N-Acetyl-L-γ-glutamyl Derivatives of p-Nitroaniline,Sulphamethoxazole and Sulphamethizole for Kidney-specific Drug Delivery in Rats

Kidney-specific delivery of p-nitroaniline, sulphamethoxazole and sulphamethizole after either intravenous administration of the L-γ-glutamyl or N-acetyl-L-γ-glutamyl derivatives or the parent drugs has been examined in a rat model. All L-γ-glutamyl derivatives were converted to the corresponding parent drugs within 60 min whereas the N-acetyl-L-γ-glutamyl derivatives were fairly stable in the systemic circulation after parenteral administration. Concentrations of p-nitroaniline and sulphamethoxazole 20 min after administration of the parent drugs were somewhat higher in the kidney than in the liver and lung. The concentration of sulphamethizole in the kidney was dramatically higher than those in the hepatic and pulmonary tissue. Kidney-specific delivery of the drugs of interest was evaluated by determining the tissue concentrations of the released parent drug and the total drug levels (i.e. drug levels after hydrolysis of all conjugate to the parent drug). For L-γ-glutamyl-p-nitroaniline released renal levels of p-nitroaniline and total p-nitroaniline concentrations were both higher than those obtained after p-nitroaniline dosing. Use of L-γ-glutamylsulphamethoxazole resulted in higher total sulphamethoxazole concentrations in the kidney, but did not lead to an increase in released (unconjugated) sulphamethoxazole levels. In contrast, no kidney-selective distribution was observed for L-γ-glutamylsulphamethizole. Markedly increased kidney distribution was observed for both N-acetyl-L-γ-glutamyl-p-nitroaniline and N-acetyl-L-γ-glutamylsulpha-methoxazole and the liver and lung concentrations were correspondingly reduced in comparison with parent drug dosing. Use of the N-acetyl-L-γ-glutamyl-p-nitroaniline conjugate increased the concentration of p-nitroaniline in the kidney to the same extent as did L-γ-glutamyl-p-nitroaniline. In conclusion, N-acetyl-L-γ-glutamyl derivatization of certain compounds seems to be useful for kidney-specific ***drug delivery and preliminary data suggests that lipophilic drugs are better substrates than hydrophilic compounds. Results related to the selectivity of tissue distribution of the derivatives and species differences are discussed.     

Torsion of the hernia sac within a hydrocele of the scrotum in a child

Torsion of the hernia sac is a rare disease that presents as acute scrotum in children. Including the present case, only six cases have been reported in the English literature. We report a 10-year-old boy who presented with pain and swelling of his right scrotum. Ultrasonography revealed a hypoechoic region adjacent to the normal right testis. The inflammatory changes of the right scrotum deteriorated. The patient underwent surgery and a necrotic cyst was recognized within a hydrocele of the scrotum. The cyst was not connected with the testis or epididymis and was twisted at an angle of 270 degrees. The cause of the necrotic cyst observed was anatomical and pathological torsion of the hernia sac.     

Infection-induced urethral defect treated by urethral reconstruction with a radial forearm flap

Abstract A 47-year-old man was admitted with the chief complaint of a urethral defect. An approximately 17-cm defect of the urethra seemed to have been occurred by the infection of implanted foreign bodies in the penile skin. Reconstruction of the urethra and the ventral skin was performed with a free radial forearm flap. A fistula formed at the proximal anastomosis after the operation, but was controlled conservatively. Urethral stricture at the proximal anastomosis subsequently developed. A urethral stent made of shape memory alloy was placed with the preservation of voiding function.     

Antiplatelet therapy and spontaneous perirenal hematoma

This case report clarifies an adverse reaction of antiplatelet therapy which has been a standard prophylactic method for patients harboring significant risks of thromboembolic events. A 71-year-old Japanese man who had been taking aspirin tablets (81 mg) for a year presented with sudden colic pain in the left flank region. An abdominal computed tomography scan revealed a significant perirenal hematoma of the left kidney. There were no pathological kidney conditions, such as renal tumors, calculi or vascular diseases, found by magnetic resonance imaging examination. After cessation of aspirin administration followed by conservative management, the hematoma completely disappeared 6 months later. This is the first documented case of spontaneous perirenal hematoma secondary to low-dose aspirin treatment. While such unpleasant events occur extraordinarily, this should be noted as a severe risk of antiplatelet therapy.     

Oral Assessment Guide – test of reliability and validity for patients receiving radiotherapy to the head and neck region

KNÖÖS M. & ÖSTMAN M. (2009) European Journal of Cancer Care 19 , 53–60
Oral Assessment Guide – test of reliability and validity for patients receiving radiotherapy to the head and neck region
Radiotherapy to the head and neck region leads to severe side effects in the oral cavity but knowledge about severity and onset is scarce among oncology nurses in a radiotherapy department. The aim was to test the Oral Assessment Guide for reliability and validity for patients receiving radiotherapy to the head and neck region. A prospective design with repeated assessments was selected. Thirty-six outpatients admitted to the department for radiotherapy to the head and neck region were included. In connection with the treatment session, the oral cavity was examined every second day by a nurse and once a week by an oncologist. The results were documented on separate forms. All patients showed alterations in the oral cavity and side effects started early during the first week of treatment. The result from inter-rater reliability showed a high concordance in all categories (>71%). Cohen's kappa ( k ) showed good agreement for voice, swallow and saliva and moderate for lips, tongue, mucous membranes, gums and teeth/dentures. The association, the sensitivity, between dose of radiation and side effects was weak or moderate and the acceptability with patients and staff was generally good.     

Lung cancer in a health area of Spain: incidence,characteristics and survival

GARCÍA PRIM J.M., GONZÁLEZ BARCALA F.J., PAZ ESQUEJE J., POSE REINO A., FONDEVILA LÓPEZ A. & VALDÉS CUADRADO L. (2010) European Journal of Cancer Care 19 , 227–233
Lung cancer in a health area of Spain: incidence, characteristics and survival To examine the incidence, characteristics, therapeutic approach and survival of diagnosed lung cancer (LC) in the Santiago de Compostela Health Area. A retrospective study was carried out on LC for a period of 3 years. Of the 481 cases collected, 92.7% were male. The median age was 66.93 years. The crude incidence for men and women was 80.71 and 5.84 per 100 000 inhabitants respectively. Among the non‐small cell lung cancers (NSCLC), 68.1% were diagnosed in stage IIIB or IV. The cancer had already spread in 62.2% of the small cell lung cancer (SCLC). Chemotherapy was used in 51.6% of patients. The survival probability from the first to the fifth year was 47.7%, 24.3%, 12.9%, 10% and 8.9% respectively. The median survival at 5 years was 12.12 months for NSCLC, rising to 29.8 months in stage I, and 8.85 months in SCLC. In our Health Area LC occurs more often in men, in whom the prevalence of smoking is very high. The most common histology type was squamous cell carcinoma. In the majority of cases, the diagnosis is made in the advanced stages, which accounts for the low percentage of surgical treatments and the short survival.