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Biomedical subjects

K W Chu

Publications and source records attributed to K W Chu.

49 records · Page 3Linked to original sources

Kinetic mechanism of histidinol dehydrogenase: histidinol binding and exchange reactions.

Salmonella typhimurium histidinol dehydrogenase produces histidine from the amino alcohol histidinol by two sequential NAD-linked oxidations which form and oxidize a stable enzyme-bound histidinaldehyde intermediate. The enzyme was found to catalyze the exchange of 3H between histidinol and [4(R)-3H]NADH and between NAD and [4(S)-3H]NADH. The latter reaction proceeded at rates greater than kcat for the net reaction and was about 3-fold faster than the former. Histidine did not support an NAD/NADH exchange, demonstrating kinetic irreversibility in the second half-reaction. Specific activity measurements on [3H]histidinol produced during the histidinol/NADH exchange reaction showed that only a single hydrogen was exchanged between the two reactants, demonstrating that under the conditions employed this exchange reaction arises only from the reversal of the alcohol dehydrogenase step and not the aldehyde dehydrogenase reaction. The kinetics of the NAD/NADH exchange reaction demonstrated a hyperbolic dependence on the concentration of NAD and NADH when the two were present in a 1:2 molar ratio. The histidinol/NADH exchange showed severe inhibition by high NAD and NADH under the same conditions, indicating that histidinol cannot dissociate directly from the ternary enzyme-NAD-histidinol complex; in other words, the binding of substrate is ordered with histidinol leading. Binding studies indicated that [3H]histidinol bound to 1.7 sites on the dimeric enzyme (0.85 site/monomer) with a KD of 10 microM. No binding of [3H]NAD or [3H]NADH was detected. The nucleotides could, however, displace histidinol dehydrogenase from Cibacron Blue-agarose.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Oxidoreductases↗

A scientific evaluation of operative choledochoscopy in acute cholangitis.

A prospective study to determine the safety and effectiveness of choledochoscopy in acute cholangitis and acute suppurative cholangitis due to common bile duct stones was conducted on 70 patients. Common bile duct pressures determined on the first 20 patients showed that choledochoscopy was unlikely to cause cholangiovenous reflux. Laboratory and clinical parameters revealed that choledochoscopy did not cause septicemia, worsen cholangitis, or provoke acute pancreatitis. There was no iatrogenic injury during choledochoscopy, and the choledochoscopic views were minimally affected by cholangitis. Choledochoscopy detected overlooked stones after conventional methods of exploration of common bile ducts in 14.3% of patients and it helped to remove impacted stones in 2.9% of patients. As a result, the incidence of retained stones after choledochoscopy was 1.4%. Time spent in choledochoscopy was short, and the total postoperative septic complication rate was only 10%. There was no operative mortality. It is concluded that choledochoscopy is safe and effective in cholangitis.

Acute Disease↗

Acute appendicitis in children.

A prospective study was conducted on 344 children aged from 3 months to 16 years with acute appendicitis. Most children presented with typical features of acute appendicitis (70%) or peritonitis (28%). Atypical presentation was uncommon and occurred only in seven young children, masquerading as intestinal obstruction, gastroenteritis or urinary tract infection. Prolonged delay in surgery was associated with a rise in incidence of late appendicitis (gangrenous and perforated appendicitis). This rise was especially marked 37 h after onset of symptoms. The main causes of delay were inability of the parents and primary care medical practitioners to recognize the disease early. Surgeons contributed very little to the delay. High risk factors for postappendectomy sepsis were young children under 6 years old, late appendicitis, obese patients, inferior systemic antibiotic regimes and inexperienced surgeons. Young children had high postoperative sepsis mainly because of the high incidence of late appendicitis due to their inability to express their symptoms properly. They were not especially prone to postappendectomy sepsis; they had the same degree of appendicitis compared with older children. Measures to decrease the postappendectomy morbidity are suggested.

Acute Disease↗

Preoperative and intraoperative localisation of gastrointestinal bleeding of obscure origin.

In the past six years, 37 patients with gastrointestinal bleeding of obscure origin had their bleeding sites localised preoperatively or intraoperatively. Preoperative investigations followed a regime consisting of endoscopy, barium meal and follow through, small bowel enema, 99mTc pertechnetate scan, 99mTc-labelled red blood cell scan and selective coeliac and mesenteric angiography. Bleeding lesions were localised preoperatively in 36 patients. In one patient, diagnostic laparotomy had to be carried out immediately before any investigation because the bleeding was severe. At operation, angiosarcoma of ileum was found. Unless preoperative investigations showed the lesions to be in anatomically fixed organs like the duodenum or colon, the lesions had still to be found at operation. Palpation and transillumination detected the lesion intraoperatively in 21 patients while only some lesions were found in three patients with multiple lesions. Sigmoidoscopy through enterotomies was required in one patient. Intraoperative enteroscopy was done for small lesions not found grossly at operation in nine patients, to detect additional lesions in three patients or to rule out suspicious lesion shown on preoperative tests in one patient. In another patient with diffuse lymphoma of small bowel with bleeding from only a small segment of jejunum, injection of methylene blue intraoperatively through a previously placed angiographic catheter stained the bleeding segment of jejunum blue. This segment was identified easily and resected. These preoperative and intraoperative localisation procedures were simple and effective and we recommend them to be used more freely.

Adolescent↗

Intra-operative fibreoptic enteroscopy for bleeding lesions in the small intestine.

Twenty-five patients with gastrointestinal bleeding proved to have lesions in the small intestine. Intra-operative fibreoptic enteroscopy was performed on seven patients, in six patients through the anus and in one patient through an enterotomy and the anus. The indications for fibreoptic enteroscopy were inability to find the lesions in the 3 patients, multiple small lesions in 3 patients and to rule out suspicious pathology in the jejunum shown on a small bowel enema in a patient with ileal ulcers. In all instances, the fibreoptic enteroscopy was useful in localizing lesions, in detecting additional lesions and in ruling out the suspicious lesions. It can be performed easily and is safe. No complication developed from its use in this series.

Endoscopy↗

Combined topical povidone-iodine and systemic antibiotics in postappendicectomy wound sepsis.

Three hundred and fifteen patients with appendicitis were randomized into two groups. One group received pre-operative systemic gentamicin and metronidazole while the other group received 1 per cent topical povidone-iodine solution in addition to the antibiotics. For early appendicitis including normal and acutely inflamed appendices, only one dose of antibiotics was used. The postoperative wound sepsis was very low in both groups of patients and there was no statistical difference between them. For late appendicitis including gangrenous and perforated appendices, the antibiotics were continued for 7 days. Eight out of 51 patients who had the topical agent developed wound sepsis compared with one out of 52 patients who received no topical agent. This difference is statistically significant (P = 0.03). All wound infections presented within 2 weeks of operation and were deep. Povidone-iodine, 1 per cent, adversely affects the wound infection rate in late appendicitis and should not be used.

Administration, Topical↗

Conventional vs. triple rubber band ligation for hemorrhoids. A prospective, randomized trial.

Two hundred five patients with symptomatic first- and second-degree hemorrhoids were randomized to receive either conventional rubber band ligation or triple rubber band ligation. In conventional rubber band ligation, the hemorrhoids were ligated at one primary site per session at intervals of four weeks until symptoms were relieved or when all three hemorrhoids were ligated. In triple rubber band ligation, all three primary hemorrhoids were ligated in a single session. After completion of treatment, the patients were examined every three months, or earlier if symptoms recurred. Both methods were effective in the treatment of early hemorrhoids and the incidence of postligation pain and complications was similar. The advantages of having the treatment completed at the initial visit in triple rubber band ligation are obvious. Furthermore, less treatment sessions were required for triple rubber band ligation to control symptoms than for conventional rubber band ligation. Triple rubber band ligation is more cost-effective and therefore is recommended.

Clinical Trials as Topic↗

Cefoxitin versus gentamicin and metronidazole in prevention of post-appendicectomy sepsis: a randomized, prospective trial.

Three hundred and seven patients with appendicitis were randomized to receive cefoxitin or gentamicin and metronidazole. For early appendicitis, a single preoperative dose of antibiotics was given. For late cases, the antibiotics were continued postoperatively for seven days. Both cefoxitin and gentamicin-metronidazole were effective in the reduction of post-appendicectomy septic complications in early or late appendicitis and there was no statistically significant difference between them. Mild transient and reversible nephrotoxicity was detected in 1.9% of patients who received gentamicin-metronidazole for seven days. Nephrotoxicity was not detected in any other patients. The cost of cefoxitin is higher, but this has to be balanced against the costs of monitoring serum gentamicin and creatinine levels, and the need to adjust the gentamicin dosage in 19% of patients when gentamicin-metronidazole was used. Both cefoxitin and gentamicin-metronidazole are effective and safe when used carefully. Cefoxitin has a slight advantage in its lack of potential nephrotoxicity and ototoxicity.

Adolescent↗

The clinical significance of routine histopathologic study of the resected appendix and safety of appendiceal inversion.

A prospective study was done on 1,699 patients operated upon for appendicitis to correlate the operative diagnosis of the surgeon and the histopathologic diagnosis of the pathologist. There are surgeons who only send the appendices for histopathologic study when the operative findings are inconclusive and surgeons who invert rather than resect the appendices on finding a grossly normal appendix at operation. This study was done to find out whether or not these practices of leaving some of the appendix unexamined histopathologically are clinically safe. In this study, surgeons missed abnormal pathologic findings in the appendix in ten of 13 patients and this is irrespective of whether the appendix was normal, acutely inflamed, gangrenous or perforated. The majority of these lesions either require further investigation, treatment or they affected the prognosis of the patient. Nineteen per cent of the patients diagnosed as having normal appendices grossly were found to have acute appendicitis and 7.7 per cent diagnosed as acute appendicitis were normal. Based upon these data, we conclude that the operative diagnosis of the surgeon cannot be relied on to detect abnormal pathologic findings in the appendix. Additional important clinical information can be gained by routine histopathologic study of the resected specimens, and inversion of the appendix is clinically not safe.

Acute Disease↗

Randomized, prospective, and double-blind trial of new beta-lactams in the treatment of appendicitis.

A prospective, randomized, and double-blind study was conducted with 864 patients operated on for appendicitis. In early cases, including normal and acute appendicitis, one dose of antibiotic was given. The rate of postappendectomy septic complications in patients who received cefotaxime, cefoperazone, or moxalactam was very low (about 3%), and there was no statistical difference between the drugs. For late cases, including gangrenous and perforated appendicitis, the antibiotics were continued for 5 days. Moxalactam decreased significantly the septic complications in these patients when compared with the other two drugs. It is safe, free from serious toxic side effects, and more convenient and easier to administer than combination antibiotic therapy. The main disadvantage of moxalactam is its high cost, but this has to be balanced against the savings in nursing time, the cost of monitoring renal function and serum level when aminoglycosides are used, and the reduced usage and manipulation of infusion sets.

Anti-Bacterial Agents↗

Acute appendicitis in the elderly.

A prospective study was done on 104 patients more than 60 years old with appendicitis. The clinical features are by and large, similar to that of the younger patient. However, four patients presented atypically with abdominal distension with little or no pain. A statistically significant increase in appendiceal perforation is found in patients more than 70 years old and in patients with prolonged delay in operation. However, delay on the part of the surgeon contributed only slightly to the high appendiceal perforation as 85.6 per cent of patients who were operated upon within 24 hours of admission. Appendicitis in the elderly patient appeared to progress to perforation faster and perforation occurred in about 40 per cent of patients within 24 hours of onset of symptoms. Five patients died and 29 postoperative complications occurred in 24 more patients. An associated medical disease is linked to a statistically significant increase in mortality. Appendiceal perforation and a total delay of more than 37 hours are associated with a statistically significant increase in morbidity.

Acute Disease↗

Negative findings at appendectomy.

A prospective study was conducted on 107 patients with negative findings at appendectomy. The operation was unnecessary in 94 of the patients. A cause for the symptoms could be found in 43 patients, 32 during operation and 11 later by investigation or by a second operation. Diagnosis remained unclear in 64 patients. There are many diseases that mimic acute appendicitis, and based on the disease entities encountered in this series, the surgeon must examine the abdominal organs carefully if the appendix is normal. The financial loss of negative appendectomy was substantial in our study, and the total early and late complication rate was 14 percent. Patients with negative appendectomy should be regularly followed up to 1 year, since 9.3 percent of patients had a diagnosis made later by investigation, and 12.1 percent had moderate to severe pain on follow-up. Possible means to cut down the negative appendectomy rate without increasing the perforation rate have been suggested herein for further evaluation.

Abdomen, Acute↗