Intra-arterial cisplatin--associated optic and otic toxicity.

Over a 22-month period, we investigated optic and otic toxicity accompanying intra-arterial cisplatin therapy. Baseline and serial neurologic and ophthalmologic examinations, visual evoked potentials, and brain-stem auditory evoked potentials were performed in six patients, aged 37 to 53 years. Patients received infraophthalmic intra-arterial cisplatin (60 mg/m2) every month for three to 10 treatments (mean, six treatments). Five of the six patients had progressive optic toxicity. In two patients, the visual evoked potential prolongation preceded acuity loss by at least 4 months. Two patients had evidence of otic toxicity by either brain-stem auditory evoked potential or click threshold and brain-stem auditory evoked potential. Intra-arterial cisplatin neurotoxicity may be significant in patients with already limited survival. Visual evoked potential and brain-stem auditory evoked potential should be used to monitor patients receiving potentially neurotoxic therapy.

Rapid method for the isolation of neutrophils in high yield without the use of dextran or density gradient polymers.

A simple, rapid and economical method for the isolation of polymorphonuclear leucocytes (PMNs) from whole blood is compared with dextran and dextran/Lymphoprep gradient techniques. The method eliminates the use of dextran and density gradient polymers such as Ficoll which have been shown to affect PMNs adversely. The technique is based on the lysis of red cells with isotonic ammonium chloride solution followed by differential centrifugation to separate the PMNs. This method gave a PMN yield of 73% (SD +/- 3.5) and a purity of 78% (SD +/- 2.5). Both morphology and functional activity were preserved, as assessed by bacterial phagocytosis and killing, chemotaxis, polarising response, superoxide production and adherence. In contrast, the dextran and dextran/Lymphoprep techniques gave yields of 50% and 15% with purities of 78% and 91% respectively. In a series of 14 PMN isolations, the differential centrifugation method gave an average yield of 63% with an average purity of 83%.

Performance of converted pressure cookers and two conventional jars for anaerobic bacterial culture.

The simple conversion of commercial pressure cookers into inexpensive anaerobic jars is described. These containers were shown to be as good as the small conventional BBL polycarbonate GasPak and large vented 150 gas-replacement jars when assessed by means of three biological indicators: Pseudomonas aeruginosa, Bacteroides melaninogenicus, and Bacteroides fragilis. Ps. aeruginosa seeded on Simmond's citrate agar was shown to be the most sensitive indicator of the three for traces of oxygen.

A concise biotyping system for differentiating strains of Escherichia coli.

A six test biotyping system comprising fermentation of dulcitol, sorbose, raffinose, and 5 ketogluconate, motility and production of beta-haemolysis was used to obtain biotype profiles for 514 strains of Escherichia coli isolated from the urinary tract. This profile was suffixed to the API-20E code, recorded when the strains were originally identified. An expanded and reliable biotyping system was thus created giving a greater number of possible biotypes than with either system alone. The sensitivity in terms of distinguishing the organisms studied was therefore greatly increased. The use of O-serotyping in combination with biotyping is discussed. Biotyping can also be usefully supplemented by the determination of the eight commonest E coli O-serotypes. This is of value in many clinical situations where differentiation of organisms is vital to the proper analysis of results.

Activity of FL 1060, a new beta-lactam antibiotic, against urinary tract pathogens.

The effect of the new beta-lactam antibiotic FL 1060 on urinary tract pathogens, of which 71 were sensitive to and 100 resistant to ampicillin, is presented here. When tested by conventional methods FL 1060 was found to be highly active against ampicillin-sensitive strains of E. coli but phenotypically resistant variants readily emerged, particularly when a large inoculum was used. Thirty-one per cent of ampicillin-resistant strains were found to be sensitive to less than 500 mug FL 1060 per ml, and in general this antibiotic was more active than ampicillin against resistant strains. In a system simulating the mechanical features of the urinary bladder the activity of FL 1060 against three sensitive strains of E. coli was found to be greater than ampicillin in conditions of low, but not high, osmolality.

Phenomenon of resistance to Augmentin associated with sensitivity to ampicillin: occurrence and explanation.

Ampicillin was found to be some tenfold more active than amoxycillin against Enterobacter cloacae. This finding explains the observation that some Ent cloacae strains are sensitive to ampicillin in the disc test but resistant to Augmentin. Ampicillin was also found to be more active than amoxycillin against Citrobacter freundii and Serratia marcescens. In view of these findings, the practice of using ampicillin discs to predict sensitivity to amoxycillin should be reconsidered. The use of both ampicillin and amoxycillin discs is appropriate if errors are to be avoided.

Pre-opsonisation of Escherichia coli induces resistance to neutrophil killing in serum and urine: relationship to growth phase.

Tests of phagocytosis and killing by polymorphonuclear neutrophil leucocytes (PMNL) are usually done with pre-opsonised organisms. Phagocytosis of 11 strains of Escherichia coli, pre-opsonised, and in the stationary phase, resulted in the killing of only one strain although all the organisms were phagocytosed. However, when the same strains were added unopsonised to a PMNL-serum mixture, eight were killed after phagocytosis. With two of these strains, the amount of killing was inversely proportional to the time of pre-oposonisation. E. coli incubated for 30 min in dilute peptone water in Hanks's Balanced Salts Solution before phagocytosis also became resistant to killing; bacterial division did not occur during this period. Experiments with bacteria in urine confirmed these findings and showed that E. coli exposed to serum or urine before phagocytosis became resistant to killing by PMNL. E. coli rapidly changes its sensitivity to phagolysosome killing during transition from stationary to lag phase in a nutrient medium. This resistance is retained through the exponential phase but is lost during the stationary phase. The killing of Pseudomonas, Enterobacter, and Acinetobacter by PMNL was unaffected by varying the method of opsonisation or the phase of growth. If this phenomenon occurs in vivo it may affect the outcome of infections caused by strains of E. coli that survive killing by PMNL.

Effect of bacterial products including endotoxin on neutrophil function in infected urine.

Experiments were performed to determine the effects of products of bacterial growth (including endotoxin) on phagocytosis and intracellular killing by polymorphonuclear leucocytes (PMNL) in urine. Bacteriologically filtered supernates of two strains of Escherichia coli grown in urine were added in varying amounts to mixtures of PMNL and E. coli, also in urine. Phagocytosis of the two strains was reduced from > 90% in controls to 66% and 48%, respectively, in the presence of undiluted culture filtrate (containing endotoxin 2-2.5 micrograms/ml). Intracellular killing was also decreased and was abolished by dilutions corresponding to endotoxin concentrations of 0.6 and 0.75 micrograms/ml. When PMNL exposed to these inhibitory dilutions were resuspended in fresh urine, their phagocytic ability was fully restored and 13-24% of their killing activity was regained. A minimum concentration of commercially purified E. coli endotoxin of 200 micrograms/ml was required to abolished PMNL killing, with phagocytosis uninhibited. The results strongly suggest that bacterial growth metabolites, not endotoxin, are responsible for the depression of phagocytosis and intracellular killing in infected urine. A moderate dilution of the bacterial products in urine permits good PMNL function. Extrapolating this to the clinical situation, diluting the urine by water loading (as recommended for patients with urinary infections) should ensure efficient activity of PMNL under in-vivo conditions providing urinary pH and osmolality are not adversely affected.

Spontaneous thoracic spinal cord herniation. A case report.

STUDY DESIGN: This is a case report. OBJECTIVE: To focus attention on spontaneous spinal cord herniation as a rare cause of myelopathy that can be diagnosed preoperatively and can be corrected surgically. SUMMARY OF BACKGROUND DATA: A 34-year-old woman presented with spastic paraparesis. Magnetic resonance imaging scan of the thoracic spine revealed anterior displacement and tethering of the cord at T6-T7 and a dorsal intradural arachnoid cyst. Excision of the cyst was performed without improvement in symptomatology. During reoperation the thoracic spinal cord hernia was discovered and was reduced intradurally. METHODS: The authors describe the clinical, radiographic, and surgical findings of this patient and review the findings from other reported cases. They discuss the proposed theories for the pathophysiology of the cord herniation and the surgical management. RESULTS: The patient had idiopathic thoracic spinal cord herniation as there was no history of previous spine surgery or injury. The authors believe that the cord herniated through a congenital dural defect, which resulted in the development of a pseudoarachnoid cyst dorsally to the hernia. The patient improved after intradural reduction of the hernia and closure of the dural defect. CONCLUSION: Idiopathic spinal cord herniation should be recognized as a cause of progressive myelopathy that can be managed successfully with microsurgical techniques.

The use of erythromycin as prophylaxis in chronic bronchitis: a cohort study from general practice.

A cohort of patients with chronic bronchitis were invited to take erythromycin prophylactically to reduce the number of exacerbations of their disease. The cohort was followed for three years. The bacteriological nature of the exacerbation together with the patient acceptability were recorded.

Nursing management of the patient with meningeal carcinomatosis.

The care of the patient with meningeal carcinomatosis is not unlike the care of any other patient. Despite varying symptomatology, the nurse views the patient holistically. The nurse helps the patient and family adjust to a disease process which at present, shows a gradual deterioration of function even with current therapy.

Rapid screening for urease inhibitors.

Two methods are described that are suitable for the rapid screening of compounds as urease inhibitors. The first utilizes an electrode sensitive to NH4+ ions; the second is dependent on pH rise. A feature of both is a direct readout of reaction rate.

Opsonophagocytosis in infected urine: relation to pH and osmolality.

Polymorphonuclear neutrophils (PMN) in freshly voided urines from 20 symptomatic bacteriuric patients were examined. Although the PMN were viable (median 85%), in only 2 cases could phagocytosis of the infecting organisms be demonstrated, even after the addition of serum opsonins. Polymorphonuclear neutrophils from urines of 12 patients were also unable to phagocytose added opsonized Staphylococcus aureus. These urines were found to be of pH < 6.0 and/or osmolality > 700, or < 180 mOsm. However, the phagocytic function of these PMN was restored when transferred to Hanks balanced salt solution (HBSS). By contrast, most PMN in urines of suitable pH (> or = 6.0) and osmolality (between 200 to 700 mOsm.) phagocytosed the opsonized S. aureus. When bacteria cultured from the infected urine were incubated in the same urine and then transferred to HBSS, in 17 of 19 cases opsonization occurred and the organisms were phagocytosed when PMN, isolated from blood, were added. IgG appeared to be the prime opsonin in the urines, and heat-stable opsonins for S. aureus were also present. It is concluded that lack of opsonization is not a major cause of the absence of phagocytosis by urinary PMN. Low pH and adverse osmolality are largely responsible, correction of which may restore PMN function in vivo.

Effect of alkalinisation and increased fluid intake on bacterial phagocytosis and killing in urine.

The effect of alkalinisation and increased fluid intake on bacterial phagocytosis and killing in urine was studied. Phagocytosis of Escherichia coli and Staphylococcus saprophyticus by polymorphonuclear neutrophils (PMN) took place in only one of three first voided early morning urine samples from volunteers, and no bacterial killing occurred. This was attributed to the high osmolality (690 to 720 mOsm) and low pH of the early morning urine; two samples were pH 5.8 and the third, in which phagocytosis occurred, was pH 6.4. Afternoon urine samples from the same volunteers had lower osmolality and a higher pH, with a high rate of phagocytosis (> or = 88%) and 55-69% killing. PMN remained viable (mean 94%) after exposure for 1 h to both early morning and afternoon urine. Volunteers taking 4 g sodium citrate showed a mean rise of urinary pH of 1 unit. Water loading in patients with urinary tract infections produced a bacteria to neutrophil ratio conducive to bacterial killing, bacterial counts being reduced by a mean of 2.5 logs after 1-3 h without a corresponding reduction in neutrophils. Thus, raising the pH and reducing the osmolality of urine increases the ability of neutrophils to eliminate infecting organisms.

Effect of pH and osmolality on in vitro phagocytosis and killing by neutrophils in urine.

Phagocytosis and intracellular killing of two strains of Escherichia coli and a Staphylococcus saprophyticus by polymorphonuclear neutrophils (PMN) in pooled sterile urine at three osmolalities (800, 485, and 200 mosM/kg of H2O) between pHs 5 and 8 was investigated. Urine at 800 mosM virtually abolished phagocytosis of both E. coli strains, regardless of pH, and reduced the phagocytosis of S. saprophyticus to 30%; no killing of any organisms took place at this osmolality. On the other hand, phagocytosis was a good in urine as in Hanks balanced salt solution at both 485 and 200 mosM between pHs 6 and 8. Phagocytosis of all three strains was virtually abolished at pH 5. Killing of the strains by PMN was optimal between pHs 6.5 and 7.5 in urine at 485 mosM (being at least 90% of the control values in Hanks balanced salt solution), whereas at 200 mosM killing was reduced to 50 to 70% of these values. Reduced killing of all three strains occurred at pH 8, whereas at pH 6 only S. saprophyticus was killed. Thus, the bactericidal activity of PMN in urine was more sensitive than phagocytic function to alterations in pH. The dominant modulating factor affecting PMN function in urine of 500 mosM or less was pH, but osmolality had a greater influence at 800 mosM. Thus, raising the pH of urine and reducing the osmolality may increase the ability of natural defense mechanisms to eliminate infecting organisms.

Antibody-coated bacteria in urine: criterion for a positive test and its value in defining a higher risk of treatment failure.

Midstream urines from 237 patients with significant bacteriuria were examined for antibody-coated bacteria (ACB): 113 urines gave a positive result. When more than 25 000 organisms from the ACB-positive urines were scanned either fewer than 100 or more than 250 fluorescent bacteria (ie, greater than 1%) were found: thus the distribution of the fluorescent bacteria was bimodal. To compare the effectiveness of therapy in patients with ACB-positive and ACB-negative bacteriuria, 120 randomly selected patients were given a 7-day course of appropriate therapy. The results were assessed after 6 weeks. In 66 ACB-negative patients the cure rate was 84.8%, which was not significantly different from that found in 26 patients (80.7%) whose urine contained ACB in small numbers (less than 1%). In contrast, in 28 patients whose urine contained greater than 1% ACB the cure rate was only 36%. There was no correlation between the immunoglobulin class coating the bacteria and the response to treatment. The presence of greater than 1% ACB in the midstream urine thus identifies patients who are at high risk of treatment failure.

Periurethral enterobacterial carriage preceding urinary infection.

The periurethral enterobacterial flora was identified before infective episodes in 56 patients with recurrent urinary infection. There were 91 episodes of infection, with colonisation by aerobic gram-negative bacilli in 60. In only 31 (34%) episodes were patients colonised with the infective strain. In 31 episodes there was no colonisation of the perineum and in 29 there was heterologous colonisation. In another group of 54 women investigated during an enterobacterial infection of the urine there was colonisation with the infecting organism in 55 (86%) of 64 episodes; in 2 there was no colonisation; and 7 (11%) were associated with a heterologous strain. Women who have recurrent urinary infections are susceptible to perineal and periurethral colonisation with gram-negative bacteria but the infection need not be with the colonising enterobacteria.

A clinical comparison between Macrodantin and trimethoprim for prophylaxis in women with recurrent urinary infections.

Seventy-two patients with a history of at least three attacks of urinary infection in the previous 12 months were assigned randomly to long-term prophylaxis with 100 mg at night of either Macrodantin (34 patients) or trimethoprim (38 patients). The mean interval between symptomatic attacks while on either treatment was increased three-fold compared with the pretreatment period. Macrodantin was significantly more effective (P less than 0.05) at preventing bacteriuria. Prophylaxis was equally effective in patients with and without a radiological abnormality. Side effects were significantly more common (P less than 0.05) in the group taking Macrodantin. In patients taking trimethoprim acquisition of resistance by faecal coliforms occurred at a rate of about 5%/month, and breakthrough infections were almost exclusively caused by trimethoprim-resistant coliforms. No acquisition of resistance occurred in patients taking Macrodantin, and the few breakthrough infections noted were due to sensitive bacteria.

Comparative trial of trimethoprim and co-trimoxazole in recurrent urinary infections.

Eighty-nine patients with a history of recurrent urinary infection who required immediate treatment for significant bacteriuria were treated with either trimethoprim (300 mg at night) or with the standard course of co-trimoxazole (two tablets 12-hourly) for seven days. Cure rates one week after the end of treatment were 74.4% and 80.4%, respectively. During the following month the relapse rate was lower in the group given trimethoprim than among those who had received co-trimoxazole. Consequently, the cure rates six weeks after the start of treatment were 71.4% in the trimethoprim group and 58.5% in the co-trimoxazole group. These results suggest that in this type of patient, it may be possible to reduce the incidence of bacteriological relapse by giving antibiotics in larger doses and at less frequent intervals than are at present generally recommended.