beta-Glucosidase activity in fetal bovine serum renders the plant glucoside, hypoxoside, cytotoxic toward B16-F10-BL-6 mouse melanoma cells.

By using p-nitrophenyl-beta-D-glucopyranoside as substrate, beta-glucosidase activity was observed in fetal bovine serum (FBS). This activity could be inhibited by heat inactivation of the serum. Gel chromatography of FBS indicated the presence of beta-glucosidase activity with an apparent molecular mass of 29 kDa. In McCoy's 5A medium supplemented with non-heat inactivated FBS, the diglucoside hypoxoside ([E]-1,5-bis[4'beta-D-glucopyranosyloxy-3'-hydroxyphenyl]pent-4-en - 1-yne) showed cytotoxicity toward B16-F10-BL-6 mouse melanoma cells. In incubations where the media were supplemented with FBS previously heat inactivated at 56 degrees C for 1 h or more, no cytotoxicity was observed in the presence of hypoxoside. The aglucone of hypoxoside, rooperol ([E]-1,5-bis[3',4'-dihydroxyphenyl]pent-4-en-1-yne), showed cytotoxicity regardless of whether the serum was heat inactivated or not. The kinetics of the heat inactivation of the beta-glucosidase activity in FBS coincided with the loss of apparent cytotoxicity of hypoxoside. High performance liquid chromatography analysis showed that rooperol could be generated by incubation of hypoxoside in non-heat inactivated FBS, but that this ability was lost in serum that was heat inactivated for 1 h or longer. Newborn bovine serum did not contain any beta-glucosidase activity whereas it was found in three different commercial sources of FBS. This observation is of practical importance because conventional heat inactivation of FBS at 56 degrees C for 30 min was not sufficient to inactivate the beta-glucosidase activity completely.

Bacteraemia in shock. A prospective study.

Previous studies showed that bacteraemia occurs in shocked dogs and rats. The present study shows that it also occurs in shocked patients and that Gram-positive bacteria, especially staphylococci, feature prominently. Gram-positive bacteraemia may constitute an important link between shock and sepsis. Antibiotic prophylaxis covering Gram-positive bacteria is suggested for patients with severe shock.

The diagnosis of abdominal injuries in comatose patients.

The clinical course of 95 comatose trauma patients was prospectively evaluated. The role of clinical findings and diagnostic peritoneal lavage (DPL) combined with computed tomography (CT) were assessed in the diagnosis of abdominal injuries. Seven per cent of the patients were comatose due to hypoperfusion, and did not have a primary brain injury. Of the remaining 88 patients, 28% had an associated abdominal injury. Hypotension predicted an associated abdominal injury with an accuracy of 72%, and a haematocrit less than 30% had an accuracy of 82%. Clinical examination was 50% accurate. DPL was 93% accurate, with a false-positive rate of 10%. No abdominal injuries were present in the group in whom the lavage results were negative, while no unnecessary laparotomies were performed in the group with a 4+ or 5+ positive DPL (calorimetric method). In the group with 1+, 2+ and 3+ positive DPL, 3/15 laparotomies (12%) were done for minor abdominal injuries. Minimising unnecessary laparotomies was achieved by utilising CT to determine the nature and extent of the injury. By using DPL as a screening test, and CT to quantify the injury, unnecessary operations can be avoided, and all injuries can still be diagnosed.

[Appendicitis in the Black population]. / Appendisitis by die Swart bevolking.

In this retrospective study important aspects of appendicitis in 252 Blacks were studied and some interesting conclusions were drawn from clinical and operative data. Certain widely accepted impressions and beliefs are substantiated and others are refuted by the evidence found. In 38% of patients see, symptoms were present for more than 4 days before admission, but the clinical picture corresponded remarkably well with the textbook description. Operative findings revealed a diagnostic error rate of 18%, and the eventual mortality of 2% was confined to the 1st and 5th decades.

The utilization of transcutaneous electric nerve stimulation in postoperative ileus.

Pain stimuli with resulting sympathetic hyperactivity are responsible for the inhibition of intestinal motility. In this clinical study on 30 adult patients after laparotomy, the effect of intermittent transcutaneous stimulation with a diadynamic current on intestinal motility was determined. It was established that bowel sounds return soon after transcutaneous nerve stimulation, and more than 50% of the patients passed flatus within 24 hours after the commencement of stimulation.

Treatment of septic burns with a third-generation cephalosporin (cefatriaxon).

Effective and safe antibiotic control combined with surgical measures is the mainstay of the management of serious sepsis in burn wounds. To determine the effects of the third-generation cephalosporins on the clinical and bacteriological course of burn sepsis, 30 adult patients with a comparable degree of burn sepsis were treated with cefatriaxon (Ro 13-9904 (Rocephin); Roche). No significant side-effects were observed, and clinical observation showed a marked to moderate improvement in wound sepsis in 26 cases. Of 61 wound cultures obtained after completion of the course of cefatriaxon, only 19 yielded a positive growth. The beneficial role of the third-generation cephalosporins indicated by this prospective trial could be very important in the management of extensive burn wound sepsis.

Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy.

Hypoxoside is the major diglucoside isolated from the corms of the plant family Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit with two distal catechol groups to which the glucose moieties are attached. It is non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in order to destroy endogenous beta-glucosidase activity. The latter catalyses hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10 micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect of rooperol manifested as vacuolisation of the cytoplasm and formation of pores in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic studies on mice dosed intragastrically with hypoxoside showed that it was deconjugated by bacterial beta-glucosidase to form rooperol in the colon. Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase II biotransformation products (sulphates and glucuronides) were present in the portal blood and bile. In contrast, however, in human serum after oral ingestion of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol metabolites isolated from human urine were non-toxic for BL6 melanoma cells in culture up to a concentration of 200 micrograms/ml. In the presence of beta-glucuronidase, which released rooperol from the metabolites, 50% growth inhibition was achieved at a 75 micrograms/ml metabolite concentration. The supernatant of a human melanoma homogenate could also cause deconjugation of the metabolites to form rooperol.(ABSTRACT TRUNCATED AT 250 WORDS)

Rupture of the head of the pancreas by blunt trauma. A case report.

An unusual injury to the head of the pancreas is described. The various surgical options are discussed and the literature is reviewed. The Roux-en-Y pancreaticojejunostomy for a major isolated rupture of the head of the pancreas is considered to be the operation of choice.

Thermal injury in pregnancy--the neglected tragedy.

Thermal injury sustained during pregnancy presents special management problems for the gravid woman and her unborn child. Because of the reported high morbidity and mortality and lack of available data in South Africa, a multicentre retrospective review was undertaken by five burn centres. Thirty-three patients (average age 25,7 years) with mean 30% (range 1-80%) total body surface area burn were assessed. A review of the clinical material led to the following observations and conclusions. Pregnancy does not influence maternal outcome after thermal injury and maternal survival is usually accompanied by fetal survival in the absence of significant maternal complications. Maternal survival is less likely if the burn wound exceeds 50% total body surface area. Thermal injury does increase the risk of spontaneous abortion and premature labour, and fetal survival depends on fetal maturity. Early obstetric intervention is only indicated in the gravely ill patient where complications (hypoxia, hypotension, sepsis) jeopardize the life of a viable fetus. The mode of delivery should be determined by obstetric considerations.