The role of cannabinoids in the treatment of cancer.

AIM: The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients. METHOD: According to the PRISMA protocol, we have included data from a total of 105 articles. RESULTS: Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response. CONCLUSION: In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids (Tab. 1, Fig. 1, Ref. 167).

[Opposite trends in the incidence of gonorrhea and syphilis in the East Bohemian Region - 30 years of surveillance]. / Protikladný vývoj trendu incidence kapavky a syfilis ve východoceském regionu - 30 let surveillance.

The epidemiology of selected sexually transmitted diseases in the Czech Republic has been carefully evaluated for many years. Data from 1981-2011 for eastern Bohemia shows a sharp decrease in the incidence of gonorrhea in 1993-1994 and a very low incidence thereafter with a slightly higher prevalence in males. However, syphilis and genitourinary infections with Chlamydia trachomatis show entirely opposite trends. Also, for the similar number of diagnostic tests performed, Chlamydia had a 10 fold higher rate of positive results. This underscores the changing epidemiology of sexually transmitted infections (STI) and necessity for adapting the reporting algorithms accordingly.

[Legionella infection--a neglected problem]. / Legionelové infekce - opomíjený problém.

UNLABELLED: Pathogenic species of the Legionella genus can cause respiratory diseases ranging in severity from benign Pontiac fever to life-threatening Legionnaires disease often characterized by severe pneumonia, high fever, and multiple organ involvement. Predisposing underlying conditions, such as immunosuppression, chronic lung disease, and malignancies and other variables such as smoking and higher age constitute high-risk factors. Legionalla has been isolated from natural aquatic habitats (freshwater streams and lakes, water reservoirs, etc.), artificial sources, and also from humid soil. These pathogens are distributed worldwide. Besides water reservoirs (surface and underground water, fresh and salt water), they occur in a wide range of technical devices and systems - water distribution systems, showers, pools, spa systems, perlators, foggy makers, irrigation systems with sprinklers, cooling towers, etc. About 20% of detected Legionella infections in Europe have been associated with travel history. Travel-associated cases present a particular difficulty in terms of identifying the source of infection and implementing remedial measures. KEYWORDS: Legionella pneumophila - Legionnaires disease - Pontiac fever - nosocomial infections.

[Cases of menstrual toxic shock syndrome in the Czech Republic in 1997-2011]. / Prípady menstruální formy syndromu toxického soku v Ceské republice v letech 1997-2011.

AIM: To determine toxigenicity and other basic characteristics of 47 strains of Staphylococcus aureus referred to the National Reference Laboratory for Staphylococci (NRL) as suspected causative agents of menstrual toxic shock syndrome (MTSS). MATERIAL AND METHODS: S. aureus strains were collected from 11 administrative regions of the Czech Republic in 1997-2011. The diagnosis was based on phenotypic (reverse latex agglutination test) and genotypic (polymerase chain reaction) methods. RESULTS: Forty-four S. aureus strains were producers of toxic shock syndrome toxin 1 (TSST-1), either alone or in combination with staphylococcal enterotoxin. Three strains only produced enterotoxin (B, C, and H). CONCLUSION: MTSS is a serious multisystem disease. In this study, MTSS often had a severe course requiring intensive care. All MTSS patients used vaginal tampons that had been identified in the literature as a risk factor for MTSS. The case of MTSS in a 36-year-old woman caused by an enterotoxin H positive strain of S. aureus is probably the first to be reported in the world.

[Penetration of ceftriaxone into the cerebrospinal fluid and its relationship to inflammatory markers during bacterial meningitis]. / Prunik ceftriaxonu do likvoru a jeho v vztah k markerum zánetu v prubehu invazivní bakteriální infekce.

AIM: To evaluate the penetration of ceftriaxone into the cerebrospinal fluid (CSF) in patients with invasive bacterial infection and to define correlation between the penetration and laboratory markers of inflammation. MATERIAL AND METHODS: Levels of ceftriaxone in the serum and CSF of 17 patients with purulent meningitis were examined. Serum concentrations of ceftriaxone before and after its administration were measured in 9 patients (18 samples, 52.9 %) by microbiological assay based on the agar diffusion test. In all patients, the CSF/serum quotient for ceftriaxone was calculated and correlated with laboratory markers of inflammation (C-reactive protein, fibrinogen and neutrophils). The CSF from nine patients with positive culture for bacteria was used for a modified bactericidal test. RESULTS: Ceftriaxone levels in the serum before and after administration (31.2 mg/l -/+ SD 12.29 and 300.0 mg/l -/+ SD 125.9, respectively) were different (p = 0.000156). The decrease of ceftriaxone levels in the CSF was gradual. There was also a significant difference between the levels of inflammatory markers and CSF/serum quotient of ceftriaxone. Patients with the values higher than 0.1 had higher CRP serum levels (p = 0.00192), fibrinogen serum levels (p = 0.0178) as well as neutrophil count in the CSF (p = 0.0112). However, no inflammatory markers (or their combinations) predicted the extent of penetration of ceftriaxone into the CSF. CONCLUSION: High serum concentration of ceftriaxone causes higher penetration through the inflamed blood-brain barrier. Higher antibiotic penetration correlated with the extent of systemic inflammatory response. However, no inflammatory marker predicted the rate of ceftriaxone crossing the blood-brain barrier. Ceftriaxone penetration, with a 24-hour regimen of administration, remains reliable and efficient therapy of purulent meningitis.

[Current options for the diagnosis and therapy of toxoplasmosis in HIV-negative patients]. / Soucasné moznosti diagnostiky a terapie toxoplazmózy u HIV negativních pacientu.

Infections caused by Toxoplasma gondii follow, in general, a mild or asymptomatic course. However, certain individuals, such as immunocompromised patients or those undergoing immunosuppressive therapy, pregnant women, newborns and patients with chorioretinitis, an ocular forms of toxoplasmosis, are at risk for more severe forms of toxoplasmosis. In these patients, rapid diagnosis and timely initiation of the appropriate treatment is of the utmost importance. The standard therapeutic regimen for the treatment of toxoplasmosis is represented by a combination of pyrimethamine and sulfadiazine. In European countries, this regimen is usually initiated during the 15th week of gestation. Until then, spiramycin is the treatment of choice. In newborns, congenital infection is usually treated with the standard therapeutic regimen which may be alternated with spiramycin. Severe ocular forms of toxoplasmosis are also usually treated with the standard regimen but sulfadiazine may be substituted by clindamycin. The preferred treatment in immunocompromised patients is, once again, the standard combination of pyrimethamine and sulfadiazine. However, due to frequent serious side effects, alternative treatments are possible. In some patients, especially those undergoing immunosuppression due to stem cell transplantation, primary prophylaxis of cerebral toxoplasmosis is achieved by co-trimoxazole. Reduced doses of the standard regimen may be used as secondary prophylaxis during severe immunosuppression in these patients. However, due to an increased risk of myelotoxicity, other therapeutic measures have to be used.

[Difficulties in laboratory diagnosis of cerebral toxoplasmosis]. / Uskalí laboratorní diagnostiky mozkové toxoplazmózy.

Toxoplasmosis is the most wide-spread parasitic disease in the Czech Republic. According to the results of serological studies, about 25-50% of its population come in contact with this protozoan. A serious form of the disease may develop in severely immunocompromised patients. In these patients, problems with diagnosing toxoplasmosis may occur, especially in the case of its rare but serious cerebral form. The aim of the case report is to present potential difficulties in the diagnosis of cerebral toxoplasmosis.

Cerebral toxoplasmosis in an allogeneic peripheral stem cell transplant recipient: case report and review of literature.

We present a patient who underwent allogeneic peripheral stem cell transplantation (PSCT) for chronic myelocytic leukemia. Twenty months after the PSCT he experienced status epilepticus. Magnetic resonance imaging (MRI) revealed a focus in the ventral thalamus-hypothalamus region. Using stereotactic biopsy with histology and specific polymerase chain reaction investigation from brain tissue, cerebral toxoplasmosis was diagnosed and treated with antiparasitic therapy. Early recognition of such serious and potentially lethal disease enabled prompt specific treatment. This case report emphasizes the role of stereotactic biopsy in diagnosis of cerebral toxoplasmosis. Other methods such as MRI are non-invasive but not sufficiently specific and sensitive.

[Congenital toxoplasmosis: possibilities for laboratory diagnosis]. / Kongenitální toxoplazmóza: moznosti laboratorní diagnostiky.

A case history and the steps taken in diagnosing congenital toxoplasmosis in a child whose mother experienced asymptomatic infection with the protozoon Toxoplasma gondii are presented. At pregnancy week 35, amniocentesis was performed because of fetal hydrops, ascites, hepatosplenomegaly and dilated left lateral brain ventricle on sonography. Laboratory tests showed high titers of IgM, IgE and IgA antibodies (acute infection markers) against Toxoplasma gondii in serum of the pregnant woman. Congenital toxoplasmosis in the new-born spontaneously delivered at week 41 was confirmed by detection of Toxoplasma gondii DNA in blood, acute infection markers in serum and hydrocephalus and calcifications on brain sonography. The woman received intensive treatment for toxoplasmosis during the last pregnancy trimester and her new-born child's treatment started immediately after delivery. The accurate diagnosis and early institution of therapy in both the pregnant woman and her child led to progressive normalization of laboratory tests (decreased titers of antibodies and Toxoplasma gondii DNA negativity) and significant regression of the brain lesions in the child.

Endoscopic retrograde cholangiopancreatography in children: A surgeon's perspective.

PURPOSE: The aim of this study was to review the indications, success rate, and complications of endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric age group. METHODS: From 1990 to 1999, 21 ERCP procedures were attempted in 20 patients. They consisted of 8 boys and 12 girls whose age ranged from 4 to 17 years (mean, 11.3 years). Fourteen were performed under deep sedation (mean age, 12.8 years), and 7 were done under general anesthesia (mean age, 7.6 years). All ERCP procedures were performed by experienced adult endoscopists. RESULTS: The indication for ERCP was biliary in 15 patients. Eleven had suspected choledocholithiasis by either ultrasound scan, intraoperative cholangiogram or magnetic resonance imaging (MRI). In 6 cases, the ERCP was done for pancreatic pathology. In 11 patients, the ERCP was diagnostic only, and in 10 a therapeutic procedure was done. The overall success rate was 90.5%. Post-ERCP complications consisted of 6 episodes of pancreatitis (28.5%), 4 of which followed a therapeutic procedure, and 1 episode of bleeding. Pancreatitis resolved 2 to 6 days post-ERCP. The patients underwent follow-up between 2 and 56 months after the ERCP (mean, 11 months). CONCLUSIONS: The authors conclude that even in experienced hands, ERCP in the pediatric population has a much higher complication rate than in adults (33.3%). We recommend that very specific indications be met before subjecting a pediatric patient to an endoscopic retrograde cholangiopancreatography.

Delayed presentation of a congenital recto-vaginal fistula associated with a recto-sigmoid tubular duplication and spinal cord and vertebral anomalies.

Tubular duplication of the recto-sigmoid colon is a rare entity. Associated anomalies including fistulae to the genitourinary tract may be found. A baby girl was found to have duplication of the recto-sigmoid colon, anomalies of sacral vertebra from S1 to S5, and solitary right kidney. The septum of this duplication was divided using staplers. Because of a history of stool coming from the vagina, a meticulous examination perioperatively was performed, but no fistula could be found. Further extensive investigation failed to show any fistula. At the age of 10 she was operated on for a tethered cord. At age 14, she experienced passage of a small amount of liquid stool per vaginum. A recto-vaginal fistula was found. Via a posterior sagittal incision, the fistula was closed by a transrectal approach. She remained asymptomatic for 16 months until the fistula recurred. Using a perineal approach, a very short fistula between the vagina and the rectum was closed. The closure was reinforced by a vaginal flap. Four months later, she remains without signs of recurrence.

Should malrotation in children be treated differently according to age?

PURPOSE: The aim of this study was to better define the mode of presentation, rate of volvulus, and surgical findings in children younger than 2 versus older than 2 years of age with malrotation. METHODS: The authors reviewed the charts of all patients with malrotation admitted to their hospital between January 1980 and December 1998, excluding patients having malrotation as a secondary finding. RESULTS: An upper gastrointestinal series was done in 90 patients (6% falsely negative) and a barium enema in 20 patients (40% read as normal). Fifty-eight patients had 114 associated congenital anomalies. Volvulus was found at the time of surgery in 28 patients, 5 of whom were older than 2 years. Three presented with acute symptoms and 2 with chronic symptoms. Surgery was performed by laparotomy in 103 patients and by laparoscopy in 3. Mean length of stay was 13.6 days. Mean follow-up was 19 months. Death occurred in 4 patients; postoperative bowel obstruction was seen in 3 patients (only 1 required surgery). CONCLUSIONS: Children with malrotation who are older than 2 years old have a significant risk of volvulus that is difficult to predict radiologically. They require surgical attention even if asymptomatic. Laparoscopy allows evaluation of the base of the mesentery and completion of the Ladd's procedure.

Juvenile xanthogranuloma presenting as obstructive jaundice.

The authors report the case of a 9-month-old infant presenting with obstructive jaundice. Preoperative investigation findings showed distension of the extrahepatic biliary tract. Urine analysis result was positive for cytomegalovirus. At laparotomy, a 1-cm round mass was found within the head of the pancreas, near its upper border and in the course of the common bile duct. Findings on frozen sections could not rule out a malignant process and an hepaticoduodenostomy was constructed. Final diagnosis was juvenile xanthogranuloma. An association between cytomegalovirus and juvenile xanthogranuloma has been reported previously in the literature.