A surgical approach in the management of mucormycosis in a trauma patient.

Mucormycosis as a consequence of trauma is a devastating complication; these infections are challenging to control, with a fatality rate approaching 96% in immunocompromised patients. We present a case where a proactive approach was successfully employed to treat mucormycosis following complex polytrauma. Aggressive repeated surgical debridement, in combination with appropriate antifungal therapy, proved successful in this instance. In our opinion, mucormycosis in trauma mandates an aggressive surgical approach. This prevents ascending dissemination of mucormycosis and certainly reduces the risk of patient mortality as a direct result. Anti-fungal therapy should be used secondarily as an adjunct together with surgical debridement, or as an alternative when surgical intervention is not feasible.

An efficient process for production of N-acetylneuraminic acid using N-acetylneuraminic acid aldolase.

N-acetyl-D-neuraminic acid (Neu5Ac) aldolase (EC 4.1.3.3) has bee reported for synthesis of Neu5Ac,1-5 but there are no reports of processes which do not have significant drawbacks for large-scale operation. Here, Neu5Ac aldolase from an overexpressing recombinant strain of Escherichia coli has been used to develop an immobilized enzyme process for production of Neu5Ac. The enzyme was immobilized onto Eupergit-C and could be reused many times in the reaction. Base-catalyzed epimerization of N-acetyl-D-glucosamine (GlcNAc) yielded GlcNAc/N-acetyl-D-mannosamine (ManNAc) mixtures (c 4:1) which could be used directly in the aldolase reaction; however, inhibition of the enzyme by GlcNAc limited the concentration of ManNAc which could be used in the reaction by this approach. This necessitated the addition of a large molar excess of pyruvate (five- to seven-fold) to drive the equilibrium over to Neu5Ac; nevertheless, a method has been developed to remove the excess pyruvate effectively by complexation with bisulfite, thus allowing Neu5Ac to be recovered by absorption onto an anion-exchange resin. In a second approach, a method has been developed to enrich GlcNAc/ManNAc mixtures for ManNAc. ManNAc can be used at high concentrations in the reaction, thus obviating the need to use a large molar excess of pyruvate. Neu5Ac can be isolated from such reaction mixtures by a simple crystallization. This work shows the importance of integrated process solutions for the effective scale-up of biotransformation reactions.

The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. V. Minor metabolites.

The isolation and structure determination of 3H and 13C NMR and MS of 24 novel squalestatins from cultures of Phoma sp. C2932 is described.

Enzymatic production of optically pure (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC, lamivudine): a potent anti-HIV agent.

Although equipotent in terms of antiviral activity, the two enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) differ markedly in their cytotoxicity. (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC) is substantially less toxic than its optical antipode, and is undergoing development for the therapy of HIV infection. Cytidine deaminase from Escherichia coli is shown here to deaminate 2'-deoxy-3'-thiacytidine enantioselectively to leave 3TC essentially optically pure. This reaction has been used to develop a process for production of 3TC in multikilogram amounts. The production of cytidine deaminase was enhanced by strain improvement, fermentation development, and finally by cloning and overexpression of the gene. The enzyme was immobilized on Eupergit-C, which allowed it to be reused many times. The biotransformation conditions were optimized so that the best use could be made of the catalyst. A robust scaleable product isolation process was developed to yield the crystalline product. Overall, yields through the resolution process of 76% were obtained. All aspects of this process are capable of substantial further scaleup with only minor modifications.

Valve data collection: problems and pitfalls.

Since 1981, the Department of Medical Physics and Clinical Engineering at the University of Sheffield has been responsible for the organization, management and data collection associated with the largest multicentre heart valve implant patient follow-up study in the Western world. At the present time, the database comprises information on over 16,000 valve implants, which have been provided by 57 surgeons working at 22 centres in the UK. All this data is available for in-depth statistical analysis. Over 30 individual valve models presently are included in the Study and these can be categorized into five main types: ball, disc, porcine, pericardial and homograft. Analysis includes descriptive statistics as well as valuable information on the various performances of the different valves. Survival and event-free survival graphs are obtained by actuarial methods and individual valve types can be studied in depth in terms of freedom from thromboembolic complications and valve dysfunction. Whilst this approach provides interesting and valuable survival data, it does not take account of the wide variation in prognostic factors which occur within large groups of patients. This latter problem can be addressed by the use of proportional hazards analysis and this paper provides details of this approach and typical results obtained from the use of this method. These include the comparative performances of the major types of valves currently in use in terms of the event-free survival of the patients.

Pancreatitis associated with pancreas divisum: results of surgical intervention.

The embryologic defect that results when the ventral and dorsal anlages of the pancreas do not fuse has been referred to as pancreas divisum. The patients who present with recurrent pancreatitis or pancreatitis-like pain in association with pancreas divisum should be investigated to determine the presence of minor papilla stenosis. In the present study of 11 patients, 9 became asymptomatic with surgical decompression of the dorsal pancreatic duct. Two surgical failures were related to wrong diagnosis and restenosis of the sphincteroplasty. A delay in the clearance of dye from the dorsal pancreatic duct after endoscopic retrograde cholangiopancreatography was utilized to determine minor papilla stenosis. In the future, secretin ultrasound tests should prove of value in assessing minor papilla stenosis. Once the diagnosis is made, sphincteroplasty of the minor papilla is the most logical procedure because of the good results obtained. In the present study, pancreaticojejunostomy provided good duct decompression as well.

Cytomegalovirus infection of the gastrointestinal tract in a patient with late onset immunodeficiency syndrome.

An adult with the late onset immunodeficiency syndrome developed intractable diarrhea. Widespread cytomegalovirus (CMV) infection of the gastrointestinal tract was detected antemortem with detailed morphological studies and viral culture. The CMV-type cells were especially numerous in his severely ulcerated colon. Electron microscopy of infected cells in rectal biopsy material revealed the characteristic features of CMV infection. It is likely that the CMV infection contributed to the symptom complex and the mucosal injury. Unusual opportunistic infections as a cause of diarrhea should be considered in patients with late onset immunodefociency, especially if Giardiasis is ruled out.

Endoscopic laser treatment. II. Comparison of the efficacy of high and low power photocoagulation in control of severely bleeding experimental ulcers in dogs.

The coagulative efficacy of a "high power" argon laser which delivers 6.5 +/- 1.0 w was compared to that of a "low power" argon laser which delivers 1.0 +/- 0.1 w. The wave-guide angle of divergence was 8 degrees. For the high power laser, the distance between the wave-guide tip and the mucosa varied from 1.0 to 1.5 cm with a delivered power density range of 160 to 487 w per cm2. For the low power laser, the distance between the tip and mucosa varied from 0.7 to 1.3 cm with a power density of 35 to 146 w per cm2. Group A consisted of acute experiments in 6 heparinized dogs in which 51 standard-sized acute gastric ulcers extending into the submucosa were made at laparotomy via a large gastrotomy. Ulcer bleeding rates were quantified into three categories of severity. Within each category, ulcers were randomized to high power, low power, or untreated control. All 19 low power-treated ulcers and 16 untreated controls continued bleeding; 13 of 16 high power-treated ulcers stopped bleeding completely. Representative ulcers were examined histologically. Group B consisted of chronic experiments on 31 ulcers in 7 unheparinized dogs. These ulcers were either treated with high power or left as untreated controls. Dogs were killed and the ulcers were examined histologically at 7, 14, and 28 days. Only rarely did the laser injury penetrate into the muscularis externa. There were no perforations. By 14 days, all lesions were covered with normal surface epithelium. These data encourage further development of congruent to 7.0 w argon laser photocoagulation for eventual clinical use in man.

Cytomegalovirus-associated gastric ulcer.

A patients with a cytomegalovirus (CMV) post-transfusion syndrome developed upper gastrointestinal tract bleeding; subsequently, a gastric ulcer was found. CMV was searched for in the gastroscopic biopsy material because the gastric ulcer had occurred in a setting of CMV mononucleosis. CMV cells were found in gastroscopic biopsy sections and CMV was also cultured from biopsy material. This study illustrates the feasibility of antemortem diagnosis of CMV-associated disease of the upper gastrointestinal tract.

A reproducible animal model of acute bleeding ulcer-the "ulcer maker".

An instrument has been developed which creates an experimental model of an acute bleeding gastric ulcer. The diameter and depth of these gastric ulcers are reproducible. The instrument can be used endoscopically or at laparotomy. Using this ulcer model nonsurgical modalities for the treatment of upper gastrointestinal bleeding can be compared in a controlled manner. This standard experimental model may also facilitate comparison of results among different research groups.