Plasma and soft tissue pharmacokinetics of ceftolozane/tazobactam in healthy volunteers after single and multiple intravenous infusion: a microdialysis study.

OBJECTIVES: To investigate ceftolozane/tazobactam pharmacokinetics (PK) in plasma and interstitial space fluid (ISF) of muscle and subcutaneous tissue and establish a population PK model. METHODS: Eight healthy volunteers received four IV doses of 1000/500 mg ceftolozane/tazobactam q8h in a prospective, open-labelled PK study. ISF concentration-time profiles were determined via in vivo microdialysis up to 8 h post-dose and efficacy of unbound ceftolozane and tazobactam was estimated using the time above MIC (%ƒT>MIC) and time above threshold concentration (%T>CT), respectively. A population PK model was established by merging derived plasma and soft tissue PK data. RESULTS: Ceftolozane reached %ƒT>MIC values of 100% in plasma, muscle and subcutaneous ISF for Enterobacteriaceae and 87%, 89% and 87%, respectively, for Pseudomonas aeruginosa. Tazobactam %T>CT was 21%, 22% and 21% in plasma, muscle and subcutaneous ISF, respectively. Plasma protein binding was 6.3% for ceftolozane and 8.0% for tazobactam. Multiple-dose ceftolozane AUC0-8 ISF/plasma ratios were 0.92 ±â€Š0.17 in muscle and 0.88 ±â€Š0.18 in subcutis, and tazobactam ratios were 0.89 ±â€Š0.25 in muscle and 0.87 ±â€Š0.21 in subcutis, suggesting substantial soft tissue penetration. CONCLUSIONS: Tazobactam %T>CT values were distinctly below proposed target values, indicating that tazobactam might be underdosed in the investigated drug combination. However, ISF/unbound plasma ratios of ceftolozane and tazobactam support their use in soft tissue infections. A plasma and soft tissue PK model adds important information on the PK profile of ceftolozane/tazobactam. Further investigations in patients suffering from wound infections are needed to confirm these findings.

Gonadotropins, testosterone and prolactin in men with abnormal semen findings and an evaluation of the hormone profile.

Over a 4-year period, 259 men were investigated regarding primary (86.5%) or secondary (13.5%) infertility. Men with azoospermia had significantly higher concentrations of FSH and LH and lower concentrations of testosterone than those with spermatozoa. High concentrations of FSH and LH in serum were found in case of low sperm density. Men with low testicular volume had high concentrations of FSH and LH and low concentrations of testosterone. FSH was closely correlated with LH and also with total testicular volume. A negative correlation was found between both gonadotropins and testosterone. The correlation between LH and testosterone was stronger in axoospermic men than in those with spermatozoa in semen. Serum concentrations of prolactin were higher in men with high sperm motility than among men with low motility of spermatozoa. Otherwise, prolactin concentrations were not correlated either with sperm density or with the morphology of spermatozoa or total testicular volume. A 'hormone profile' of FSH, LH and testosterone concentrations is suggested useful in the routine investigation of the infertile man, as more information is given by this profile than by FSH concentrations alone.

Diagnostic aspects of bladder angiography in urinary bladder tuberculosis.

Histopathological and angiographic findings were correlated in 6 cases of tuberculosis of the urinary bladder. The number of vessels was only slightly increased in the initial and fibrotic stages, whereas hypervascularization was observed in the exudative and productive stages. Otherwise the angiographic changes were nonspecific. Thus it was not possible to distinguish tuberculous cystitis from cystitis of other genesis, and in some instances from tumours of the urinary bladder either.

Bone marrow examination as a diagnostic tool in carcinoma of the prostate.

155 patients with a newly discovered carcinoma of the prostate were investigated for the presence of bone metastases. Straight X-ray (conventional X-ray) revealed such secondary in 38 cases and bone marrow examination in 20. Three patients with a normal X-ray picture nevertheless showed cancer cells on bone marrow examination. The authors consider bone marrow examination as a valuable complement to the routine invedtigation of the patients with carcinoma of the prostate.

Painful testicular lithiasis.

Testicular pain both acute and chronic is quite common and may result from many different diseases located both in and outside of the testis. Diffuse testicular microlithiasis is a rarely encountered problem in urology and up to now a unique sonographic appearance. We here report a case with combination of both signs and give a short review of the literature.

A prognostic score for subfertile men based on anamnestic data and semen variables.

Over a 4-year period, 259 men were investigated for primary (86%) or secondary (14%) infertility. Some 3-5 years after the initial investigation, 200 of these men were followed up and the conception rate of their partners assessed. Their age at investigation, total testicular volume, sperm density, sperm motility, percentage morphologically normal sperm and the duration of infertility all gave information about the prospects of conception. A stepwise discriminant analysis showed that the age of the men at investigation, sperm density, sperm motility and the duration of infertility all had a strong discriminant bearing on future conception. A score based on these four variables for the estimation of prognosis in 'subfertile' men has been devised and would seem to be clinically useful.

Translabial ultrasonography with pulsed colour-Doppler in the diagnosis of female urethral diverticula.

Urethral diverticulum in female can be easy to detect by physical examination but sometimes the diagnosis can be difficult. The classical radiographic diagnosis has traditionally been based on urethrography. Ultrasonographic approach is gaining more acceptance for the diagnosis of female diverticula. Transabdominal (1977), transrectal, transperineal and transvaginal techniques were described earlier. We here present a new and improved technique: i.e. the translabial ultrasonographic approach in combination with pulsed colour-doppler examination. An endovaginal 5 MHz probe was used. The transducer was placed directly against labia minora and the urethral orifice. The character of the diverticula and it's spatial relationship to the urethra could be described in 5 women. There was no need for other radiological examination preoperatively. The advantages of translabial sonographic technique are absence of ionizing radiation, reduced risk of infection, noninvasivity and comfortability. It is also a quick and reliable technique.

Translabial sonography in evaluating the lower female urogenital tract.

Transvaginal sonography has become an invaluable technique for examining the uterus, adnexa, and other nongynecologic structures in the pelvis because it provides better spatial resolution than transabdominal sonography [1]. Transvaginal sonography is a technique that complements manometric urodynamic examination by permitting a precise study of periurethral soft tissue. However, the principal disadvantage of transvaginal sonography is the distortion it provokes in vesicourethral anatomy [2]. Furthermore, transvaginal sonography cannot be used in small girls, virgins, and women with narrow vaginas, nor can it be used in assessing incontinence and other voiding dysfunctions because of direct effects on the physiology of the urinary tract caused by the probe itself [3]. Translabial sonography, which we have routinely used since 1990 [4], is an excellent alternative means of examination for these patients and for disorders of the lower urogenital tract. We have used translabial sonography in different types of incontinence. To learn more about the physiology of micturition, using translabial sonography, we let patients micturate not only in a recumbent position but also standing while straining and coughing. The latter position simulates a provocative cystometry. In this paper, we describe the translabial sonographic technique and some of the disorders we have encountered.

Spread of tuberculosis from obstructed and non-obstructed upper urinary tract.

As part of an experimental study of the spread of urogenital tuberculosis, male guinea pigs were inoculated with tubercle bacilli (H37Rv) in the upper part of the ureter. Half of the animals were prepared by ligature of the ureter below the injection site prior to inoculation. Spread of the infection to the lower urinary tract and the genitalia occurred whether the ureter was intact or ligated. It is concluded that lymphatic spread is possible and seems to be more common than urinary (canalicular) spread.

Conception rate for infertile couples. The importance of anamnesis and signs of genital disease in men with abnormal semen findings.

During a 4-year period, 259 men were investigated for primary (86%) or secondary (14%) infertility. Some 3-5 years after the initial investigation, a follow-up study of conception rate, was performed in 200 of these cases. Conception had occurred in 79 couples (39%). Sperm density was lower among men with a history of genital disease(s) than amongst men without such a history, but conception rate was not influenced by a positive history. Men with signs of genital disease(s) had lower sperm density, a smaller proportion of morphologically normal spermatozoa and lower sperm motility, than men with a normal finding at physical examination. Men with such signs had the same conception rate as men with normal physical findings. The only subgroup, in which conception rate was lower than in men with no physical abnormalities, was men with palpatory abnormal epididymis(des).

Angiography in urinary bladder tuberculosis.

Angiography was performed in 6 cases of bacteriologically and microscopically verified tuberculosis of the urinary bladder. As a rule, general or locally accentuated hypervascularization in the bladder wall could be demonstrated in the arterial phase but no venous abnormalities were observed. The circulation time was usually not changed. Thus the angiographic appearances were non-specific. Angiographically it is impossible to differentiate between tuberculous cystitis, cystitis of other genesis or even tumour of the bladder.

Experimental male genital tuberculosis-appraisal of protective value of BCG vaccination.

As part of an experimental study of the spread of urogenital tuberculosis, the development of tuberculous infection was compared in vaccinated and non-vaccinated guinea pigs after challenge with Mycobacterium tuberculosis strain H37Rv into the seminal vesicle. The animals were saccrified 35 days after challenge. Morphological observations indicate that tuberculous infection in an immunized animal is retarded, but spreads by the same routes as in an nonimmunized animal. On microbial enumeration significantly lower numbers of organisms were recovered from the inoculated seminal vesicle and regional iliac lymph nodes of the BCG-vaccinated guinea pigs.

Somatic chromosomal aberrations and male infertility.

A significant correlation was found between the frequency of chromosomally aberrant peripheral lymphocytes and a low frequency of morphologically normal spermatozoa in men. No correlation was found between increased chromosomal breakage, other sperm parameters and density, motility or agglutination of spermatozoa. Smokers had significantly more cells with aberrations than nonsmokers. The significance of induced lesions in peripheral lymphocytes and their relationship to reproduction was discussed.

Screening of patients with hereditary spastic paraparesis and Addison's disease for adrenoleukodystrophy/adrenomyeloneuropathy.

X-linked adrenoleukodystrophy/adrenomyeloneuropathy presents a wide variation of clinical manifestations and may mimic several diseases. A screening investigation by measuring plasma saturated very long-chain fatty acids was performed in two groups of patients. Among six patients with hereditary spastic paraparesis one woman was detected to be a heterozygous gene carrier. However, in a group of eleven adult men with idiopathic Addison's disease the plasma concentrations of very long-chain fatty acids were all within normal limits. We conclude that X-linked adrenoleukodystrophy and symptomatic heterozygous females should be considered in cases of progressive spastic paraparesis.

Carcinoma of the penis. Treatment by surgery or combined bleomycin and radiation therapy.

Forty-four patients with squamous cell carcinoma of the penis stage T1-T2, N0 were either treated surgically (n = 19) or with a combination of irradiation and bleomycin (n = 25). The overall actuarial survival rate was 80% at 3 years, 77% at 5 years and 60% at 10 years. The result of irradiation treatment combined with bleomycin was in stage N0 equivalent to that of surgical therapy. The non-surgical treatment had the advantage of preserved sexual ability.

Tamoxifen treatment of idiopathic oligozoospermia: effect on hCG-induced testicular steroidogenesis and semen variables.

The mechanisms behind the effects of antioestrogens on semen variables and steroidogenesis in patients with oligozoospermia are unknown. In order to further elucidate this, the steroidogenic response to acute hCG-stimulation was studied in patients with idiopathic oligozoospermia before and during treatment with the antioestrogen Tamoxifen. Also an evaluation of semen variables in these patients was performed. During Tamoxifen treatment serum concentrations of LH, FSH, progesterone, 17 alpha-progesterone, testosterone and oestradiol-17 beta increased whereas no effect was observed on prolactin and SHBG concentrations. A similar pattern in steroidogenic response to hCG-stimulation was observed before and during Tamoxifen treatment. Sperm density, motility and morphology all improved after Tamoxifen treatment. The present results are discussed in relation to the possible mechanism of action of antioestrogens in patients with oligozoospermia.

Non-cardiogenic pulmonary oedema. A serious complication of transurethral prostatectomy. A case report.

A patient undergoing prostatectomy under epidural analgesia developed clinical signs of a severe TURP syndrome. During resuscitation, it was revealed that serum sodium was only moderately decreased. Plasma oncotic pressure was, however, markedly decreased and the pressure gradient between plasma oncotic pressure and pulmonary capillary wedge pressure (approximately hydrostatic pressure) was 1 mmHg (0.13 kPa) only, allowing almost free filtration of fluid through the pulmonary capillary wall, resulting in a non-cardiogenic pulmonary edema. The patient was successfully resuscitated with albumin and inotropic stimulation with prenalterol.