Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis

Eight adult patients without peritonitis maintained on chronic ambulatory peritoneal dialysis (CAPD) were administered a single oral dose of 320 mg trimethoprim (TMP) and 1600 mg sulfamethoxazole (SMX) to characterize the pharmacokinetics of TMP and SMX. Ten blood samples were drawn following the dose. TMP and SMX-active (SMXA) concentrations were quantified in serum and dialysate. The half-life of TMP and SMXA determined by model independent methods were 33.7 +/- 10.5 h (mean +/- SD) and 13.8 +/- 2.2 h respectively. Total body clearance of TMP was 32.8 +/- 10.1 ml/min and SMXA was 21.9 +/- 6.4 ml/min. CAPD clearance of TMP was 2.27 +/- 0.81 ml/min and SMXA was 1.72 +/- 0.93 ml/min. The average peritoneal dialysate concentrations over the 72-hour collection period of TMP and SMXA were 0.9 +/- 0.1 mg/l and 5.3 +/- 0.8 mg/l respectively. A dose of 320 mg TMP and 1600 mg SMX every 48 hours is recommended for CAPD patients with mild to moderate systemic infections.     

Toxoplasma gondii primary infection in renal transplant recipients. Two case reports and literature review

Toxoplasmosis after solid organ transplantation is a complication associated with high morbidity and mortality. Universal prophylaxis with trimethoprim–sulfamethoxazole (TMP‐SMX) is effective to prevent post‐transplant toxoplasmosis. We report two cases of renal transplant recipients with negative antibodies against Toxoplasma gondii pretransplant who developed toxoplasmosis after TMP‐SMX discontinuation. We have also performed a review of published cases of primary toxoplasmosis after renal transplantation. Of 20 cases reviewed, 11 were male and the mean age was 37.8 years (SD = 13.8). Donor serology for T. gondii was determined in 15 donors, two of them (13%) with negative immunoglobulin (Ig)G and four (27%) with positive IgG and IgM antibodies. Fever was present in 85% of primary toxoplasmosis and hematologic abnormalities were observed in 69% of the cases. Ten patients died (50%). All patients with fatal outcomes had clinical evidence of toxoplasmosis during the early post‐transplant period (first 90 days), while no patient with late toxoplasmosis died (P = 0.003). Primary toxoplasmosis is associated with high mortality rates and TMP‐SMX prophylaxis can delay the onset of symptoms resulting in an improvement of prognosis.     

Current therapy of acute uncomplicated cystitis

Acute uncomplicated cystitis (AUC) is one of the most common bacterial urinary tract infections. AUC frequently occurs in young sexually active, as well as postmenopausal, women. According to the guidelines published by the Infectious Diseases Society of America in 1999, the standard antimicrobial regimen for treatment of AUC is 3 days with trimethoprim–sulfamethoxazole (TMP/SMX); however, today the most popular antibiotics are the fluoroquinolones because of the emergence of uropathogens that are resistant to TMP/SMX. Fluoroquinolone resistance is also increasing worldwide, although the resistance rates have not been as high as those for TMP/SMX. Extended‐spectrum β‐lactamase (ESBL)‐producing strains are another problem because most nosocomial ESBL producers are also resistant to non‐β‐lactams, such as the fluoroquinolones. Under such circumstances, 3 days of therapy with fluoroquinolones or 7 days with β‐lactams is recommended for empirical therapy, although these regimens should be re‐evaluated in the next decade. Low‐dose fluoroquinolones should no longer be used because of the potential for emergence of resistance.     

Chemotherapy of acute bone and joint infections.

A series of 72 cases of acute osteomyelitis and acute septic arthritis has been presented. Operative intervention was necessary in 71% of our cases. All patients were treated with antibiotics. The initial antibiotic treatment in 39% of the cases was a combination of trimethoprim and sulfamethoxazole (TMP/SMX). This combination gave the lowest average time for subsidence of general symptoms and local signs. Staphylococcus aureus was the causative organism in 87% of our cases. Streptococcus pyogenes and Pneumococcus were the other causative organisms. Over half of the S. aureus infections were resistant to penicillin but none were resistant to TMP/SMX. Considering the low toxicity, good clinical response, lack of bacterial resistance, presence of synergy and broad antibacterial spectrum, the use of TMP/SMX is recommended in acute pyogenic bone and joint infections.     

The use of donor and recipient screening for toxoplasma in the era of universal trimethoprim sulfamethoxazole prophylaxis

BACKGROUND: Toxoplasmosis is a serious complication of solid organ transplantation. The highest risk of infection and disease occurs in heart recipients with primary infection transmitted by a seropositive donor to a seronegative recipient (donor-recipient mismatch). Toxoplasmosis has been reported to occur in noncardiac transplant recipients; however, no large studies examining the frequency of such events or the need for serologic screening exist. METHODS: A retrospective cohort study of 1,006 solid organ transplant recipients transplanted in our center between 1984 and 1997 was performed to examine the incidence of Toxoplasma seroconversion, reactivation, and clinical toxoplasmosis and to evaluate the impact of trimethoprim sulfamethoxazole (TMP/SMX) prophylaxis on these outcomes. RESULTS: Pretransplant Toxoplasma seroprevalence was 13.4% in donors and 17.8% in recipients. The incidence of Toxoplasma donor-recipient mismatch was 9.5% during the 14-year study period, and only 39.1% of mismatched recipients received TMP/SMX prophylaxis. Only four patients seroconverted, of whom two had received prophylaxis. There were no cases of clinical disease; either primary or reactivation. CONCLUSIONS: We therefore conclude that in transplant centers with low Toxoplasma seroprevalence, routine screening for Toxoplasma in solid organ donors and recipients is not necessary, particularly in the era of routine TMP/SMX prophylaxis.     

Nocardia infection in lung transplant recipients

Nocardia is a well-recognized pathogen in immunocompromised hosts, but the incidence of Nocardia infections in lung transplant recipients is not well defined. A chart review from 1990 to 2007 at Clarian Hospital Lung Transplant Center and Indiana University Medical Center revealed Nocardia infections in four of 410 lung transplant recipients despite prophylaxis. All infections were confined to lung and occurred at a median time of 315 d after transplantation. Nocardia nova was isolated in two patients, Nocardia farcinica in one, and unspecified Nocardia sp. in one. Nocardia isolates were susceptible to trimethoprim sulfa (TMP/SMX). Our data suggest that the dose of TMP/SMX, commonly used for Pneumocystis prophylaxis is not protective for Nocardia. Contrary to historic data reporting 40% mortality, none of the patients in our study died because of Nocardia. Nocardia infection is an under-recognized entity in lung transplant recipients, and the optimal duration of therapy and prophylaxis are unclear.     

Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole

BACKGROUND: The efficacy of trimethoprim-sulfamethoxazole (TMP/SMX) in the prevention of toxoplasmosis after orthotopic cardiac transplantation has been the subject of some controversy, with many transplant groups preferring to use the combination of pyrimethamine and sulfadiazine. Although effective, this latter regimen does not offer equal protection against other pathogens, such as or. To assess the value of TMP/SMX, we reviewed the experience in our heart transplant patients, all of whom received TMP/SMX (160/800 mg) three times weekly for approximately 8 months after transplantation. METHODS: We report on 417 orthotopic cardiac transplants during a 17-year period. We have 100% one-year patient follow-up after transplantation. Data was collected on pretransplantation donor and recipient anti- serology, immunosuppression, allograft rejection, survival, yearly posttransplantation anti- serology, development of acute toxoplasmosis, and the occurrence of other infections. RESULTS: In this cohort, acute toxoplasmosis developed after transplantation in one case (0.2%). Among the highest risk patients (D+R-) who were treated for at least one episode of rejection, the risk of acute toxoplasmosis was 5% (1 of 22 patients). No change in survival was found between the different anti- IgG serogroups (D-R-, D-R+, D+R-, or D+R+). Anti- IgG seroconversion occurred in eight -seronegative recipients after transplantation; all patients, except the case already noted, were asymptomatic and required no specific anti- therapy. No cases of, or infections were identified. Five proven and two suspected cases of pneumonia were found (only 2 of these 7 patients were receiving TMP/SMX at the time of pneumonia diagnosis). CONCLUSIONS: These data demonstrate that TMP/SMX prophylaxis (160/800 mg) three times per week is effective prophylaxis after orthotopic cardiac transplantation and has prophylactic benefits against other posttransplantation opportunistic pathogens.     

Incidence of urinary tract infections caused by germs resistant to antibiotics commonly used after renal transplantation

BACKGROUND: The inadequate utilization of antibiotics is responsible for the development of urinary tract infections (UTI) after renal transplantation (RT), through the induction of resistance to the antibiotics themselves. The purpose of this study was to evaluate the incidence of resistance to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), routinely used for surgical perioperative prophylaxis and prevention of Pneumocystis carinii, respectively. MATERIALS AND METHODS: We enrolled all adult patients having received an RT from 2001 to 2006 and having a minimum follow-up of 6 months. Urine cultures (UC) were routinely performed at every outpatient clinic control and whenever required by the onset of significant clinical signs/symptoms. UTI was diagnosed by the presence of a positive UC. The endpoint of the study was the emergence of bacterial strains resistant to either CEF or TMP/SMX. RESULTS: We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9+/-523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. When gram-negative bacteria were considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were available in about only 7 gram-positive infections (5/7, 71%). CEF was tested less frequently with 21/43 (49%) germs resistant to this molecule. CONCLUSIONS: The onset of bacterial resistance to either TMP/SMX or CEF is frequent after RT. A wiser stricter utilization of antibiotics is mandatory. Standard antibiotic protocols should be revised.     

Isolation of Stenotrophomonas maltophilia in asymptomatic lung transplant recipients: effects of treatment on eradication and outcome

In this retrospective, single‐center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log‐rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome.     

Antibiotic prophylaxis by low-dose cefaclor in children with vesicoureteral reflux

Sulfamethoxazole/trimethoprim (SMX/TMP) and nitrofurantoin are the most frequently used agents for prophylaxis to reduce the risk of recurrent urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR). Nitrofurantoin, however, is not available in Japan and increasing resistance of organisms to SMX/TMP has recently raised doubts about its effectiveness as a prophylactic agent. This study was conducted to investigate whether antibiotic prophylaxis using low-dose cefaclor can effectively reduce the risk of recurrent UTIs. Thirty-nine children (31 male, 8 female) with primary VUR were enrolled. Ages varied from 0.5 to 111 months (mean 10.6 months). A prophylactic dose of 5-10 mg cefaclor per kg per day was given 1-3 times daily depending on the patient's age. Mean duration of prophylactic treatment was 15.5 months. Eleven children (ten male, one female) developed breakthrough UTIs during a total of 606 months treatment (or about one further infection in 55 months). Resistance to cefaclor was noted in three organisms: Enterococcus spp., Morganella spp., and Pseudomonas spp. Evidence of antibacterial activity was present in the morning urine samples from all of seven children tested. Cefaclor was well accepted and tolerated by all subjects. None withdrew from the study because of side effects. These results suggest that cefaclor can be an alternative choice for prophylactic treatment because of its safety, good compliance and low rates of resistant Escherichia coli.     

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children.

BACKGROUND: Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. OBJECTIVE: To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children. METHODS: A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. RESULTS: Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively. CONCLUSION: Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.     

Prophylactic co-trimoxazole and trimethoprim in the management of urinary tract infection in children

In a prospective study of low-dose antibacterial prophylaxis of childhood urinary tract infection (UTI), co-trimoxazole and trimethoprim (TMP) have been compared for efficacy in preventing UTI, for their effect on the rectal flora and for secular selection of TMP-resistant organisms.Between 1979 and 1986, 334 children who had proven infection of an unobstructed urinary tract complied in a regimen of low-dose prophylaxis together with measures to eliminate residual urine for at least 6 months. Of these children, 167 had vesico-ureteric reflux and 27 had renal scarring. There was no difference between the two drugs in compliance, which was very good, or in the occurrence of side-effects, which were minimal. Recurrence rates of further infection were 1 per 22 child years for the 226 children receiving cotrimoxazole and 1 per 18 child years for the 108 receiving TMP. All but one of these urinary pathogens were resistant to TMP and reinfection of the urinary tract generally occurred following lapses in attention to complete bladder emptying. Neither a secular increase in recurrent infections during this period, nor a significant change in the proportions of TMP-resistant faecal coliform organisms, was observed. TMP and co-trimoxazole appeared to be equally effective prophylactic agents.     

Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim‐sulfamethoxazole (TMP‐SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO₂ < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β‐d ‐glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP‐SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6‐12 months post–transplant, preferably with TMP‐SMX.     

Management of urinary tract infections: historical perspective and current strategies: Part 2--Modern management

PURPOSE: An understanding of the microbial origin of infectious diseases and the introduction of antimicrobial therapy stimulated more advances in the management of urinary tract infections (UTIs) in the 20th century than had occurred in the previous 5 centuries. MATERIALS AND METHODS: Numerous resources were used to collect the information described in this review. Medical texts from the 19th and 20th century contain information regarding the traditional contemporary treatment of UTI during those eras. Early volumes of the Journal of Urology from the beginning of the 20th century describe the first attempts at chemotherapy for UTI. MEDLINE searches were used to collect appropriate information after 1969. Modern medical journals and modern medical texts were used to collect information on antimicrobial therapy since the late 1960s through today. RESULTS: Numerous advances in the diagnosis and management of UTI were made during the 20th century. Advances in microbiological and chemical assays have facilitated the development of historical uroscopy into modern day urinalysis and culture techniques, which are the cornerstone of UTI diagnosis. Imaging technologies, including x-ray, ultrasound, nuclear imaging, magnetic resonance and computerized tomography, have been particularly helpful in the diagnosis of complicated or recurrent UTIs. Major innovations in nonpharmacological therapy include noninvasive shock wave lithotripsy and percutaneous drainage of kidney abscesses. The most profound advance in UTI management during the 20th century was the discovery of antimicrobial agents. Nitrofurantoin was the first truly effective and safe antimicrobial therapy for UTI but its spectrum of activity is limited. Broad use of amoxicillin (and other beta-lactams) after its introduction in the 1970s led to the development of resistance to this antimicrobial, prompting a gradual change to trimethoprim/sulfamethoxazole (TMP/SMX) as first line therapy for UTI. However, wide use of TMP/SMX also resulted in the progressive emergence of resistance, limiting the clinical usefulness of this therapy in the modern management of UTI. Fluoroquinolones offer an attractive alternative to TMP/SMX, and American and European guidelines recommend their empirical use in areas where TMP/SMX resistance is 10% or higher. CONCLUSIONS: The development of antimicrobial therapy was the defining moment of 20th century medicine and one of the key innovations in medical history. While the initial promise of antimicrobials has been validated in clinical practice, overuse of certain agents has led to the emergence of resistance, illustrating the importance of using evidence based strategies to select therapy.     

Lysosomal enzyme levels and tumor growth in steroid-treated rat model

Elevations in lysosomal enzyme levels have been shown to correlate with tumor progression or metastasis. Furthermore, evidence suggests that liberation of lysosomal enzymes may affect tumor growth patterns, immunologic responses, and development of cachexia in the host. As glucocorticoids are known to stabilize lysosomal membranes, as well as to produce significant effects in overall cellular metabolism and growth, effects of methylprednisolone acetate (MPA) on lysosomal enzymes and tumor growth were studied using a nonmetastasizing mammary carcinoma model. Fischer 344 rats (N = 41) were randomly divided into six groups: control (C), tumor (T), rats steroid-treated for 2 weeks prior to sacrifice (MP₂), or those given a single steroid dose 2 days before sacrifice (MP), and animals with tumor given steroids in a single dose (TMP), or for 2 weeks (TMP₂). At the time of sacrifice, carcass, liver, and tumor weights were calculated: samples of plasma, muscle, liver, and tumor were assayed for cathepsin D, a proteolytic lysosomal enzyme. With prolonged MPA treatment (TMP₂), as compared to groups T and TMP, significant reduction in tumor size was noted. Lysosomal enzymes in liver and muscle were increased with either MPA therapy or tumor, except in group TMP₂, where liver and muscle cathepsin D was markedly decreased. While elevation in cathepsin levels resulted from steroid treatment in nontumor rats, reduction in tumor size and concomitant decline in cathepsin D levels in rats with tumor implicate lysosomes as indicators of tumor regression, and suggest a role of lysosomal enzymes in host-tumor interaction.     

Effect of prostaglandin E1 (PGE1) and sildenafil on serotonin metabolism and some oxidative damage markers in rat prostate gland and brain

The aim of this study was to evaluate the effect of sildenafil and prostaglandin E1 (PGE1) (drugs used in erectile dysfunction) on production of free radicals in prostate and brain of rat. A single dose of sildenafil (10 mg kg(-1) ) and PGE1 (20 μg kg(-1) ) was given to Sprague-Dawley rats (300 g weight) intraperitoneally. The levels of testosterone were measured in blood. Their brains and prostate glands were separated to measure lipid peroxidation, Na(+) and K(+) ATPase activity, reduced glutathione (GSH) and serotonin levels, by means of validated methods. The levels of testosterone increased slightly in animals treated with sildenafil and PGE1. The activity of total ATPase was increased in the prostate of animals treated with sildenafil + PGE1 but decreased in those that received sildenafil alone. PGE1 caused significant diminution of GSH levels in both organs. Sildenafil increased the levels of serotonine in brain, whereas in prostate they decreased instead. Our results suggest that sildenafil induced changes in GSH levels as well as in the serotonergic metabolism, alone or with PGE1 in prostate and brain, respectively. Thus, the combination therapy may be ideal to sustain the biochemical balance due to biphasic stimulation on brain and prostate.     

Comparative study of zinc levels in benign and malignant lesions of the prostate

OBJECTIVES: The normal human prostate accumulates the highest levels of zinc of any soft tissue in the body. The presence of zinc in the prostate of a number of mammalian species, including rhesus monkeys and humans, has been well documented. The aims of this study were to investigate the concentrations of zinc in various disorders of the prostate and to find a correlation between them. MATERIAL AND METHODS: A total of 80 cases were studied (20 normal, 50 benign, 10 carcinomatous). A plasma sample was taken and zinc levels were analyzed using atomic absorption spectrophotometry. RESULTS: The mean (+/-SD) plasma zinc level in the normal cases was 94.5+/-10.38 microg/100 ml. Amongst patients with benign diseases of the prostate gland, the plasma zinc level was 145.4+/-9.67, 162.4+/-2.22 and 172.7+/-5.27 microg/100 ml (78% rise compared to normal patients) in those with a fibromuscular prostate, chronic prostatitis and benign prostatic hyperplasia, respectively, whilst patients with malignancy had a plasma zinc level of 59.6+/-3.08 microg/100 ml (37% fall compared to normal patients). There was a highly statistically significant (p < 0.01) difference in plasma zinc levels between patients with benign and malignant prostate diseases. The effect of metastasis of carcinoma of the prostate on plasma zinc levels was not significant (p > 0.05), while there was a highly statistically significant (p < 0.01) correlation between serum prostate-specific antigen and plasma zinc levels in malignancy. CONCLUSIONS: There appears to be a strong correlation between plasma zinc levels and various prostatic diseases. Therefore, the determination of zinc levels can be used as a diagnostic or screening tool and may lead to the formulation of methods in which zinc is used to evaluate prostatic pathology.     

Implications of circulating chromogranin A in prostate cancer

OBJECTIVE: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. MATERIAL AND METHODS: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. RESULTS: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). CONCLUSIONS: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.     

Modulation of rat prostatic inhibinlike peptide (PIP) by steroids and protein hormones

Prostatic inhibinlike peptide (PIP) was detected in the ventral but not in the dorsal lobe of rat prostate. On orchiectomy, PIP concentration in the ventral prostate increased significantly, whereas it decreased on testosterone administration and attained value comparable with that in intact control. Estradiol-17 beta treated animals exhibited high levels of PIP in absence of significant alterations in the protein content. The effect of prolactin and human chorionic gonadotropin on PIP concentration was not so prominent at the dose levels studied. The present study thus demonstrates negative regulation of PIP by testosterone and stimulatory effect of estradiol-17 beta on PIP in rat ventral prostrate.     

The effect of different doses of nasal salmon calcitonin on plasma cyclic AMP and serum ionized calcium

Summary To investigate the effect of low doses of intranasal salmon calcitonin on plasma cyclic AMP (cAMP) and serum ionized calcium, 40 healthy postmenopausal women were randomized to receive a single dose of either placebo or 50, 100, or 200 IU of salmon calcitonin as a nasal spray. Blood samples were collected throughout an 8-hour period. None of the doses could provoke detectable hypocalcemia, whereas 100 and 200 IU of salmon calcitonin were associated with an increase in plasma cAMP after 15 minutes. Measurable plasma levels of salmon calcitonin were demonstrated in all active treatment groups, and the calculated areas under the curves showed a dose-dependent increase.