniation is a serious complication of operative laparoscopy. Herniations occur through ports > or = mm in size at both umbilical and extraumbilical sites. New techniques are needed to avoid this serious complication.

Adult

Requirement for negative charge on "activation loop" of protein kinase C.

Increasing evidence has implicated a post-translational phosphorylation in the production of a catalytically competent protein kinase C. Here we present structural and biochemical evidence that Thr500 of protein kinase C-beta II is the residue phosphorylated by another kinase. Modeling studies indicate that this residue is part of a "lip" structure at the entrance of the catalytic site; phosphorylation on this lip, or "activation loop," is central to the regulation of three kinases whose structures have been elucidated (Taylor, S. S., and Radzio-Andzelm, E. (1994) Structure 2, 345-355). Biochemical data reveal that mutation of Thr500 to an acidic residue (Glu) results in expression of catalytically active protein kinase C in COS cells. In contrast, mutation of this residue to a neutral, non-phosphorylatable residue (Val) results in expression of inactive enzyme. Thus, negative charge at position 500 is required for catalytically competent protein kinase C-beta II. These data suggest that signal processing by protein kinase C cannot occur until the enzyme is first phosphorylated by a protein kinase C kinase.

Amino Acid Sequence

Intrapeptide regulation of protein kinase C.

Protein kinase C is allosterically activated by diacylglycerol and phosphatidylserine. The enzyme is also activated by surprisingly dissimilar compounds such as short chained phosphatidylcholines and protamine sulfate. Here we show that conventional and nonconventional activators of protein kinase C beta II produce the same structural alteration. They expose Arg19 of the autoinhibitory pseudosubstrate domain to proteolysis. Molecular modeling of protein kinase C beta II's catalytic domain, based on the structure of the cAMP-dependent kinase's catalytic domain, indicates that Arg19 is shielded by a cluster of acidic residues when the pseudosubstrate occupies the substrate-binding site. Our biochemical data and structural modeling indicate a common mechanism of intrapeptide regulation of protein kinase C by all activators that involves release of the pseudosubstrate from the active site.

Allosteric Regulation

Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol.

The lipid activators of protein kinase C, phosphatidylserine and diacylglycerol, induce a reversible conformational change that exposes the auto-inhibitory pseudosubstrate domain of the enzyme. The pseudosubstrate domain of beta-II protein kinase C is cleaved after the first residue, arginine 19, by the endoproteinase Arg-C only when the kinase is bound to the activating lipid phosphatidylserine. Exposure of this residue is markedly enhanced by diacylglycerol. In contrast, the pseudosubstrate domain is not cleaved in the absence of lipids, when protein kinase C is bound to non-activating acidic lipids, when the kinase has autophosphorylated on the amino terminus, or after dilution of the activating lipids. This work reveals specificity in the interaction of protein kinase C with phosphatidylserine since only this phospholipid causes the specific conformational change detected in the regulatory domain of the enzyme, and demonstrates that allosteric regulators expose the intramolecular auto-inhibitory domain of a kinase.

Amino Acid Sequence

Interaction of protein kinase C with phosphatidylserine. 1. Cooperativity in lipid binding.

The basis for the apparent cooperativity in the activation of protein kinase C by phosphatidylserine has been addressed using proteolytic sensitivity, resonance energy transfer, and enzymatic activity. We show that binding of protein kinase C to detergent-lipid mixed micelles and model membranes is cooperatively regulated by phosphatidylserine. The sigmoidal dependence on phosphatidylserine for binding is indistinguishable from that observed for the activation of the kinase by this lipid [Newton & Koshland (1989) J. Biol. Chem. 264, 14909-14915]. Thus, protein kinase C activity is linearly related to the amount of phosphatidylserine bound. Furthermore, under conditions where protein kinase C is bound to micelles at all lipid concentrations, activation of the enzyme continues to display a sigmoidal dependence on the phosphatidylserine content of the micelle. This indicates that the apparent cooperativity in binding does not arise because protein kinase C senses a higher concentration of phosphatidylserine once recruited to the micelle. Our results reveal that the affinity of protein kinase C for phosphatidylserine increases as more of this lipid binds, supporting the hypothesis that a domain of phosphatidylserine is cooperatively sequestered around the enzyme.

Animals

Interaction of protein kinase C with phosphatidylserine. 2. Specificity and regulation.

The roles of specific and nonspecific interactions in the regulation of protein kinase C by lipid have been examined. Binding and activity measurements reveal two mechanisms by which protein kinase C interacts with membranes: (1) a specific binding to the activating lipid phosphatidylserine and (2) a nonspecific binding to nonactivating, acidic lipids. The specific interaction with phosphatidylserine is relatively insensitive to ionic strength, surface charge, and the presence of nonactivating lipids. The two second messengers of the kinase, diacylglycerol and Ca2+, increase markedly the affinity of the kinase for phosphatidylserine. In contrast, the nonspecific interaction is sensitive to ionic strength and surface charge, and is unaffected by diacylglycerol. These results suggest that electrostatic interactions promote the binding of protein kinase C to membranes but the cooperative and selective binding of phosphatidylserine is the dominant driving force in a productive protein-lipid interaction.

Animals

The efficacy and safety of the cytobrush during pregnancy.

The safety and efficacy of abrasive cytology, using the cytobrush, were evaluated in 300 pregnant patients. When compared to conventional cytology obtained with a cotton-tipped applicator there was no difference in adverse pregnancy events. Smear adequacy (containing endocervical cells) was statistically (P less than 0.01) and clinically increased from 21 to 86%. The use of abrasive cervical cytology was associated with a twofold increase in the incidence of abnormal smears.

Adult

Surgical staging of uterine cancer: an analysis of perioperative morbidity.

Surgical staging documented extrauterine disease in 27.9% of 168 patients with apparent early-clinical-stage uterine cancer. An analysis of operative time (78 +/- 21 min), blood loss (332 +/- 160 cc), and surgical site infection risks (4.7%) indicated little additional risk of lymphadenectomy. The long-term risk of lymphocyst (1.3%) or lymphedema (0.7%) was small. The histologic information obtained from staging was utilized to rationally guide the need for adjunctive teletherapy. The overall risk of recurrence (median follow-up, 26 months) with surgical Stage I disease was 2.6%.

Combined Modality Therapy

Surgical aspects of cervical cancer.

Surgery maintains an important role in the diagnosis and treatment of premalignant as well as early invasive and recurrent cervical cancer. Although the indications for and benefits of surgical staging remain to be determined, specific procedures frequently are necessary to manage treatment-related complications. The authors review the indications, morbidity, and outcome of these procedures.

Carcinoma in Situ

Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma.

Serum CA 125 levels were normal preoperatively in 123 of 125 (98.4%) patients with clinical and surgical stage I or II endometrial adenocarcinoma, and remained so in all patients who remained without evidence of either isolated vaginal recurrence or postoperative radiation enteritis. Recurrent disease developed in 13 patients. All of those who had pelvic (1), abdominal (4), or pulmonary (2) metastases had elevated serum CA 125 levels. None of the six patients with isolated vaginal recurrences had elevated CA 125 levels. Four patients had small bowel obstruction as a result of postoperative pelvic radiation, and all had elevated CA 125 levels during these episodes, although no evidence of recurrent disease was found during exploratory laparotomy for intestinal bypass. Serum CA 125 levels may have a role in the posttreatment surveillance of patients with early-stage endometrial carcinoma, but may be falsely elevated in the presence of severe radiation injury and at a normal level in the presence of isolated vaginal metastases.

Adenocarcinoma

Continuous or interrupted fascial closure: a prospective evaluation of No. 1 Maxon suture in 402 gynecologic procedures.

During a 14-month period of using a long-term absorbable suture (No. 1 Maxon), 402 patients were entered into a prospective, randomized trial of fascial closure. Patients were randomized between a continuous closure (201 patients) and an interrupted en bloc (201 patients) technique. Each patient was subjected to a preoperative and intraoperative protocol for wound management. There were no acute wound failures. Wound infection rates and risk of hernia were not apparently affected by closure technique.

Adult

Single-dose antibiotic prophylaxis for patients undergoing extended pelvic surgery for gynecologic malignancy.

The comparative efficacy of single-dose antibiotic prophylaxis was retrospectively evaluated in 116 patients undergoing extended pelvic surgical procedures with curative intent. During the 24-month period, other important variables such as surgeon's experience, duration of preoperative hospitalization, preoperative preparation, method of hair removal, suture type, suture size, use of drains, use of cautery, and abdominal closure were controlled. The overall surgical site infection rate was 4.3% after radical hysterectomy with lymphadenectomy and 4.5% after total hysterectomy with lymphadenectomy. In this clinical situation the use of a single dose of antibiotic prophylaxis theoretically decreases cost and patient exposure and appears to be as efficacious as a multiple-dose regimen.

Anti-Bacterial Agents

Intestinal complications associated with use of the Dexon mesh sling in gynecologic oncology patients.

Three cases of postoperative enterocutaneous fistula formation following use of the Dexon mesh sling are reported from two gynecologic oncology services. Two patients had intestinal trauma or bowel resection at the time of mesh placement. Postoperative submesh abscess formation was noted in only one patient. Factors which might predispose to fistula formation after mesh placement, particularly in previously radiated patients, and techniques which might be used to avoid this complication are discussed.

Adult

Stapler resection of Meckel's diverticulum during gynecologic cancer surgery.

Stapler resection of Meckel's diverticulum was performed on 16 patients with known or presumed gynecologic malignancy at the time of extended abdominal surgery. All diverticulectomies were done quickly and without morbidity. Heterotropic gastric epithelium was found in one diverticulum, and one other patient with stage III ovarian adenocarcinoma had metastases to the serosa of her Meckel's diverticulum.

Adult