New opportunities for screening and early detection of bladder cancer. In the United States, over 51,000 new cases of urinary bladder tumors are diagnosed annually. Approximately 75-85% of all newly diagnosed cases are superficial transitional cell carcinomas (TCCs). Incidence is highest (80% of the cases) in the 50-79 year age group. Recent studies have reported that 21-25% of risk for bladder cancer among United States white males is due to occupational exposure. The DuPont Chambers Works in Deepwater, New Jersey, was a major producer of two chemicals now known to be human bladder carcinogens (beta-naphthylamine and benzidine) as well as two suspected human bladder carcinogens [ortho-toluidine and 4,4'-methylene- bis,2-chloroaniline (MOCA)]. Between 1954 and 1982, DuPont screened 1723 exposed employees annually at the Chambers Works using the Papanicolaou test for urinary cytology and microscopic urinalysis. A review of the prior screening program found that employees who developed bladder cancer during this time period were approximately twice as likely to have had hematuria than those comparably exposed who did not develop bladder cancer. Building on this finding, a three-year screening study evaluated a home self-test for microscopic hematuria to aid early detection of treatable urologic conditions among exposed workers at this chemical plant. Every six months, subjects tested their urine at home for 14 consecutive days, for the presence of blood. A high degree of adherence to our protocol (over 92% completed and returned the self-testing record) as well as high compliance with repeat screening (85% returned for screening in subsequent quarters) demonstrated good acceptance and performance of the recommended schedule of self-testing. Through the first 7 periods of screening, two new cases and one recurrence of TCC of the bladder were detected.


Chemoprevention of experimental bladder cancer. The chemopreventive efficacy of several compounds was evaluated in the N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary bladder cancer model using C57BL/6 x DBA/2F1 (BDF) male mice. Compounds were administered in a defined semipurified diet (AIN-76-A) either as single agents or in combination. As single agents and at the doses employed, 2-alpha-difluoromethylornithine (DFMO), piroxicam, oltipraz, and sodium molybdate effectively inhibited the incidence of transitional cell carcinoma (TCC). 4-Hydroxyphenyl retinamide (4-HPR) was ineffective. Body weight gain and survival was not affected by the doses of agents used. Combinations of two agents which increased efficacy were 4-HPR+DFMO, DFMO+piroxicam, 4-HPR+oltipraz, and DFMO+oltipraz. Three-agent combinations which showed enhanced efficacy against TCC induction were 4-HPR+Na molybdate+DFMO, 4-HPR+DFMO+piroxicam, and 4-HPR+DFMO+oltipraz. Although the three-agent combinations were, for the most part, no more effective than the two-agent combinations at the doses employed, all combination regimens significantly reduced bladder cancer incidence even when single agent administration did not.


Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint. The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (+/- SE) S-phase and G2+M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 +/- 4.1% to 7.5 +/- 3.3% and 10.3 +/- 2.2% to 5.2 +/- 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 +/- 3.4% to 12.4 +/- 2.7% and 9.8 +/- 1.6% to 12.6 +/- 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case.(ABSTRACT TRUNCATED AT 250 WORDS)


13-cis-retinoic acid in chemoprevention of superficial bladder cancer. The National Bladder Cancer Group. Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study.


A prospective clinical trial of difluoromethylornithine (DFMO) in patients with resected superficial bladder cancer. Difluoromethylornithine (DFMO) is a promising chemopreventive agent which is excreted unchanged in the urine, is active in vivo against superficial bladder cancer in animal tumor model systems, and has cytotoxic activity in vitro against superficial bladder cancer cells. Thus, DFMO may be particularly efficacious in preventing the development of bladder tumors and/or for the therapy of established superficial bladder cancer. To examine this hypothesis, an intergroup clinical trial is currently accruing patients with cystoscopically resected superficial bladder cancer (who would otherwise simply be observed). While the primary goal of this protocol is to define a daily dose of DFMO having little or no toxicity for use in future randomized chemoprevention trials, the rate of recurrent bladder tumors will also be followed in the hope that DFMO will inhibit the development of recurrent bladder cancers.


Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention. Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in host antitumor immunity. For example, high levels of tissue PGE2 are frequently associated with suppression of immune surveillance and killing of malignant cells. Conversely, immune responses are generally enhanced by drugs that inhibit prostaglandin synthesis. PGE2 can act as a feedback inhibitor for cellular immune processes, such as T-cell proliferation, lymphokine production, and cytotoxicity. This effect is also seen for macrophage activity and natural killer cell toxicity. In general, either increased production of PGE2 or increased sensitivity to normal amounts of PGE2 results in depressed cellular immunity. Cyclooxygenase inhibitors (NSAIDs) such as piroxicam which decrease PGE2 production can stimulate cellular immune function both in vitro and in vivo. A variety of tumor cell lines and human malignancies produce large quantities of prostaglandins.(ABSTRACT TRUNCATED AT 400 WORDS)


Mechanisms of chemoprotection by oltipraz. 1,2-Dithiole-3-thiones are five-membered cyclic sulfur-containing compounds with antioxidant, chemotherapeutic, radioprotective and cancer chemoprotective properties. One substituted dithiolethione, oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione], originally developed as an antischistosomal agent, has recently been observed to protect against chemically induced carcinogenesis in lung, trachea, forestomach, colon, breast, skin, liver and urinary bladder in rodents. The induction of electrophilic detoxication enzymes, which result in diminished carcinogen-DNA adduct formation and reduced cytotoxicity, appears to be an important component of the anticarcinogenic action of oltipraz and other dithiolethiones. Phase I trials of oltipraz are presently underway in the United States. Subsequent trials might be most appropriately targeted towards individuals at high risk for occupational or environmental exposures to genotoxic carcinogens.


Bladder cancer from a perspective of 40 years. The key events leading to a better understanding of the natural history of urothelial tumors of the bladder are summarized. These were: the recognition of flat carcinoma in situ and related lesions (intraurothelial neoplasia) as principal sources of invasive cancer; identification of the unique structure of the urothelium; analysis of DNA content and the recognition of two pathways of urothelial tumors. A brief comment on the current status of immunologic and molecular genetic markers is appended.


Natural history of early bladder cancer. Non-invasive transitional cell carcinoma (TCC) occurs as two distinct growth patterns, papillary and non-papillary (flat), which display significant differences in biologic potential. Papillary carcinoma usually presents as a low-grade lesion which frequently recurs multiple times prior to invasion; conversely, non-papillary (flat) carcinoma in situ is usually high-grade at presentation (carcinoma in situ) and frequently associated with invasion. These lesions may occur together, although papillary cancer is more easily visualized cystoscopically due to its exophytic growth; flat carcinoma in situ is often cystoscopically invisible. This report reviews existing data concerning the prognostic value of pathologic grading and staging of non-invasive and early invasive TCC. Emphasis is placed on those studies reporting surgical treatment rather than other forms of treatment.


Pathology of carcinoma in situ of the urinary bladder and related lesions. In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)


Papillary tumors of the bladder.

Papillary tumors of the bladder. The most common neoplasms of the urinary bladder are papillary tumors that vary histologically and cytologically from very well differentiated to highly anaplastic patterns. Biologic behavior of these tumors is closely correlated with morphology, so that cytologically benign tumors (papillomas) are benign in behavior, and increasing anaplasia is associated with increasing clinical aggressiveness. By this definition, 20% or more of bladder tumors should be classified as papillomas. The development of carcinoma occurs in a series of steps, progressing through atypia and carcinoma in situ to invasion. Finally, evidence is presented to show that invasive carcinoma often begins from areas of flat carcinoma in situ associated with, but not within, co-existing papillary tumors.


Blood group antigens in normal and neoplastic urothelium. The ABO and Lewis blood group antigens are cell surface carbohydrate determinants formed by the sequential addition of saccharides to precursor backbone structures of membrane lipids and proteins. Suppression of normally active glycosyltransferases results in the absence of antigens that are normally expressed. ABH antigen deletion in malignant and premalignant urothelium has been extensively evaluated; it appears to correlate with significantly higher rates of tumor recurrence and disease progression. However, we have recently shown that the ABH blood group system is differentially expressed in the normal urothelium of secretors in contrast to nonsecretor individuals. The normal urothelium of nonsecretors does not express A, B or H determinants; therefore, deletion of ABH antigens can only be ascertained in secretor individuals. Although nonsecretors only comprise 22-24% of the population, this observation mandates a reevaluation of earlier studies. Deletion of A, B or H antigens is noted in carcinoma in situ (CIS), and in invasive and metastatic transitional cell carcinoma (TCC) of secretor individuals. Increased synthesis or activation of normally quiescent glycosyltransferases in bladder tumors can result in the expression of aberrant tumor-associated blood group antigens. Immunohistochemical analysis has demonstrated that Lewis X (Le(x)) is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas, CIS and TCC expressed Le(x) in 84% of cases, regardless of grade, stage, blood type or secretor status of the individual. The presence of Le(x)-positive cells in bladder lavage specimens enhanced the detection of urothelial tumor cells, correctly identifying bladder tumors in 253/293 (86%) cases compared to a 63% sensitivity for cytology alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidermal growth factor and its receptor: markers of--and targets for--chemoprevention of bladder cancer. Epidermal growth factor (EGF) is excreted in urine in high concentrations in a biologically active form. Several lines of evidence indicate that EGF plays a role in transitional cell carcinoma (TCC) development and growth. These include: (1) EGF in the normal urine of rats promotes chemically initiated TCC; (2) EGF in normal human urine stimulates the clonal growth of human TCC cells in vitro; (3) EGF stimulates the in vitro growth of human TCC cells, but not normal human urothelial cells; (4) the density and distribution of the EGF receptor (EGF-R) on human urothelial tissues permits significant access of premalignant, dysplastic, and malignant cells to EGF; and (5) the concentration of EGF in the voided urine of patients with TCC is reduced, implying that EGF may be "extracted" from urine by the greater number of EGF-Rs in patients with urothelial malignancy. Abnormal expression of the urothelial EGF-R and/or altered excretion of EGF may well precede overt evidence of TCC and thus may serve as markers of risk or exposure. Similarly, reversion of EGF-R expression or the return of excreted EGF to normal levels may provide a marker of response for preventive and therapeutic strategies. Interference with the EGF/EGF-R interaction through dietary or pharmacological manipulations of the urine, or via targeting strategies employing intravesical administration of conjugated toxins or isotopes is already being employed in experimental and clinical studies. These approaches offer promising new tools in the detection, monitoring, prevention, and management of early stage bladder cancer.


Alterations in antigen expression in superficial bladder cancer. Bladder cancer can be viewed as a prototype for carcinogen-induced neoplasia. This has been demonstrated experimentally in a variety of systems and in man through epidemiological studies of occupational exposure to putative carcinogens. The natural history of this neoplasm demonstrates recurrence in time and space, i.e., multifocal disease. This clinical scenario is precisely what would be expected if a target tissue, e.g., urothelium, was continuously exposed to a weak carcinogen. The detection of gross disease is clinically easy. However, the ability to intervene at early stages and monitor the success of this treatment requires the definition of early markers for bladder cancer. Integrins are a family of cell surface proteins, many of which function as receptors for extracellular matrix components. Normal epithelial cells express the integrin alpha 6 beta 4 in association with an anchoring structure known as the hemidesmosome. Urothelium expresses alpha 6 beta 4 on the basal layer of cells similar to the distribution seen on other epithelial surfaces. Even early stages of bladder cancer demonstrate an alteration in the expression of this integrin. Low-stage bladder tumors express alpha 6 beta 4 diffusely throughout the tumor as well as at the invading margin. Altered expression of alpha 6 beta 4 may be an early marker for bladder cancer which may contribute to an invasive phenotype. A second potential marker is detected by DD23, an IgG1 murine monoclonal antibody triggered by the immunization of a BALB/c mouse with a fresh human bladder tumor specimen. The antigen detected by DD23 is not present on normal urothelial specimens.(ABSTRACT TRUNCATED AT 250 WORDS)


Altered RB expression is a prognostic clinical marker involved in human bladder tumorigenesis. We are now beginning to understand the development of bladder cancer at the molecular level. Tumor evolution involves the interaction of both oncogenes and tumor suppressor genes. One of the key tumor suppressor genes in this process is the retinoblastoma (RB) gene. Much has been learned recently about the role of this gene in the tumor progression and prognosis of bladder cancer, although several questions are still unanswered. The progress made on this subject in our laboratory as well as others will be the focus of this report.


Cytology.

Cytology. Exfoliative cytology is a relatively sensitive, highly specific technique for the detection and diagnosis of bladder cancer, and for monitoring conservative treatment. Cytologic diagnosis is based on cellular changes in DNA content, chromatin structure, and metabolic activities which are characteristic of cancer cells and can be recognized in desquamated isolated cells or cell clusters. The cytologic techniques are most effective in identifying low stage flat or papillary carcinoma, but not cytologically benign papillomas or ulcerating invasive cancers that do not easily shed cancer cells. With the growing number of pathologists who, in recent years, have become skilled cytopathologists, urinary tract cytology has developed into an essential diagnostic tool for the urologist.


Chromosome changes in early bladder neoplasms. There are few cytogenetic studies of early (non-invasive) bladder cancer, particularly in situ carcinoma, due to technical difficulties in examining such lesions. The best approach is to extrapolate from chromosomal changes in more advanced cancers. Although no specific chromosomal changes have been established in either early or fully developed bladder cancers, certain recurrent anomalies have been encountered. Anomalies such as +1, +7, -9, 5q- or i(5p), 11p- and -Y appear to constitute part of the multistep carcinogenetic process by which clinically and pathologically recognizable bladder cancers develop. Since loss of part or all of chromosome 9 (-9) is a common and early cytogenetic event in bladder cancer, the detection of -9 in bladder washings or urine by fluorescence in situ hybridization (FISH) may be a promising test for early or recurrent bladder cancer. Although less frequent than -9, trisomy 7 (+7) is common enough to serve a similar purpose. In contrast, loss of the Y chromosome may indicate an advanced stage of bladder cancer. Thus, FISH studies utilizing probes for chromosomes 7, 9, and Y should yield cogent information to identify early bladder cancer. Cytogenetic (including FISH) studies combined with certain molecular approaches (e.g., p53 mutations detected immunochemically) may not only serve to differentiate early cancer from benign tumors or conditions, but may also help establish cancer stage. This would supply data of considerable usefulness to the clinician and pathologist.


Evaluation of DNA flow cytometry as a screening test for bladder cancer. At this present time, we feel that there is no role for DNA flow cytometry (FCM), or indeed DNA studies by any other method, to be used as a screening procedure for patients with no prior history of bladder cancer due to the high false-positive rate found when monitoring exfoliated urothelial cells. On the other hand, for patients who have had a superficial transitional cell carcinoma (TCC), which has a documented 50% recurrence rate, and depending on pathological features, a progression rate from 7 to 45%, DNA FCM provides a sensitive method to predict future disease recurrence. It provides an extremely effective way to predict future progression and further acts as a method to monitor changes in the malignant potential of the patient's disease. For those patients with a past history of superficial TCC who develop abnormal ploidy without any overt tumor, 80% will, within the next four years, suffer a disease recurrence. For the patient who has a Ta TCC and receives intravesical Bacillus Calmette-Guerin (BCG), the development of abnormal ploidy in bladder washing specimens is the single best indicator for future disease recurrence. Similarly, a negative DNA FCM of a bladder washing at six months after intravesical therapy is an excellent predictor of no further occurrence. In patients with superficial TCC, ploidy of the initial and recurrent tumor predicts for future progression. Half of those patients with stage Ta bladder cancer with two successive aneuploid bladder tumors develop muscle invasive disease within one year, while three-fourths develop advanced disease within two years after recurrence of their second aneuploid lesion.(ABSTRACT TRUNCATED AT 250 WORDS)


Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder. Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events.


Intermediate endpoint biomarkers for chemoprevention. The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigenesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, exposure, effect, or disease. This paper reviews several years of research on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experiments, mice were dosed with N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) while co-administering N-(4-hydroxyphenyl)retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor differentiation and, consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic process. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) could be redifferentiated with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-actin, a cytoskeletal biomarker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO. A clinical evaluation of F-actin in patients with varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. These studies confirmed that G-actin, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantitated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185 (neu oncogene product), to DNA aneuploidy and, finally, to visual morphology.(ABSTRACT TRUNCATED AT 400 WORDS)


Application of information systems to AIDS risk reduction. Acquired immune deficiency syndrome (AIDS) is a specific group of diseases which are indicative of severe immunosuppression related to infection with the human immunodeficiency virus (HIV). In response to the epidemic, a variety of intervention and prevention has been instituted. In such intervention and prevention activities, the role played by information systems becomes more and more important. This paper describes the design and implementation of an information system for AIDS intervention and prevention.


Training needs for information management: a national programme. This paper briefly describes major changes in the, management and organization of the English National Health Service from 1985. The information consequences of those changes and the central programme necessary both to realize and to achieve them, are summarized. The requirements for training flowing from these developments are analysed, as are some of the obstacles to be overcome in meeting them. The national programme of training in information management, currently in its third year, is set out, and its particular aims described.


Training of health care personnel towards the implementation and use of electronic health care records using integrated imaging technology. The hospital of the future will be a place in which Health Care providers of various disciplines will have access to all information about a patient in a timely fashion, and where the communication system will be able to cope with all information representations ranging through data, text, images and voice. Multimedia systems offer the facilities to cope with the specific problems of the mainly manual approach for the effective and efficient organization of information related to facts and findings in medical care. In this article we outline the training needs for future users of such systems.


Galactokinase activity in patients with idiopathic presenile and senile cataract. The activity of galactokinase in red blood cells of 30 patients affected by idiophatic presenile and senile cataract, and of 20 age-matched controls with perfectly transparent lenses, was investigated. The results obtained show a partial deficiency of the galactokinase activity in the patients affected by presenile idiopathic cataract. There is, moreover, a significant relationship between the cortical form of cataract and enzymatic reduction.


Trilateral retinoblastoma.

Trilateral retinoblastoma. Retinoblastoma is the most common intraocular malignancy of childhood. Trilateral retinoblastoma is a syndrome characterized by bilateral ocular retinoblastoma in conjunction with an intracranial neuroblastic neoplasm in the pineal body, or in supraseller or parasellar location. We report the case of a three year old girl with trilateral retinoblastoma and review the literature on this subject.


Object-orientated DBMS techniques for time-oriented medical record. In implementing time-orientated medical record (TOMR) management systems, use of a relational model played a big role. Many applications have been developed to extend query and data manipulation languages to temporal aspects of information. Our experience in developing TOMR revealed some deficiencies inside the relational model, such as: (a) abstract data type definition; (b) unified view of data, at a programming level; (c) management of temporal data; (d) management of signals and images. We identified some first topics to face by an object-orientated approach to database design. This paper describes the first steps in designing and implementing a TOMR by an object-orientated DBMS.


Design and implementation of computer-readable patient data cards--applications in Europe. Computers have been widely accepted today as essential tools for handling and processing an ever-increasing flood of information. At the same time people, including patients and medical staff, are becoming more mobile and face the problem of interacting with the different computerized systems. We are also experiencing the acceptance of the small rectangular plastic cards as the instrument for vast numbers of transactions throughout the world. These factors have highlighted the possible attractions of machine-readable patient data cards that can be carried by the patients themselves. The patient data card is expected to provide quick reference information to any physician or health worker consulted by the carrier. This information should avoid duplication of diagnostic, therapeutic and prescription measures and help give a conveniently structured summary of the patient's medical history. Advances in technology have made it possible to move from the familiar credit card which can store only a limited amount of information, to new, similarly shaped cards with much greater capabilities. The basic technologies for patient data cards are examined. An analysis is then attempted of the possible information contents of such a card that could be used at a national and European level, and of the field trials in Europe so far. Questions of security and standardization are also addressed. A number of conclusions and recommendations are also made which are based on the experience gained from a relevant implementation attempted, and participation in a recent study undertaken by the EEC in the area.


Pars plana versus limbal lensectomy in soft cataract. With the use of automated vitrectomy instruments a new dimension has been added to the treatment of soft cataracts. Surgical approach through the limbus and pars plicata has been described previously. This work is to compare the results of both surgical techniques. Twenty eyes of soft cataract underwent lensectomy and vitrectomy using the vitrophage. Pars plana approach was applied to 10 eyes, while limbal approach was applied to the rest of the cases. No major preoperative or postoperative complication were encountered in both techniques in a follow up period up to 12 months. However, pars plana lensectomy and vitrectomy offers many advantages over the limbal one with minimal complications.


An entity-relation model for a tocho-gynaecology service. There is a trend, both at national and European levels, towards the use of standards in hardware, software and communications. This implies a common root for the design of unified databases which will result in the homogeneity and interchangeability of data and knowledge. The technological solution exists and is imposed. The problem then is not the tools to be used as information support but how this information is organized and structured. According the the standards proposed by the Plan de Dotación Informática para la Asistencia Sanitaria (DIAS), and with respect to the problem of computer coverage of specialties, we present in this work an entity-relation model for a generic service within our project of integrally computerizing a tocho-gynaecology area. It is a multidisciplinary job between doctors and physicists where we use a planning strategy in order to identify the functions, processes and activities, making the traditional clinical management structure compatible with the one proposed. This means that if we want the introduction of the system to be effective, we have to make all the clinical and sanitary staff participate in the project. We must induce the need for change and carry out the process of change gradually, so that only a change in the support, and not in the organization, is initially perceived.


Portable medical records on microchip cards: the Tournai experiment. A test of the use of microchip cards as portable medical records has been organized and evaluated in a small Belgian town. The portable record was accepted by patients and could be a useful innovation for emergency situations. A comparative evaluation of other portable media is needed.


Hemicentral and hemispheric retinal vein occlusions. Since some authors have considered useless a differentiation between hemicentral retinal vein occlusion (HCRVO) and hemispheric retinal vein occlusion (HSRVO), we have conducted a prospective research in order to evaluate the clinical and prognostic features of these diseases. We have followed prospectively 26 cases of HCRVO and 25 cases of HSRVO. The most important risk factors were hypertension, diabetes mellitus and glaucoma in HCRVO, and hypertension in HSRVO. In the HCRVO group 20 cases (76.9%) were of the non-ischemic type and six cases (23.1%) were ischemic-type, whereas in the HSRVO seven (28%) were non-ischemic type and 18 cases (72%) were ischemic-type. Our results demonstrate that the two retinal vein occlusions are quite different with regards to pathogenesis, clinical evolution and visual outcome and point out the necessity to achieve a precise diagnosis.


MCHS: an application software for family welfare programmes. At the level of first contact, a primary health care centre, information management is an unwieldy task, therefore health information systems are reported to be inadequate and weak. Microcomputers could improve information management at this level, but there is little success due to a lack of specialized application software. In this paper we describe software developed after a multi-centre systems analysis study, on an essential data set, to support the delivery of the public health programmes for family welfare, i.e. maternal health care, family planning and immunization programmes. The modular approach was taken to develop a common application software for information management use at multiple sites. The software is tested in a laboratory mode by retrospective data entry from sites in Sweden and in India. All the information could be entered and site-specific reports that were generated are compared. The software provided a common data collection format, an essential platform for outcomes research.


[Analysis of early and late results of progressive Graves-Basedow ophthalmopathy treatment with different methods]. The early (immediately after the end of treatment) and late (from 12 to 91, mean 46.3 months after the end of treatment) results of progressive Graves-Basedow ophthalmopathy treatment were evaluated in 71 patients (57 women and 14 men, aged 25-66, mean 47.3 years). In all patients the thorough ophthalmological evaluation was performed early and late after treatment and the abnormalities found were classified according to Werner's method and Donaldson's ophthalmopathy index. The patients were divided into 7 groups according to different methods of treatment. Groups I-V consisted of 31 patients treated with glucocorticoids or glucocorticoids with azathioprine (Imuran) in the first stage of medication (30 patients). Plasmapheresis (7 patients) or tele-cobalt irradiation (3 patients) was applied as the second stage of treatment when the first stage was ineffective. In one person plasmapheresis and tele-cobalt irradiation was applied without previous glucocorticoid therapy. Two patients were treated successively by glucocorticoids, plasmapheresis and tele-cobalt irradiation. Very good and good late results of treatment were found in 95% of patients out of 22 reexamined persons of groups 1-5. Group 6 consisted of 7 patients treated with cobalt irradiation alone, in all 6 patients evaluated late results were good or very good. Out of 33 patients of group 7 treated by combination of glucocorticoids and telecobalt irradiation 23 were evaluated late and the results were found good or very good in 96%. The results suggest that combined treatment of progressive endocrine ophthalmopathy with glucocorticoids and cobalt irradiation is the most effective method of treatment at present. The affectivity of stage treatment is comparable with combined treatment but lasts longer and usually is more expansive.(ABSTRACT TRUNCATED AT 250 WORDS)


[Arterial hypertension associated with hyper and hypothyroidism]. 45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established.


[Humoral indices of the inflammatory process in psoriasis]. Immune complexes were determined in 104 patients with psoriasis, aged between 19 and 55 years. Duration of the disease, extension of lesions, and effects of infections preceding skin eruptions were considered. The studies showed the activation of immunological mechanism in psoriasis manifested by the increase in IgG and IgA levels, unchanged IgM levels, significantly more frequent negative values of IgD, significant increase in complement C4 component levels in all forms of the disease, and C3 activation in the acute and generalized chronic form. A significant increase in alpha 2 Mg was noted independently of the evolution and extension of skin lesions. An increase in alpha 1 AT was noted only in the initial phase of skin eruptions. An increase in Hp, Cr, CRP, and CIC was noted only during exacerbations. CIC were noted most frequently in postinfection psoriasis.


[Use of estrogens in skin patches in treatment of pre-menstrual syndrome]. A consequence of the diminishing the normal functioning of ovaries is progressing decrease in the levels of sex steroids leading to the clinical symptoms termed menopausal syndrome. This study aimed at evaluating the efficiency of Estraderm TTS-50 (Ciba-Geigy) in the treatment of this syndrome. The study involved 33 female patients, aged between 30 and 65 years. Estraderm in the form of patches containing 0.004 g of 17-estradiol was administered for 3 weeks every month, for 9 weeks. Kupperman's index, cytohormonal tests, and blood serum FSH and LH were tested before, during and after the treatment. A diminishing of the most common symptoms manifested by a statistically significant decrease in Kupperman's index and FSH, and LH levels with significant increase in serum estradiol was noted in 75% of patients following a 9-week treatment with Estraderm. Changes in the sex steroids levels led to a marked increase in the percentage of superficial cells, assessed with cytohormonal tests. Transdermal administration of estrogens in the form of Estraderm TTS-50 is the treatment of choice in the menopausal syndrome.


[Familial hypoadrenalism].

[Familial hypoadrenalism]. Congenital hypoadrenalism was diagnosed in a 18-month boy. It is suspected that hypoplasia of the adrenals is determined genetically due to the similar course and the results of autopsy in his deceased sister.


[The possibility of replacing blood serum with sputum for monitoring of therapy with lithium carbonate]. Lithium concentration was determined in both sputum and blood serum of 31 patients treated with lithium carbonate. It was found that lithium concentration rate in the sputum/blood serum is 2.17 +/- 0.16, and is constant in all patients, except one, for a long time. A high correlation index between lithium concentration in the sputum and blood serum (r = 0.9025, and without two assays in the above mentioned patient r = 0.9858) as well as stability of sputum/serum lithium levels enable -- in the opinion of the authors -- to control lithium concentration in the body, using sputum for the assays. These assays are easy to perform with the aid of the kit called "Salivette" (Sarstedt, Germany). Its principle was discussed, too.


[Growth hormone concentration following various factors stimulating its release]. Growth hormone concentration has been assayed in 105 children (45 girls and 60 boys) during starvation and following its stimulation with clonidine and insulin and during the sleep. A significant difference between growth hormone concentration during fasting and after stimulation has been noted. No statistically significant difference between growth hormone concentrations during the sleep and following insulin has been found. The most intensive growth hormone release has been observed during the sleep. Test with clonidine is technically simple and may be performed also in the out-patient clinics.


[Blood pressure and blood lipids in normotensive patients with diabetes mellitus type I with microalbuminuria]. The study involved 50 normotensive men (means age = 34 years) with diabetes mellitus type I (mean duration of the disease 14 years). Group I included 29 patients with normal albumin excretion with the urine (UAE below 30 mg daily), and group II-21 patients with microalbuminuria (UAE 30-300 mg daily). Both groups were similar in relation to the age and duration of diabetes mellitus. Blood cholesterol was significantly higher in patients of group II than in patients of group I (p = 0.02) similarly to blood triglycerides levels (p = 0.01). Mean arterial pressure was lower in patients of group I than that in patients of group II (94.3 +/- 7.0 vs 99.1 +/- 6.0 mm Hg; p = 0.01). HbA1c was positively correlated with blood cholesterol (p = 0.01) and blood triglycerides levels (p = 0.05).


[Cholesterol and its lipoprotein fraction in serum and bile of patients with cholelithiasis]. Total cholesterol, HDL, LDL and triglycerides were assayed in the blood serum and bile from the liver and gallbladder of both normal individuals and patients with cholelithiasis. It was found that all assayed parameters are significantly higher in patients with cholelithiasis. An increase in total cholesterol and HDL was seen in the bile from the liver whereas an increase in the level of unstable LDL by about four fold with simultaneous decrease in HDL level were found in the bile from the gallbladder. These differences in lipoprotein fractions level in patients with cholelithiasis indicate systemic disorders in cholesterol metabolism.


[Effect of 5-month guanfacine treatment on the renin-angiotensin-aldosterone system and some metabolic factors in patients with diabetes mellitus type II and hypertension]. The group of the investigated included 25 individuals (11 F, 14 M), aged 55 +/- 1.5 years, with diabetes type II and hypertension. Known diabetes duration was 4.9 +/- 0.8 years and known hypertension duration--7.4 +/- 1.4 years. Two weeks after administering placebo in place of hypertension drugs applied so far, guanfacine was included as the only hypertensive drug. The dosage was increased from 0.5 mg up to 3 mg daily until a good control of blood pressure was achieved. The diabetic treatment, diet and the smoking habit were unchanged. The resting activity of the renin-angiotension-aldosterone system (RAA), cholesterol, triglycerides, HDL and LDL, serum glucose levels and HbA1c were assayed after a 5-month guanfacine period. After treatment a significant decrease in blood pressure both systolic and diastolic (p < 0.001), heart rate (p < 0.005) and plasma renin activity (p < 0.02) were observed. Preliminary measurements of RAA activity and its changes during treatment were not helpful in predicting guanfacine hypotensive effect. The level of lipids, lipoproteins, atherogenic factors, glucose and HbA1c did not change significantly during the study.


[Effect of compositional modification of coffee on certain indices of lipid metabolism in healthy volunteers and patients with hyperlipoproteinemia]. An effect of a 14-day drinking of coffee on some blood serum indices of lipid metabolism was investigated in 20 healthy volunteers and 20 patients with hyper lipoproteinemia (type IIb). The study was carried out in two subgroups: healthy volunteers or patients with hyperlipoproteinemia assigned to the first subgroup drank ordinary coffee and patients assigned to the second subgroup drank coffee deprived of irritant substances (4 glasses daily). It was found that ordinary coffee significantly increased total serum cholesterol and decreased serum HDL-cholesterol in healthy volunteers. Such effects were not seen in subgroup drinking coffee deprived of irritant substances. More significant increase in serum total cholesterol and decrease in serum HDL-cholesterol were found in patients with hyperlipoproteinemia. Drinking of modified coffee does not cause any significant changes in serum lipid metabolism. The authors concluded that drinking of the ordinary coffee should be restricted in patients with hyperlipoproteinemia and use of coffee deprived of irritant substances might be recommended to patients with this disease.


[Circadian changes in levels of magnesium in serum of healthy individuals]. Circadian changes in blood serum magnesium levels in healthy individuals. We examined circadian changes of the serum magnesium in 20 healthy subjects. Blood samples were taken every second hour during the 24 hours. Male serum magnesium concentrations increased from the lowest level (0.810 +/- 0.035 mmol/l) observed at 8.00 am to the highest level (1.028 +/- 0.084 mmol/l) at 6.00 pm. Female-we observed two peaks of serum magnesium concentrations: first at 8.00 pm (0.992 +/- 0.103 mmol/l) and second at 4.00 am. (0.982 +/- 0.094 mmol/l) with the lowest level at noon) 0.789 +/- 0.043 mmol/l. Differences between extreme levels were statistically significant.


[Effect of ACE inhibitors on proteinuria and renal functioning in primary glomerulopathies]. Angiotensin converting enzyme inhibitors was given to 16 patients with glomerular nephritis in whom a complete remission of nephrotic syndrome could not be achieved with immunosuppressive-anti-inflammatory therapy. Captopril in the daily dose of 25-75 mg and enalapril in the daily dose of 10 mg were administered for 1-36 months (mean 12.6 months). Daily proteinuria decreased by 40-80% comparing with baseline value in 2/3 of patients. Total protein and albumin serum levels increased simultaneously. No changes in blood creatinine were noted in patients with initially normal renal functioning except one patient. Renal functioning was stable in 50% of patients with increased blood creatinine levels (mean 200 mumol/L). Blood creatinine was increasing in the remaining patients.


[Estimation of hearing in patients with end stage renal failure being peritoneally dialyzed with and without furosemide in the dialysis fluid]. The purpose of our study was to estimate hearing state and effect of intraperitoneal administration of furosemide on an organ of hearing in the patients with end-stage renal failure being treated with intermittent peritoneal dialysis. Ten patients divided into two groups, were observed for three months. A weekly dosage of 1.2-2.0 g of furosemide was administered to the patients of first group while the patients of second group were not given furosemide. Based upon the studies, which had been carried out by pure tone audiometry method and Fowler's test and Belesy's audiometry, it was found the lesion of hearing, mainly in the range of higher frequency, having a character of cochlear hypoacusia. The further lesion of hearing was not seen within three months of regular treatment with intermittent peritoneal dialysis. The audiometric studies which had been carried out in different stages of treatment, did not show ototoxicity influence of furosemide added to dialysis fluid.


[Clinical estimation of 1-alpha-hydroxycholecalciferol in treatment of patients with chronic renal failure]. 31 adult patients (15 male and 16 female) with chronic renal failure were treated for 6 months with 1-alfa-hydroxycholecalciferol on a dose 0.25-2.0 micrograms/24 h. 15 patients with not very advanced renal failure (serum creatinine level 176.8-442 mumol/l) received conservative therapy (group I), 16 patients with serum creatinine value 884-1326 mumol/l were treated by intermittent hemodialysis (group II). The statistically significant decrease of serum alkaline phosphatase activity in group I and II (p < 0.01), the rise of serum calcium level in group I (p < 0.005) were determined. Half of the patients from both the groups stated the relief or disappearance of bone and joint pains and muscle weakness. Besides in group I significant decrease of creatinine clearance (p < 0.001) and increase of serum urea and creatinine value (p < 0.01) were noticed. On the basis of these results we can conclude that the treatment with 1-alfa-hydroxycholecalciferol, produced by "Polfa", ought to be introduced gradually with increasing doses and frequent monitoring of calcium-phosphate metabolism and renal function parameters.


[Usefulness of computed tomography for diagnostic differentiation of complications after renal transplantation]. This paper demonstrates the usefulness of Computer Tomography (CT) for diagnosing the commonest complications after kidney transplantation. It was pointed out that CT is particularly helpful in detection and differentiation of perirenal fluids as well as in diagnosing of kidney rupture.


[Comparison of treatment outcome in patients with rheumatoid arthritis treated with TFX- Polfa or gold salts after a one year follow up]. Thirty five patients with rheumatoid arthritis were given TFX Polfa, initially everyday in the intramuscular injections in the dose of 10 mg TFX protein for 60 days, followed by 1 injection of 10 mg TFX protein a week for 10 months. Other 30 patients with rheumatoid arthritis treated with gold salts were used for comparison. Several clinical and laboratory tests were performed before the treatment and after 1 year. A one-year therapy significantly improved all clinical parameters in both groups. A significant increase in hemoglobin and erythrocyte count was noted in patients treated with TFX. A significant decrease in the markers of inflammation was seen. A percentage of both early and delayed E rosettes increased highly significantly. The obtained results suggest that TFX Polfa is efficient in these cases of the rheumatoid arthritis which cannot be treated with gold salts.


[Pefloxacin in the treatment of chronic urinary infection]. This study aimed at determining sensitivity of the hospital isolates to pefloxacin compared with other urinary antiseptics and assessment of its efficiency in the treatment of the chronic urinary infections. Disc diffusion technique was used to determine bacterial sensitivity to pefloxacin and other agents. Bacteria were isolated from the urine of the hospitalized patients. All tested strains were sensitive to pefloxacin. Its sensitivity exceeded in vitro 80%. Fifteen patients full sensitive to pefloxacin were treated. No bacteria were seen in the urine of 8 patients in two bacteriological cultures following the treatment, 3 patients stopped therapy due to adverse reactions, and no sterile urine was noted in 4 patients despite following a complete cycle of therapy.


[Reversible renal failure in female patients with acute interstitial nephritis caused by cloxacillin]. Cloxacillin was not listed as one of the drugs causing the acute interstitial nephritis, yet. A case of a 50-year female patient treated with cloxacillin is presented. Therapy was followed by nausea, vomiting, myalgia and arthralgia, and the symptoms of the acute renal failure which completely diminished after prednisone therapy despite of co-existing peptic ulcer. Low doses of corticosteroids seem helpful in the treatment of the acute interstitial nephritis following therapy with cloxacillin even after a long time of the onset.


Relationship between cardiovascular functions and ionic hypocalcemia induced by citrate infusion in anhepatic swines: CaCl2 therapy in severe ionic hypocalcemia. Baseline and serial values of serum [Ca++], [K+], [Na+], arterial blood gas tensions, acid-base status, temperature and hemodynamic functions were measured during infusion of citrate-phosphate-dextrose (CPD) solution (0.35 ml.kg-1 x min-1) in anhepatic pigs of three randomized groups. Thirteen pigs (group I) continued to receive intravenous infusion of CPD solution until cardiac arrest. When mean arterial pressure (MAP) decreased to about 50 mmHg (group II, n = 7), or 40 mmHg (group III, n = 7) infusion of CPD solution was discontinued, and pigs received CaCl2 (20 mg/kg) intravenously. Serial (1, 4, 8, and 12 min after CaCl2 administration) values of all the above variables and serum citrate at baseline and lowest [Ca++] were measured. After hepatectomy and venovenous bypass, cardiac output (CO) decreased 30%. When ionic hypocalcemia was above 0.7 mM, there was no significant change of cardiovascular functions. When [Ca++] was between 0.34-0.7 mM, there were linear relationships between [Ca++] and CO, systemic vascular resistance (SVR) and MAP, respectively. When [Ca++] was below 0.34 mM, cardiovascular functions decreased abruptly, and the pigs died at [Ca++] of 0.26 +/- 0.06 mM. When [Ca++] decreased to 0.36 +/- 0.06 mM and MAP to 50 +/- 4 mmHg, most hemodynamic functions could be reversed by calcium therapy. However, when [Ca++] decreased to 0.33 +/- 0.05 mM and MAP to 40 +/- 2 mmHg, hemodynamic functions could not be reversed by calcium therapy alone.


Effects of toluene on the morphology of neuropeptide secretory neurons of the rat hypothalamus. The effect of toluene on the hypothalamic hormone-secreting neurons and neurotransmitter-containing fibers in the rat was investigated by immunohistochemical methods. Multiple intraperitoneal injections of toluene (totally 7.5 ml) led to significant decreases of the neuronal numbers of vasopressin, oxytocin and neuropeptide Y in the preoptic and hypothalamic areas. The densities of vasopressin, oxytocin, norepinephrine and neuropeptide Y immunoreactive fibers of the toluene dose group decreased markedly in the median eminence. In contrast, LHRH neurons remained unchanged.


High resolution electron microscopic investigation of atomic structural images in human atherosclerotic plaque. Atomic structural images in the calcified matrix of human atherosclerotic plaques were characterized by high-resolution electron microscopy (HREM). The mineral elements distributed in the calcified matrix were analysed by energy dispersive X-ray microanalysis. Careful HREM observations revealed that a large number of microcrystallites and crystal particles with a broad spectrum of crystal size and perfection were embedded in the amorphous matrix of the calcified plaques. The amorphous phase in the calcified matrix was made up of a dense network of granulo-fibrillar substructures. The lattice-fringes with regular arrangement of atom columns along the lattice arrays were clearly demonstrated in the crystalline particles of the calcified plaques. A number of characteristic granulo-fibrillar substructures in the amorphous phase could be seen to be tightly connected to the lattice-fringes in the crystalline phase along the interfaces between the amorphous and crystalline phases. The crystal lattices at the boundary between two crystals were very well matched with the periodicity of visible atoms continuous through the two crystals. The mineral elements such as calcium and phosphorus were detected to be diffusely distributed in the calcified matrix of the atherosclerotic plaques. Based on these findings, it is concluded that: (1) an interlacing network of granulo-fibrillar substructures in the amorphous matrix may play a structural and/or regulatory role for the organic matrix by providing sites for nucleation; and (2) the deposition of the mineral elements may be effective for the transformation of the amorphous nucleation phase to well-crystallized nucleation phase.


Analysis of ragweed allergens recognized by monoclonal antibody 8-5 using two-dimensional gel electrophoresis and immunoblotting. A series of MoAbs against major allergens (Amb a I and Amb a II) of the short ragweed pollen is reported by this laboratory. One of these MoAbs, 8-5, showed strong reactivity to Amb a II, weak reactivity to Amb a I-B and I-C, and no reactivity to Amb a I-B2 of the short ragweed pollen by SDS-PAGE and immunoblotting. In the present study, ragweed allergens recognized by MoAb 8-5 were further analyzed by two-dimensional gel electrophoresis and immunoblotting. The results showed that MoAb 36-6, which has been identified to be reactive with Amb a I only, reacted mainly with components with MW of about 39 kD, which corresponded to creatine kinase charge standards from -14 to -20 in both the Amb a I-B and I-C preparation and the crude extract of the short ragweed pollen. However, MoAb 8-5 showed strong reactivity to components with about the same MW but charge standards from -8 to -13 in Amb a II and the crude extract of the short ragweed pollen. Furthermore, a weak positive reactivity of MoAb 8-5 to components with MW of about 39 kD and charge standards from -8 to -14 in Amb a I-B and I-C was also observed. It was thus concluded that MoAb 8-5 reacted with Amb a II only.(ABSTRACT TRUNCATED AT 250 WORDS)


Production of cephalexin by Gluconobacter oxydans CCRC 10383. Intact cells of Gluconobacter oxydans CCRC 10383 produced cephalexin from 7-amino-3-deacetoxy cephalosporanic acid (7-ADCA) and D-alpha-phenylglycine methylester HC1 (PGM). Factors affecting the production of cephalexin by G. oxydans CCRC 10383 were studied. The optimum pH and temperature for the synthetic reaction of cephalexin were 6.0 and 42 degrees C, respectively. A higher concentration of PGM than 7-ADCA was required to obtain a good yield of cephalexin.


[The comparison of dynamics in humoral responses in health personnel after vaccination against hepatitis B using Engerix B and Gen-H-B-vax]. The dynamics of humoral response in two groups of health care workers vaccinated according to the schedule 0, 1, 6 months, using two different recombinant vaccines has been comprised. In the group of persons vaccinated with Engerix B, 63 completed the full cycle of vaccination. Protective titer of anti-HBs (> or = 10 IU/L) was obtained in 93.6% of vaccinated. In the group of persons vaccinated with Gen-H-B-Vax, 62 completed the full cycle of vaccination, and protective titer of anti-HBs amounted to 90.3% of vaccinated. The humoral response on the protective level in both groups was not statistically different. However, the percentage of the persons with very high anti-HBs titers (10,000 and more IU/L) was higher after Engerix B.


[Long term results of vaccination against viral hepatitis B using recombinant vaccine Engerix B]. Among nineteen persons vaccinated against hepatitis B (recombinant Engerix B vaccine) fifteen (80 per cent) have developed anti-HBs (investigated 30 days after the third doses) on the protective level (10 U/l). After three and a half year three of them lost antibodies, and four had anti-HBs at level below 100 U/l. All of them received a booster doses, which resulted in a very high anti-HBs level one month later. Four persons without anti-HBs after the basic vaccination received in turn two booster doses: at the 3rd and 46th month. Only one person of them have remained a non-responder. We suggest to control a level of anti-HBs one month after basic vaccination for individual determination of the term of booster dose.


[Familial incidence of hepatitis b].

[Familial incidence of hepatitis b]. Among 693 patients treated in our Hospital with HBV, we separated 88 persons from 34 familial focuses. In those separated cases the most likely way of transmission were the familial contacts, without data indicating the other sources of infection (surgery, blood transfusions). The most common source of infection were children. We postulate vaccination of the HBsAg(-) person, staying in the familial contact with HBV patients.


[The course of acute HCV infection in patients with chronic non-A, non-B hepatitis]. Among 52 patients with chronic non-A, non-B hepatitis, observed for many years in the Department of Infectious Diseases of Pomeranian Medical Academy, retrospectively diagnosed towards HCV infection, 45 proved to be anti-HCV positive. Sera stored in the bank of sera were examined using 2nd generation tests: ABBOTT HCV EIA (Abbott), ORTHO RIBA (Ortho Diagnostics) and UBI HCV EIA (Organon), showing 85% of positivity. Mostly HCV infection was connected with the blood transfusion. The course of acute phase of HCV infection was mild, short lasting, with no or sporadic extrahepatic symptoms; the activity of aminotransferases and the bilirubin level were of average value. The only characteristic feature of the acute HCV infection was fluctuating aminotransferase activity, which can be the good sign of progression.


[Analysis of the correlation between measles and subacute sclerosis panencephalitis (SSPE) before and after introduction of vaccination in Poland]. Number of SSPE cases were analysed depending on epidemiologic situation of measles in Poland. Statistic analysis exhibit significant correlation between measles incidence in first year of live and total number of SSPE cases born in the same years. Problems antimeasles vaccination for eradication measles and SSPE were discussed based on the correlation.


[Serologic surveillance of influenza during the epidemic season 1990/91 in Poland]. The level of antibodies was tested in 9 age groups since 6 years up to over 75 years of age for H and N of influenza A(H1N1), A(H3N2) and B in epidemic season 1990/91. The highest GMT were found in all age groups for H3-A/Shanghai/16/88, much lower for H1-A/Taiwan/1/86. The titers were almost the same in all age groups excluding 6-8 years where GMT was much higher. The lowest titers were found for hemagglutinin of B/Yamagata/16/88 and different in different age groups. The highest GMT of neuraminidase were found for N2 in group 41-50 years old, in other groups were different. GMT for N1 were differentiated, but in 51-64 years old group was 3.5 times higher in comparing to the lowest value. For B neuraminidase the titer of antibodies was the highest in 31-40 years old group, and the lowest for 41-50 old people.


[Endemic occurrence of lyme disease in the forested areas of the Piła district]. Lyme disease (L.D.) caused by Borrelia burgdorferi and spread by Ixodes ticks arouses great interest with more and more clinicians and other scientists. It may be very difficult to diagnose a disease as L.D. because of its various clinical symptoms expressions. This is why it is often called "the great imitator". There are three phases in the natural history of the disease. Diagnostic problems come from the fact that early phases are often lacking. The disease may begin with any symptom of any stage. In our paper we present the endemicity of Lyme disease among a group of 28 people who spent their summer holidays on a forest camp near Piła (in the north-western part of Poland) in July 1991. We diagnosed 15 of them as having early stages of L.D.


[Isolation of Clostridium perfringens from a wound in a case of post-traumatic gas gangrene. Diagnostics remarks]. The authors described a case of post traumatic gas gangrene in a young man. Rapid clinical and microbiological diagnosis with isolation of Clostridium strain, and immediate therapy, including hyperbaric chamber, brought complete recovery without incapacitation.


[Evaluation of safety and immunogenicity of the Td vaccine in laboratory studies]. The new vaccine recommended as the booster dose contains in 0.5 ml: 10 BU Te-toxoid, 2 Lf Di-toxoid, 4.5-0.5 mg Al and 0.01% merthiolate. In 7 consecutive series it was state, the vaccine was safety and stable. The potency was 40-50 JO for Te and 30-40 for Di. The last series was recommended for vaccination under clinical control.


[Evaluation of vaccination reactions and serologic responses after Td vaccine in pilot studies]. Fifty six young adults volunteers received 10 BU tetanus and 2 Lf Diphtheria adsorbed vaccine (Td). Reactogenicity was noted in the special formulas, the serological response was determined by the passive hemagglutination in sera collected before and in 4 week after the vaccination. Twelve persons were not immunity for diphtheria before booster. The results confirmed the safety and efficacy of the polish Td vaccine.


[Elaboration and examination of the functioning of a new system for collection and analysis of information on foodborne and waterborne diseases in Poland]. During 1986-1989 the new computerized system of collection and analysis of foodborne and waterborne infections and intoxications (based on the proposition of World Health Organization) was developed in the Department of Epidemiology of the National Institute of Hygiene in Warsaw. System consists of the new forms (including computer's form) and adapted original programming. The new forms were officially introduced by the Ministry of Health and Welfare for the use by the all Sanitary Stations in Poland from the beginning of 1991. That system was served to present data on epidemiological situation of foodborne and waterborne infections and intoxications in Poland in 1988-1991, demonstrated in the paper. Criteria of analysis were adapted to meet conditions of the international cooperation, and-first of all-to the requirements of Polish epidemiological situation.


[Infant mortality and perinatal mortality in Poland in the eighties]. The dynamics of the changes in the level of infant mortality and perinatal mortality in Poland during 1980-89 by age and cause is presented. The statistical definitions concerning the perinatal period are used according to the World Health Organization's recommendations. There is stronger decline in postneonatal mortality rates then in neonatal rates during the eighties. The level of neonatal mortality rates (14.8 in 1989) and perinatal mortality rates (19.6 in 1989) is high comparing to the developed countries.


[Upper respiratory tract infections as a hypothetical source of sudden infant death syndrome (SIDS)]. A hypothesis that the common bacterial toxins are the possible cause of the Sudden Infant Death Syndrome (SIDS) was discussed. Recently, even botulinum toxin and Clostridium perfringens Type A enterotoxin are mentioned.


[Tobacco smoking and alcohol consumption as risk factors for stomach cancer in different locations and histologic types]. A multicancer hospital based case-control study involving interviews with 741 incident male and female gastric cancer cases under the age of 75 years and an equal number of age and sex matched controls has been carried out in Poland. Smoking cigarettes without filter increased the risk for intestinal cancer in the cardia part of the stomach (OR = 3.72, 95% CI: 1.35-10.23). Relative risk of the intestinal type of cancer in the distal part of the stomach was augmented with the increasing frequency and amount of vodka drinking. Subjects who drank vodka at least once a week had about 4.5 times the risk of intestinal cancer of the gastric corpus compared to non-drinkers (RR = 4.45, CI: 2.26-8.75). The relative risk of intestinal carcinoma in the distal stomach due to vodka drinking among those who used to drink vodka on an empty stomach was also elevated (RR = 3.28, CI: 1.33-8.13), but the effect of years of vodka drinking habit failed to show significant association with gastric cancer. A weak interaction effect between smoking and vodka drinking was found for intestinal cardia cancer. Diffuse type gastric carcinoma or mixed type carcinoma were not significantly related to smoking or vodka drinking habits.


[Iron deficiency and anemia in professional working women]. The hematological indices (Hb, Ht, MCHC) and iron status (serum iron, TIBC, LIBC, transferrin saturation), the prevalence of iron deficiency anemia in 224 women aged 31 to 47 years, working in textile industry in Lódź were examined. Nutritional status was evaluated as follow: body height and weight, body mass index (BMI kg/m2) and body fat content (%) calculated from the four skinfolds sum. Anemia (Hb < 12 g/dl) was stated in 11.2% participating women, evident iron deficiency (Fes < 60 micrograms/dl, Sat % < 16) in 13.4% of population. The positive correlation was found among hematological indices and body weight, body mass index and body fat content and relationships among iron status indices (Fes mu/dl, Sat%-positive correlation; TIBC microgram/dl, LIBC microgram/dl-negative relationship) and body fat content (%). The prevalence of iron deficiency and anemia were lower than in other women population in Poland examined in 1974-1986. The relationships among energy and protein nutrition and iron status and iron deficiency anemia suggest, that the menstruating overweight women or with obesity may be the group with lower risk of iron deficiency anemia.


Description of Dogielius molnari n. sp. (Monogenea: Dactylogyridae) from the gills of an Iranian freshwater fish, Cyprinion macrostomum (Heckel). The occurrence of a new Dogielius species is reported from the gills of Cyprinion macrostomum (Cyprinidae), an endemic fish of the River Tigris water system. The species is described as Dogielius molnari n. sp.


Effect of acute salinomycin-tiamulin toxicity on the lipid peroxide and antioxidant status of broiler chicken. The combined effect, if any, of salinomycin poisoning and salinomycin-tiamulin interaction on lipid-peroxidative processes and the antioxidative defence system of the liver was studied in domestic fowl. Male broilers (28-day-old), reared on a diet containing 60 mg/kg salinomycin, were treated intraoesophageally with salinomycin (140 mg/kg body mass) or tiamulin (50 mg/kg body mass). Malondialdehyde, reduced glutathione and cytochrome P-450 concentrations as well as glutathione peroxidase and catalase activities of the liver were determined. Liver malondialdehyde concentration rose in the salinomycin-treated group while the amount of cytochrome P-450 increased in both groups treated. Glutathione concentration and glutathione peroxidase activity of the liver decreased rapidly but hepatic catalase activity increased in both groups after the treatment. Manifestation of the effect exerted by salinomycin and salinomycin-tiamulin on lipid-peroxidative processes nearly coincided with the onset of clinical signs and preceded the increase of hepatic cytochrome P-450 concentration. According to the results, the background of the previously reported incompatibility between salinomycin and tiamulin is the synergistic effect exerted on the antioxidant (glutathione) system.


The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. VI. Superoxide dismutase and lipoprotein lipase activities. The kinetics of superoxide anion production in polymorphonuclear leukocytes of bronchopneumonic calves, as well as superoxide dismutase and lipoprotein lipase activities in the blood plasma of these animals were studied. Granulocytes of bronchopneumonic calves were found to produce 10 times as much O2- radicals as those of healthy animals. Superoxide dismutase and lipoprotein lipase activities were lower in the plasma of bronchopneumonic calves. Escherichia coli endotoxin was found to stimulate superoxide anion production in polymorphonuclear leukocytes in a dose-dependent manner. These facts suggest that an endogenous mediator, probably cachectin or some other monokine(s), plays a role in granulocyte activation during calf bronchopneumonia.


The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. VII. Granulocyte activation by arachidonic acid. Arachidonic acid-induced granulocyte activation was studied in calves. Both in healthy and in bronchopneumonic animals, neutrophil stimulation with 67 microM arachidonic acid caused a rise in granulocyte exocytosis. This event, however, was much more intense in granulocytes from diseased calves. Fatty acids were found to stimulate granule exocytosis from granulocytes. Oleic acid possessed the weakest while dihomo-gamma-linoleic acid showed the strongest activity of this type. It is suggested that arachidonic acid may be an important mediator of calf bronchopneumonia.


Activity of serum creatine kinase, lactate dehydrogenase and LD isoenzymes in piglets affected with congenital tremor: a case report. The activities of serum creatine kinase (CK), lactate dehydrogenase (LD) and LD isoenzymes were studied in 14 Prestice black pied pigs from a herd affected with congenital tremor. Mean CK activity was 19.57 +/- 3.56 mu kat.l-1 for 6 adult pigs, and it was 21.03 +/- 1.33 mu kat.l-1 and 20.42 +/- 1.23 mu kat.l-1 for the affected (n = 5) and control (n = 3) piglets, respectively. No significant differences were demonstrable between the groups in CK activity. Total serum LD and LD-4 as well as LD-5 isoenzyme activities were higher in sows. Piglets affected with congenital tremor showed an increase in total LD enzyme and LD-5 isoenzyme activity. It is concluded that no relationship exists between congenital tremor and serum CK activity in piglets. At the same time, there is a positive relationship between congenital tremor and significantly (P < 0.01) elevated LD enzyme and LD-5 isoenzyme activity. The results allow us to suggest that total lactate dehydrogenase and LD-5 isoenzyme activities could be used as biological markers of congenital tremor in piglets.


Is there lipid peroxidation induced malondialdehyde production during egg shell formation? The marked increase observed in malondialdehyde concentration of the blood plasma and liver of laying hens during egg shell formation in a previous experiment (Mézes and Lencsés, 1985) were explained as a possible consequence of physiologically controlled lipid peroxidation. In this experiment, 54-week-old laying hens were treated intrauterinally with indomethacin (1.0 and 2.0 mg/kg body mass) after oviposition. Two other groups of hens were treated per os with excess amounts of vitamin E (100 and 200 mg/bird). The higher dose of indomethacin significantly decreased the PGF2 alpha production and malondialdehyde content of the sell gland, as well as the malondialdehyde concentration of the plasma. The excess amount of vitamin E had the same effect. The results suggest that during egg shell formation malondialdehyde is derived from prostanoid biosynthesis rather than from a free-radical initiated lipid peroxidative process. On the other hand, the excess amount of vitamin E inhibited prostaglandin biosynthesis as well as malondialdehyde production.


Checking of immunity against Newcastle disease by ELISA. A total of 284 seven- to twelve-week-old Tetra SL chickens were assigned to 18 groups and immunized with a full or fractional dose of monovalent or multivalent inactivated vaccines subcutaneously or intramuscularly. Sera were taken from the birds at the time of challenge and tested for antibodies to Newcastle disease virus (NDV) by enzyme-linked immunosorbent assay (ELISA). The vaccinated birds were challenged with 10(6) ELD50 of virulent NDV subcutaneously. A close positive correlation (r = 0.954) was found between the protection percentage of the different groups and the group's arithmetical mean net extinction percentage (NE%) calculated from the net extinction values obtained for sera of birds belonging to the given group. NE% is easy to calculate and a good indicator of the flocks' immunity status. In our case: if NE% exceeded 80, the protection percentage of the flock was between 93.3 and 100%; if NE% was between 60 and 80, the protection percentage was between 75 and 87%, while with an NE% less than 60 the protection percentage ranged between 6.7 and 64.3%.


Pathogenic properties of Newcastle disease virus isolates in the Sudan. Six Newcastle disease virus (NDV) isolates were obtained from disease outbreaks on different poultry farms in the Sudan between 1988 and 1991. The pathogenic properties of these isolates were studied in comparison to those of strain Herts 33/56. All the isolates were similar in that they killed chicken embryos quickly, in mean death time (MDT) and embryo lethal dose 50 per cent (ELD50), had higher intracerebral pathogenicity indices (ICPI), and produced viscerotropic lesions in the infected chickens. The field isolates had the characteristics of the velogenic viscerotopic strains of NDV. The pathogenesis of infection caused by one of the isolates was studied. The virus was first detected in different organs and in oral and cloacal swabs on the third day after infection.


[Contribution of chemiluminescence for determination of low value TSH in patients with dysthyroidism during negative TRH test]. TSH values performed by immunoradiometric method were compared with chemiluminescent method in 28 hyperthyroid patients with negative TRH-test. This last method gives a better sensitivity (0.020 mUI/L vs. 0.050 mUI/L) and reproducibility (5% V.C. vs. 40%). The measure of undetectable TSH by immunoradiometric assay becomes possible with chemiluminescence. Due to this increase of sensitivity, the TRH-test needs to be reconsidered and allows to discriminate various degrees of TSH suppression.


[Serum human growth hormone assay. Comparison of six assay kits]. Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children.


[Acromegaly and bronchial carcinoid tumor. Apropos of a case]. Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. A 29-year-old woman with acromegaly secondary to ectopic GHRH secretion by a bronchial carcinoid tumor is presented. Normalization of GHRH levels, reversal of pituitary hyperplasia and regression of acromegaly followed resection of the bronchial tumor. The authors stressed the interest of GHRH dosage in patients with acromegaly and pituitary hyperplasia.


[MRI exploration of the hypothalamo-hypophyseal axis]. MR Imaging has become the procedure of choice for the exploration of the pituitary region. MR contrast resolution is far better than the finest CT examination, especially concerning the microadenomas and the neurohypophysis. The present paper concerns, at first the major principles of magnetic resonance imaging, its application for the study of the pituitary region including the use of contrast agent (Gadolinium). Lastly, MR anatomy and physiological variations are presented.


Growth hormone treatment in idiopathic short stature: a preliminary analysis of cardiovascular effects. Growth hormone (GH) hypersecretion is associated with an increased incidence of hypertension and cardiac hypertrophy, resulting in excess cardiovascular morbidity and mortality. Abnormalities in the renin-angiotensin-aldosterone (RAA) system have been reported in acromegaly and in normal adults treated with recombinant human GH. The RAA system was investigated in prepubertal children with idiopathic short stature during treatment with recombinant human GH in doses up to 40 IU/m2/week. In addition, left ventricular size and function were assessed by serial echocardiography over an initial 12-month period. Modest and transient increases in blood pressure and body weight were observed during the first 7 days of GH treatment, but this was not accompanied by activation of the RAA system. Echocardiographic parameters of left ventricular size and function remained within the normal range for age and body size. Short-term GH treatment of idiopathic short stature was thus not associated with an increase in risk factors known to be associated with later cardiovascular morbidity. Longer follow-up studies will be required to confirm the safety of high-dose GH in this respect.


Biological standardization of pollen allergens from India. Standardization of allergens are achieved by in vitro and in vivo methods. Some of the allergens from Western countries are standardized using biological potency of the extracts but no attempt has been made till now to standardize any of the pollen extracts from India based on biological units. Therefore, we have attempted to standardize two important pollen allergens Ricinus communis and Holoptelea integrifolia by biological methods. Broadly the methods adopted by Dreborg and Grimmer (1983) was followed. Skin prick tests were carried out with the extracts of R. communis and H. integrifolia on 15 allergic patients in five three fold log dilutions starting with 1:10, in 50% glycerinated buffer. Glycerinated buffer (50%) and histamine dihydrochloride (1 mg/ml) were used as negative and positive controls, respectively. The mean wheal diameter obtained with different concentrations showed a gradual systematic fall with increase in dilution. The mean relative diameter (% of histamine reaction) varied from 124.1 +/- 8.9 to 33.7 +/- 6.1 and 78.9 +/- 5.5 to 21.4 +/- 3.8 with the highest and lowest concentrations of R. communis and H. integrifolia pollen antigens, respectively. The histamine equivalent concentration of antigen 1,000 Biological Units (BU) obtained for crude pollen extracts of R. communis and H. integrifolia was 1:17 and 1:22 respectively.


Ice cube test in children with cold urticaria. The ice cube test performed in 24 children (6 cold urticaria, 6 healthy, 6 allergic and 6 chronic urticaria) showed that a 3 and 5-minute ice cube test was the appropriate time for the diagnosis of cold urticaria without false positive results. If the test was prolonged to 10 and 20 minutes, 17% and 33% respectively showed false positive results in chronic urticaria other than cold urticaria patients. After four weeks of cyproheptadine therapy, the ice cube test showed only 17% positive at 3 minutes and 33% at 5 minutes. When the ice cube test was performed for 10 and 20 minutes, 67% showed positive results. In conclusion, the ice cube test should be performed for 3 to 5 minutes to diagnose cold urticaria in children. The time should be increased to 10 or 20 minutes if the test shows negative results at 3 to 5 minutes after antihistamine therapy.


Bone marrow transplantation in Ramathibodi Hospital: progress report. Bone marrow transplantation has become the accepted treatment for several hematologic disorders. We have done 3 autologous and 6 allogeneic bone marrow transplantations at Ramathibodi Hospital since July 1989 in patients with acute lymphoblastic leukemia, acute non-lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma and severe aplastic anemia. Only one patient with aplastic anemia had late graft rejection, but the rest of them engrafted and did well during the median follow up period of 317 days (range: 39 to 962 days) post transplantation. None of the allogeneic BMT had graft-versus-host disease. We use cyclosporin and short course methotrexate for post transplantation immunosuppression.


Monoclonal gammopathies and the related autoimmune manifestations in Taiwan. A total of 50,000 patients were surveyed for the presence of monoclonal immunoglobulins during the past two decades. There were 411 cases of monoclonal gammopathies including 243 cases of plasma cell neoplasms and 168 cases of secondary plasma-cell dyscrasia. Among the 227 cases of multiple myeloma and Waldenström's macroglobulinemia, there were 49.3% IgG class, 22.9% IgA class, 9.7% IgM class and 13.2% light chain type. In addition, there were 1.3% of nonexcretory myeloma including an IgM type. A relatively high frequency (4.8%) of IgD M-proteins was detected but heavy chain disease was not encountered in the present series. Purified M-components from patients with possible autoimmune manifestations were subjected to immunofluorescence studies. Autoimmune activity of M-proteins was found in a patient of Waldenström's macroglobulinemia with peripheral neuropathy, and another patient of cryofibrinogenemia with recurrent purpura and gangrene. In conclusion, a high frequency of IgD myeloma is found in Chinese patients of this area. M-components may have autoimmune activity resulting in unusual clinical manifestations.


Interaction of respiratory syncytial virus with human cord blood mononuclear cells. This study on the interaction between respiratory syncytial virus (RSV) and human cord blood mononuclear cells shows that RSV replication can occur in neonatal macrophages. Although neonatal lymphocytes were not supportive of RSV replication, exposure to RSV resulted in significant inhibition of mitogen-induced transformation. Both adult and neonatal NK cell cytotoxicity were unaffected by exposure to RSV. These results suggest that RSV has preferential effects on human cord blood mononuclear cell subpopulations.


Comparative evaluation of HIV infected foreign students and Indian with AIDS in Chandigarh, India. Out of a total of 1,600 foreign students who came to India between June 1989 and October 1990, 22 were seropositive for HIV-1. Ten showed antibodies to all the gene products. Antibodies to gp160 and p24 were present in all the seropositives while antibodies to p53, p15/17 were significantly higher in healthy seropositives than in patients with full blown AIDS. Absence of antibodies to p15/17 and p53 thus appeared to be a more sensitive criterion of end stage disease than absence of anti- p24 antibodies. When seropositive samples from African students were checked for HIV-2 antibodies by ELISA, 13/22 were found to be positive. Further, 2/10 Indians with full blown AIDS were also strongly positive for HIV-2. These data could be of relevance for formulating future strategies for population-based screening for HIV-2.


Immunoassays of amphetamines: immunogen structure vs antibody specificity. Various immunoassays have been developed for the detection of amphetamines. These have varying degrees of cross-reactivity to other drug and food components. Information on the immunogen structures used, and the specificities of the antibodies obtained, have allowed formulation of a "structure-specificity" pattern delineated on the basis of immunochemistry and stereochemistry. The 'structure-specificity' relationship should be useful to future developments of these immunoassays. Specifically, immunoassays intended to detect either amphetamine or methamphetamine with minimal cross-reaction, should employ immunogens with amphetamine (or methamphetamine) derivatized via the para position of the phenyl ring. Such assays should show minimal cross-reaction with other secondary (or tertiary) amines but should strongly cross-react with phenyl ring substituted analogs. On the other hand, assays intended for detection of both amphetamine and methamphetamine should employ amphetamine (rather than methamphetamine) derivatized via its amino group as an immunogen. Such assays should show minimal cross-reaction with other tertiary amines and phenyl-substituted amphetamine/methamphetamine.


A comparison of different intervals of administration of inhaled terbutaline in children with acute asthma. Thirty asthmatic children, 5 to 14 years of age, 20 boys and 10 girls, were studied while having acute asthmatic attacks. Each group of 10 children received either a single dose of 6 puffs (1500 micrograms) or 3 doses of 2 puffs (500 micrograms) at 5-minute or 15-minute intervals of terbutaline pressurized aerosol inhaler through a 750-ml volumetric spacer. The onset of bronchodilatation was observed within 2 minutes in all. The 3 doses at 15-minute intervals gave the greatest bronchodilatation throughout the 6-hour study period in comparing with the other two regimens. Slightly insignificant increases in systolic blood pressure and heart rate were observed in all groups and there were no statistically significant differences among them. No serious side effects were observed.


Detection of IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one by RAST: a serological diagnostic method for sensitivity to pyrazoline drugs. Certain adverse reactions to pyrazoline drugs resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions is not fully demonstrated. In this study, IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one have been found in 17 out of 19 serum samples from individuals sensitive to pyrazoline drugs with 4-aminoantipyrine discs by Radio Allergo Sorbent Test (RAST). In contrast, we have not found any positive results from 10 normal donors without sensitivity to pyrazoline drugs after ingestion of metamizol 500 mg/day for 14 days. Therefore, our results provide further evidence in favor of an IgE-dependent mechanism in patients suffering from sensitivity to pyrazoline drugs. The determination of specific IgE antibodies could be used as a serodiagnostics method.


[Genetic polymorphism of complement component six (C6) in five Han subpopulations]. By using polyacrylamide gel isoelectric focusing followed by immunoassay, the polymorphism of Complement Component Six (C6) was investigated in five Han subpopulations in China. The following gene frequencies were obtained Zhengzhou Han: C6*A 0.4521, C6*B 0.5228, C 6*B2 0.0183, C6*R 0.0068; Lanzhou Han: C6*A 0.4612, C6*B 0.5218, C6*B2 0.0170; Huhhot Han: C6*A 0.4452, C6*B 0.5286, C6*B2 0.0214, C6*R 0.0048; Xi'an Han: C6*A 0.4899, C6*B 0.4874, C6*B2 0.0126, C6*R 0.0101; Hakka of Meizhou, Guangdong Province: C6*A 0.4569, C6*B 0.5152, C6*B 0.0279 (C6*R is the frequency of rare alleles).


[A computer simulated test for the long-time change of heterozygote. Analysis of possibility on preserving the heterozygote for long-time in population]. Under the conditions of random mating and selecting. The research by computer simulation analysed the possibility of long-time conserving heterozygote in colong. An important conclusion was obtained. It was impossible to conserve heterozygote for a long time in colong. Therefore it is not necessary to control inbreeding for conserving all genes of colong by reducing gene purity in the work of conserving breeds for farm animal and poultry.


[Effects of several primary factors related to establishment of mouse embryo pluripotent stem cell lines (ES cell line)]. Several primary factors related to establishment of mouse embryo pluripotent stem cell lines (ES cell lines) have been tested comparatively. The results of 825 embryos indicated: (1) Delayed blastocysts were more conducive than normal ones to proliferation of inner cell mass (ICM). (2) Culture medium DMEM with 4 500 mg/l glucose was more advantageous than DMEM with 1000 mg/l glucose to the attachment of explanted blastocysts and to the proliferation of ICM. (3) DMEM without sodium pyruvate was beneficial to appearance of ES cell colonies and to their growth. (4) Feeder layer prepared from the primary culture of mouse embryos had very good effects to the growth and culture of ES cells.


[Cloning and expression of alpha-hydroxy-gamma-aminobutyl acylase gene of Bacillus circulans NRRL-B3312]. With shot-gun cloning strategy, we used pUB110 plasmid as a vactor to clone DNA fragment of Bacillus circulans NRRL-B3312, which is butirosin producer, into Bacllus subtilis 168. Among the transformants, the results of TLC, bioautography and FAB mass, spectrum analysis for the bioconversion product of No. 733 transformant showed that this transformant could transform kanamycin into amikacin. According to these results, the HABA acylase gene locates on the insert fragment of pUBC733 plasmid harbouring No. 733 transformant. We can confirm that the HABA acylase gene was cloned and expressed in B. subtilis 168. Molecular weight of pUBC733 is 7.3kb. Southern hybridization demonstrated that the 2.8 kb inserted fragment of this plasmid originated from B. circulans NRRL-B3312. The restriction map of pUBC733 plasmid was constructed.