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Biomedical subjects

C M Ferguson

Publications and source records attributed to C M Ferguson.

At least 19 recordsLinked to original sources

Soil inactivation of DNA viruses in septic seepage.

AIMS: To generate field-relevant inactivation data for incorporation into models to predict the likelihood of viral contamination of surface waters by septic seepage. METHODS AND RESULTS: Inactivation rates were determined for PRD1 bacteriophage and Adenovirus 2 in two catchment soils under a range of temperature, moisture and biotic status regimes. Inactivation rates presented for both viruses were significantly different at different temperatures and in different soil types (alpha = 0.05). Soil moisture generally did not significantly affect virus inactivation rate. Biotic status significantly affected inactivation rates of PRD1 in the loam soil but not the clay-loam soil. Adenovirus 2 was inactivated more rapidly in the loam soil than PRD1 bacteriophage. CONCLUSIONS: Virus inactivation rates incorporated into models should be appropriate for the climate/catchment in question with particular regard to soil type and temperature. Given that PRD1 is similar in size to adenoviruses, yet more conservative with regard to inactivation in soil, it may be a useful surrogate in studies of Adenovirus fate and transport. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of the factors that govern virus fate and transport in catchments would facilitate the design of barrier measures to prevent viral contamination of surface waters by septic seepage.

Adenoviridae↗

Environmental inactivation of Cryptosporidium oocysts in catchment soils.

AIMS: To generate field-relevant inactivation rates for Cryptosporidium oocysts in soil that may serve as parameter values in models to predict the terrestrial fate and transport of oocysts in catchments. METHODS AND RESULTS: The inactivation of Cryptosporidium oocysts in closed soil microcosms over time was monitored using fluorescence in situ hybridization (FISH) as an estimate of oocyst 'viability'. Inactivation rates for Cryptosporidium in two soils were determined under a range of temperature, moisture and biotic status regimes. Temperature and soil type emerged as significantly influential factors (P < 0.05) for Cryptosporidium inactivation. In particular, temperatures as high as 35 degrees C may result in enhanced inactivation. CONCLUSIONS: When modelling the fate of Cryptosporidium oocysts in catchment soils, the use of inactivation rates that are appropriate for the specific catchment climate and soil types is essential. FISH was considered cost-effective and appropriate for determining oocyst inactivation rates in soil. SIGNIFICANCE AND IMPACT OF THE STUDY: Previous models for predicting the fate of pathogens in catchments have either made nonvalidated assumptions regarding inactivation of Cryptosporidium in the terrestrial environment or have not considered it at all. Field-relevant inactivation data are presented, with significant implications for the management of catchments in warm temperate and tropical environments.

Animals↗

A deterministic model to quantify pathogen loads in drinking water catchments: pathogen budget for the Wingecarribee.

This paper describes the development and testing of a mathematical model as a tool to quantify pathogen loads in Sydney's drinking water catchments. It has been used to identify, quantify and prioritise sources of Cryptosporidium, Giardia and E. coli in the Wingecarribee catchment. The pathogen model promotes understanding of the relative significance of different sources of pathogen risks as well as their fate and transport as they move through the subcatchments. This pathogen model not only enables water utility managers to identify those catchment segments that may contribute the highest load of pathogens, but also where management options will be most effective.

Animals↗

Evidence for the existence of Cryptosporidium oocysts as single entities in surface runoff.

There is uncertainty whether Cryptosporidium oocysts attach to particles or to each other under ambient water conditions. Particle size distributions of Cryptosporidium oocyst suspensions were determined over a range of ionic strengths and pHs to determine under those environmental conditions that may promote oocyst aggregation. Cryptosporidium oocysts were shown to only aggregate in high ionic strength solutions (>0.45 M) and remain largely as single entities at ionic strengths and pHs that were likely to be encountered in surface runoff. Similarly, in loam soil suspensions, rather than attaching to the soil particles the majority of oocysts also remained as single entities. Overall, oocysts are expected to remain largely unattached to either themselves or soil particles in overland runoff. This has implications for pathogen transport and modelling since oocysts that are freely suspended are more likely to be transported in runoff to surface waters than if attached to more dense soil/faecal particles.

Animals↗

PTHrP expression in chick sternal chondrocytes is regulated by TGF-beta through Smad-mediated signaling.

PTHrP regulates the rate of chondrocyte differentiation during endochondral bone formation. The expression of PTHrP and its regulation by TGF-beta, BMP-2, and PTHrP was examined in upper sternal chondrocytes following 1, 3, and 5 days of continuous treatment. While TGF-beta stimulated the expression of PTHrP (5-fold), PTHrP caused a slight inhibition, and BMP-2 markedly inhibited PTHrP mRNA expression. The effect of these factors on PTHrP expression was not simply related to the maturational state of the cells, since BMP-2 increased, while both PTHrP and TGF-beta decreased the expression of type X collagen. TGF-beta isoforms 1, 2, and 3 all stimulated PTHrP expression. Signaling events involved in the induction of PTHrP by TGF-beta were further evaluated in a PTHrP-promoter CAT construct. The effect of TGF-beta, BMP-2, and PTHrP on the PTHrP-promoter paralleled their effects on mRNA expression, with TGF-beta significantly increasing CAT activity, BMP-2 decreasing CAT activity, and PTHrP having a minimal effect. Co-transfection of the TGF-beta signaling molecule, Smad 3, mimicked the effect of TGF-beta (induction of PTHrP promoter), while dominant negative Smad 3 inhibited the induction of the PTHrP promoter by TGF-beta. Furthermore, infection with a Smad 3-expressing retrovirus mimicked the effects of exogenously added TGF-beta, and induced PTHrP mRNA expression in the infected chondrocyte culture. In contrast, a dominant negative Smad 3 completely inhibited PTHrP promoter stimulation by TGF-beta, but only partially blocked the effect of TGF-beta on PTHrP mRNA synthesis. These findings demonstrate that PTHrP is expressed in chondrocytes undergoing endochondral ossification, and show regulation, at least in part, by TGF-beta through Smad mediated signaling events.

Animals↗

Biotransformations of paralytic shellfish toxins by bacteria isolated from bivalve molluscs.

Due to the possibility that bacteria could be involved in the clearance of paralytic shellfish toxins (PST) from bivalve molluscs, investigations into which, if any, bacteria were able to grow at the expense of PST focused on several common shellfish species. These species were blue mussels, oysters, razor fish, cockles, and queen and king scallops. Bacteria associated with these shellfish were isolated on marine agar 2216 and characterized by their carbon utilization profiles (BIOLOG). Selected isolates from groups demonstrating 90% similarity were screened for their ability to metabolize a range of PST (gonyautoxins 1 and 4 [GTX 1/4], GTX 2/3, GTX 5, saxitoxin, and neosaxitoxin) using a novel screening method and confirming its results by high-performance liquid chromatography. Results suggest that molluscan bacteria have different capacities to utilize and transform PST analogues. For example, isolates M12 and R65 were able to reductively transform GTX 1/4 with concomitant production of GTX 2/3, while isolate Q5 apparently degraded GTX 1/4 without the appearance of other GTXs. Other observed possible mechanisms of PST transformations include decarbamoylation by isolate M12 and sulfation of GTXs by isolates Q5, R65, M12, and C3. These findings raise questions as to the possible role of bacteria resident in the shellfish food transport system. Some researchers have suggested that the microflora play a role in supplying nutritional requirements of the host. This study demonstrates that bacteria may also be involved in PST transformation and elimination in molluscan species.

Animals↗

An ELISA for the detection of Bacillus subtilis L-form bacteria confirms their symbiosis in strawberry.

AIMS: To develop an ELISA for the detection of antigens derived from stable Bacillus subtilis L-form bacteria and to detect these in plants injected with L-form bacteria. METHODS AND RESULTS: A sandwich ELISA was developed and its specificity was investigated using L-forms and cell-walled forms of B. subtilis, different Bacillus species and a range of bacteria isolated from glasshouse-grown strawberry plants. The detection limits of the ELISA were approximately 10(3) viable cells ml(-1) for L-forms compared with 10(7) viable cells ml(-1) for cell-walled forms. Results showed that L-forms survived and moved within strawberry tissues injected with L-form bacteria. CONCLUSION: An ELISA that selectively detects B. subtilis L-form bacteria was developed and shown to confirm the presence of L-forms in plants. SIGNIFICANCE AND IMPACT OF THE STUDY: This will be a valuable rapid method to further studies on L-form plant interactions.

Bacillus subtilis↗

Smad2 and 3 mediate transforming growth factor-beta1-induced inhibition of chondrocyte maturation.

Transforming growth factor-beta (TGF-beta) is a multifunctional regulator of a variety of cellular functions, including proliferation, differentiation, matrix synthesis, and apoptosis. In growth plate chondrocytes, TGF-beta slows the rate of maturation. Because the current paradigm of TGF-beta signaling involves Smad proteins as downstream regulators of target genes, we have characterized their role as mediators of TGF-beta effects on chondrocyte maturation. Both Smad2 and 3 translocated to the nucleus upon TGF-beta1 signaling, but not upon BMP-2 signaling. Cotransfection experiments using the TGF-beta responsive and Smad3 sensitive p3TP-Lux luciferase reporter demonstrated that wild-type Smad3 potentiated, whereas dominant negative Smad3 inhibited TGF-beta1 induced luciferase activity. To confirm the role of Smad2 and 3 as essential mediators of TGF-beta1 effects on chondrocyte maturation, we overexpressed both wild-type and dominant negative Smad2 and 3 in virally infected chondrocyte cultures. Overexpression of both wild-type Smad2 and 3 potentiated the inhibitory effect of TGF-beta on chondrocyte maturation, as determined by colx and alkaline phosphatase activity, whereas dominant negative Smad2 and 3 blocked these effects. Wild-type and dominant negative forms of Smad3 had more pronounced effects than Smad2. Our results define Smad2 and 3 as key mediators of the inhibitory effect of TGF-beta1 signaling on chondrocyte maturation.

Alkaline Phosphatase↗

Common molecular pathways in skeletal morphogenesis and repair.

The formation of bone is a continual process in vertebrate development, initiated during fetal development and persisting in adulthood in the form of remodeling and repair. The remarkable capacity of skeletal tissues to regenerate has led to the hypothesis that the molecular signaling pathways regulating skeletogenesis are shared during fetal development and adult wound healing. A number of key regulatory pathways that are required for endochondral ossification during fetal development are described, and their reintroduction in fracture repair demonstrated. Secreted proteins such as Sonic and Indian hedgehog exert their effect on pattern formation and chondrogenesis in the appendicular skeleton, partly through regulation of molecules such as bone morphogenic proteins (Bmps) and parathyroid hormone-related peptide (PTHrP). Once chondrocytes have matured and hypertrophied, they undergo apoptosis and are replaced by bone; the transcription factor Cbfal plays a critical role in this process of chondrocyte differentiation and ossification. Analyses of the expression patterns of these genes during fracture healing strongly suggest that they play equivalent roles in adult wound repair. Knowledge acquired through the study of fetal skeletogenesis will undoubtedly contribute to an understanding of fracture repair, and subsequently guide the development of biologically based therapeutic interventions.

Animals↗

Laparoscopic common bile duct exploration: practical application.

OBJECTIVE: To evaluate the effectiveness of laparoscopic common bile duct exploration in unselected patients. DESIGN: Consecutive sample. SETTING: Tertiary care general hospital. PATIENTS: Three hundred and two patients with symptomatic cholelithiasis presenting to a single surgeon during a 5-year period. INTERVENTIONS: Laparoscopic cholecystectomy, cholangiography, and common bile duct exploration. MAIN OUTCOME MEASURES: Successful laparoscopic cholecystectomy and common bile duct exploration. RESULTS: Three hundred and two consecutive patients underwent cholecystectomy for symptomatic cholelithiasis; 280 of the procedures were successfully completed laparoscopically. Cholangiography was attempted in 269 patients, was successful in 239, and revealed evidence of choledocholithiasis in 25. Preoperative ultrasonography and liver function tests predicted the presence of common bile duct stones in 24% and 32% of patients, respectively. Seven of the patients with choledocholithiasis presented with biliary colic, 7 with biliary colic and jaundice, 8 with acute cholecystitis (3 with gallbladder perforation), 1 with acute cholecystitis and jaundice, and 2 with gallstone pancreatitis. Four of 5 patients underwent successful transcystic exploration with a biliary Fogarty catheter, 12 of 16 patients underwent successful transcystic choledochoscopy and stone basket extraction, and all 4 attempts at choledochotomy and choledochoscopic stone basket extraction were successful, for a total success rate of 80% with laparoscopic common bile duct exploration. One of the failures was converted to an open procedure, and 4 of the failures had successful postoperative endoscopic retrograde cholangiopancreatography and extraction of stones. CONCLUSIONS: Laparoscopic cholecystectomy and common bile duct exploration is a highly successful procedure for the management of common duct stones in an unselected group of patients. Choledochotomy with choledochoscopy is the preferred method of common bile duct exploration.

Cholangiography↗

Initial experience with laparoscopic Nissen fundoplication.

In an effort to explore the utility of classic Nissen fundoplication performed laparoscopically, 16 adult patients with well documented gastroesophageal reflux underwent laparoscopic Nissen fundoplication. A full gastric fundal dissection was performed, with division of at least 2 short gastric vessels. The crura were approximated with 1-3 sutures, and a loose fundoplication was performed over an esophageal dilator (minimum 46 F) with three stitches, encompassing the esophageal wall (2.5 cm in length). All patients had symptoms of reflux refractory to medical therapy, and four had an esophageal stricture requiring preoperative dilatation. Fifteen of 16 procedures were completed laparoscopically; one patient required conversion to an open procedure to control bleeding from a posterior gastric vein. There were no other operative complications. The average operative time was 180 minutes (range 120-285). Clear liquids were begun at the passage of flatus (average 2.7 days postop), and patients were discharged an average of 4.1 days postoperatively. Postoperative complications included ileus (1 patient for 6 days), severe subcutaneous emphysema (1 patient), and dysphagia requiring dilatation (5 patients). In short follow-up (mean 4.43 mo., range 1-12 mo.) 14 of 15 patients had complete abolition of reflux symptoms, but one patient with persistent heartburn had reflux demonstrated on a postoperative upper GI series. Thirteen of 16 patients returned to full function within 14 days of surgery. We conclude that standard Nissen fundoplication is possible laparoscopically, and allows a rapid recovery from surgery. However, it is difficult, time consuming, and associated with a significant rate of recurrence in the short term (6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tumor thickness in early tongue cancer.

OBJECTIVE: To review the relationship between tumor thickness and the subsequent development of cervical nodal metastases in 26 patients with stage I and II carcinomas of the oral tongue. METHODS: The histologic features of 26 consecutive patients treated for squamous carcinoma of the oral tongue were reviewed "blindly" by a pathologist, and the variables were correlated with clinical outcome. RESULTS: No association between tumor thickness and nodal metastases was found. Perineural infiltration was the only factor to approach statistical significance. There was also no statistically significant correlation between tumor thickness and patient survival. CONCLUSIONS: The histologic factors considered herein probably should be controlled for when comparing results of treatment of cancer of the oral tongue.

Carcinoma, Squamous Cell↗

Bile duct injury in laparoscopic cholecystectomy.

Bile duct injury is an unusual complication of laparoscopic cholecystectomy. Although the exact incidence is yet to be determined, it does appear to be more common than bile duct injury during open cholecystectomy. Previous publications have attempted to document the incidence of bile duct injuries and methods to prevent it. We reviewed our experience with 11 bile duct injuries from laparoscopic cholecystectomy. Such injuries were manifested by abdominal pain, low-grade fever, and hyperbilirubinemia or biliary fistula. These patients' injuries were treated by using drainage or reexploration and ligation of cystic duct and subcholecystic duct leaks and Roux-en-Y hepaticojejunostomy for common duct strictures and lacerations.

Adult↗

Electrosurgical laparoscopic cholecystectomy.

Though laparoscopic cholecystectomy has become widespread, questions remain as to its success rate, its role in acute cholecystitis, the role of cholangiography, and whether laser use is necessary. To attempt to answer these questions, the first 100 patients undergoing laparoscopic cholecystectomy at Emory University using electrosurgical diathermy were reviewed. Patients underwent cholecystectomy for biliary colic (87), gallstone pancreatitis (1), and acute cholecystitis (12). The average length of hospital stay was 29 hours (range: 12 hours to 5 days). Laparoscopic cholecystectomy was not possible in 7 patients because of gangrenous cholecystitis (2), adhesions from previous surgery (2), equipment failure (2), and choledochoduodenal fistula found at surgery (1). Two patients developed bile leaks from accessory bile ducts that healed spontaneously. There were no other complications. The average time required to complete the laparoscopic cholecystectomy was 115 minutes (range: 45 to 238 minutes) and was not significantly different in those patients undergoing intraoperative cholangiography (117 minutes) versus those without (109 minutes). Common duct stones were uncommon in this series. Thirty-three patients underwent intraoperative cholangiogram. One patient was found to have a common duct stone, which was pushed into the duodenum using a Fogarty catheter (American Edwards Laboratories; Anasco, Puerto Rico) inserted through the cystic duct at the time of laparoscopic cholecystectomy. Twelve patients with acute cholecystitis underwent an attempt at laparoscopic cholecystectomy that was successful in nine. These procedures were difficult and lengthy (mean of 143 minutes). Causes for failure were gangrenous cholecystitis (2) and equipment failure (1). In conclusion, laparoscopic cholecystectomy can be performed with a high success rate (93%) and low morbidity (2%). No complications seemed attributable to electrosurgical dissection.

Adolescent↗

Complications of hepatic resection for colorectal carcinoma metastasis.

Hepatic resection of metastatic colorectal carcinoma is widely advocated with 5-year survival rates quoted at 20 to 25 per cent. However, concerns about the morbidity and mortality for this procedure still exist. It is estimated that only 25 per cent of patients potentially eligible for hepatic resection are actually referred for evaluation, possibly secondary to concerns about the morbidity and mortality of the surgical procedure involved. All patients undergoing such resections at the Emory University Affiliated Hospitals between January 1, 1984 and December 31, 1989 were reviewed to determine the associated morbidity and mortality. Forty-three patients were identified (23 men, 20 women, ranging in age from 32 to 80 years (mean of 60.8). The average postoperative intensive care unit (ICU) stay was 3.2 days (range 1 to 12) and the average hospital stay was 15 days (range 6 to 45). There were no postoperative deaths, and 10 patients (23%) developed significant complications (1 biliary fistula, 2 thrombophlebitis, 3 abscess/wound infections, 1 hepatic insufficiency, 1 pneumothorax, 1 pleural effusion, 1 lobar pulmonary collapse). The occurrence of complications was not related to preoperative liver enzymes, absolute tumor mass present, or associated co-morbid disease. The extent of liver resection, length of operation, and number of units of blood transfused were all correlated with the occurrence of complications (P = 0.01, 0.01, and 0.05, respectively). Likewise, the length of hospital stay and ICU stay were directly related to the extent of hepatic resection (P = 0.05 and 0.09) and number of transfusions (P = 0.05 and 0.01). The length of operation showed such a trend but was not statistically significant (P = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A prospective evaluation of diversion colitis.

Numerous case reports suggest that diversion of the fecal stream results in nonspecific colitis, with abnormalities ranging from minimal friability to gross ulceration. Published reports consist largely of patients with symptomatic colitis, and there are scant data suggesting at what frequency diversion colitis actually occurs. In an attempt to identify the frequency of diversion colitis and any associated etiologic factors, 20 patients scheduled for colostomy closure at Grady Memorial Hospital between 8/1/88 and 6/15/89 underwent colonoscopy, including the excluded segment, to evaluate for diversion colitis. Colostomies were performed for the management of diverticulitis, trauma, cancer, protection of an anastomosis, and diversion of fecal fistula. Patients with ulcerative colitis or Crohn's disease were excluded. The colon was classified grossly as normal or colitis (including easy friability, edema, inflammation, and ulceration as colitis). Fourteen of the 20 patients (70%) had findings of diversion colitis (DC), while six had a normal exam (NL). Nine biopsies were performed in the DC group and all revealed microscopic abnormalities. One of the normal patients was also biopsied, revealing mild, nonspecific changes. There was no difference in mean age (DC 49.3, NL 48.2), interval from formation of colostomy (DC 9.21 +/- 7.27 months, NL 2.83 +/- 1.94 months), type of colostomy, or reason for colostomy in the two groups. None of the DC patients had symptoms of colitis (mucous or bloody discharge, tenesmus, or pain), and one of the DC patients manifested symptoms of colitis after colostomy closure. We conclude that diversion colitis is a common subclinical problem in patients with a diverting colostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Ileal pouch-anal anastomosis. The Emory University experience.

The ileal pouch-anal anastomosis has become a practical alternative to proctocolectomy for the treatment of ulcerative colitis and polyposis coli. To evaluate its success, the Emory University Affiliated Hospital experience from February 1984 to March 1989 was retrospectively reviewed. There were a total of 50 patients identified; 84 per cent had ulcerative colitis, and 16 per cent had polyposis coli (familial polyposis and Gardner's syndrome). The majority of these patients underwent a two-stage operation, but one-third required a three-stage procedure due to difficulty in mucosal proctectomy or toxic megacolon. J-pouch construction was performed in 72 per cent of patients, S-pouch construction in 14 per cent, straight ileo-anal anastomosis in 8 per cent, and lateral isoperistaltic ileo-anal anastomosis in 6 per cent. Of the 50 patients, 36 (72%) have had closure of the temporary ileostomy. Fourteen patients have not had ileostomy closure due to change in diagnosis to Crohn's disease, operative complications, or ileostomy closure pending. The combined operative morbidity per patient for the ileal pouch-anal anastomosis and the closure of the ileostomy was 32 per cent. This included bowel obstruction, 16 per cent; pelvic abscess, 6 per cent; and ileo-anal separation, 4 per cent. Follow-up on patients with ileostomy closure ranged from 6 months to 4 years (mean, 1.3 years). Stool frequency was 5.9 stools per 24 hours at 6 months and improved with time. During the follow-up period, all patients were eventually completely continent of stool during the day, and most became completely continent of stool at night.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenomatous Polyposis Coli↗