New aspects of immunotherapy of leptomeningeal metastasis

Immunotherapeutic approaches to leptomeningeal metastasis (LM) include the intrathecal application of cytokines such as interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and lymphokine-activated killer cells (LAK cells). Results in a rodent model of leptomeningeal gliomatosis with intrathecal IL-2 application are discouraging, but some clinical improvement and clearance of neoplastic cells from CSF have been seen in patients with LM from melanoma treated with intrathecal IL-2 alone, and in patients with LM from primary brain tumors and squamous cell carcinoma of the tongue treated with intrathecal LAK cells and IL-2. The neurotoxicity of this therapy, mainly increased intracranial pressure, has been considerable but generally manageable. However, IFN-alpha caused severe neurotoxicity in form of an only partly reversible progressive vegetative state in the majority of patients. Considering the small number of patients treated with IL-2 and LAK cells, its value for the treatment of LM could only be stated by further investigation. In future, the application of recently discovered cytokines such as Fas-ligand, the continuous paracrine cytokine release by genetically modified cells, or vaccination strategies using genetically modified tumor cells might offer new immunotherapeutic approaches in LM.     

In situ hybridization: a possible diagnostic aid in leptomeningeal metastasis

In this review we discuss the clinical features and pathophysiology of leptomeningeal metastasis (LM), and elaborate on diagnostic tools for the detection of this serious complication of cancer. Because of the low sensitivity of the cytologic examination, new diagnostic approaches have been developed. The in situ hybridization technique may prove to be a reliable and early test for the detection of LM.     

Adrenocortical carcinoma. Current approaches in diagnosis and treatment

Adrenocortical carcinoma is a rare malignant tumor. The survival rate is related to a radical tumor resection. However, adrenocortical carcinomas are usually diagnosed in advanced stage. Although some cases of long-term regressions of metastases under op'-DDD (Mitotane) therapy have been sometimes reported the overall efficiency of mitotane in prolonging life remains controversial. Between May 1975 and January 1994, 9 patients were surgically treated for adrenocortical carcinoma at our institution. There were 6 females and 3 males, mean age 40.8 years (median 40 years). Five (55.6%) patients presented with abdominal pain, whereas 4 (44.4%) patients had symptoms of hormone secretion (cortisol). One patient was lost at follow-up. Overall survival rate was 16.8 +/- 5.9 months, the survival rates according to tumor stage were: stage I. 58 months (1 case), stage II. 6 and 16 (2 cases; mean 11 months), stage III. 7, 15.17 and 22 (4 cases, mean 15 months) and stage IV. 9 months (1 case). The progression of the disease is not controlled by the administration of op'-DDD and the best treatment is represented by surgery.     

Current aspects of the diagnosis and treatment of prostatic cancer]

Prostate cancer is becoming the most frequent malignant disease in men. Its present-day diagnosis in based on the combination of digital rectal examination, detection of the prostate-specific antigen in blood serum and multifocal transrectal biopsy of the prostate under ultrasonic control. The elevation of the level of prostate-specific antigen correlates with spread of the process and extracapsular penetration of the tumor. Asymmetry of the prostate and hypoechogenic foci represent the main ultrasonic signs of adenocarcinoma of the prostate. When the histological findings speak about the absence of atypical cells, another complex examination with rebiopsy is indicated in 6 months. The principal radical method of treatment of prostate cancer is prostatectomy performed mainly for the T1-T2 stages. At the preoperative period the neoadjuvant androgen deprivation can be performed in order to lessen the tumour volume and risk of a positive surgical margin.     

Current concept in the diagnosis and treatment of childhood pulmonary tuberculosis

In India, an estimated 80% of children are infected with tubercle bacillus by 10 years of age. Elimination of tuberculosis depends on finding all infectious patients and providing them with curative chemotherapy. Pulmonary tuberculosis--the most common form in children--is diagnosed when a child presents with fever, prolonged cough, weight loss, recurrent wheezing, or chest infection; the chest x-ray is suggestive of tuberculosis; and three or more of the following conditions exist: 1) Mantoux test result of 10 mm or more, 2) tuberculosis lymphadenitis by fine needle aspiration cytology, 3) grade III malnutrition, 4) no BCG vaccination, 5) positive family history of tuberculosis, and 6) recent history of pertussis or measles. Recommended, for children with pulmonary tuberculosis, is a regimen of isoniazid, rifampicin, and pyrazinamide daily for 2 months, followed by the first two drugs daily for an additional 4 months. The poor tuberculosis cure rates in most developing countries reflect patient non-compliance with treatment regimens.     

Current problems in the diagnosis and treatment of acute exogenous poisonings]

Information, toxicometry and detoxication are most important problems of clinical toxicology today because exchange of information perfect the skill of toxicologist in diagnosis and choice of treatment, whereas measurement of the toxic factor, blood poison concentrations enables systemic computer analysis of critical conditions caused by poisonings. Treatment of acute poisoning produces the highest effect if detoxication method is used including blood detoxication by sorption-dialysis methods and intestinal lavage in combination with physiohemotherapy. This approach provides a rapid elimination of poison from the body and effective correction of homeostasis.     

Current aspects in the diagnosis and treatment of chronic cystitis in women

Chronic cystitis (CC) in females is annually encountered now in 15,000-20,000 per 1,000,000. Etiological and pathogenetic factors in CC are closely related. Bacteriologically, CC is represented primarily by Enterobacter. The infection, as a rule, ascends the lower urinary tracts. The contributing factors are: weak local antibacterial mechanisms of the urogenital system, anatomical variants and anomalies of the urethra and introitus, sexual activity, impaired urodynamics of the lower urinary tracts. The diagnosis of chronic inflammation of the bladder is made mainly endoscopically, with obligatory endovesical multifocal biopsy of the bladder followed by histological examination. The treatment of CC includes antibacterial, general and local antiinflammatory therapy, measures to normalize urodynamics of the lower urinary tracts, correction of hygienic and sexual factors, immunostimulation. 16 nonresponders to conservative treatment of interstitial cystitis with progressive contraction of the bladder were subjected to supratrigonal or subtotal resection of the bladder with one-stage ileocystoplasty.     

The value of interphase cytogenetics in cytology for the diagnosis of leptomeningeal metastases

We studied the use of fluorescence in situ hybridization (FISH) in CSF to enhance the diagnostic yield for the detection of malignancy on the first lumbar puncture in patients clinically suspected of having leptomeningeal metastases (LMM). Although repeated lumbar punctures were still needed in some patients, the use of FISH did speed up the diagnosis in approximately one-third of the patients clinically suspected of having LMM with atypical cells at first cytology. This eliminates the need for repeated lumbar punctures in these patients and enables an earlier start of treatment.     

The facial nerve. Current trends in diagnosis, treatment, and rehabilitation

Facial paralysis is a potentially devastating disorder with numerous implications. Multiple entities must be considered in its etiology, and recent advances in microbiology, radiographic imaging, electrodiagnostic testing, and microsurgery have provided great insight into the pathophysiology, diagnosis, treatment, and rehabilitation of the facial nerve. Recent DNA PCR testing has shed new insight into the potential cause for Bell's palsy. This article focuses on the evaluation, differential diagnosis, medical treatment, and rehabilitation of facial nerve pathology with primary emphasis on facial paralysis. Surgical management is also discussed, including reanimation of the paralyzed face.     

Nevus of Ota and leptomeningeal melanocytic lesions

We quantitated glomerular and cortical interstitial structures in nine type I mesangiocapillary glomerulonephritis (MCGN) patients aged 6 to 20 years whose creatinine clearance (CCr) was 10 to 129 ml/min/1.73 m,2 as compared to age-matched normal controls. Mean glomerular volume and mesangial volume fraction [Vv(mes/glom)] were increased and the percentage of the capillary endothelial circumference which was defined as filtration surface was decreased in type I MCGN patients. Vv(mes/glom) was inversely related to filtration surface area per glomerulus (r = -0.73, P < 0.05) and directly to volume density of cortical interstitium [Vv(int/cortex)] (r = +0.90; P < 0.01). Vv(mes/glom) (r = -0.87; P < 0.01), filtration surface area per glomerulus (r = +0.83; P < 0.01) and Vv(int/cortex) (r = -0.86; P < 0.01) were correlated with CCr. Thus, in type I MCGN, measures both of glomerular and of cortical interstitial structure are highly correlated with glomerular function.     

Current diagnosis of chronic nonviral hepatitis

Apart from viruses, hepatotoxins, hereditary metabolic disorders, immunological factors and cholestasis may cause chronic hepatitis both clinically and histologically. As far as the etiology is concerned, a complete history can be very helpful. The clinical examination, however, is rarely diagnostic. Nevertheless, some clinical signs (e.g. ascites, splenomegaly, spider naevi) are suggestive of cirrhosis. The activities of gammaglutamyl transferase and ALT in the serum are augmented in most of the patients with chronic hepatitis independent of its etiology. Electrophoresis reveals disturbance of serum albumin and globulin ratios. "Basic' laboratory tests are supplemented by carefully selected additional investigations (e.g. immunological tests) according to the history and clinical data of the individual patient. Retrograde cholangiography is diagnostic in the majority of patients suffering from primary-sclerosing cholangitis. Liver histology, best obtained during laparoscopy, allows classification (and prognosis) of the underlying liver disease in many patients. Results of iron and copper determination in liver tissue are diagnostic in cases of congenital liver disease (hemochromatosis, M. Wilson).     

Current problems of diagnosis and prevention of occupational diseases

Occupational diseases in Far Northern conditions are aggravated by severe climate conditions. The role of allergic diseases becomes higher. The authors suggest ecologic and genetic concept of occupational diseases formation.     

Current aspects of diagnosis and therapy of nasal polyposis

Nasal polyps are tumor-like, hyperplastic swellings of the nasal mucous membranes. The histology may vary. The clinical picture shows a great heterogeneity, ranging from single polyps (so-called choanal polyps) to almost complete polypoid transformation of the mucosa in all paranasal sinuses. Nasal polyps may be associated with different inflammatory nasal diseases such as chronic rhino-sinusitis, cystic fibrosis and Kartagener's syndrome. The exact pathogenesis of nasal polyps is unknown. Several theories have been formulated over the past 20 years attributing nasal polyps to a variety of causes including allergy, genetic predisposition and inflammation. Recently, a relationship has been demonstrated between the production of cytokines and the formation and activation of inflammatory cells in the polyps. The diagnosis and surgical treatment of nasal polyposis has been decisively developed over the past decade. Current diagnostic and therapeutic concepts are presented for the treatment of nasal polyposis. Precise indications for medical and surgical treatment of nasal polyposis can be derived from an evaluation of the allergic endoscopic and radiological examinations. Glucocorticoids play a dominant role in conservative therapy. Topical application of steroids is the preferred route. Surgical therapy should not be radical. It should focus on the lateral nasal wall rather than on the healthy mucosa of the sinuses itself.     

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis

We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.