Nurses' professionalism in Canada: a labor process analysis.

This article draws on a body of research conducted by the author over the past ten years on the social organization of nursing work. It explores questions surrounding nurses' contemporary labor process control and its meaning for nurses' professionalization and proletarianization. Both are dynamic processes, changing as public administration of the Canadian health care system changes and as nurses are successful in winning more complete self-regulation. Nurses are currently being articulated more and more securely to dominant ideas of public sector management through textually mediated technologies. Nurses find new upwardly mobile careers and challenging, responsible, and more respected work. However, as the generation of objective information for professional accountability, cost-accounting, and managerial decision-making becomes unified in computerized patient information systems, producing and using such information becomes a central and determining core of everyday nursing work. It organizes nurses into a "managed" practice of patient care, contradictory for them in many ways. Outstanding among these contradictions is a new professionalized standpoint of cost-efficiency that subordinates nurses' traditional interests and grounding of their work in the standpoint of care.


From a policy of inequality to a proposal of equity: political processes and health care in the municipality of São Paulo.

A tentative analysis is made of the recent São Paulo experience in health care management, in which the chief guideline has been to create institutional space for grass-roots and health worker participation within the State apparatus. The analysis takes Brazil's recent health policies and the so-called Sanitary Reform movement as reference points. The issue is approached from the angle of democracy and democracy's possibilities in the context of a society characterized by tremendous social inequalities, and in the context of the current international and national neoliberal offensive.


Tsutsugamushi disease (scrub typhus).

Two patients with Tsutsugamushi disease (fever) were successfully treated with tetracycline derivatives after typical eschars were found, although one of the patients was initially misdiagnosed as having a drug reaction eruption. Prompt diagnosis and treatment are important because this disease can be associated with considerable morbidity and simple effective treatment is easily available.


Granuloma inguinale: three cases diagnosed in Toronto, Canada.

Granuloma inguinale (GI) is a sexually transmitted disease seldom seen in the United States and Canada. We are reporting three cases recently seen in Toronto, Ontario, two in immigrants, and one in a native born Canadian who had an intimate relationship with a foreign visitor. The basic features of the disease are discussed.


Microbiology of secondarily infected diaper dermatitis.

Specimens obtained from 67 infants with secondarily infected diaper dermatitis were cultured for aerobic and anaerobic bacteria. Bacteria growth was obtained in 58. Aerobic facultative bacteria or Candida sp. only were present in 28 patients (48%), anaerobic bacteria only in 11 (19%), and mixed anaerobic with aerobic, facultative, or yeast flora was present in 19 (33%). Ninety-one bacterial or fungal isolates were recovered (1.6 per specimen), 54 (0.9 per specimen) aerobic or facultative bacteria, 8 (0.1 per specimen) Candida sp., and 31 (0.6 per specimen) strict anaerobes. The predominant aerobic and facultative bacteria were Staphylococcus aureus (23 isolates), Streptococcus sp. (16), and Escherichia coli (6). The predominant anaerobes included Bacteroides sp. (12, including 9 Bacteroides fragilis group) and Peptostreptococcus sp. (11). Single bacterial isolates were recovered in 32 (55%) patients, 18 of which were S. aureus. Twenty-five beta-lactamase-producing bacteria were detected in 22 (51%) of the 43 tested patients. These included 16 S. aureus and 6 B. fragilis group. These data highlight the importance of anaerobic bacteria in the polymicrobial nature of secondarily infected diaper dermatitis.


Pilomatricoma: a retrospective study.

A study of 53 Pakistani patients with pilomatricoma diagnosed at AFIP during 1985-1989 is presented. It constituted 37.2% of all benign adnexal tumors, during the same period. 56.2% of patients were more than 30 years of age. Differences in site, sex, and age distribution from Western reports were observed. Unusual clinical presentations were also noted. This study outlines the clinicopathologic features of pilomatricoma in Pakistan.


Terbinafine: efficacy and safety in the treatment of dermatophytosis.

A double-blind study with terbinafine was performed in 39 patients with dermatophyte infection, between 1987 and 1989, to compare the safety and efficacy of two dosage schedules of 125 mg twice daily versus 250 mg once daily. Mycologic assessments were negative by microscopic examination and Sabouraud's culture in 59% and 100% of patients in the first and the fourth weeks of treatment, respectively. There was no statistically significant difference between the two groups of patients receiving 125 mg b.i.d. and 250 mg q.d. with respect to the safety and efficacy of the treatment; however, the differences between the sums of clinical scores before and after the treatment were statistically significant. There were no adverse effects, and the drug was well tolerated.


Enalapril: a powerful in vitro non-thiol acantholytic agent.

Drugs containing sulfhydryl groups (thiol drugs) (e.g., penicillamine, captopril, thiopronine) can induce pemphigus in vivo and provoke acantholysis in vitro. Enalapril, like captopril, is an angiotensin-converting enzyme (ACE) inhibitor largely used as an antihypertensive drug; it has recently been reported to induce pemphigus, though it is not a thiol drug. In this study we investigated the possible in vitro acantholytic effect of enalapril on normal human skin from donors. The drug induced severe acantholytic changes of keratinocytes and complete suprabasal splitting at one tenth the concentration required by thiol drugs in similar experiments, even after a shorter period of culture. All skin samples from different donors was highly susceptible to the acantholytic effect of enalapril. In our experience, enalapril is the most powerful acantholytic drug in vitro.


Saperconazole in the treatment of systemic and subcutaneous mycoses.

In a 2-year period, 30 patients with culture-proven mycoses (chromoblastomycosis, sporotrichosis, and paracoccidioidomycosis) were treated with the new orally administered triazole, saperconazole (SPZ) (R66905). The daily dose varied from 100 to 200 mg. All patients responded to treatment; the mean time required to heal the lesions and convert the cultures to negative was 3.5 months for sporotrichosis, 4.6 for paracoccidioidomycosis, and 9.0 for chromoblastomycosis. Evaluation by a scoring system indicated that 36.6% of the patients achieved complete resolution of the pretherapy abnormalities, while the remaining (63.3%) experienced major improvement. No collateral effects were reported; there were no bone-marrow or liver toxicities. SPZ is an effective drug for the treatment of the above-mentioned mycoses and appears to be suitable for the control of chromoblastomycosis.


Recessive dystrophic epidermolysis bullosa treated with phenytoin.

Three patients with severe recessive dystrophic epidermolysis bullosa were treated with oral phenytoin and palliative and supportive measures for variable periods. Their progress was compared with that of three milder cases managed only with palliative and supportive measures. The phenytoin-treated group showed marked decrease in blister count, increase in trauma tolerance, a rise in hemoglobin level, and considerable weight gain. The results support earlier reports that collagenase inhibitors are useful in controlling blister formation in recessive dystrophic epidermolysis bullosa.


Maternal alcohol consumption and child development.

Studies of development and behaviour from shortly after birth up to the age of 7 years are reviewed. Maternal alcohol consumption above 150-200 g/week is related to behaviour in many studies, but below this level there is little epidemiological evidence of association. There is no evidence that the levels of consumption associated with adverse behaviour are lower than those associated with adverse pregnancy outcome.


Animal models of prenatal alcohol exposure.

Since the first reports of fetal alcohol syndrome (FAS), thousands of studies have examined the effects of antenatal alcohol exposure in humans and in animal models. Research with animal models has led to discoveries which would be difficult if not impossible in human subjects. Most importantly, these models have resulted in valuable insights into the actions of alcohol on various parts of the developing embryo and have helped researchers come closer to identifying the mechanisms of its teratogenic action. Both the direct and indirect biological effects of alcohol exposure in utero appear to work in conjunction with other concurrent and predisposing factors such as genotype, nutritional status, pattern of exposure and use of other drugs such as nicotine and cocaine. At present animal research indicates a multifactorial mechanism of the teratogenicity of alcohol resulting from nutrient deficiencies, fetal hypoxia and alterations in enzyme activities and cell function important in cell division and membrane integrity. This review examines how animal models are used to clarify issues associated with alcohol-related birth defects and to shed light on the underlying mechanisms.


The impact of alcohol misclassification on the relationship between alcohol and pregnancy outcome.

Underreporting, more than overreporting, is a problem in studies of the effects of alcohol consumption using self-reported data. Numerical examples illustrate that in studies of the effect of alcohol, nondifferential misclassification of alcohol consumption due to underreporting may lead to a bias away from the null value. It may also cause a true threshold level for alcohol to appear as a dose-response relationship. It is shown that the effect of misclassification on effect estimates will depend on the true frequency of abstainers in the studied population.


EUROMAC. A European concerted action: maternal alcohol consumption and its relation to the outcome of pregnancy and child development at 18 months. Results--strategy of analysis and analysis of pregnancy outcome.

Analyses were made of the relation between maternal alcohol consumption before and in early pregnancy and five infant outcome variables: birthweight, crown-heel length, occipitofrontal circumference and the Apgar scores at 1 and 5 minutes. The data were analysed for all centres combined and separately. From tabulation of the mean values of the outcome variables by alcohol consumption, it appeared that a poorer outcome was related to consumption of 120 g/week absolute alcohol or more. Multiple regression analysis was used to allow for possible confounding by the child's gestational age at birth and sex, the mother's age, parity and smoking habit, and survey centre. Two threshold models were applied to the combined data, taking the confounders into account. The offset threshold model (assuming no effect of alcohol up to a threshold value, and then a constant multiplicative effect at higher levels) suggested a negative effect on birthweight at about 60 g/week absolute alcohol, but with a wide 85% confidence interval of 5-130 g/week. A step function threshold model, which assumes a constant effect above the threshold value, behaved erratically. Similar analyses for crown-heel length and occipitofrontal circumference provided only a very poor fit to the data. Data on reported congenital anomalies are presented by survey centre and maternal alcohol consumption, but due to the unstandardized method of collection they were not analysed further.


EUROMAC. A European concerted action: maternal alcohol consumption and its relation to the outcome of pregnancy and child development at 18 months. Results--child development at age 18 months.

Children seen in the first part of the study in Berlin, Dundee and Odense were followed up at age 18 months and tested using the Bayley Scales of Infant Development. Five scores were recorded: the Mental Development Index (MDI), the Psychomotor Development Index (PDI) and scores for responsiveness, attention span and activity. The data were analysed for the centres combined and separately, allowing for confounding variables as in the previous chapter. In none of the comparisons was the mean score found to be significantly less in the children of drinkers than in those of abstainers. In many of the comparisons the children of abstainers had the lowest mean scores. In a number of comparisons in Berlin and Dundee, the MDI or PDI was found to be significantly higher in the children of women who had drunk at the upper end of the consumption distribution.


Alcohol and the fetus.

The teratogenic effects of alcohol have been recognized in the fetal alcohol syndrome. The syndrome is associated with very high levels of maternal consumption. Studies of the relation between much lower levels of consumption and pregnancy outcome seem to indicate consistently lower birthweight among children born to mothers drinking more than 140 g absolute alcohol per week, or about two drinks a day.


Endometrial stromal sarcomas of the uterus with extensive endometrioid glandular differentiation: a report of three cases that caused problems in differential diagnosis.

Three cases of endometrial stromal sarcoma (ESS) with prominent glandular differentiation within the primary or recurrent tumors are described. Each case posed a problem in diagnosis and classification. The patients, who ranged in age from 41 to 47 years, presented with abnormal uterine bleeding, a pelvic mass, or a combination thereof. All the patients underwent hysterectomy with or without bilateral salpingo-oophorectomy. There was no evidence of extrauterine spread of tumor in any case. Polypoid tumors involved the endometrium in two cases, and in one of them, tumor deeply invaded the myometrium. The tumor in the third case was an infiltrative mass that was confined to the myometrium and its vessels. On microscopic examination, the tumors were low-grade ESSs that contained large numbers of endometrioid glands, which were benign appearing in two cases, and in the third varied from atypical to carcinomatous. In one of the cases in the first group, the glandular component was present only in recurrent tumor excised 10 years after hysterectomy; prominent foci of sex-cord-like differentiation were also present in the recurrent tumor. This patient was clinically free of tumor 27 months later; follow-up in the other two patients was uneventful. ESSs with prominent numbers of benign-appearing glands should be distinguished from adenomyosis, endometriosis, ESSs arising in adenomyosis or endometriosis, ESSs with sex-cord-like differentiation, and müllerian adenosarcomas. ESSs with carcinomatous glands should be distinguished from endometrial adenocarcinomas and malignant müllerian mixed tumors (carcinosarcomas). Extrauterine lesions that have been designated "aggressive endometriosis" may be examples of extrauterine ESS with prominent glandular differentiation.


Nd:YAG laser endometrial ablation: histological aspects of uterine healing.

Laser ablation of the endometrium performed under hysteroscopic control is a novel procedure for the conservative management of menorrhagia in cases of dysfunctional uterine bleeding. The effect this has on the uterine cavity and the mechanism of reepithelialisation and endometrial regeneration have been examined by means of histological examination of endometrial biopsies and four hysterectomy specimens obtained for various indications at varying time intervals after laser endometrial ablation. During the first 3 months, fragments of necrotic and granulation tissue are found surrounded by a limited polymorph response. By 3 months, the uterine cavity appears to be completely reepithelialised. After 6 months, areas of normal-appearing endometrium may persist, but in other areas there is an attenuated cuboidal surface epithelium closely applied, to the underlying myometrium. Stromal fibrosis reminiscent of Asherman syndrome is also apparent.


Hereditary ovarian cancer: a clinicopathological study.

Hereditary ovarian cancer (HOC) is rare and little recognized. Over the years, we have identified 37 HOC patients from HOC syndrome kindreds with documented cancers of ovary, breast, colon, or endometrium in two or more first-degree relatives. The age and clinical stage at diagnosis and overall 5-year survival of HOC patients were compared with those of ovarian cancers in the unselected patients. The gross and microscopic features of the tumors are compared with a set of 34 consecutively chosen ovarian cancer cases with documented negative family histories. The mean age of HOC patients at diagnosis was significantly lower (50.2 years) than that of the unselected control population (59 years) (p less than 0.001). Detailed pedigree analysis breaks down the HOC group into (a) site-specific ovarian cancer, 5 cases, 56.4 years mean age; (b) breast-ovarian cancer syndrome, 28 cases, 50.46 years mean age; and (c) Lynch syndrome II (colon/endometrial cancer), 4 cases, mean age 41 years. The age differences were statistically significant (p = 0.050). The most prevalent International Federation of Gynecology and Obstetrics clinical stage at diagnosis of HOC (stage III) was the same as for the control group. Histologically, all (100%) HOC tumors were surface epithelial cancers with predominance of serous papillary type moderate to high grade (89 versus 71% in control, p = 0.07). No other pathologic features appeared to be significant. In conclusion, HOC is a serous papillary tumor and characterized by early age of onset and excess of breast/ovary/colon-endometrial cancers in first-degree relatives of patients with specific HOC syndromes.


Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.


Distribution of tumor-associated glycoprotein-72 (TAG-72) expression throughout the normal female reproductive tract.

Compared with the degree of investigation of stage-specific expression of tumor-associated glycoprotein-72 (TAG-72) in fundal endometrium, other regions of the female reproductive tract have not received comparable attention. Regional, cell-type-specific, and temporal differences in estrogen receptor and progesterone receptor distribution and concentration among these tissues should make such examination beneficial to our understanding of hormonal regulation of TAG-72 expression. The pattern of monoclonal antibody (MAb) B72.3 recognition in the cervix, uterus, oviduct, and ovary was examined by immunohistochemistry during both the proliferative and secretory intervals of the normal menstrual cycle. Intense immunoreactivity in fundal endometrium was limited to the secretory menstrual interval. Conversely, TAG-72 expression was generally weaker, sporadically distributed, and not stage specific in the lower uterine segment, endocervix, and cervix; no expression was detected in the oviduct or ovary. The disparity in both temporal and spatial distribution of TAG-72 expression throughout the female reproductive tract does not appear to be directly associated with the well-described changes in circulating estradiol or progesterone or the receptors for these steroids. Results suggest that regulation of TAG-72 expression may involve local paracrine/autocrine mechanisms, which in turn may be subject to hormonal influence.


Epithelioid hemangioendothelioma of the clitoris: a case report with immunohistochemical and ultrastructural findings.

A 30-year-old woman was referred for evaluation of a small nodule of the clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma. This rare vascular tumor of intermediate malignancy has not been previously described in the vulva. The patient underwent a modified radical vulvectomy and bilateral inguinal lymph node dissection, and subsequently received photon therapy. She is alive with no evidence of disease 27 months after diagnosis.


Polypoid cystic adenomyosis of the uterus: report of a case.

A case of focal adenomyosis of the uterus with unusual gross features is presented. The patient, a 43-year-old woman, had experienced abnormal vaginal bleeding for 8 years. Hysteroscopy revealed a polypoid mass compatible with a submucosal leiomyoma, and a hysterectomy was performed. The uterus showed a 7 x 5 x 3-cm firm polypoid mass attached to the anterior wall that occupied most of the uterine cavity and protruded through the cervical os. It contained a large, central, cystic cavity filled with bloody fluid that communicated with the endometrial cavity through a fistula-like tract. Both the surface of the mass and the inside of the cystic cavity were covered by endometrial mucosa, and there were endometrial islands in the intervening wall. The differential diagnosis of this unique form of adenomyosis included polypoid submucosal leiomyoma with invagination of endometrium, endometrial polyp, submucosal leiomyoma with invagination of endometrium, endometrial polyp, and uterine diverticulum.


Expression of epidermal growth factor receptor in normal ovary and in ovarian tumors.

Increased expression of epidermal growth factor (EGF) receptor has been recorded in many types of human tumors and has been associated with reduced survival in ovarian carcinoma. The purpose of this study was to examine the immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30) and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in the granulosa cells of a developing follicle, and in surface epithelium. Forty-seven of 103 malignant common epithelial tumors were immunopositive. Staining was usually focal, always confined to the neoplastic epithelium, and showed a cytoplasmic distribution. There was a slight trend for increased EGF receptor expression in more advanced common epithelial malignancies, but this was not statistically significant. No correlation between immunoreactivity and histological subtype or grade of tumor was seen. A few other tumors were also examined: one each of Brenner tumor, mature teratoma, mature teratoma with squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.


Clomiphene's effect on endometrium in infertility.

Secretory-phase endometrium from patients receiving clomiphene has an identifiable, distinctive character. We reviewed 710 endometrial biopsies from 566 infertility patients, including 108 from 79 patients receiving clomiphene. Endometrial glands in biopsies from clomiphene-treated patients were straight, narrow, and less tortuous than normal. Gland-to-stroma ratio was decreased. In the early secretory phase, glands had crisp subnuclear vacuoles and distinct glandular lumenal borders. Secretions were scant throughout the secretory phase, with few apical snouts. Lumenal secretions appeared inspissated and hyaline-like. Late secretory epithelium was generally low cuboidal and rarely showed hypersecretory change. Stromal predecidualization in the late phase showed progression, but in some cases decidual cells were smaller than usual. All of these features are consistent with a hypoestrogenic effect.


Diffuse adenomatoid tumor of the uterus with a serosal papillary cystic component.

A 39-year-old woman undergoing immunosuppressive therapy following kidney transplantation for systemic lupus erythematosus presented with a uterine adenomatoid tumor that diffusely infiltrated the entire myometrium and contained a serosal papillary cystic component that resembled a cystic mesothelioma. This is the first reported case of an adenomatoid tumor showing both of these features. Although adenomatoid tumors are considered benign, the patient may be at risk for recurrence of the papillary cystic component (which is known to recur in 50% of cases) if this tumor reflects an inability to limit neoplastic processes.


Endometrial stromal nodule with smooth and skeletal muscle components simulating stromal sarcoma.

A stromal nodule was found in a hysterectomy specimen from a 29-year-old woman with a history of menometrorrhagia. Endometrial curettings had revealed stromal cells admixed with well-defined bundles of smooth muscle cells, a finding that had led to the erroneous diagnosis of stromal sarcoma invading the myometrium. Ultrastructural and immunohistochemical studies demonstrated several components: stromal cells, smooth muscle cells, sex-cord-like structures, and a hitherto undescribed component of skeletal muscle cells.


Cytologic features of malignant ovarian monodermal teratoma with an ependymal component in peritoneal washings.

A case of malignant neuroectodermal tumor of the ovary (monodermal teratoma) with a predominant ependymal component in the peritoneal washings of a 27-year-old woman obtained on second-look laparotomy is presented and discussed. The smear and cell block preparations showed sheets and clusters of cells containing oval nuclei with finely granular chromatin and small nucleoli. The cell nuclear/cytoplasmic ratio was within normal limits, and minimal cytologic atypia was observed. The clusters were rimmed by columnar-oriented cells lined by cilia. This is the first reported case of this rare ovarian neoplasm present on fluid cytology. Its bland cytologic appearance could be confused with endosalpingiosis.


The partial characterization of proteases present in the excretory/secretory products and exsheathing fluid of the infective (L3) larva of Necator americanus.

Following the observation that live third-stage larvae (L3) could digest gelatin in vitro, gelatinolytic protease activity has been demonstrated at pH 8.5, in both exsheathing fluid (EF) and excretory/secretory (ES) products of infective L3 of Necator americanus. EF resolved as a single band of proteolytic activity, with a mol. wt of 116 kDa, while L3 ES products exhibited multiple bands of proteolysis, at 219, 200, 195, 166, 137, 92, 72 and 62 kDa; weak bands were detectable at 92 and 72 kDa. The EF protease was characterized as cysteine, whereas ES apparently possessed one serine (195 kDa) and seven (219, 200, 166, 137, 92, 72 and 62 kDa) cysteine protease bands and a combination of metallo- and cysteine proteases of approximately the same mol. wts (62, 137 and 219 kDa). Though EF was not able to cleave immunoglobulins, ES was shown to cleave IgG, IgA and IgM, but not IgD or IgE. The activity appeared to be directed toward the Fc portion of the molecule, and was inhibited by PMSF, which is indicative of serine protease activity. The significance of the presence of such apparently diverse proteases in larval products is discussed.


Skin penetration by ensheathed third-stage infective larvae of Necator americanus, and the host's immune response to larval antigens.

In vitro experiments were conducted to assess skin penetration by ensheathed third-stage infective larvae (L3) of Necator americanus. The fact that only a small proportion of larval sheaths was recoverable from the outer skin surface suggested that some larvae penetrate mouse skin without undergoing exsheathment. Penetration by ensheathed larvae was confirmed visually using a novel fluorescein isothiocyanate (FITC)-labelling technique in which viable ensheathed larvae were fluoresceinated, applied onto intact mouse skin, and their progress monitored in frozen skin sections. This direct observation that the L2-derived sheath can present antigens to the host's immune system was also monitored by immunoassay to provide confirmatory information regarding skin penetration by ensheathed larvae. Sera from humans infected with Necator americanus were shown to react in ELISA against antigens stripped by detergent (cetyltrimethylammonium bromide) from the sheath surface, and with antigens contained in L3-exsheathing fluid. These data suggest that the host's immune response, as a result of antigenic stimulation by the cast sheath and exsheathing fluid, could in fact be diverted away from the potentially vulnerable L3 stage.


Allozyme variation between laboratory reared and wild populations of Teladorsagia circumcincta.

The technique of allozyme electrophoresis was applied to two laboratory strains (isolated from the center or south-east of France) and wild populations of Teladorsagia circumcincta from the center of France. Five systems out of 13 (GPI, MPI, MDH, LDH, PGM) could be interpreted. By means of a multivariate analysis, it was shown that the laboratory strains were very similar with each other and genetically different from the wild populations. A deficiency of heterozygotes was recorded for each enzyme locus (except for MDH) in all populations studied.


Incorporation of radiolabelled amino acids by adult Schistosoma japonicum: further characterization of a putative eggshell precursor protein.

The synthesis patterns of female-specific proteins of Schistosoma japonicum were further investigated with particular reference to the 34 kDa putative eggshell precursor protein. Adult male and female worms of S. japonicum were metabolically labelled with 14C-tyrosine, 14C-glycine and 35S-methionine in vitro. The rates of amino acid incorporation for female worms were significantly higher than for males in all radiolabelling experiments. Labelled proteins were resolved by two-dimensional gel electrophoresis and visualized by fluorography. By using 14C-tyrosine and 14C-glycine, the 34 kDa female protein band resolved into three major spots with pI 6.0, 5.8 and 5.6. On the other hand, labelling studies using 35S-methionine failed to reveal synthesis of any corresponding spots at Mr 34 kDa. These results, together with the observations that eggshell hydrolysates are very rich in glycine but poor in methionine, suggested that the 34 kDa putative eggshell precursor protein of S. japonicum consists of at least three isoelectric forms. In addition, we have demonstrated several other female-specific polypeptides synthesized by this worm.


Patent infections of Ascaris suum in pigs: effect of previous exposure to multiple, high doses of eggs and various treatment regimes.

Fifty-four crossbred, 4-week-old pigs divided into nine equal groups were used to test whether multiple inoculations with high numbers of A. suum eggs with or without anthelmintic would result in patent infections. All pigs exposed to multiple prechallenge inoculations of 500, 1000, 2000, 5000, 10,000 and 20,000 and challenged orally 2 weeks later with 10,000 eggs harboured adult worms. When prechallenge infections were removed by pyrantel tartrate treatment the animals were more susceptible to challenge than controls not previously exposed to infections. The same drug used from 2 days before until 10 days after the last prechallenge infection eliminated that effect. Pigs subjected to the same multiple egg dosing regimen but given feed containing fenbendazole immediately before, during and for 10 days after multiple dosing developed significantly more adult intestinal worms after challenge than any other group. These worms were, however, significantly shorter than those that developed in any group of pigs. Adult worms from all these groups produced eggs that after embryonation were infective to mice.


Identification of immunodominant Trypanosoma musculi antigens recognized by monoclonal antibody and curative immunoglobulin G2a antibody.

Trypanosoma musculi obtained from normal or irradiated (900 rad) hosts or from in vitro cultures were lysed and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Similar protein banding patterns with a molecular weight (mol. wt) range from 34 to 68 kDa were observed between the two bloodstream forms. In comparison, lysates of cultured parasites showed a unique banding pattern of antigens within the same mol. wt range. Western blot of bloodstream form lysates, probed with immune plasma (IP), revealed a wide range of parasite proteins. However, when probed with the IgG2a-enriched fraction of IP, a major band of approximately 66 kDa was detected on the blot. Several bands of higher mol. wt were also observed. When anti-T. musculi monoclonal antibodies were used to probe the blot, the 66 kDa protein was again recognized. Using indirect fluorescence, live bloodstream form parasites were analysed by flow cytometry and the p66 protein was determined to be a surface molecule. Finally, lysates of 35S-methionine-labelled trypanosomes were immunoprecipitated with Sepharose linked anti-T. musculi monoclonal antibodies and the eluted ligand analysed by SDS-PAGE and autoradiographed. The 66 kDa band was identified, therefore confirming that this protein was of parasite origin.


Ultrastructural observations on the marginal hooklets of the monogenean gill parasite Cichlidogyrus halli typicus.

The marginal hooklets of adult Cichlidogyrus halli typicus have the same morphology, each being composed of a handle, a curved blade with a tapering guard and an accessory domus. In addition, all the hooklets except those of pair II have a long extension attached to the proximal end of the handle. Ultrastructural observations reveal that the handle consists of three distinct layers whereas both the guard and the proximal region of the blade lack the outer electron-dense layer. The dense core is absent from the rest of the blade. The extension has a fibrous structure and an affinity for eosin, unlike the rest of the hooklet. There is a conspicuous cavity associated with each hooklet. The cavity is partly lined with a syncytial cytoplasmic epithelium containing secretory bodies. The lining is completed by the cytoplasmic covering of the handle; this covering may be the surviving oncoblast cell and has knob-like structures of unknown function projecting into the cavity. The domus has the appearance of two filaments with the light microscope but with the electron microscope these are seen to be the thickened edges of a single gutter-shaped sclerite.


Vaccination of cattle with dextran sulphate-binding Babesia bigemina antigens.

Dextran sulphate-bound Babesia bigemina antigens were used in a preliminary vaccination study and were shown to elicit a protective immune response in cattle. A dextran sulphate-binding fraction of B. bigemina was further subfractionated on a Phenyl Sepharose column to give two fractions--one that strongly bound to the column (bound fraction) and one that did not (unbound fraction). Two groups of cattle were each vaccinated with either the bound or the unbound fraction. These two groups of animals along with a control group were then challenged with B. bigemina-infected erythrocytes. Both groups of vaccinated animals showed considerably lower mean daily parasitaemias as compared to the control group.


Demonstration of the humoral immune response of horses to Babesia caballi by western blotting.

Babesia caballi-infected or normal equine erythrocytes were solubilized in sodium dodecyl sulfate (SDS) buffer and analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Antigens were allowed to react with sera from horses experimentally or field-infected with B. caballi and with sera from non-infected horses. Major babesial antigens recognized by immune sera had apparent mol. wts of 141, 112, 70, 50, 48, 34, and 30 kDa. The polypeptides at 50 and 48 kDa were recognized earliest and throughout infection, but also weakly by 3/100 equine sera tested negative and 1/33 sera tested false positive by the complement fixation test (CFT) and immunofluorescence antibody test (IFAT). Thus, further characterization and purification of B. caballi antigens are required to identify target antigens for an improved enzyme immuno assay. Until such an assay is available, Western blotting can provide a specific tool for the diagnosis of B. caballi infections, particularly in cases of contradicting CFT and IFAT results.


Sparganum proliferum: an overview of its structure and ultrastructure.

A detailed study of the structure and ultrastructure of Sparganum proliferum was made possible for the first time thanks to the successful in vitro and in vivo maintenance of this rare parasite. Although S. proliferum exhibits many of the classical tegumental and parenchymal structures previously described for other larval cestodes, these are either arranged in a distinct fashion or, in some cases, may be completely different. Among the latter and of special interest are the single or multiple parenchymal cavities, surrounded by tegument, which in some instances appear to act as a primitive digestive tract.


The development and mortality of the free-living stages of Haemonchus contortus in laboratory culture.

Haemonchus contortus eggs were cultured in intact fecal pellets at various temperatures (5-35 degrees C) for 22 days. Temperature and relative humidity were kept constant throughout the incubation period. Nl larval development occurred at 5 degrees C; peak third-stage larval recovery occurred at 20 degrees C. Egg mortality was an age-dependent phenomenon, whereas larval mortality remained constant irrespective of larval age. Development was characterized by a minimum development time followed by a transition to the next stage which occurred at a constant rate. All rates were temperature dependent. The minimum development times reported here are much less than those previously reported. Based on these results a mathematical model was used to describe the demography of the free-living stages of H. contortus at various temperatures.


Biology and pathogenicity of Eimeria spinosa Henry, 1931 in experimentally infected pigs.

A single-species isolate of E. spinosa from a diarrheic weaned pig was used to determine the endogenous development and pathogenicity of this swine coccidium. Seven out of 14 inoculated pigs developed endogenous stages or passed oocysts of E. spinosa in their feces. Immunosuppressive treatment with cyclophosphamide had no effect on the susceptibility to infection with E. spinosa in young pigs. The endogenous stages developed within the apical cytoplasm of the enterocytes lining the distal part of the villi in the posterior jejunum. The asexual development comprised three generations of meronts, which were seen at 5, 7 and 9 days post-infection (DPI). Meronts of the first generation measured 6-8 microns and produced 10-14 merozoites 4-6 microns in length. The second generation of meronts measured 6-8 microns and contained 10-20 merozoites 4-6 microns in length. Third generation mature meronts (8-10 microns) on DPI 9 contained 12-20 merozoites measuring 5-7 microns, which were more crescent-shaped and less blunt than the merozoites at 5 and 7 DPI. Merogony continued after formation of the gametes and the first fully developed macrogametes (10-14 microns), microgametes (9-12 microns), and oocysts were also seen at 9 DPI. The prepatent period was 8 or 9 days, but the patent period was not determined. In the present study E. spinosa infection did not produce overt clinical signs. Pathological changes consisted of an inflammatory infiltration in the lamina propria of the posterior jejunum, Peyer's patches activation and sporadic erosions scattered at the villous tips. No villous atrophy in association with a large number of endogenous stages was observed.


The importance of sculpin (Myoxocephalus scorpius) as intermediate host and transmitter of the sealworm Pseudoterranova decipiens.

A total of 186 sculpins (Myoxocephalus scorpius) were caught at Vega, Nordland, Norway, and examined for sealworm larvae (Pseudoterranova decipiens). Over 80% of the fish were infected. Very high infections were found with a maximum of nearly 300 larvae in one sculpin. Infections of this magnitude have so far not been reported from sculpins or any other fish species of this size. The importance of the sculpin in the life cycle and in the transmission of P. decipiens to seals or other fish species is briefly discussed.


Seasonal intensity of Angiostrongylus cantonensis in the intermediate host, Laevicaulis alte.

The slug, Laevicaulis alte, is a vector of Angiostrongylus cantonensis in the Greater Bombay area. The seasonal prevalence of A. cantonensis was investigated to determine the maximum intensity of the parasite in a field population occupying an area of approximately 400 m2. The maximum intensity of larvae was observed in the rainy months, June-November. Investigations showed that individual L. alte could tolerate an infecting dose of 150 first-stage A. cantonensis larvae before mortalities occurred.


Responses of Echinostoma caproni miracidia to gravity, light, and chemicals.

In a four-tube vertical system, Echinostoma caproni miracidia exhibited a strong negative geotaxis which was dominated by a positive phototaxis. In horizontal chambers a positive phototactic response was also demonstrated. These miracidia showed a positive chemoresponse, as determined in phi-chambers, to glutamic and aspartic acids but not leucine. Positive responses were also elicited to snail-conditioned water and sulfuric and acetic acids. Ammonia, Mg2+, and HCl produced no significant reactions. Responses of E. caproni and Schistosoma mansoni miracidia, both of which develop in Biomphalaria glabrata snails, were similar providing further evidence that miracidia mimic the behavioral patterns of compatible snail species.


Natural Echinococcus multilocularis infection in a Norway rat, Rattus norvegicus, in southern Hokkaido, Japan.

Forty-two rats, Rattus norvegicus, captured at a garbage dump in southern Hokkaido, Japan, were examined, and one was found to be infected with Echinococcus multilocularis. The lesions were found in the liver, lung, mesenteric lymph nodes, greater omentum and also free in the abdominal cavity. No necrosis was observed in any of the lesions, and inflammatory reactions were mild. Protoscoleces were observed in the large liver cysts. A homogenate of these cysts, when transplanted into the abdominal cavity of three Mongolian gerbils and a rat, yielded numerous fully developed protoscoleces at 4-7 months post-inoculation. Judging from this, it is postulated that the rat could become a natural intermediate host for E. multilocularis in this area.


Nucleotide sequence of a cDNA from Onchocerca gibsoni encoding a novel repetitive antigen.

mRNA from uterine microfilariae of the cattle parasite Onchocerca gibsoni was used for the construction of cDNA libraries. A cDNA clone encoding an antigen recognized by serum from human individuals infected with O. volvulus was found to contain five copies of an 87 bp unit. These 87 bp units were present in the genome in high copy number as long tandem arrays. These are the first cDNA sequence data obtained directly from larvae of any Onchocerca species.


Orthogonal solid-phase synthesis of a monobiotinylated analog of neuropeptide Y.

Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl protective group strategy. Instead of Asn7 in the native sequence, Boc-Lys(Alloc)-OH was incorporated. At the end of the synthesis the Alloc group was selectively removed by palladium-catalyzed hydrostannolysis and biotin coupled to the epsilon-amino group of Lys7. After cleavage and characterization with plasma desorption mass spectrometry the N epsilon,7-biotinyl-[Lys7]-NPY and the nonbiotinylated analog [Lys7]-NPY were investigated as ligands to the NPY receptor from rat cerebral cortex. Both analogs were found to be high affinity ligands to the NPY receptor and bound with essentially the same affinity as unmodified NPY.


Fmoc-amino acid chlorides in solid phase synthesis of opioid peptides.

Fmoc-amino acid chlorides were employed in the solid phase synthesis of the opioid peptides [Leu]enkephalin, [Leu]enkephalin amide, and dermorphin. The conventional polystyrene-based Merrifield resin or Wang's resin served as solid support. A binary salt of either triethylamine or diisopropylethylamine in the presence of 1-hydroxybenzotriazole or pivalic acid was used for acylation. The coupling rates were quite fast, being comparatively faster when 1-hydroxybenzotriazole was used along with triethylamine or diisopropylethylamine. The peptides obtained in good yields showed, after purification, biological and spectral properties identical with those of the natural peptides.


Potent agonists of growth hormone-releasing hormone. Part I.

Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Conformational investigation of alpha, beta-dehydropeptides. Part III. Molecular and crystal structure of acetyl-L-prolyl-alpha, beta-dehydrovaline methylamide.

The crystal structure of Ac-Pro-delta Val-NHCH3 was examined to determine the influence of the alpha,beta-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4 degrees in needle-shaped form in orthorhombic space group P2(1)2(1)2(1) with a = 11.384(2) A, b = 13.277(2) A, c = 9.942(1) A, V = 1502.7(4) A3, Z = 4, Dm = 1.17 g.cm-3 and Dc = 1.18 g.cm-3. The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a beta-bend between the type I and the type III conformation with phi 1 = -68.3(4) degrees, psi 1 = -20.1(4) degrees, phi 2 = -73.5(4) degrees and psi 2 = -14.1(4) degrees. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue stabilizes the beta-bend. An additional intermolecular N...O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single alpha,beta-dehydroamino acid residue in the (i + 2) position and forming a beta-bend reveal a type II conformation.


Crystal structure and conformation of a highly constrained linear tetrapeptide Boc-Leu-dehydro Phe-Ala-Leu-OCH3.

The conformation of a tetrapeptide containing a dehydro amino acid, delta ZPhe, in its sequence has been determined in the crystalline state using X-ray crystallographic techniques. The tetrapeptide, Boc-Leu-delta ZPhe-Ala-Leu-OCH3, crystallizes in the orthorhombic space group P2(1)2(1)2(1) with four molecules in a unit cell of dimensions a = 11.655(1) A, b = 15.698(6) A and c = 18.651(3) A V = 3414.9 A and Dcalc = 1.12 g/cm-3. The asymmetric unit contains one tetrapeptide molecule, C30H46N4O7, a total of 41 nonhydrogen atoms. The structure was determined using the direct methods program SHELXS86 and refined to an R-factor of 0.049 for 3347 reflections (I3.0(I). The linear tetrapeptide in the crystal exhibits a double bend of the Type III-I, with Leu1 (phi = -54.1 degrees, psi = -34.5 degrees) and delta ZPhe2 (phi = -59.9 degrees, psi = -17.1 degrees) as the corner residues of Type III turn and delta ZPhe2 (phi = -59.9 degrees, psi = -17.1 degrees) and Ala3 (phi = -80.4 degrees, psi = 0.5 degrees) residues occupying the corners of Type I turn, with delta ZPhe as the common residue in the double bend. The turn structures are further stabilized by two intramolecular 4----1 type hydrogen bonds.


Racemization studies in peptide synthesis through the separation of protected epimeric peptides by reversed-phase high performance liquid chromatography.

Separation of protected epimeric peptides, Z-Gly-Xaa-Xbb-OMe (where Xaa and Xbb = chiral amino acid residues), by reversed-phase HPLC was utilized for studying racemization in peptide synthesis. Thus, the following factors which might affect the extent of racemization during the coupling by the carbodiimide method were investigated: the combination of amino acid residues to be coupled, coexisting tertiary amine salts, and the relative configuration of the amino acid residues. The following points were revealed: the combination of bulky residues at the coupling site results in extensive racemization in a polar solvent such as DMF, the amine hydrochlorides cause less racemization than the p-toluene-sulfonates in DMF, and the influence of relative configuration differs depending on the solvent and the individuality of the amino components. Furthermore, the racemization-suppressing effect of some additives in the carbodiimide method was reevaluated by employing the same procedure.


Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the carbodiimide method.

Copper(II) chloride was found to be an extremely efficient racemization-suppressing additive in the DCC method as compared with the hitherto known ones, by employing the model coupling Z-Gly-L-Val-OH + H-L-Val-OMe in DMF. Although some other copper salts also had a profound effect, copper(II) chloride was the best from the viewpoint of both racemization suppression and coupling efficiency. The effectiveness of copper(II) chloride was further confirmed by employing the EDC-mediated couplings of Z-Gly-containing dipeptides with amino acid esters or dipeptide esters, and those of Z-L-Ala (or L-Val)-L-Val-OH with amino acid esters or dipeptide esters. In almost all the cases studied, no detectable amount (less than 0.1%) of epimer was observed by the HPLC analysis in the presence of copper(II) chloride. This was also the case even with an extremely stringent coupling system Z-L-Pro-L-Val-OH + H-L-Pro-OMe. With reference to the mechanism of racemization suppression, it was found that copper(II) chloride has a strong ability to suppress the racemization of the 5(4H)-oxazolone, which may be formed from an activated carboxyl component during the coupling.


Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile.

Two molecular forms of prolactin (PRL), glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 M sucrose, 1 mM NH4HCO3, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26,000 and 24,000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26,000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24,000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and Ile for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.


Crystal structure and molecular conformation of achatin-I (H-Gly-D-Phe-Ala-Asp-OH), an endogenous neuropeptide containing a D-amino acid residue.

In order to investigate the active conformation of achatin-I (H-Gly-D-Phe-Ala-Asp-OH), an endogenous neuropeptide from the Achatina fulica ganglia, its crystal structure and molecular conformation were analysed by the X-ray diffraction method. Crystals from methanol/dioxane are monoclinic, space group P2(1) with a = 5.083(1), b = 9.125(1), c = 20.939(3) A, beta = 94.73(1) degrees. The structure was solved by direct methods and refined to R = 0.051 for 1714 independent reflections with /Fo/ greater than sigma (Fo). The molecule exists as a zwitterion with the Gly N-terminal end protonated and Asp beta-carboxyl deprotonated; the C-terminal of Asp is in a neutral state. The molecule takes a kind of beta turn structure with the D-Phe-Ala residues at the corner of the bend. This turn conformation is primarily formed by the strong intramolecular hydrogen bonds of NH(Gly)...O delta 1 (Asp) and NH(Asp)...O delta 1 (Asp) pairs, thus forming a 15-membered ring structure. Judging from the published data concerning the structure-activity relationship, this turn conformation may reflect an important feature related to the neuroexcitatory activity of achatin-I.


Studies on cell-clearing activity in alpha-lactalbumin. Effects of calcium removal on activity and conformation.

Effects of calcium removal on the cell-clearing activity of alpha-lactalbumin (alpha-LA) and concomitant changes in conformational structure have been investigated as part of a continuing study of the activity found earlier [McKenzie, H.A. & White, F.H., Jr. (1987) Biochem. Int. 14, 347]. This activity is similar to that of lysozyme, whereby lysis of the bacterial cell wall is catalyzed. However, the specific activity of alpha-LA is on the order of 10(-6) that of lysozyme. Under conditions where activities of apo and native alpha-LA were approximately linear functions of the protein concentration, the maximal ratio of apo to native activity was 5.7:1, determined by comparison of second order velocity constants. The CD spectrum of apo alpha-LA is intermediate between that of the A state and the native protein. By NMR, the conformation of apo alpha-LA is similar to, but distinctly different from, that of the native protein. The apo form did not revert completely to the native state when Ca(II) was resupplied, consistent with a role for this cation in folding. It is suggested that the activity increase may result from a diminished constriction of the "cleft" region in alpha-LA.


"Carba" peptide bond surrogates. Different approaches to Gly-psi(CH2-CH2)-D,L-Xaa pseudo-dipeptide units.

Racemic "carba" pseudo-dipeptide units such as Gly-psi(CH2-CH2)-D,L-Xaa were obtained either through the Horner-Emmons condensation of N-tert.-butyloxycarbonyl-beta alaninal with the appropriate substituted triethyl phosphonacetate, or from commercially available 3-carbethoxy-2-piperidone.


Continuous flow synthesis of peptides using a polyacrylamide gel resin (Expansin).

The continuous flow syntheses of endothelin 1, proendothelin 2, ATP binding site of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by using a polyacrylamide gel resin Expansin (about 0.6 mmol NH2/g) with the glycolamidic ester handle as labile anchorage. In addition, we report here a method of air oxidation which reduces the formation of side-products related to the formation of intermolecular disulfide bridges.


Survey of conformational role of ester bonds in a cyclic depsipeptide. Study on cyclo(-L-Ala-L-Hmb-)2 by energy calculation and NMR spectroscopy.

The effect of ester bond on the conformation of peptide molecule was studied by designing and synthesizing a model tetradepsipeptide cyclo(-L-Ala-L-Hmb-)2 and by analyzing the conformation both theoretically and experimentally. Theoretical analysis showed that both ester and peptide bonds in the calculated low-energy conformations within 3 kcal/mol of the global minimum take a trans but distorted configuration. The distortion is larger in ester bonds than in peptide bonds. Further, the four carbonyls project from one side of the plane of the cyclic backbone, whereas the side chains project from the other side. These results are consistent with the experimental results obtained by NMR measurement; first, the coupling constant deduced from 1H-NMR species in DMSO-d6 is consistent with the dihedral angles of the calculated low-energy conformations; second, results of NOE measurement can reproduce the calculated configuration of the carbonyls and side chains. From the consistency between theoretical and experimental results, it is concluded that this model tetradepsipeptide takes an all-trans backbone conformation in solution and this backbone conformation is stabilized by large distortion in the ester bond, which compensates the strain resulted from the 12-membered cyclic backbone structure consisting only of L-residues.


Use of tetrabutylammonium salts of amino acids in peptide synthesis.

Tetrabutylammonium (TBA) salts of amino acids and peptides have increased solubility, as compared with that of alkali metals salts, in organic solvents. We have compared the reaction rates for tripeptide formation in methylene chloride from Boc-Gly-Phe activated with various phenols, N-oxysuccinimide and azide, and TBA-salt of tryptophan, as well as Trp-OCH3. H-Trp-O-.TBA+ as an amino component significantly accelerates the rate of reaction. Although a significant degree of racemization has been found, the use of TBA-salt of amino acids and peptides is justified in many cases due to high conversion rates.


Peptide inhibitors of E. collagenolyticum bacterial collagenase--effect of N-methylation. Consequences on biological activity and conformational properties.

Peptide inhibitors of E. collagenolyticum bacterial collagenase, HS-CH2-CH2-CO-Pro-Yaa (Yaa = Ala, Leu, Nle), have been N-methylated at the Yaa position. The N-methylation slightly increases the inhibitory potency of the modified peptides as compared to the parent compounds. The conformational effects of the N-methylation have been investigated by both 1H 2D-NMR and molecular mechanics energy minimization. Three low-energy conformers have been predicted for the unmethylated parent compounds (Yaa = Ala, Leu, Nle). They are characterized by the psi value of the central proline residue: psi Pro = 150 degrees (trans' conformation), psi Pro = 70 degrees (C7 conformation) and psi Pro = -50 degrees (cis' conformation). The N-methylation has been found to strongly increase the energy of the C7 conformer and to a less extent the energy of the cis' conformer. This leaves the trans' conformation as the only low-energy conformer. The ROESY experiments have established that both the N-methyl peptides and the parent compounds adopt the same preferred backbone conformation in water solution, i.e. the trans' conformation. Based on these results, the activities of the N-methyl peptides are discussed and a possible conformation of the inhibitor in the bound state is proposed.


Racemization free coupling of peptide segments. Synthesis of an insect neuropeptide.

The total synthesis of the insect neuropeptide derivative Z-Gly-Gly-Ser-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 has been carried out by a convergent solid phase strategy. For the coupling of the N-terminal pentapeptide to the C-terminal tetrapeptide, three different methods were assayed. Racemization of the acyl activated amino acid during the fragment condensation reaction was monitored by HPLC. Best results were obtained by enzymatic coupling in a low water containing media using adsorbed alpha-chymotrypsin. An optically pure product was obtained in 82% yield after 1 h of reaction. Chemical methods such as DIC/HOBt and BOP/HOBt/NMM always rendered highly optically impure products containing 10-20% of the D-epimer.


Novel cyclization chemistry especially suited for biologically derived, unprotected peptides.

A novel method is described for the cyclization of peptides--or segments of polypeptides--which requires a free N-terminal alpha-amino group and a distal amino acid residue containing a nucleophilic side chain. The reaction is conducted in two steps, both in the aqueous phase. The first step involves acylation of the N-terminal alpha-amino group with iodoacetic anhydride at pH 6. This acylation reaction has greater than 90% specificity for peptide alpha-amino groups and gives no alkylation of Arg, His, Lys or Met by the iodoacetate side product (R. Wetzel et al., Bioconjugate Chem., 1, 114-122, 1990). In the second step, the acylation reaction mixture or the isolated iodoacetyl-peptide is incubated at room temperature to give the cyclic peptide formed by reaction of the nucleophilic side chain with the iodoacetyl moiety. The pH dependence of the cyclization reaction by Met, Lys, Arg or His is consistent with the pKa of the nucleophilic side chain. Thus, peptides containing Met plus other nucleophilic amino acids should preferentially cyclize via Met at low pH. In this paper, preparation of cyclic peptides containing 3-6 amino acids is described; the full range of ring sizes and sequences which can undergo this cyclization has not been further explored. Preliminary results suggest that this method is also fairly general with respect to the amino acid sequence being cyclized. The reaction appears to be particularly suited for cyclization via Lys and Met side chains. All of the cyclized products are sufficiently stable for many biological applications.(ABSTRACT TRUNCATED AT 250 WORDS)


Design of hydropathically complementary peptides for Big Endothelin affinity purification.

Molecular recognition between Big Endothelin (Big ET) and a computer generated peptide hydropathically complementary to Big ET[16-29] sequence has been studied by analytical high performance liquid affinity chromatography (HPLAC), circular dichroism (CD) and nuclear magnetic resonance (NMR) experiments. Specific binding was observed between solid support immobilized complementary peptide and Big ET[1-38], [1-32], and [16-32], but not with Big ET fragments [1-21], [16-21], [22-32], and [22-38], obtained by chymotrypsin proteolytic degradation. Selectivity in the recognition process was clearly demonstrated by the ability of complementary peptide affinity column to purify the Big ET molecule from complex peptide mixtures, even when present in very low concentrations. Similar selectivity was evidenced with the Big ET fragment [16-32], [NH2-HLDIIWVNTPEHIVPYG-COOH] containing the entire hydropathically complementary sequence. Binding was followed by marked spectroscopic changes, as monitored by circular dichroism and one- and two-dimensional nuclear magnetic resonance experiments. The NMR spectra of the complementary peptides 1:1 mixture showed variations in the chemical shifts of proton resonances in several residues, both in the main chain (amide protons) and in the side chains (aliphatic and aromatic protons). These data support the hypothesis of a multilocalized type of interaction between complementary peptides, where many residues along the peptide chains participate in co-operative stabilizing contacts in the forming complex.


Affinity enhancement of complementary peptide recognition.

A peptide hydropathically complementary to Big Endothelin [Big ET] residues 16-29 has been synthesized in a multimeric form starting from an octadentate polylysine core, essentially in a way similar to the procedure used for the production of multiple antigenic peptides [MAP's]. Interaction between the multimeric complementary peptide [8 delta ET] and the Big ET fragment 16-32 containing the target complementary region, also synthesized in a multimeric form [8ET], was evaluated by analytical high performance affinity chromatography and solid phase binding assays. While the binding interaction between the monomerics peptide pair was in the micromolar range, the recognition between the corresponding multimeric form was characterized by enhanced binding affinity of at least two orders of magnitude. In solution, complex formation between multimeric complementary peptide and target Big ET sequence in the monomeric and multimeric form was accompanied by precipitation at concentrations higher than 0.5 mg/mL and 0.1 mg/mL, respectively. Polyclonal antibodies raised against the multimeric target sequence recognized multimeric and monomeric ET target sequences with binding affinities similar to binding affinities exhibited by the multimeric complementary peptide. Multimerization of hydropathically complementary peptides could provide an improved opportunity to measure and thus probe quantitative binding properties of complementary peptides.


The psychoanalytic theory of change.

The concept of change by psychoanalysis has undergone an historical process related to the course and development of psychoanalytic theory. Change has changed from an effect on symptoms, to underlying etiologic conflicts, to background character, to the functioning of psychic structural systems. The psychoanalytic process does not overlap with the process of change. The former may be present without the latter. The will to recover is accompanied by the unconscious need to cover. The methodology of change is examined with regard to process, agent(s), and intrapsychic results. Every analysis is a training and supervised analysis. With increasing autonomy of the ego, the patient, identifying with the analysing functioning of the analyst, becomes his own analyst. The theory of change is related to the psychoanalytic theory of neurosis of which it is part, and differs in alternative theories extant today. The dynamic occurrences I have described as bringing about change rest upon my view of 'total composite psychoanalytic theory' as evolved to the present.


Interpretation between determinism and hermeneutics: a restatement of the problem.

The author opposes the two principal conceptions of interpretation: the deterministic conception predominant in Freud, in which the present is determined by the subject's actual past; and the creative hermeneutic conception, which traces its origins back not only to Heidegger and Ricoeur but also to Jung; in the latter view, interpretation cannot but be retroactive, assigning significance to a meaningless past. The author shows that Freud, in exactly the same way as the hermeneuts in the opposing camp, remains the prisoner of the antithesis of factual reality and a purely subjective interpretation close to fantasy. He lacks a third category, that of the message whose meaning is immanent, in particular taking the form of the mostly non-verbal sexual messages conveyed by the adult to the small child. The development of the human individual is to be understood as an attempt to master, to translate, these enigmatic, traumatizing messages. Analysis is first and foremost a method of deconstruction (ana-lysis), with the aim of clearing the way for a new construction, which is the task of the analysand.


An infantile trauma, a trauma during analysis, and their psychic connexion.

The case described here involves a patient who suffered a trauma while in the final stages of a successful analysis. The trauma temporarily eclipsed many of the gains of the analysis. Surprisingly, however, the regression caused by this trauma led to further lifting of repression. This resulted in new information, greater affective expression and a greater therapeutic gain than would have otherwise been possible. The clinical technique devised for this special situation is described.


From acting out to words and meaning.

This paper presents an explanation and illustration of the behavioural phenomenon of concretization through acting out. The phenomenon refers to the realization of fantasies and psychic conflicts pertaining to the traumatic past of Holocaust survivor parents, which might have been transmitted to the next generation narratively or beyond words. I have illustrated this phenomenon by material taken from the first stages of the analysis of a young man who shot and wounded his father during the latter's attempt to save him from suicide. The analytic experience facilitated the stabilization of ego boundaries and the emergence of a more secure sense of self.


Love and male impotence.

This paper deals with male impotence in relation to love. A detailed clinical presentation attempts to show how the symptom was embedded in faulty processes of separation-individuation, whereby regression in the service of intercourse, passion and love is hindered by the fears and fantasies underlying merging experiences. These problems are examined as they appear interwoven in transference and counter-transference phenomena. The clinical case presentation is followed by a discussion of different forms of male impotence from a more general viewpoint; its relation not only to castration and phallic anxiety, but also to earlier developmental aspects. Finally, some reflections about male and female gender differences in relation to symbiotic experience.


The Isakower phenomenon revisited: a case study.

The Isakower phenomenon is a situation in which an individual typically experiences perceptions of enlargement or thickening, altered states of consciousness, sensations of floating, and impressions of the emergence and disappearance of an oral mass. This paper defines the phenomenon, reviews the literature, and describes a case in which a patient experienced it. The patient manifested the phenomenon symptomatically in the aftermath of a toxic state, and the elements were analysed for several years. There was support for Isakower's original thesis that the regressive states serve to defend against threatening incestuous fantasies. However, the Isakower phenomenon in this patient was the result of a multiplicity of determinants, largely defensive, involving many developmental levels.


Problems in the psychoanalysis of certain narcissistic disorders.

This paper considers the psychopathology and treatment of a particular group of narcissistic disorders which can be characterized by their use of 'simulation' in their attempt to resolve the conflicts of the Core Complex. The invasive, narcissistic mother's demand for success is responded to with an evident compliance but with a covert rebellion manifested in failure, accompanied by intense feelings of shame and low self-esteem. This is seen in the analysis in the patient's apparently positive response being followed by a Negative Therapeutic Reaction. The structure is seen to be as much concerned with protecting the mother from the infant's destructiveness as it is with protecting the infant from the colonizing mother (cf. Winnicott's 'False Self'). What is regarded as the hallmark of narcissistic disorders, namely shame, is found to be part of a defensive structure concerned with the exclusion of extreme violence and intolerable guilt. The significance of the father is discussed. Difficulties that arise in the analysis of such patients are considered.


The child and/or the picture. Motherhood and creativity: their vicissitudes.

The development of this clinical case, that of a young mother who was a painter, illustrates the link between motherhood and sublimated creativity. The importance of male identifications, the difficulties of identification with the mother and the guilt connected with penis envy are emphasized. Castration anxiety is attached to the child, experienced as a penis equivalent. Anal fixation also plays a crucial part, aggravating the refusal of an excessively guilt-ridden genital sexuality. The vicissitudes and conditions of female sublimation are discussed.


The dialectically constituted/decentred subject of psychoanalysis. I. The Freudian subject.

Central among the irreducible elements that define a psychoanalytic understanding of man is Freud's conception of the subject, and yet this theme remained a largely implicit one in Freud's writing. The Freudian conception of the process by which the subject is constituted is fundamentally dialectical in nature and involves the notion that the subject is created and sustained (and at the same time decentred from itself) through the dialectical interplay of consciousness and unconsciousness. The contribution of psychoanalysis to a theory of subjectivity involves the formation of a concept of the subject in which neither consciousness nor unconsciousness holds a privileged position in relation to the other; the two coexist in a mutually creating, preserving and negating relationship to one another. The principle of presence-in-absence and absence-in-presence subtends the dialectical movement between conscious and unconscious dimensions of subjectivity.


Mourning and erotic transference.

This article proposes that the clinical mourning process is a critical factor in transforming an aggressively-laden erotic transference, and its potential for use as resistance, into a conscious erotic transference that progressively mobilizes the psychoanalytic treatment process. A psychoanalytic case is used to illustrate that the mourning of the pre-oedipal object allows an erotic transference to emerge into consciousness in treatment. The case also demonstrates that the erotic transference takes the form, not only of desiring, but also of mourning the oedipal level object. The case serves as a case in point in illustrating that erotic transference appears in cases in which female analysts treat male analysands. Further, it illustrates that erotic transference remains a primarily object-related phenomenon as opposed to being a merely narcissistic phenomenon. Finally, it illustrates the course of working through the erotic transference in an analytic treatment in which the therapeutic object relationship facilitates mourning.


The countertransference position and the countertransference.

The concept of countertransference assumes different meanings depending on the context in which it is used. And yet it is an essential concept whose absence would have important theoretical and practical consequences. At the risk of increasing the psychoanalytic Babel, I propose the concept of the counter-transferential position which, in my view, allows a better understanding of the multiple determinations which impinge upon the analyst during the session. In a brief clinical example, I examine a 'countertransferential symptom' and the analyst's function of 'listening to listening'.


On the survival function of autistic manoeuvres in adult patients.

This paper highlights features of the work on autism of Tustin and others pertaining to the analysis of adult patients. Several clinical illustrations from the analysis of neurotic, borderline and psychotic patients emphasizing the survival function of autistic shapes, objects and delusions are presented. The need for further discrimination between autistic states of mind and other primitive mental states is recommended.


Transference and countertransference. From deployment against feelings of loss--through psychotic regressions--to a better capacity to feel and to mourn.

Problems relating to the treatment of deployed patients are described and discussed through the case material on David Fisher. Since the deployments are not merely the defences or resistances we meet in neurotics, but a way of life with which these persons are strongly identified--deploying forces against the subjective experience of psychic pain--a different approach is felt to be required. I call this an affect-focused approach. Some of the major curative factors which have been found useful in persons with deployment are described and illustrated.


[Management of patient flows. Evaluation of the hospital supply].

To propose a decision analysis model from the analysis of care process and management indicators. After defining institutional purpose and with the Hospital's structural size and activity analysis, this model allows to know the hospital supply related to demand. According to the knowledge of the frequency of the activity to perform, it could be possible to avoid inefficacy.


On criteria for hearing impairment in children.

As objective criteria concerning hearing impairment/disability may be poorly related to the behavioral patterns of children with hearing deficits, the present investigation was performed. A consecutive series of 172 children, who were examined for the first time at the Audiological Department, was subdivided according to age into two groups: one comprising 98 children at an age from 49 to 84 months, the other comprising 74 children greater than 84 months of age. This second group is supposed to complain of hearing problems if present, and thus constitutes a reference group. Using the criterion for hearing impairment: BEHL 0.5-4 kHz greater than 20 dB HL, the data demonstrated that the frequency of correct and false positive suspicion (detection) of a hearing impairment is similar in parents and professionals with an observer sensitivity of 88%. In addition the frequency of suspicion in parents and professionals in relation to degree of hearing loss corresponds to the frequency of hearing problems, as experienced in the reference group of older children. A certain discrepancy exists between the applied criterion of BEHL 0.5-4 kHz greater than 20 dB and the hearing level resulting in deviating behavioral pattern or experienced hearing deficit in children. This may be ascribed to the predominantly conductive hearing loss in the examined sample. It is concluded that additional investigations on criteria for hearing impairment/disability, including also children with sensorineural hearing loss should be undertaken.


Childhood deafness in Malaysia.

One hundred and fifty-five children with childhood deafness were examined over a period of 4 years in order to assess the aetiology of hearing disorder. In 21 (13%) children, deafness was a sequel of meningitis. Perinatal pathology accounted for 34 (22%) cases. The aetiology of deafness was unknown in 44 (28.4%) children. The percentage of unknown causes can be reduced if the deafness is detected early. Hearing loss was diagnosed only in 30 (19%) children by the age of 2 years. The early detection of deafness can be achieved by screening the high risk infants and educating the general practitioners and health assistants.


[Length of stay in the hospital emergency department].

We evaluated the overall time spent by patients in the emergency department as well as the time employed in the different steps of emergency care and their relationship to patient's diagnosis. Data from 2421 patients, randomly selected, amongst those who attended hospital's emergency department units between november 22-28th 1990 were collected data in a specially designed form. The mean time required for examination was 13 minutes and this procedure was carried out, in average, 18 minutes after admission. The mean length of stay in emergency area was 127 minutes with a significant increase in those cases rated as "true" emergencies.


Parental smoking and persistent otitis media with effusion in children.

A total of 163 children were entered into a case-control study to determine whether any causal relationship exists between otitis media with effusion (OME) requiring grommet insertion and parental smoking. One hundred children with persistent OME formed the case group and 63 children with normal ears formed the control group. The prevalence of parental smoking in each group was then compared. Information was collected by questionnaire and further details about the subjects with regard to surgery of the upper respiratory tract were also gathered. Analysis of findings in this study and previous reports has failed to demonstrate a significantly increased prevalence of smoking in at least one parent, amongst children with persistent otitis media with effusion requiring surgical intervention.


[The effectiveness of breast cancer screening in our country].

The aim of this paper is to review the current state of breast cancer screening in our country, as well as to discuss the most appropriate approaches for its development. Firstly, the impact of breast cancer in Spain is presented, as well as the current evidence about the efficacy of the screening. The major programs and initiatives addressed to promote screening are described. Finally, a few recommendations are given in order to achieve that breast cancer screening be, not only efficacious, but also effective. It is concluded that it is necessary that health and professional authorities coordinate and monitor breast cancer screening programs.


[Risk for injuries in traffic accidents among drivers under the effect of alcohol in Navarra].

We conducted a retrospective analysis of the levels of alcohol in the blood of a group of 54 drivers who required hospital emergency care after having suffered a traffic accident on roads in the Health Area III of Navarra (Spain) from June to September 1989, and compared them to another group of 219 drivers, not victims of traffic accidents, submitted to the breathalyser (test of alcoholaemia) on the roads of the same Health Area over the same period of time. In the group of 54 accident victims, the median alcoholaemia was 100 mg/dl, with a quartile deviation of 88 mg/dl, and the percentage of positives (alcoholaemia equal to or greater than 80 mg/dl) was 50.9%. In the group of 219 drivers not victims of traffic accidents, the median alcoholaemia was 16 mg/dl, the quartile deviation 18.5 mg/dl and the percentage of positive alcoholaemia was 1.8%. Drivers with a level of blood alcohol equal to or greater than 80 mg/dl have an estimated risk (Odds Ratio) of being injured in a traffic accident 55.82 times higher than drivers with a lower level.


Medical treatment of chronic suppurative otitis media without cholesteatoma in children--a two-year follow-up.

A prospective long-term study was carried out in 48 infants and children with chronic suppurative otitis media without cholesteatoma treated initially with wide spectrum intravenous antibiotics and suction and debridement. Patients were followed for a period of two years. All children were cured after completion of therapy. At 3 and 6 months follow-up 75% of the children were still free of discharge and at 12, 18 and 24 months the proportion of dry ears dropped to 71%, 66% and 52%, respectively. Eighty percent of all recurrences developed already during the first 6 months of follow-up. Pseudomonas aeruginosa was the most common pathogen isolated, both in the initial and recurrent bouts of the disease, and was commonly associated with other pathogens. Children with early reappearance of ear discharge were less likely to benefit from further antimicrobial or surgical treatment. The recurrence rate was not affected by the antibiotic regimen, age, duration of drainage before treatment or the presence of granulation tissue. No intracranial or intratemporal complications were observed during the follow-up period.


Fiberoptic examination of the nasal cavity and nasopharynx in children.

In this prospective study, a flexible fiberoptic nasolaryngoscope with color video camera was used to examine the nasal cavity and nasopharynx in 180 pediatric patients. The relative size of the adenoid tissue was judged by endoscopy, which lead to a classification into 3 types according to the distance from the vomer to the adenoid tissue. The condition of the nasopharyngeal orifice of the Eustachian tube was also described and differentiated into 3 types relating to the condition of adenoid tissue. Assessment was performed by correlating these measurements with the tympanogram, lateral X-ray and clinical complaints. The authors conclude that: (1) fiberoptic examination allows direct visualization of the size and condition of the adenoid tissue, as well as of the condition of the nasopharyngeal orifice of the Eustachian tube. (2) The size of the adenoid tissue correlates very well with the nasal obstruction complaints as well as with the type of tympanogram. (3) The condition of the nasopharyngeal orifice of the Eustachian tube significantly corresponds with the type of tympanogram. (4) For the indication of adenoidectomy, fiberscopy gives more accurate information than standard X-ray. (5) With a correct choice of premedication and local anesthesia, it is a minor invasive technique which is very well tolerated by children. It is possible in all cases, provided it is performed by a skilled endoscopist and preceded by careful explanation to the child. (6) Finally, thanks to the possibility of direct visualization of the fiberscopic image via a monitor, it allows a better explanation of the indication for adenoidectomy to the child's parents.


Change in velopharyngeal valving after speech therapy in cleft palate patients. A videonasopharyngoscopic and multi-view videofluoroscopic study.

Thirty-one cleft palate patients with velopharyngeal insufficiency and compensatory articulation in association with hypernasality after palate closure were studied. Videonasopharyngoscopy and multi-view videofluoroscopy were performed to all patients before and after speech therapy for correcting compensatory articulation. The ratios of movement of velopharyngeal structures were significantly increased after compensatory articulation had been corrected. Furthermore, the size of the gap at the velopharyngeal sphincter during closure was significantly reduced. The results in this study support the statement that articulation disorders in association with hypernasality in cleft palate patients should be corrected prior to the implementation of surgery for velopharyngeal insufficiency after palate closure.


[Age-period-cohort analysis of mortality caused by ischemic cardiopathy in Spain 1965-1985].

With the objective of studying the temporal evolution of ischaemic cardiopathy (IC), or coronary heart disease mortality, in Spain, we carried out a cohort analysis with conventional graphic techniques and modern statistical methods. This permits better understanding and quantification of the age-period-cohort effects and identification of the potential factors operating upon them. To this end, loglineal (Poisson regression) models were constructed of the IC mortality rates for both sexes, using the GLIM package, in which the regression coefficients are the natural Relative Risk (RR) logarithms of the various age groups (35-74 years), period of death (1970-1985) and birth cohort (1985-1960) with respect to the reference group mortality, controlled by the effect of other groups. In respect of the results, the maximum RR value corresponds to decrease year 1975, and falls progressively to 1985, though at all times remaining above the 1970 value. The effect of 1985, though less than 1980, does not present significant differences from the latter. Nevertheless, no clear cohort effect was found. As a probable explanation for the pattern observed, this would suggest recent changes in life style and in medical attention. There is a discussion of the consistency of the models selected with the graphical results and with present knowledge of the natural history of IC and with the evolution of its determining factors, together with validation of the models. In summary, the IC mortality patterns observed show an increase up to the mid-seventies, and stabilization from that date onwards, in all age and sex groups, which is consistent with an age-period effect.


Body growth in relation to tonsillar enlargement and tonsillectomy.

Severe airway obstruction caused by tonsillar enlargement can result in disturbances in body growth. The effect of this interference and of tonsillectomy in the child with only moderate symptoms have been less satisfactoril evaluated. In this study, 122 children with symptoms and signs of tonsillar obstruction were investigated concerning the height and weight before and after tonsillectomy. None of the individuals demonstrated cardiopulmonary complications of tonsillar obstruction. Altogether 10% of the children exhibited abnormalities in body weight and/or length prior to surgery. Especially during the first postoperative year, the weight and height gain exceeded the expected in 75% of the patients. The accelerated weight gain increased with tonsil size, but there was no relation to the extent of difficulties in swallowing or sleeping disruptions. The results support the hypothesis that tonsillar hypertrophy frequently is associated with disturbances in body growth and that this is seldom demonstrable prior to tonsillectomy.


Swallowing disorders in a population of children with cerebral palsy.

One of the disabilities in patients with cerebral palsy (CP) is dysphagia. To establish the prevalence of dysphagia in a population of children with CP, and to determine if any factors are related to dysphagia, we studied 56 CP patients, 5-21 years, enrolled in a primary school for the disabled. Fifteen patients (27%) had either radiographic or clinical evidence of dysphagia. These 15 patients were compared to the remaining 41 patients without dysphagia. Using data obtained from chart review and interviews with speech pathologists, several factors that contributed to dysphagia were found. These included: bite reflexes, slowness of oral intake, poor trunk control, inability to feed independently, anticonvulsant medication, coughing with meals, choking, and pneumonia. We also noted trends in the following factors: presence of tongue thrusting, presence of drooling, severity of CP, poor head control, severity of mental retardation, seizures, and speech disorders. Factors not related to the presence of dysphagia include: subject age, cause of CP, and type of CP. Early, aggressive work-up and identification in CP patients with the risk factors outlined above can reduce the associated pulmonary complications.


Pediatric laryngobronchoscopy. 1332 procedures stored in a data base.

Laryngobronchoscopy (LBS), using both rigid and flexible bronchoscopes, has become a frequently performed operation in children. A data base was established to enable retrospective evaluation of a large number of LBSs carried out in a pediatric center. Experience with 1332 cases of LBS involving 808 patients over an 8-year period is presented. The main indications for LBS were inspiratory stridor, atelectasis, and suspected foreign body aspiration. Most frequent diagnoses at LBS were bronchopneumonia, intubation trauma, tracheomalacia, laryngomalacia, and foreign body aspiration. Only 25 complications occurred (1.9%) including two cases of xylometazoline intoxication.


Urgent adenotonsillectomy for upper airway obstruction.

Adenotonsillar hypertrophy has been documented to cause chronic upper airway obstruction resulting in cardiopulmonary sequelae in children. It has been less recognized that long-term adenotonsillar hypertrophy may additionally cause acute, life-threatening airway obstruction. A review of 5000 adenotonsillectomies performed at 3 New York Medical College affiliated hospitals from 1982 to 1989 showed 6 pediatric patients with progressive upper airway obstruction severe enough to necessitate intubation in the emergency room or operating room, and subsequent urgent adenotonsillectomy after cardiorespiratory stabilization. Patients were monitored in the ICU with pre- and postoperative blood gases. Observations of cyanosis, cor pulmonale, and use of accessory respiratory muscles were carefully recorded. This study illustrates that life-threatening upper airway obstruction may be due to chronic adenotonsillar enlargement and require treatment by urgent adenotonsillectomy.


Long-term results of surgery for childhood cholesteatoma.

The study includes 54 cholesteatomatous ears in 50 children aged 16 years or less. The mean follow-up period after surgery was 7.1 years. In 26% of the ears the cholesteatoma was 'huge' involving the middle ear and the attic and filling the entire mastoid air cell system. A patient had lateral sinus thrombophlebitis. Patients with large cholesteatomas underwent canal wall down mastoidectomy with simultaneous tympanoplasty and, in most cases, cavity obliteration. Limited cholesteatomas were removed using either intact canal wall mastoidectomy or tympanotomy approach. Recurrence rate (including both residual and recurrent cholesteatomas) for the total series was 15% and 12% for the 50 cases undergoing one-stage surgery. Serviceable hearing (< or = 30 dB) was achieved in 57% of the ears. A reoperation was necessary in 26% and a third operation in 2%. At last follow-up examination, 94% of the ears had intact tympanic membranes but 4 patients (8%) suffered from cavity-related problems. Possible reasons for the disappointing results of surgical treatment for childhood cholesteatoma are discussed.


Results of surgical treatment for chronic noncholesteatomatous otitis media in the pediatric population.

The long-term results of surgery for chronic otitis media without cholesteatoma were analyzed in 76 ears of children aged 16 years or less. The mean follow-up period was 6.0 years. Thirty-four ears were subjected to mastoid surgery for chronic otorrhea; at final follow-up examination the disease was found to be cured in all but one patient. Forty-two patients with sequelae to chronic otitis media underwent tympanoplasty without mastoidectomy which was successful in 38 (91%) of these. At follow-up, 84% of the patients had hearing levels of 20 dB or better. Outcome of surgery and hearing results in children were as good as or even better than those obtained in adult patients. Complications of surgery were rare.


Central nervous system complications secondary to oto-rhinologic infections. An analysis of 39 pediatric cases.

Fifty-eight central nervous system complications were noted in 39 pediatric patients with a primary oto-rhinological infection. The ages ranged from 1 to 15 years. Eleven patients (25%) had more than one complication. 12.8% of the cases died. Leptomeningitis was the most common intracranial complication (54%) Lateral sinus thrombosis (LST) occurring in 10 patients (26%) was accompanied with other intracranial abnormalities in 80% of cases. Brain abscess as an initial or concomitant complication was associated with the highest mortality rates (40%). In two of these fatal cases multiple brain abscesses were detected. The low incidence of intracranial infections secondary to oto-rhinologic infections and the masking effect of antibiotics present difficulties in the early recognition of the CNS complication. Despite the value of the modern imaging techniques in the investigation of the CNS complication, the clinical oto-rhinologic examination is of paramount importance in detecting the original infection in the pneumatic spaces of the upper respiratory tract. Additionally, bone scans were found of value in demonstrating the osteitic process of these cases.


Long-term results of Goode's tympanostomy tubes in children.

The results of a retrospective study of the complications of middle ear ventilation by Goode's T-tubes in children are presented. 248 T-tubes were inserted into 119 patients. 16.9% progressed to spontaneous extrusion with a mean period of ventilation approaching 20 months. 54.9% of patients experienced otorrhoea which was found to be significantly more common in those ears with a mucoid effusion at the time of T-tube insertion. 21.1% of ears developed a persistent perforation where spontaneous extrusion had occurred or the T-tubes had been removed. Perforation also occurred more frequently in those with otorrhoea.


Tissue-integrated implants in children.

The aim of this study is to present our clinical experience with tissue-integrated extra-oral implants in children. Thirty consecutive cases of children with a total of 59 standard titanium fixtures inserted in the temporal bones and used as bone-anchorage for auricular epistheses (14 cases) and hearing aids (16 cases) were studied. The surgical procedure is performed in two steps and involves an extremely gentle handling of the soft tissue and bone. The patients were followed with regular check-ups for an average of 40 months after hearing aid/prosthesis fitting. The fixture survival rate was 96.6% for the whole group. The hearing aids had a reaction-free skin penetration in 91.67% of the postoperative observations and the prostheses had a reaction-free skin penetration in 75.00% of the postoperative observations. It is concluded that the use of 'osseointegrated', implants in carefully selected cases, in children, appears to be a reliable method for bone anchorage of epistheses and bone conduction hearing aids. A close follow-up and control of this patient category is especially important with respect to the long-term results.