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Biomedical subjects

M L Eckhauser

Publications and source records attributed to M L Eckhauser.

At least 19 recordsLinked to original sources

Photofrin photosensitization. Correlation of Photofrin:erythrocyte binding processes with photolysis.

Unilamellar suspensions of dimyristoylphosphatidylcholine (DMPC) can be utilized to remove Photofrin from the erythrocyte. This enables correlation of the Photofrin membrane-binding processes with Photofrin-sensitized photolysis. The observed rates of erythrocyte biding as well as the observed rates of removal of PHotofrin from the erythrocyte membrane suggest the existence of two Photofrin species that differ in their rates of exchange between the erythrocyte and buffer phases. Selective depletion and readdition of these Photofrin species to the erythrocyte membrane permits evaluation of their separate and joint photolytic efficiencies. These rapidly and slowly exchanging membrane-bound Photofrin species are separately much less efficient photosensitizers than the two species together. The two Photofrin species exhibit essentially identical fluorescence emission spectra in the presence of DMPC. Nevertheless, models consistent with the results involve partitioning by chemically distinct Photofrin components or partitioning of chemically similar Photofrin components into distinct membrane environments, or a combination of these.

Dihematoporphyrin Ether↗

Rare bile duct anomalies. A case report and implications for laparoscopic cholecystectomy.

Anomalies of the biliary ductal system are not uncommon, and are of variable clinical significance. A case is reported of an extremely unusual variation, with the cystic duct entering the left hepatic duct. Preoperative delineation of the anomaly in this patient by endoscopic retrograde cholangiography assisted in the subsequent performance of a safe laparoscopic cholecystectomy. Awareness of potential biliary variations is one factor in avoidance of ductal injuries during laparoscopic surgery.

Aged↗

The management of common bile duct stones in patients undergoing laparoscopic cholecystectomy.

The management of suspected and/or unsuspected common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy (LC) is controversial. Decisions on whether to perform an open CBD exploration versus employing therapeutic options such as preoperative/post-operative endoscopic retrograde cholangiography (ERCP) or endoscopic duct exploration are polemic. To determine indications, timing, benefits, and potential morbidity of these approaches, we gathered data on 401 patients undergoing LC within the last 18 months. Indications for preoperative ERCP included jaundice (40%), dilated ducts (28%), elevated amylase (19%) or alkaline phosphatase (21%), suspicion of CBD stones by ultrasound (17%) and "other" (17%). Indications for postoperative ERCP were retained stones (33%) and CBD evaluation (67%). Indications for CBD exploration included abnormal cholangiogram (64%), palpable stones (18%), and other (18%). A significant correlation was observed between suspected stones by ultrasound and stones found by ERCP (P < 0.01). For patients in the "other" category, preoperative ERCP was universally negative (P = 0.04). Overall ERCP morbidity was 4/59 (6.8%), and the overall failure rate for clearing CBD stones was 2/28 (7.1%). The timing of the ERCP did not affect morbidity/mortality. Multivariate analysis revealed that age (P << 0.001), the presence of pre-existing medical risk factors (P << 0.001), and duration of LC (P = 0.0034), but not ERCP (P = 0.08), were the important factors determining LC morbidity. In summary, common bile duct stones can be successfully cleared endoscopically in the majority of patients undergoing LC. Patients with suspected CBD stones should undergo pre-operative ERCP, and strict criteria should be applied in the selection of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Correlation between photodynamic efficacy of differing porphyrins and membrane partitioning behavior.

The ability of a photosensitizer to partition into membrane is determined by its structure and physical properties. Partitioning behavior can be quantitated as the partition coefficient (Kp) for a particular drug. This property may be an important determinant of cytocidal efficacy in photodynamic therapy. The Kp of five photoactive drugs--13,17-ditetraammonium protoporphyrin (PH1008), photofrin II (PII), hematoporphyrin (Hp), benzoporphyrin derivative monoacid (BPD-MA), coproporphyrin (Cp), and uroporphyrin (Up)--was determined using a simple liposome system composed of sonicated egg phosphatidylcholine single bilayer vesicles. The cytocidal efficacy of each drug was compared by determining the concentration of drug resulting in 50% maximal lysis (C50) obtained by measuring the hemoglobin absorbance at 414 nm released from lysed human red blood cells. The percentage lysis at 1 microM final drug concentration was also determined. An argon-dye laser was used to administer light of 630-nm wavelength for a total exposure of 5 J/cm2. Porphyrins with a greater tendency to partition into phosphocholine bilayer membranes demonstrated a greater lytic efficacy in the rbc system utilized. The comparison of physical properties with lytic ability may be useful in understanding the mechanism by which PDT exerts its effects and in predicting the clinical efficacy of different drugs.

Cell Membrane↗

Early response of canine temporomandibular joint tissues to arthroscopically guided neodymium: YAG laser wounds.

A neodymium yttrium aluminum garnet (Nd:YAG) laser inserted through an operating arthroscope was used to introduce applied energy to synovial tissues, articular discs, and bone in the temporomandibular joint of mongrel dogs. Arthroscopic inspection of the wounds was performed at 1 and 2 weeks postoperatively. The animals were killed and the temporomandibular joints were examined grossly and histologically to determine the extent of injury and healing. The results show that laser wounds of bone and articular disc undergo no repair, whereas laser wounds of synovium show rapid repair. Laser damage to condylar marrow under an articular disc wound was unexpectedly found.

Animals↗

A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells.

Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.

Humans↗

Laser therapy of colorectal carcinoma.

A plethora of literature is available demonstrating the efficacy of Nd:YAG laser therapy for obstructing or bleeding colorectal cancers. The in-hospital mortality and morbidity rates can be reduced when Nd:YAG laser therapy is used to avoid operative diversion prior to resection and anastomosis. The Nd:YAG laser used to control bleeding or obstruction in those patients with either widely metastatic or unresectable locoregional disease has been successful in the majority of patients and has been associated with minimal morbidity and mortality rates. This laser may be the only treatment modality that may substitute for operative diversion in hopeless clinical situations such as hemorrhage or obstruction in patients with advanced disease. The utility of photodynamic therapy for colorectal cancer will require definition in further controlled trials.

Carcinoma↗

Endoscopic laser therapy for obstructing and/or bleeding colorectal carcinoma.

The primary role of the neodymium yttrium aluminum garnet (Nd:YAG) laser has been to relieve obstruction and to control hemorrhage associated with malignant neoplasms throughout the gastrointestinal tract. In an initial series (IS), the authors demonstrated the efficacy of the Nd:YAG laser as initial preresectional therapy (PR) in 11 patients with obstructing and resectable left colonic or rectal tumors obviating initial operative diversion and allowing for primary resection and anastomosis. In addition, the authors have illustrated the benefit of the Nd:YAG laser in relieving obstruction and arresting bleeding in those patients with either widely metastatic or nonresectable (NR) locoregional disease. Their cumulative experience from 1985 to the present includes 53 patients (PR: 29 and NR: 24). In the PR group, 25 lesions were above the peritoneal reflection and 4 below. Twenty-five patients underwent low anterior resection and four abdominoperineal resection. In the NR group, 17 patients were treated for imminent obstruction and 7 for bleeding. Ten lesions were above and 14 below the peritoneal reflection. There was one laser-related complication in the series (1.8%). There was no significant morbidity or mortality in the PR group. The reduction in length of stay (LOS) and total hospital costs (THC), when compared to the IS has continued to be significant. Laser therapy for those patients in the NR groups is a safe and acceptable alternative to permanent colostomy with its accompanying morbidity and mortality.

Academic Medical Centers↗

Endoscopic intervention: a useful alternative to operation in the treatment of upper gastrointestinal hemorrhage.

Hemorrhage of the upper gastrointestinal tract (UGI) remains a serious clinical problem. Age of the patient, the presence of shock, transfusion requirements and concurrent serious illnesses are predictors of outcome. Operative intervention is promulgated if a visible vessel in an ulcer crater is identified because most will rebleed. From 1986 to 1988, 40 patients with 46 actively bleeding upper gastrointestinal lesions were treated with endoscopic intervention (EI). The Nd:YAG (neodymium yttrium aluminum garnet) laser using the noncontact method was used exclusively. All patients had orthostatic hypotension on admission and had serious intercurrent illnesses. Admission hematocrit ranged from 13 per cent to 36 per cent (median, 24%) and patients had been transfused an average of 4 units of blood before EI. Gastric and duodenal ulcers were the most common bleeding sites. All gastric and duodenal ulcers had visible vessels and 19 were actively bleeding. Endoscopic intervention was initially successful in 35 of 40 (87.5%) patients. The five patients who did not respond required urgent operation with a mortality rate of 40 per cent. Four patients rebled after EI but responded to repeat EI. The mortality rate in the EI group was 8.6 per cent. These results suggest that EI is a useful alternative in UGI bleeding for a select group of those patients at high risk for operative intervention.

Adult↗

Photodynamic therapy for multiple primary bronchogenic carcinoma.

In recent years, multiple primary lung cancers have been reported with greater frequency, partly as a result of technologic advances in the detection of lung cancer and therapeutic achievements in its management. Photodynamic therapy (PDT) is a relatively new therapy used with increasing frequency in the treatment of a wide variety of malignancies, including central lung cancers. In PDT, the differential retention of an injected photosensitizer by malignant tissue is exploited by treatment with a low-power laser beam delivered endoscopically. Since 1980, 145 patients with central lung cancers, including 35 cases of endoscopically evaluated early-stage lesions were treated with PDT at Tokyo Medical College. Thirteen of these 145 patients had multiple primary bronchogenic carcinomas, five cases of which were synchronous with the rest, metachronous. Three of 13 patients with multiple tumors had early-stage lesions and were treated with endoscopic PDT alone. In the other ten cases, PDT was used to treat accessible early-stage foci although operative excision was required for advanced lesions. Mean survival after PDT, alone or in combination with surgery, was 38 months (range, 14 to 87 months), and seven patients remain alive to date. It was concluded that PDT is useful in extending the therapeutic options for, and improving the prognosis of patients with, multiple primary bronchogenic carcinomas.

Adenocarcinoma↗

The neodymium-YAG laser and gastrointestinal malignancy.

Thirty-seven patients with either bleeding or obstructive metastatic gastrointestinal malignant neoplasms were treated with the neodymium-YAG laser between June 1985 and December 1988. The age range for the group was 55 to 99 years, with a mean of 71 years. There were 25 upper gastrointestinal lesions, including 22 obstructive lesions (20 esophageal and two prepyloric gastric) and three bleeding lesions (one metastatic melanoma to the stomach, one duodenal, and one pancreatic carcinoma). Of the esophageal tumors, three were proximal, eight were middle, and nine were distal third. The mean number of laser treatments was 2.6, and the overall survival ranged from 1 to 20 months, with a median of 8 months. The dysphagia grade was improved overall but depended on the site of the tumor. All bleeding lesions were successfully photocoagulated. Twelve colorectal malignant neoplasms were treated palliatively, six for obstruction (three intraperitoneal colon and three rectal) and six for bleeding (three intraperitoneal and three rectal). The mean number of treatments for the group was 1.5, and the overall survival ranged from 2 to 38 months, with a median survival of 15 months. The neodymium-YAG laser was found to be effective as a palliative mode of therapy for the management of malignant gastrointestinal lesions.

Adult↗

Photodynamic therapy of esophageal carcinoma.

Photodynamic therapy (PDT) utilizing either hematoporphyrin derivative or Photofrin II is proving to be an effective modality in the treatment of early superficial (ES) or advanced invasive (AI) carcinoma of the esophagus. An argon-pumped dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel of a gastroscope after intravenous injection of photosensitizer. Between 1982 and 1989, 20 patients (ES = 6; AI = 14) were treated in this manner. Complete remission was obtained in 4 of 6 ES cases, and the mean survival after PDT alone or in combination with other therapy was 27 months. Five patients remain alive to date. In the AI group, significant remissions were obtained in 6 cases while partial remissions were observed in another 8. The mean dysphagia grade improved from 4.0 to 2.8. We conclude that PDT is efficacious in the treatment of ES esophageal cancer, where complete remission may be achieved, and as palliative therapy in advanced cases to alleviate dysphagia.

Aged↗

Palliative therapy of upper gastrointestinal malignancies using the Nd-YAG laser.

The principal role of the Neodymium yttrium aluminum garnet (Nd-YAG) laser has been to alleviate obstruction and to arrest hemorrhage secondary to metastatic or locally unresectable malignant lesions throughout the gastrointestinal (GI) tract. Between June 1985 and December 1988, 26 patients have been treated for advanced upper GI malignancy: 20 obstructing esophageal carcinomas (three proximal, eight middle, and nine distal third); two prepyloric obstructing and one bleeding gastric lesion; one bleeding pancreatic carcinoma eroding into the duodenum; and two primary duodenal lesions (one partially obstructing and one bleeding). The dysphagia grade improved in all patients with esophageal carcinoma, but less so for those with proximal tumors. The obstructing gastric lesions were recanalized and bleeding was arrested. The pancreatic and duodenal lesions were successfully managed with one treatment. There were no perforations or other laser-related complications. The approaches to palliation must be conceived in a fashion to improve the quality of life with minimal risk and discomfort. Although ultimate survival is determined by the stage of the disease, the Nd:YAG laser can restore gastrointestinal continuity and, in so doing, significantly palliate the patient.

Adult↗

Morphologic and histologic changes in canine temporomandibular joint tissues following arthroscopic guided neodymium:YAG laser exposure.

A neodymium:yttrium aluminum garnet (Nd:YAG) laser beam was introduced by a quartz fiber passed arthroscopically into the superior joint space of the temporomandibular joints (TMJ) of five mongrel dogs, with one joint serving as a control without laser wounds. Immediate postoperative death and examination of the disc grossly and histologically revealed different patterns for contact and noncontact burn wounds. The wounds exhibited signs of thermal coagulation necrosis similar to those reported in other tissues. The potential implications of the adaptation of the Nd:YAG laser to TMJ arthroscopic surgery are discussed.

Animals↗

The role of pre-resectional laser recanalization for obstructing carcinomas of the colon and rectum.

The Nd:YAG laser has proved its efficacy for recanalizing obstructing lesions throughout the gastrointestinal tract. In a preliminary report using the Nd:YAG laser as a pre-resectional treatment for functionally obstructing colorectal carcinoma we showed that this modality accomplished good decompression, allowing for formal bowel preparation, a definitive one-stage operation with no increased mortality or morbidity, and that the use of the Nd:YAG laser was significantly cost-effective. Our cumulative experience from 1985 to 1988 includes 11 patients; nine underwent pre-resection laser therapy followed by primary resection and anastomosis, and two underwent abdominoperineal resection. Tumors were located above the peritoneal reflection in nine patients and below in two patients. All patients had orthograde bowel preparation with Golytley the day after laser therapy and underwent definitive surgery. There were no wound or intra-abdominal infections or postoperative fatalities. These 11 laser-treated patients were compared with age-matched controls who had undergone earlier colonic diversion. No significant differences were noted for age, sex, tumor location or differentiation, stage, or overall survival. Comparisons between laser-treated patients and controls for the preoperative length of stay and total length of stay were significantly different (p = 0.002 and p = 0.001, respectively). When comparing laser-treated patients and controls, preoperative and total hospital costs were significantly different (p = 0.003 and p = 0.01). We have found that pre-resectional laser recanalization has allowed for primary resection and anastomosis in patients who have obstructing left colon and rectal carcinomas without compromising patient safety.

Carcinoma↗