Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs

Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.     

Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin three different parenteral administrations compared in 30 arthroplasties

• (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
• (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
• (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
• (iv) Large inter-individual variation in bone concentration was observed.
• (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.

     

Net postprandial utilization of [15N]-labeled milk protein nitrogen is influenced by diet composition in humans

The aim of this study was to follow the fate of dietary nitrogen to assess the postprandial utilization of purified milk protein and to determine the acute influence of energy nutrients. For this purpose, a [15N]-labeling dietary protein approach was used. Twenty-five subjects swallowed an ileal tube and ingested [15 N]-milk protein alone or supplemented with either milk fat or sucrose. The absorption and postprandial deamination of dietary protein was monitored for 8 h. Sucrose delayed the absorption of protein longer than fat, but the ileal digestibility did not differ among groups (94.5-94.8%). Sucrose, but not fat, significantly reduced the postprandial transfer of [15N]-milk nitrogen to urea. Consequently, the net postprandial protein utilization (NPPU) of milk protein calculated 8 h after meal ingestion was 80% when ingested either alone or supplemented with fat and was significantly greater with sucrose (NPPU = 85%). This study shows that energy nutrients do not affect the nitrogen absorption but modify the metabolic utilization of dietary protein in the phase of nitrogen gain. Our method provides information concerning the deamination kinetics of dietary amino acids and further allows the detection of differences of dietary protein utilization in acute conditions. The diet composition should be carefully considered, and protein quality must be determined under optimal conditions of utilization.     

Impact of graft ischemic time on outcomes after bilateral sequential single-lung transplantation

Background. Graft ischemic time (GIT) is a potential limiting factor in lung transplantation.

Methods. Seventy-four patients who underwent bilateral sequential single-lung transplantation were divided into three groups: group I, GIT less than 5 hours (n = 20); group II, GIT between 5 and 8 hours (n = 39); and group III, GIT more than 8 hours (n = 15). We compared early allograft function (ratio of arterial oxygen tension to inspired oxygen fraction and alveolar–arterial oxygen gradient), blood loss, the need for tracheostomy, the duration of ventilation, intensive care unit stay, and hospital stay. We also compared prevalences of acute and chronic rejection, airway complications, lung function test, and 2-year survival.

Results. Early allograft function in group III was significantly worse than those in groups I and II. However, there was no significant difference in any other variables of early and medium-term outcomes among the three groups. No significant correlation was detected between GIT and duration of intensive care unit stay or hospital stay.

Conclusions. The limitation of acceptable GIT could be extended from the traditionally approved 4 to 5 hours, to 5 to 8 hours or even longer.     

The management of urinary candidiasis in cystectomized patients

Presentation of eight cases of urinary candidiasis in patients who underwent radical cystectomy and were managed using by-pass of the urinary tract, oral antifungal therapy and solutions in the way of intermittent instillation through nephrostomy catheters.     

Trigonocervicoprostatomy. Indications and results from 100 case reports

Trigonocervicotomy is a barely invasive technique for the treatment of infravesical obstruction, first introduced in the 60's by Turner-Warkic and Orandi. To achieve good results with this procedure, the selection criteria must take into account a series of parameters such as age, sexual activity, PSA, prostate weight (below 30 grams) and others. In addition to its low morbidity, a larger percentage of patients preserve ejaculation than with the use of other techniques, also the neck sclerosis rate being lower as seen in all our series and expertise. The efficacy of this technique was studied on 100 patients.     

Complications of Penile Lengthening and Augmentation Seen at 1 Referral Center

Purpose

Complications of the recent cosmetic technique of penile lengthening and girth enhancement are reviewed.

Materials and Methods

During a 16-month period 12 men presented with complications of penile augmentation performed elsewhere. All 12 patients had undergone release of the suspensory ligament and 10 had received autologous fat injection.

Results

the chief complaint was poor cosmetic appearance (irregular residual fat nodules in 7 men, skin deformity and scarring in 4 and scrotalization in 4). Reoperation was necessary in 6 patients, wound complications occurred in 6 and sexual dysfunction was reported by 4. Only 1 patient reported a subjective increase in penile length.

Conclusions

Although a verifiable complication rate may never by available, the morbidity of elective penile lengthening and girth enhancement is noteworthy. These cosmetic techniques should be regarded as experimental.