Holmium: YAG laser endoureterotomy for ureterointestinal strictures

PURPOSE: The management of ureterointestinal stricture in patients who have undergone urinary diversion can be challenging. Endourological techniques have been increasingly used in recent years for ureteral stricture. While long-term results may not be as reliable or durable as those of traditional open reconstructive surgical techniques, associated morbidity is much less. The holmium (Ho):YAG laser, which has cutting and coagulating properties, has been demonstrated to have many applications in urology. We report our experience with and long-term results of Ho:YAG laser endoureterotomy for ureterointestinal strictures. MATERIALS AND METHODS: We reviewed the charts and followup history of 23 patients in whom the Ho:YAG laser was used to treat ureterointestinal anastomotic stricture. Strictures were treated percutaneously via the antegrade approach with flexible endoscopes and the holmium laser. A reversed 12/6Fr endopyelotomy stent was left indwelling for 6 weeks postoperatively. Success was defined as symptomatic improvement and radiographic resolution of obstruction. RESULTS: Between 1993 and 2000, 23 patients with a mean age of 61 years underwent endo-ureterotomy using the Ho:YAG laser for 24 ureterointestinal stricture. An overall success rate of 71% (17 of 24 cases) was achieved at a mean followup of 22 months. The success rate of holmium laser endoureterotomy for ureterointestinal stricture at 1, 2 and 3 years was 85%, 72% and 56%, respectively. Seven patients had recurrent strictures of which 4 developed 16 months or more postoperatively. No complications were noted. CONCLUSIONS: Ho:YAG laser endoureterotomy for ureterointestinal stricture disease is a minimally invasive endourological procedure that may provide more durable results than other modalities used for endoureterotomy. The Ho:YAG laser with its ability to cut tissue precisely and provide hemostasis combined with its versatility and compatibility with flexible endoscopes is an ideal instrument for safely performing endoureterotomy.     

Radioiodinated styrylbenzene derivatives as potential SPECT imaging agents for amyloid plaque detection in Alzheimer's disease

Development of probes for β-amyloid (Aβ) plaques, a critical factor associated with Alzheimer’s disease (AD), provides important tools for studying their role in AD. Previously, we reported [¹²⁵I]IMSB and [¹²⁵I]ISB as excellent probes for Aβ plaque labeling. Despite their exquisite in vitro binding characteristics, low brain uptakes (likely due to two ionizable carboxylic acid groups) limited their potential as in vivo imaging agents. To improve brain penetration, we have successfully prepared a neutral radioiodinated probe [¹²⁵I]3. The improved probe displayed good binding affinity for Aβ aggregates (K_i=2.0 ± 0.2 using Aβ40 aggregates). In addition, the brominated counterpart displayed fluorescent-staining properties of Aβ plaques in postmortem AD brain sections similar to BSB, a fluoroscent probe reported previously. [¹²⁵I]3 gave excellent plaque labeling by film autoradiography of AD brain sections. Unlike [¹²⁵I]IMSB (which preferentially detects Aβ40 plaques), the improved radioioinated probe, [¹²⁵I]3, can readily detect plaques containing aggregates of both Aβ40 and Aβ42. The initial brain uptake of [¹²⁵I]3 in normal mice at 2 min p.i. was moderate (0.18% ID) and displayed a very slow washout from the brain (0.11 %.ID at 4 h p.i). Taken together, these data suggest that [¹²⁵I]3 is useful for in vitro plaque detection, it may not be suitable for in vivo monitoring of Aβ progression and deposition.     

Intranasal immunization with synthetic recombinant vaccine containing multiple epitopes of influenza virus

The oligonucleotides coding for three epitopes (HA91-108, NP55-69, and NP 147-158) of influenza virus, stimulating B-cells, T-helper cells and cytotoxic T lymphocytes (CTLs), respectively, were previously employed for expressing each epitope in flagella that induced specific humoral and cellular immune responses. We have constructed new plasmids expressing all three epitopes as a single recombinant product. Two versions have been prepared-a longer one (Fla-HNN) comprising hybrid flagella containing the epitopes, and a shorter version (HNN). Immunization of BALB/c mice with either constructs induced significant humoral immune response against influenza virus. The mice immunized with these peptides also induced higher T-helper activity, including Th1 type-cytokine (IL-2 and IFN-gamma) release. In addition, the mice immunized with HNN peptide demonstrated significant protection against sublethal viral challenge. Furthermore, this vaccine fully protected mice from lethal challenge and enhanced their recovery process. Our results indicate that a single construct expressing multiple epitopes, which stimulate different arms of the immune system, might be an appropriate candidate when the synthetic recombinant vaccine approach is considered.     

Environmental and occupational medicine and injury prevention: education and impact,classroom and community

The core value guiding the work of physicians and health workers, including those in Environmental and Occupational Epidemiology and Medicine and Injury Prevention, is to protect the health of the public, especially its most vulnerable individuals. In these fields, we emphasize teaching the use of epidemiology, the core discipline of public health, as a tool for early detection and prevention of disease and injury, as well as an instrument for hypothesis testing. The classic core topics are toxic and physical exposures and their effects, and strategies for their prevention; emerging issues are child labor, mass violence, and democide. In environmental health, students need to be prepared for the reality that the most important and severe problems are often the most difficult to investigate, solve, and evaluate. The following are some recommendations for producing graduates who are effective in protecting communities from environmental hazards and risks: (1) Teach the precautionary principle and its application; (2) Evaluate programs for teaching environmental and occupational health, medicine and epidemiology in schools of public health by their impact on the WHO health indicators and their impact on measures of ecosystem sustainability; (3) Develop problem-oriented projects and give academic credit for projects with definable public health impact and redefine the role of the health officer as the chief resident for Schools of Public Health and Community Medicine; (4) Teach the abuses of child labor and working conditions of women in the workplace and how to prevent the hazards and risks from the more common types of child work; (5) Upgrade teaching of injury prevention and prevention of deaths from external causes; (6) Teach students to recognize the insensitivity of epidemiology as a tool for early detection of true risk; (7) Teach the importance of context in the use of tests of statistical significance; (8) Teach the epidemiologic importance of short latency periods from high exposures as sentinel events for later group risk for cancer and stating the case for action; (9) Protect students and colleagues who are whistleblowers in environmental health from harassment and punishment; (10) Develop curricula and workshops that promote the use of epidemiologic tools for preventing genocide, democide, and their precursors. Schools of Public Health and Community Medicine are at the interface between the resources of academic power and the major problems of community health. Implementing the above recommendations will strengthen academic investigation and impact.     

Mammalian heparanase: involvement in cancer metastasis,angiogenesis and normal development

Cleavage of heparan sulphate proteoglycans (HSPGs) affects the integrity and functional state of tissues and thereby fundamental normal and pathological phenomena involving cell migration and response to changes in the extracellular microenvironment. Heparanase, degrading heparan sulphate (HS) at specific intrachain sites, is synthesized as a latent approximately 65 kDa protein that is processed at the N-terminus into a highly active approximately 50 kDa form. The heparanase enzyme is preferentially expressed in human tumours and its overexpression in low-metastatic tumour cells confers a highly invasive phenotype in experimental animals. Heparanase also releases angiogenic factors and accessory fragments of HS from the tumour microenvironment and induces an angiogenic response in vivo. Heparanase may thus facilitate tumour cell invasion, vascularization and survival in a given microenvironment, all critical events in cancer progression. These observations, the anticancerous effect of heparanase-inhibiting molecules, and the unexpected identification of a single predominant functional heparanase suggest that the enzyme is a promising target for drug development.     

Patient, therapist, and supervisor in a psychiatric institution: inner freedom and inner structure

The authors discuss issues concerning the psychotherapeutic process in a psychiatric institution. They develop the concept of the institution as an internalized object in addition to its being an objective object. As such, it has an effect on the inner freedom and the internal structure of the patient, the therapist, and the supervisor. It is claimed that it is crucial for the development of an identity as a psychotherapist that the supervisor be aware of the institution as an inner and real object. The authors raise questions about what kind of "space" is possible in a psychiatric institution and what influence that may have on the therapeutic process. The impact on the therapist's professional identity is discussed. They point to the process of becoming a therapist via supervision and examine some relevant dilemmas. The authors conclude by discussing the duality of inner freedom and internal structure, and their specific manifestations within an institution.     

Mechanisms of gonadotropin desensitization

The gonadotropic hormones, FSH and LH exert a major effect on ovarian and testicular function through interaction with specific seven-transmembrane domain glycoprotein receptors. Desensitization to the hormones, which can occur both in vivo and in vitro, is essential for prevention of overstimulation of the gonadal cells. The long-term process of desensitization to the gonadotropic hormones is probably mediated, in part, by extensive clustering and internalization of the hormone-receptor complex. Short-term desensitization may occur as a result of phosphorylation of serine or threonine residues on the receptor molecules, although a specific receptor kinase has not yet been identified. Recently, we have discovered a novel mechanism of gonadotropin desensitization, which is exerted by down-regulation of StAR expression and steroidogenesis mediated by MAPK activation as a result of hormone-receptor interaction, cAMP accumulation and PKA activation. Thus, PKA not only mediates gonadotropin-induced steroidogenesis, it also activates the down-regulation mechanism that can silence steroidogenesis under certain conditions. Moreover, our findings raise the possibility that activation or inhibition of ERK by other pathways could be an important mechanism for diminution or amplification of gonadotropin-stimulated steroidogenesis. This could contribute to functional luteolysis, a process in which luteinized granulosa cells show reduced sensitivity to LH despite maintenance of LH receptors, or to up-regulation of the steroidogenic machinery during luteinization of granulosa cells.     

The prognostic significance of circulating neuroendocrine markers chromogranin a, pro-gastrin-releasing peptide and neuron-specific enolase in patients with advanced non-small-cell lung cancer.

BACKGROUND: Chromogranin A (CGA), Pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) are known as immunohistochemical tissue markers closely associated with neuroendocrine differentiation in non-small-cell lung carcinoma (NSCLC). The aim of the present study was to assess the value of serum levels of these markers in predicting response to chemotherapy and survival of patients with unresectable NSCLC. METHODS: The study included 67 patients with advanced NSCLC treated with chemotherapy. Before treatment, serum levels of CGA, ProGRP and NSE were measured with commercial kits. RESULTS: No association was found between serum NSE and age, gender, histology, performance status or extent of the disease. Distribution of serum CGA differed significantly according to gender and histology, with higher levels being found in men (p = 0.01) and in squamous cell carcinoma (p = 0.01). Serum ProGRP levels correlated with disease extent, being higher in patients with metastatic disease (M1) than in those with locoregional disease (M0; p = 0.02). The association of NSE, CGA and ProGRP levels with response to chemotherapy was not significant. While NSE had no impact on survival, the median survival was shorter for patients with elevated serum CGA and longer for patients with high ProGRP levels. Association with survival was significant when the Classification and Regression Tree (CART)-derived or median cutoff points were explored. On inclusion in multivariate Cox models, both CGA and ProGRP retained significance with high levels showing an opposite effect on survival [CART-derived cutoff points: CGA, relative risk (RR) -4.0; p < 0.001, and ProGRP, RR -0.4; p = 0.006, and median cutoff points: CGA, RR -1.8; p = 0.04, and ProGRP, RR -0.5; p = 0.03]. The combined use of CGA, ProGRP and NSE allowed for definition of two sets of patients with significantly different median survival times (25.2 vs. 8.8 months, p = 0.0001). CONCLUSIONS: In the circulation, CGA and Pro-GRP appear to bear important information related to the prognosis for NSCLC patients before chemotherapy. While a high CGA before treatment was found as an unfavorable prognostic determinant, a high ProGRP conferred a survival advantage. The combined use of serum CGA, ProGRP and NSE may supply additional information to prognosis.     

Signs and symptoms of carbamazepine overdose in young children

OBJECTIVE: To examine common signs and symptoms of mild to moderate carbamazepine (CBZ) overdose in young children. METHODS: The medical records of previously healthy children admitted to the pediatric departments for acute accidental CBZ poisoning during the years 1993-1998 were evaluated retrospectively. Information was retrieved on serum CBZ levels, signs and symptoms on admission and during hospitalization, ECG findings, and chemical laboratory test. RESULTS: There were 14 exposed children all under the age of 5 years. These children accidentally took CBZ prescribed for a family member. The diagnosis of CBZ poisoning in seven children was unknown on admission because of inadequate history and was revealed only on toxicology screen. Nystagmus and drowsiness occurred in 8 of the 14 children, nystagmus and ataxia in 4 children, and drowsiness and tachycardia in another 2 children. The peak CBZ serum levels in these children ranged from 18 microg/ml to 32 microg/ml, mean + SD; 25 microg/ml + 4.64 microg/ml (therapeutic range: 5-10 microg/ml). CONCLUSION: Based on a certain group of young pediatric patients with mild to moderate CBZ poisoning, it is concluded that, nystagmus is the most common sign of this overdose. Other common signs are drowsiness and ataxia. The presence of nystagmus and CNS depression of unknown etiology, in a young child should suggest the possibility of CBZ toxicity.     

Aplasia cutis congenita in two sibs discordant for pylori atresia

We report two sibs who were the products of a consanguineous mating, and who had an extensive form of aplasia cutis congenita (ACC). In one of them the generalized skin disorder was manifested by slipping off of the epidermis and mucous membranes with the slightest trauma. This sib also had pyloric atresia and other congenital malformations. Two hypotheses are presented to explain the discordance between the siblings for the abnormalities other than the ACC. One hypothesis assumes varying degrees of severity of the same autosomal recessive disease. The second suggests linkage between the gene for ACC and the gene for an epidermolysis bullosa (EB)-like disorder and pyloric atresia. A recombination event involving the EB-pyloric atresia gene in one carrier parent would then lead to an offspring with only ACC. Prenatal diagnosis is suggested by monitoring α-fetoprotein levels in amniotic fluid.