Melanoma-associated antigen synthesized in vitro for active specific immunotherapy. The immunogenicity of the antigen molecule is a prerequisite for active specific immunotherapy for melanoma. Since most of the melanoma-associated antigens recognized by the murine immune system are known to be not immunogenic in man, a detection and analysis system for melanoma-associated antigens is required to reflect in vivo immune responses in patients with melanoma. One of the promising approaches, an attempt to develop human monoclonal antibodies from B lymphocytes of patients with melanoma, has met with limited success due to the difficulties of producing large amounts of antibodies and using them in immunochemical assays, because most of them belong to the IgM class and have low affinity. Our approach is to utilize the screening of a cDNA expression library constructed from mRNA extracted from cultured melanoma cells with antibodies from patients with melanoma. The cloned cDNA, designated as D-1, had 1029 bp and showed no significant homology with viral and mammalian sequences stored in GENETYX. cDNA D-1 hybridized to a 2.0 kb mRNA species from 3 different cell lines of human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cells, but not from a renal carcinoma cell line, normal peripheral lymphocytes, or normal fibroblasts. The in vivo expression and distribution of mRNA related to cDNA D-1 has been examined in tissue specimens by in situ hybridization and shown to be rather restricted on melanoma cells. The polypeptide antigen encoded by cDNA D-1 may be a valuable immunogen for implementing active specific immunotherapy in patients with melanoma.


Analysis of the expression of Hanganutziu-Deicher (HD) antigen in human malignant melanoma. Hanganutziu-Deicher (HD) antigen is classified as a heterophile antigen and chemically defined as a ganglioside and/or glycoprotein containing N-glycolylneuraminic acid (NeuGc). HD antigen is absent from normal tissues in humans and chickens but can be expressed in human malignant neoplasms including melanoma. We analysed HD antigen expression in ganglioside and glycoprotein fractions of human melanoma tissues by means of TLC enzyme-immunostaining and Western blotting with biotinylated affinity-purified chicken anti-NeuGc-lactosylceramide (anti-HD3) antibody. No HD-antigenic gangliosides were detected in 11 specimens of human melanoma. In the glycoprotein fractions, however, a strong HD-positive band of 58 kD was detected in 3 of 10 specimens and several minor bands (37 kD, 13.5 kD, etc.) were also found in 5 specimens. The positive bands completely disappeared after treatment with neuraminidase. These results suggest that HD antigen is expressed on the carbohydrate chains of glycoproteins but not on those of gangliosides in human melanoma.


Integrin expression in malignant melanoma and their role in cell attachment and migration on extracellular matrix proteins. The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of alpha and beta subunits and the beta 1-integrins are especially important as ECM receptors. We investigated the expression of beta 1-integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only alpha 2 beta 1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti-VLA2 monoclonal antibody (mAb). As to FN receptors, alpha 4 beta 1 and alpha 5 beta 1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti-VLA4 and anti-VLA5 mAbs. Our findings provide evidence for a role in beta 1-integrins, in particular alpha 2 beta 1, in melanoma progression and metastasis.


Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins. We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.


Aspects in neurofibromatosis from the viewpoint of dermatology. The neurofibromatoses are a heterogenous set of conditions having clinical manifestations such as skin, nervous system, bone and eye disorders. The clinical pictures of the patients will obviously differ, and there is considerable variation of manifestations even within a family. During the last twenty-five years, one thousand and two hundred patients with neurofibromatosis were personally examined. Almost all our patients had classical von Recklinghausen disease. But in addition to these cases, there are 28 cases of NF-2 and 10 patients which we call multiple neurilemmomatosis. Also, there are related groups of patients with conditions which were not neurofibromatosis, such as 40 cases of localized multiple neurofibromas and 61 cases of localized café-au-lait spots. The features of neurofibromatosis in Japan are not different, compared with foreign countries, except increased pigmentation is more common. In addition to café-au-lait spots, some 20% of Japanese neurofibromatosis patients have pigmentary conditions which I termed hairy fuscoceruleus spots. These spots are blue-brown in colour, and one can see coarse hairs in them. Our recent study indicates that the patients with neurilemmomatosis have loss of heterozygosity of chromosome 22, the same position as the site of patients with NF-2. Neurilemmomatosis may be classified as an NF-2 without acoustic tumors.


Nosological considerations of the neurofibromatoses. We are on the threshold of evaluating the NF1 and NF2 loci with respect to variant forms of the neurofibromatoses. Genetic mapping of NF1, gene cloning and characterization of its encoded product, neurofibromin, provides a framework for the evaluation of the variant forms of NF. This may also apply to NF2 variant forms in the near future. The mapping approach in evaluating variant forms of NF should begin with the rigorous clinical assessment of familial cases whereby the establishment of genetic linkage in families with overlap syndromes might determine if either NF1, NF2, or a separate locus is involved in the phenotype. Conditions mapping to the NF1 locus could then be screened for mutations in hopes of identifying the etiologies of the variant forms of NF. Mutation identification should provide a molecular-based classification scheme for the variant forms of NF, now tentatively divided into alternative and related forms. It is expected that the nosology of the neurofibromatoses will most certainly change as more is learned of the NF1 and NF2 loci.


The neurofibromatosis type 1 (NF1) gene: identification and partial characterization of a putative tumor suppressor gene. The NF1 gene has been isolated and partially characterized. The discovery that NF1 functions as a ras GTPase activator protein has led to new opportunities for understanding the pathology of this disease. The approximately 11 kilobase (kb) NF1 consensus cDNA sequence contains an open reading frame encoding a peptide of 2818 amino acids. DNA blot and polymerase chain reaction analysis indicate that the NF1 gene consists of over 50 exons spanning 300 kb of chromosome 17.


The neuropathology of tuberous sclerosis. Tuberous sclerosis, an autosomal dominant disorder associated with hamartomas in multiple organs, prominently affects the central nervous system; principle lesions include subependymal nodules and giant cell astrocytomas, white matter heterotopias, and cortical tubers. Histologic, immunocytochemical, and ultrastructural features of these processes suggest they have their basis in abnormal cell migration and differentiation. Aberrant expression of cystoskeletal proteins appears to be common to the multisystem hamartomas of this disorder and may, in part, underlie their pathogenesis.


CT and MR imaging of intracranial tuberous sclerosis. CT and MR have permitted radiology to play a greater, but not definitive, role in detecting the pathologic components of tuberous sclerosis. SEN may be identified in only 80% of patients. Tubers are more ubiquitous and readily identified by MR in children and adults when the brain is myelinated. Since tubers are predominantly peripheral hypomyelinated lesions, the detection of small lesions may be delayed until an infant is over 16-18 months of age when the myelin will have extended to the junction between the cortical white and gray matter. SEGA typically evolve later during the first and second decades of life. Successful genetic counseling implies a need to detect tuberous sclerosis at a stage during infancy when imaging may fail to confirm the diagnosis, so tuberous sclerosis remains a clinical diagnosis.


Tuberous sclerosis complex: genetic aspects. Much has been learned about tuberous sclerosis complex (TSC) since it was described at the end of the nineteenth century. TSC was recognized to be a genetic disease with autosomal dominant inheritance in the early twentieth century. The prevalence in the general population is at least 1 in 10,000 with two-thirds of cases occurring sporadically and one-third of cases being familial. The disease exhibits variable expression which may cause mildly affected individuals to be undiagnosed. Because the aberrant or missing proteins which result in TSC have eluded investigators, a positional cloning approach has been pursued to find the mutated genes. Genetic linkages have been reported to chromosomes 9, 11, and 12. There is definite evidence for a TSC-causing locus on chromosome 9 which is thought to account for between one-third and one-half of all familial cases. Investigators have narrowed the location on chromosome 9 to approximately two megabases of physical distance. There is some evidence for a locus on chromosome 11 which probably accounts only for a small percentage of familial cases. The locus proposed on chromosome 12 was reported by a single group and has not been confirmed by other research groups. Evidence for genetic heterogeneity is abundant. There is definitely a TSC-causing locus on chromosome 9q (TSC-1) and there is at least one additional locus, maybe more than one. As the molecular basis of TSC unfolds, new insight will be gained about the protean nature of the disorder and the genetic heterogeneity.


Mechanisms of local, low-dose UVB-induced immunosuppression in contact hypersensitivity. Preirradiation of contact sensitizing sites to low-dose ultraviolet B (UVB) renders animals unresponsive to challenge reaction. This unresponsiveness is known as local, low-dose UVB-induced immunosuppression. Although researchers in this area have developed theories, the exact mechanisms of UVB-induced immunosuppression are still a matter of controversy. This article reviewed various scientific data on UVB-induced immunosuppression, categorizing them into individual sequential steps in the whole cascade.


Expression of neuron-specific enolase immunoreactivity by cutaneous and extracutaneous Langerhans-cell histiocytoses ("X"). The immunohistochemical expression of Neuron-Specific Enolase (NSE) and of S100 protein was studied in 10 cases of cutaneous and 19 cases of extracutaneous Langerhans cell histiocytoses (LCH), including acute/proliferative forms (cutaneous Letterer-Siwe disease) and chronic/granulomatous forms (eosinophilic granuloma, Hand-Schüller-Christian disease). Of the LCH cases, 18 (62%) exhibited detectable NSE-immunoreactivity as compared to 82.8% for S100. NSE expression was found more frequently and intensely within acute (as compared to chronic) forms of LCH. This result lends further support to the cellular unicity of LCH, but also suggests some degree of heterogeneity among LCH cells. It can be speculated that NSE-expression is correlated with the proliferation/activation state of (abnormal) Langerhans cells.


Significance of antibodies to phenolic glycolipid-I in leprosy diagnosis. A gelatin particle agglutination assay for the detection of anti PGL-I antibodies in 40 clinically diagnosed and variously classified groups of leprosy cases revealed elevated PGL-I antibody titers in 85% of cases. In contrast, the slit-skin smear examination was positive in only 30% of cases. It was further observed that, out of 28 cases with Bacteriological Index (B.I.) zero, 22 cases (78.5%) had significant levels of PGL-I antibodies. There was no case in which the slit skin smear was positive and the PGL-I antibody titer was not significant. The elevated titers of PGL-I antibody better correlated (84%) with histopathological findings than did B.I. Thus it was concluded that estimation of PGL-I antibody titer is a better supplement to clinical diagnosis than B.I. Significant levels of PGL-I antibody were seen in 85% of cases who had no earlier chemotherapy or were treated for less than 2 months. Similar findings were observed in 12 patients who were on MDT for more than 5 months but for less than 2 years. In order to determine the significance of anti PGL-I antibodies in monitoring the response of patients to chemotherapy, a longer follow up with a greater number of cases should be contemplated.


Influence of oral metronidazole on the endocrine milieu and sebum excretion rate. As part of a study of the mechanism of metronidazole's efficacy in the treatment of acne and rosacea, its effects on the endocrine milieu and sebum excretion rate were assessed. Thirteen healthy males received oral metronidazole treatment (500 mg/day) for 4 weeks. Serum sex hormone levels were determined in all 13 subjects and the sebum excretion rate was determined in seven of them, before and after treatment. We measured serum levels of estrone (E1), estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG). There were no significant changes in E1, T, FT, DHT, or SHBG levels, but E2 and DHEA-S levels decreased significantly after treatment. In all seven subjects in whom the sebum excretion rates were determined, the amount of facial skin surface lipids decreased significantly after treatment. These results suggest that metronidazole exerts its clinical effects through suppressing the sebum excretion by a mechanism other than anti-androgenic action.


The role of metal allergy and local hyperhidrosis in the pathogenesis of pompholyx. Pompholyx (Dyshidrosis) is a disease of unknown etiology presenting as symmetrical, vesicular hand and foot dermatitis. To clarify the pathogenetic role of sweat and metal allergy, twenty five patients with pompholyx were examined with respect to their perspiration volume using equipment that continuously recorded the local perspiration volume. Patients were also examined for metal allergy by patch testing and oral challenge tests. The perspiration volumes were measured using recently developed equipment for continuous recording of local perspiration volume (Kenz-Perspiro oss-100). The perspiration volume of pompholyx patients was found to be 2.5 times higher than that of age-matched normal controls. Twenty percent of the patients showed sensitivity to chromate, 16% to cobalt, and 28% to nickel on patch testing. Six patients with positive results were challenged orally in a controlled trial with 2.5 mg nickel, 1 mg cobalt, or 2.5 mg chromium. Four of them (67%) showed vesicular reactions on their hands with challenge testing. These results indicated a sensitivity to metal compounds which, in combination with local hyperhidrosis, may contribute to the development of vesicular lesions in pompholyx.


Nodular scleroderma in systemic sclerosis under D-penicillamine therapy. A case of systemic sclerosis (SS) which developed keloidal lesions (nodular scleroderma) on the chest during D-penicillamine (DPC) therapy is reported. The 36-year-old woman showed rapidly progressing skin sclerosis with lung and esophageal involvement, and DPC was started at the age of 38. Skin sclerosis as a whole had improved to some extent, when keloidal nodules developed on the upper chest at the age of 44. Since there were no other findings suggestive of adverse reactions caused by DPC, we speculate that activation of the fibroblasts in these lesions occurred despite the suppressive effect of DPC.


An AIDS patient with atopic dermatitis-like eruption responsive to systemic anti-fungal treatment. Patients with the acquired immunodeficiency syndrome (AIDS) often develop unusual skin complications. We describe a case of a 58-year-old man with AIDS who had a history of multiple transfusions with anti-hemophilic factor A. He developed papulovesicular and lichenified skin lesions on his head, face, neck and the extensor aspects of his extremities accompanied by severe pruritus. Atopic dermatitis was suspected; however, intensive treatment with a potent topical corticosteroid and a systemic antihistamine failed. In addition to the decreased subset of CD4-positive lymphocytes characteristic of AIDS, this patient showed an elevated level of serum IgE particularly specific for Candida albicans, probably because he had a chronic candidial infection of the digestive tract. Oral administration of anti-fungal agents Diflucan and Fungizone produced almost complete relief from the atopic dermatitis-like skin disease within 2 weeks.


The effects of crowding on adults of Philophthalmus nocturnus grown in domestic chicks. The effects of crowding on growth, reproduction, rate of recovery and site of infection of Philophthalmus nocturnus were investigated by infecting various groups of day-old chicks with 25, 50, 75, or 100 excysted metacercariae and examining them at 10 or 25 days post-infection. Considerable reduction in the body length and the size of the gonads was noticed in flukes grown under crowded conditions. Crowding also caused some change in the habitat of flukes, but had no effect on their rate of recovery. Very few flukes reached the ovigerous stage under overcrowded conditions and none reached the embryonated larval stage.


Ultrastructure of the spermatid and spermatozoon of Macracanthorhynchus hirudinaceus. The ultrastructure of the spermatid and spermatozoon of Macracanthorhynchus hirudinaceus (Archiacanthocephala) was studied by means of transmission electron microscopy. The flagellum and nucleus in the spermatid gradually expanded simultaneously. The karyoplasma of the spermatid transformed into dense inclusions and a multibarrel structure, which were also found in the spermatozoan body. The multibarrel structure was located close to the flagellum and consisted of many irregular microtubes. The flagellum of the developing spermatozoon was observed in a concavity of the spermatid nucleus. The microtubule arrangement of the flagellum was "9 + 2". No mitochondria or acrosome were observed in spermatozoa.


The effect of catecholamines and catecholamine antagonists on the third larval moult of Dirofilaria immitis in vitro. Various catecholamines and catecholamine antagonists have been examined for their effects on the third larval moult of the parasitic nematode. Dirofilaria immitis, cultured in vitro. The non-selective alpha and beta agonist, noradrenaline, and the beta agonist, isoprenaline, had no effect on the timing of the third stage moult when used at a concentration of 10(-5) M. The alpha-adrenergic antagonist, phentolamine, resulted in worm mortality at 10(-5) M. At 10(-7) M, both phentolamine and the beta-antagonist, propranolol caused a significant reduction in the numbers of larvae capable of completing the third stage moult. Idazoxan, an alpha 2-antagonist, at 10(-5) M did not affect worm mortality but did completely prevent ecdysis. The potential of these compounds as possible filaricides is discussed.


The use of 35S-labelled Toxocara canis to determine larval numbers in tissues. The potential of using 35S-labelled larvae to determine the number of second-stage Toxocara canis larvae present in the tissues of infected animals was assessed. Infective larvae were labelled by in vitro culture with medium containing 35S-methionine. The amount of radiolabel attached to larvae decayed exponentially with time and had an in vitro mean half life of 3.54 +/- 0.65 days. The 'lost' radiolabel was incorporated into proteins which formed part of the worm's excretory/secretory products. The levels of radioactivity present in different organs of BALB/c mice, infected with 35S-labelled T. canis larvae, varied over the course of infection. Initially most of the radioactivity was present in liver, but over the course of infection 35S liver levels gradually decreased and brain levels increased. By day 14 post-infection the majority of the isotope was present in the brain (p < 0.01). Assessment of antibody levels on day 14 post-infection showed that infection with 35S labelled T. canis larvae induced the production of parasite-specific IgM, IgG and IgG1 antibodies.


Efficacy of ivermectin against Parastrongylus malaysiensis infection in rats. The efficacy of ivermectin on experimental infections of P. malaysiensis in rats was determined. Ivermectin was 99.4% and 97.9% effective at a dosage of 400 meg and 800 meg respectively at seven days post-infection. The same two dosages of ivermectin when given at 14 days post infection had an efficacy of 100%. However, as an adulticide it had only 40.7% efficacy. Ivermectin may therefore be useful for the treatment of parastrongyliasis due to the larval stages of the worm which can cause significant pathology in man and animals.


Immunodiagnosis of human trichinellosis using excretory-secretory (ES) antigen. Infective first stage larvae of Trichinella spiralis were recovered from muscles of laboratory infected mice by digesting the muscles with 1% HC1-1% pepsin and collecting the larvae by modified Baerman's method. The larvae were cultivated in a serum-free medium for 18 h. The ES antigen obtained from the culture medium was used in an enzyme-linked immunosorbent assay (ELISA) for detecting IgG antibodies to T. spiralis in serum samples collected from three groups of individuals. The individuals of the first group were parasitologically confirmed trichinellosis patients, while those of group 2 were patients with other helminthiasis and group 3 were healthy, parasite-free individuals. The specificity of the assay was 100%. The sensitivity of the test was also 100% when performed on sera of group 1 collected at days 57 and 120 after infection. Sera collected earlier (day 23) and those collected 700 days after infection had negligible reactivity. Thus IgG-ELISA using ES antigen of the L1 was useful not only for diagnosis but also in evaluation of cure. Western blot analysis revealed that specific antigens of T. spiralis were 94, 67, 63, and 39 kilodalton components.


Radiolabelling of the excretory-secretory and somatic antigens of Anisakis simplex larvae. Anisakis simplex larvae were cultured in vitro in medium containing 35S-methionine for ten days. The medium and the larval tissues were analysed for biosynthetically labelled polypeptide by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography. Immunoprecipitates with positive and negative human antisera were similarly analysed, using Staphylococcus aureus to absorb immuno-complexes. ES products of Anisakis larvae contained many polypeptides with molecular weights of less than 200 K. 180 KDa and 40 KDa polypeptides in ES products reacted with IgG in Anisakis-infected human sera. Somatic extracts also contained many polypeptides with molecular weights of less than 200 K. One of these polypeptides with a molecular weight of 130 K reacted with IgG in Anisakis-infected human sera. These polypeptides did not react with other nematode-infected human sera.


Isoenzymatic pattern and structure of glutamate dehydrogenase from Ascaris suum. The isoenzymatic pattern of glutamate dehydrogenase (GDH) has been described for Ascaris suum a parasite of Sus scrofa domestica. Only one band of activity has been revealed, suggesting a monomorphic condition for this enzyme. Also, the structure of GDH has been assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. Only one subunit was present with a molecular weight of about 55,000. A hexameric structure for GDH of A. suum is suggested.


Traditional Crow Indian health beliefs and practices. Toward a grounded theory. An important element in American Indian cultures is a holistic view of wellness. Nurses attempting to provide holistic, culturally sensitive health services to American Indian clients must assess the cultural orientation of their clients and have culture-specific knowledge. A pilot qualitative study was conducted at the Crow Indian Reservation in south central Montana. Qualitative analysis of data identified categories of traditional contemporary health practices of Crow Indians. These categories are use of rituals/ceremonies, indigenous healers, and sacred objects. Five patterns of use of traditional health practices were also discovered. These are (a) initial use of traditional practices followed by modern health services, (b) initial use of modern health services followed by traditional practices, (c) simultaneous bicultural use, (d) traditional use only, and (e) modern use only.


Improving organ donation rates in the black community. The risk of developing end-stage renal disease is four times higher in the Black than in the White population. The number of Blacks on dialysis or on the waiting list for transplantation continues to grow due to an insufficient number of suitable organ donors. Same-race transplants have been shown to be more successful when blood types and human leucocyte antigens are used as the matching criteria. The low levels of organ donation by Blacks has been attributed to a number of factors. This article reviews some of the more complex factors (e.g., social practices, religious beliefs, and cultural expectations) affecting the organ donation decision. In addition, some implications and strategies are suggested that may increase the rate of organ donation in the Black community.


The Soviet health care system: Glasnost, Perestroika, and health problems of the 1990s. Worsening economic conditions and political turmoil in the Soviet Union have led to significant health care problems in the 90s. The Soviet people are calling for reforms of education and the health care system that extend beyond the unsuccessful program of glasnost and perestroika. The purposes of this article are to (a) describe the health care system in the Soviet Union, (b) highlight health issues and concerns of the Soviet people, (c) describe the education of physicians and nurses, and (d) compare and contrast common and unique factors about Soviet health care with health care in the West. The data base for the article was collected from observational site visits, on-site focused interviews with key informants in Kiev and Moscow, and extensive computerized and manual literature searches. Data were also gathered from questionnaires distributed to a convenience sample of 17 nurses in Moscow. Study results include demographic information and the state of nursing education and research, including availability and access to resources to conduct nursing research in Moscow.


Perspectives on nursing care of Chinese Americans. Chinese population growth in the United States is expected to accelerate more rapidly than that of any other Asian group in the coming decades. As a result, nurses will be encountering members of this diverse and rich cultural group more frequently. A better understanding of the cultural beliefs, customs, and health care practices of Chinese Americans can only improve the quality of nursing care provided for these clients. Awareness of the barriers to health care that confront many Chinese Americans will be useful in designing appropriate nursing interventions. Knowledge of the positive and negative effects of some traditional Chinese health care practices can be incorporated into individualized client teaching plans.


A holistic approach to vaso-occlusive pain crisis in children with sickle cell disease. A significant number of children with sickle cell disease suffer from episodes of acute recurrent vaso-occlusive pain crisis. Unfortunately, very limited published information is available about specific pain management practices used for these patients. There is even less information available on the use of an interdisciplinary approach for management of sickle cell crisis pain. The purpose of this article is to review the genetic cellular pathophysiology, the sickling process, vaso-occlusive crisis, and management of pain associated with sickle cell disease in children. The article further examines an interdisciplinary approach for the management of vaso-occlusive pain crisis.


The "big three" cardiovascular risk factors among American blacks and Hispanics. Today's chronic diseases require "treatment" by shifting control of the outcome from the provider back to the individual and the environment in which one functions. There is a strong need to consider the individual in the context of ethnicity and culture, which express themselves in the prevalence and magnitude of risk factors, the biological impact of risk factors and expression of disease, and the potential for control of unhealthy behaviors. Educational and screening programs related to the risk factors of cigarette smoking, hypertension, and cholesterol must be structured so that recommended life-style changes are compatible with the individual's cultural values and beliefs.


Issues related to dust aerosols in the magnesite industry. I. Chamber exposure. The present paper is an overview of the experimental research into the effects of flue magnesite dust in the magnesite industry in which the raw material (magnesite) is processed into refractory magnesite clinker. The issues related to dust are divided into two problem areas: a) dust aerosol arising in the process of ore mining and consisting largely of magnesite (MgCO3) and b) dust aerosol originating during ore baking in rotatory furnaces and made up mostly of MgO. Thus, larger groups of people become exposed to these aerosols as a result of solid particles escaping into the atmosphere than in the case of occupational exposure. Experimental research carried out on laboratory animals after chamber exposure provided findings on the deposition, retention and elimination of magnesite dust, on impaired balance between magnesium and calcium leading to damage of biological membranes, on how the immune profile or reproduction and embryogenesis is impacted as well as on the possible interaction with sodium salicylate as a result of an impaired acid base balance. These findings are followed up by evidence produced in the course of biological monitoring (Part II).


The past and future of tropical medicine in Czechoslovakia. The authors present a short historical review on the developments in the Czechoslovak tropical health studies with special reference to the post WW II period. Perspectives for future expansion are likewise outlined.


Pilot studies on the occurrence of some infectious diseases in two different areas in south Yemen (Aden). Part I. Parasitology. Two pilot studies on malaria, leishmaniasis, schistosomiasis and intestinal parasites were carried out in 104 children 6-15 years old from villages in the lowland and highland areas of South Yemen in November 1988. Some of the results presented are in the order lowland and highland. The occurrence of malaria parasites in blood smears was 6.7% and 3.8%. P. falciparum was detected only. The antimalarial IFAT antibodies were proved in 66.7% and 11.5% respectively. IFAT antibodies against leishmania were in 43.8% and 39.3% respectively of sera examined. Ova of S. haematobium diagnosed with the frequency 29.0% and 13.3% respectively. S. mansoni infection was found in 19.2% of examined children in highland only. From parasites found in stool specimens should be mentioned E. histolytica (42.3% and 36.8%), G. lamblia (34.6% and 35.1%). The other intestinal protozoa were less frequent. Further details of sex and age groups distribution are mentioned.


Vertical transmission of hepatitis B in north India. A total of 2337 mother-baby paired sera were screened for the presence of hepatitis B surface antigen. Fifty eight mothers (2.48 per cent) were positive for HBsAg. Six babies (10.3 per cent) were positive for HBsAg at birth. The risk of the babies acquiring the infection during the first year of life varied with the serological status of the mothers. In HBeAg positive mothers the babies were at the greatest risk, with 11/15 (73.3 per cent) babies acquiring the infection by twelve months. If the mothers were only HBsAg positive the risk was lower (17.3 per cent), and if the mother was anti-HBe positive also then the baby had the least chance of becoming infected (9 per cent).


Qualification of long-stored samples of serum banks for seroepidemiological studies. Serum samples were tested for antibodies against polio virus and measles virus from two serum banks after having been stored under different conditions for several years. The results are compared with those ones obtained immediately after sampling. Despite of small increases of antibody-negative samples and of small decreases of the titres the suitability of the samples stored could be shown. Special attention should be given to the establishment, e.g. in the framework of Expanded Programme on Immunization of the World Health Organization and in order to study new pathogens unknown to date, and the technical preconditions for that should be planed.


Diagnosis of mycobacterial infection in acquired immunodeficiency syndrome (AIDS) patients and HIV carriers. Differences in tuberculosis diagnosis between infected and non-infected HIV patients were described. In Barcelona, tuberculosis is present in 41.6% of 851 patients in whom AIDS was detected between 1981 and the first quarter of 1990. We reviewed the results of the methods used for tuberculosis diagnosis in 270 AIDS patients controlled in our hospital, in whom tuberculosis was detected (33.3%), and we compared these data with the results obtained in HIV carriers with tuberculosis and with tuberculous patients without HIV infection. Statistically significant differences were found between the three groups with respect to sex, age, results of Ziehl-Neelsen stain in pulmonary specimens and skin test reaction; between AIDS patients and the non-HIV infected population differences were observed in tuberculosis site. Positive skin test reaction diminished from tuberculous individuals non-HIV infected (95%), to HIV carriers with tuberculosis (71.8%) and AIDS patients with tuberculosis (21.8%). Acid-fast smears from pulmonary specimens were positive in 35.7%, 23.5% and 43.7% respectively. Statistically significant differences were found in tuberculosis localization between tuberculous patients non-HIV infected and tuberculous patients with AIDS, in the last group tuberculosis lymphadenitis was the most frequent localization (33.3%) of extrapulmonary tuberculosis, followed by abdominal tuberculosis (15.5%). The incidence of HIV infection among tuberculous patients was 4.6 in our study, but could be higher if patients between 19 and 30 years old were always checked for anti-HIV antibodies.


Antibacterial properties of the Vietnamese cajeput oil and ocimum oil in combination with antibacterial agents. Main antibacterially active agents obtained from plants-Cajeput essential oil--1,8 cineol, linalool, alpha-terpineol and terpinen-4-ol, for example from Melalleuce leucadendron (Myrtaceae) as well as essential oil from Ocimum gratissimum (Labiatae) were combined in tests in vitro with selected antibiotics. Above mentioned plant products were found to be effective medicaments for local application in modern medical practice. Combinations with antibiotics potentiated their therapeutical action. On the basis of tests in vitro the synergistic action of these two kinds of medicaments, i.e., preparations traditionally used for a few last decades--antibiotics--might be well applied for therapeutical needs.


Yeasts at different mucosal sites in patients with carcinoma cervix before and following radiotherapy. The yeasts isolated from four superficial sites and blood were studied before and during radiotherapy in patients with carcinoma of the cervix. Significant yeast growth increased markedly in all four superficial sites during the 1st and 2nd week following radiotherapy. By the 4th week the count had decreased in all samples except in stool of 4 patients. Candida albicans was the most frequent isolate (54.3%) followed by C. tropicalis (28.3%).


C-reactive proteins, immunoglobulin profile and mycobacterial antigens in cerebrospinal fluid of patients with pyogenic and tuberculous meningitis. Cerebrospinal fluid (CSF) samples were collected from 12 patients with pyogenic meningitis (PM), 19 with tuberculous meningitis (TBM), 20 with clinically suspected but not definitely proved cases of tuberculous meningitis (STBM) and 12 normal controls. C-reactive proteins, immunoglobulins G, A, M and mycobacterial antigens were estimated in the CSF samples. Seven out of 51 (13.7%) samples obtained from the patient groups were positive for CRP. Immunoglobulins M and A were significantly raised in the PM group. When the TBM and STBM groups were compared with the controls a highly significant increase was obtained for all immunoglobulins. Mycobacterial antigens/epitopes were identified in 36.8% samples with TBAGB1 and TB68-H monoclonals and in 26.3% with WTB72-A2. In case of patients with suspected TBM, 6.6% were positive with TBAGB1 and WTB72-A2 and 13.3% with TB68-H. However, non-tuberculous patients also reacted with WTB72-A2 (10.5%) and TB68-H (21.0%). This is, to the authors' knowledge, the first report on the presence of CRP in the CSF. Technique for immunoglobulins in CSF is also updated in this paper. We infer that the monoclonal antibody TBAGB1 and immunoglobulins G and A may be safely considered as diagnostic markers of TBM. Estimation of CRP in CSF samples may be made to give a preliminary or additional diagnosis of meningitis regardless of its aetiology.


In vitro stimulation of human lymphocytes by alpha, beta and delta toxins and toxoids of Staphylococcus aureus. Alpha, beta and delta toxins of Staphylococcus aureus stimulate human peripheral blood lymphocytes to blastic transformation and formation of IgM, IgG and IgA. The toxins are efficient at concentrations that are not toxic for the cells in culture. A dose of a toxin suitable for stimulation is 100 ng/ml but a stimulation can be observed also at 10 ng/ml, in the case of Ig formation even at a concentration of 1 ng/ml. Toxoids are approximately as effective to elicit blastic transformation as the toxins themselves, their efficiency to stimulate Ig formation being somewhat lower but significant. Alpha and delta toxins and toxoids at the appropriate concentration appear to act as medium-strength polyclonal activators of lymphocytes. Beta toxin and its toxoid are weak polyclonal activators.


[Clinical study on symptoms in patients with strongyloidiasis]. We treated strongyloidiasis patients and obtained the following results: Of the 299 patients (184 males and 115 females), 81 patients (27.1%) had no complaints before treatment, 218 patients complaints of some symptoms, including arthralgia and/or lumbago (28.4%), abdominal pain and/or borborygmus (19.3%), numbness of extremities (18.1%), constipation (16.3%) and itching (15.7). We treated 219 patients with mebendazole and symptoms improved after treatment described below: Thirty-seven of the 63 patients (58.7%) with arthralgia and/or lumbago improved. Twenty-seven of the 36 patients (75.0%) with numbness of extremities improved. Thirty-one of the 32 patients (96.9%) with heartburn improved. We treated 26 patients with mebendazole plus thiabendazole and twelve of 14 patients (85.7%) with abdominal pain and/or borborygmus were improved after treatment. We treated 54 patients with ivermectin and five of 18 patients (27.8%) with arthralgia and/or lumbago were improved after treatment.


[Detection of verotoxin-producing Escherichia coli using polymerase chain reaction from dairy cattle]. The vero cytotoxin (VT) is responsible for hemorrhagic colitis and hemolytic uremic syndrome. Polymerase chain reaction (PCR) was used to detect VT-producing coliform bacteria from dairy cattle. It was found that 39 (33.3%) of the 117 fecal samples examined were recognized with VT genes in BGLB enrichment broth by the PCR method (named BGLB-PCR). Of the VT-positive samples, 31 samples (26.5%) were found to have VT-producing Escherichia coli. Frequencies of isolation in younger cattle (under 5 months) were 31.3-32.9%. On the other hand, the PCR method using the bacterial suspension of some colonies from DHL selective isolation medium (named DHL-PCR), was used for 105 samples. The DHL-PCR was validated according to the number of colonies tested for detecting VTEC. When using E. coli strains which have been stored after isolation by the conventional culture method, the VT-producing strains found were 7 (10.3%) of the 68 isolates tested. The 101 out of the 108 VTEC strains from cattle were classified into 14 O groups. 4 O serogroups (O26, O111, O145, O157) from 60% of VTEC positive cattle, were also the most common in humans with diarrhea. All E. coli O157:H7 isolates failed to ferment after 48 hrs and to hydrolyze 4-methyl-umbelliferyl-beta-D-glucuronide (MUG). These results suggests that cattle may play an important role in human VTEC infections. The BGL B-PCR technique is usefull in ecological studies for VT-producing pathogens.


[The 5th report on long-term chemotherapy using erythromycin (EM) for chronic lower airway infection--cases followed over 7 years]. Clinical studies were made over 7 years on 9 cases to whom long-term chemotherapy with EM was administered for chronic airway infection. 1) Clinical effectiveness: Highly effective in 8 cases; Improvement in QOL was observed in 8 cases. Bacteriological effect: In 7 cases, pathogenic bacteria disappeared. 2) No side effects were observed. 3) Changes in PaO2 levels with the passage of time: In most cases, PaO2 reached a plateau within 1 year. Although in some cases, there was subsequent elevation. 4) The frequency of catching cold over the 7 years period was low with an average of 1.2 times/year per subject. In only 2 cases were subject hospitalized due to acute exacerbation triggered by a cold. 5) Mucociliary transport improved in 7 out of 8 cases examined. However, only 4 of these recovered normal transport. The effect of EM in the other cases in which clinical improvement was not demonstrated was deemed slightly effective. On the basis of the above findings, it was suggested that long-term chemotherapy using EM was clinically efficacious. This is based on the fact that its efficacy, including amelioration of QOL appeared within one year of the initiation of therapy, and continued without decline for over 7 years.


[Isolation of MRSA from inpatients, staff and environment in the hospital]. The state of MRSA contamination of inpatients, hospital staff, and the hospital environment was evaluated. Nasal, pharyngeal, and digital samples from 182 patients admitted in September and October, 1990, and 288 hospital staff members and sputum, urine, and feces of the inpatients were cultured. Environmental contamination was examined in samples collected from the air by air sampling and from the floor by the wiping method. The MIC and the coagulase type of the MRSA obtained were determined, and their relationships were evaluated. MRSA was detected in 9.5% of nasal samples, 7% of pharyngeal samples, 10% of sputum samples, 0% of urine samples, and 2.6% of fecal samples from the 182 inpatients. It was detected in 4% of nasal samples, 0.7% of pharyngeal samples, and 1% of digital samples from the 288 hospital staff members. From the environment, MRSA was detected from hospital rooms of the surgery and neurosurgery wards, the nursing room and corridors of the obstetrics and gynecology ward, and the recovery room of the urology ward. The coagulase type of the MRSA obtained was the primarily type II regardless or whether the samples were obtained from the subjects or the environment. Concerning the drug sensitivity, many MRSA strains were highly resistant to DMPPC and FOM, but the sensitivity to RFP was 0.1 microgram/ml or less in all strains except for one highly resistant strain (200 micrograms/ml or above).(ABSTRACT TRUNCATED AT 250 WORDS)


[Maternal carriage and vertical transmission of group B Streptococcus (GBS)]. The pneumonia, sepsis and meningitis are common diseases of GBS infection in infants. There are early-onset and late-onset types in this disease, the result of the infection is unknown. M. Sugiyama reported that M9 is a new type of GBS in Japan in 1989. Analysis of GBS typing and serum specific antibody concentrations of the type are simple with new technics. By studying the infants' contamination we discovered that GBS appeared to originate from mother-infant sources. The infants were followed for a year. 52% of the infants had GBS contamination in their throat or stool. The most common type was Ia, followed by III, JM9 and NT6. Those types without III type had been present for more than 9 months in the infant. The contamination term of Ia or III type in infants correlated with the blood specific antibody concentration of the type.


[Bacteriological study of traveller's diarrhoea. 4) Isolation of enteropathogenic bacteria from patients with traveller's diarrhoea at Osaka Airport Quarantine Station during 1984-1991]. During the last 8 years (1984 to 1991), 16,639,233 overseas travellers were quarantined at Osaka Airport Quarantine Station and 38,326 travellers reported that they were (or had been) suffering from diarrhoea. Bacteriological examination of stools from 12,573 persons revealed the following results. 1) Various enteropathogenic bacteria were isolated from 3,669 cases (29.2%) examined. The predominant species of bacteria isolated were as follows: Salmonella, 1049 cases; Plesiomonas shigelloides, 1030 cases; Vibrio parahaemolyticus, 789 cases; Shigella, 607 cases; enterotoxigenic Escherichia coli, 422 cases; Vibrio cholerae non-O1, 212 cases. 2) There were no apparent seasonal variations in the isolation rate of these pathogens. 3) The suspected regions for infection with these pathogens were as follows: a) Salmonella, Enterotoxigenic E. coli and Plesiomonas, mainly South-East and South-West Asia. b) Shigella, South-West Asia, especially India (59.8%). c) V. parahaemolyticus and V. fluvialis, mainly South-East and East Asia. d) V. cholerae non-O1, V. mimicus, almost restricted to Asia, mainly South-East Asia. 4) 22 strains of V. cholerae O1 were isolated and 19 were Ogawa, E1 Tor. Of these strains, 13 were cholera toxin-producing strains and 9 were non-toxigenic strains. 5) Several pathogens (mixed infection) were isolated simultaneously from 670 cases. 6) The 1247 Salmonella strains were identified into 98 serovars. 7) Of 624 Shigella strains isolated, 57.9% were S. sonnei, 29.2% were S. flexneri, 8.6% were S. boydii, 4.3% were S. dysenteriae. 8) The most predominant serovar of V. parahaemolyticus was O4:K8. Of 1,247 strains isolated, 9.8% were not producing thermostable direct hemolysin (TDH). 9) 570 (91.3%) of 624 Shigella strains and 409 (32.8%) of 1,247 Salmonella strains isolated were resistant to any one of the drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). The resistance rate and the number of multiple drug-resistance strains increased year by year. 10) Enterotoxigenic E. coli was isolated from 422 cases (10.7%) of 3,939 cases. Cases with enterotoxigenic E. coli strains producing ST (heat-stable), LT (heat-labile) or both ST and LT were 53.8%, 24.2% and 14.2% respectively. The others were cases with mixed types of enterotoxin production.


Staphylococcus aureus bacteremia in patients with hematologic disorders. During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.


[Infectious complications in patients with adult T-cell leukemia]. Between January, 1982, and January, 1992, a total of 112 patients with adult T-cell leukemia (ATL) and 109 patients with non-Hodgkin's lymphoma (NHL) were admitted to our hospital. They were studied for their infectious complications. Infectious complications were seen in 90 patients (80.4%) with ATL, and 51 patients (46.8%) with NHL (p < 0.001). Documented infections were seen in 70 patients (62.5%) with ATL, and 30 patients (27.5%) with NHL (p < 0.001). Pneumonia (p < 0.005), skin infections (p < 0.05), Pneumocystis carinii pneumonia (p < 0.05), fungal infections (p < 0.05), cytomegalovirus infections (p < 0.05) and herpes simplex virus infections (p < 0.01) were identified infections at high risk for patients with ATL. Tuberculosis, listeriosis and salmonella infections were seen only in patients with ATL.


[Detection of intestinal parasites from dogs in Tochigi-City in 1979 and 1991]. To clarify whether sanitary and hygienic conditions surrounding humans and pet animals have improved or not, we examined feces from dogs for intestinal parasites in Tochigi in 1979 and 1991. Intestinal parasites were detected from 109 of the 262 dogs (41.9%) in 1979 and 86 of the 260 dogs (32.8%) in 1991. Among the parasites. Ancylostoma caninum, Tirchuris vulpis and Toxocara canis were most commonly detected, and their detection rates were higher in 1979. On the contrary, Dipylidium caninum, Strongyloides stercoralis, Isospora spp., which are important causes of human diseases, were detected at higher rates in 1991. In the dogs of outdoor feeding, the detection rates of parasites were markedly decreased, but slightly increased in the dogs of indoor feeding in 1991. These results suggest that sanitary conditions surrounding pet animals have not been sufficiently improved, in spite of the fact that humans are in more contact with their pet animals.


[Comparison of polymerase chain reaction and IDEIA Chlamydia in detection of Chlamydia trachomatis from first-voided urine of male urethritis patients]. We have reported a method for detection of Chlamydia trachomatis by polymerase chain reaction (PCR) with two oligonucleotides based on sequences within the major outer membrane protein gene from C. trachomatis serovar L2. In the previous report, in addition to treatment of the mixture of first-voided urine (FVU) sediment and 1 ml of urine with proteinase K. DNA purification by phenol extraction was necessary for preparation of template DNA for PCR. In this study, FVU sediment was suspended in 1 ml of Chlamydiazyme dilution buffer and a part of the suspension was treated with proteinase K for DNA extraction. The DNA extraction solution could be used as template for PCR without purification of DNA by phenol extraction. One hundred FVU specimens obtained from male urethritis patients were examined with the two methods (PCR and IDEIA) for detection of C. trachomatis. In 33 of 100 specimens, the DNA fragments of C. trachomatis was amplified by the PCR and in 32 of 100, the chlamydial antigen was detected by IDEIA. The positive and negative coincidence rate of the PCR to IDEIA were 93.8% (30.32) and 95.6% (65/68) respectively, resulting in a high overall coincidence rate at 95%. Thus, the improved method with PCR using FVU as a specimen is proved to be a useful, non-invasive diagnostic tool for diagnosis of chlamydial urethritis.


[Nested polymerase chain reaction for the diagnosis and follow-up of tuberculous meningitis: a case report]. We presented a case of tuberculous meningitis in which a nested polymerase chain reaction was useful for its rapid diagnosis and follow-up. A 5-month-old girl was hospitalized for gastrointestinal complaints of 4 days' duration. She initially had no meningeal signs, but showed a bulging of the anterior fontanel on the 10th day of her illness. Cerebrospinal fluid examination revealed a cell count of 886/3 microliters (80% lymphocytes), protein of 20 mg/dl, and glucose of 27 mg/dl. Tuberculous meningitis was suspected clinically and an antituberculous therapy was commenced on the 13th day. Although repeated attempts to culture Mycobacterium tuberculosis were negative, the DNA of the organism was detected sequentially from the cerebrospinal fluid of the 13th and 16th day by the method of a nested polymerase chain reaction. The final diagnosis of tuberculous meningitis was established on the basis of the positive results of the nested polymerase chain reaction, a positive tuberculin test, and typical cerebrospinal fluid findings. She recovered rapidly in response to the therapy and was discharged from the hospital without any neurological sequelae on the 89th day. The follow-up samples of the nested polymerase chain reaction resulted as negative after the 26th day of the illness.


[A case of adult respiratory distress syndrome likely due to measles and Mycoplasma pneumoniae]. We described a case of adult respiratory distress syndrome (ARDS) likely due to measles and Mycoplasma pneumoniae. A 24-year-old, previously healthy man was referred to our hospital because of respiratory arrest. He was unconscious and cyanotic. He had erythematous and polymorphic eruptions of his extremities and trunk, but his face was spared. His chest roentgenogram showed consolidation with air bronchograms affecting the whole bilateral lungs. After mechanical ventilation with positive end-expiratory pressure and administration of intravenous hydrocortisone and protease inhibitor "urinastatin" and so on, the patient recovered from his critical condition. No attributable organisms were isolated from the specimens investigated in his acute phase. Serological examinations of the specific IgM antibody to measles during the course indicated a recent measles infection. Mycoplasma pneumoniae indirect hemagglutination test rose from a titre of less than 1/40 to 1/60. ARDS is a rare complication of measles or Mycoplasma pneumoniae infection. Moreover he received measles vaccine before 1970 in Japan, so this case was suspected to be atypical measles.


Ophthalmic drug use in the OR.

Ophthalmic drug use in the OR. Categories of ophthalmic drugs used in the operating room (OR), their generic and trade names, indications for use, actions, contraindications, usual dosages, adverse reactions, and nursing concerns are presented to give the ophthalmic nurse a comprehensive knowledge of the most commonly used ocular pharmaceuticals.


QA, CQI, TQM: what's the difference?

QA, CQI, TQM: what's the difference? Total Quality Management (TQM) is not a program, but a process. It is a major cultural change of healthcare organizations. TQM should not be embraced as a "short term fix," but as the long term solution to the shortcomings in the delivery of patient care.


Nurses: advocates for nursing.

Nurses: advocates for nursing. Based on the nursing literature and my own ophthalmic nursing experience, there appears to be some confusion about how the general public, our colleagues, and physicians view the duties and responsibilities of the profession of nursing. We, as nurses, can serve as advocates for our own profession and educate the public about who we are, how we have achieved our current status and goals, and where we expect to be in the future.


Oral colon transit scintigraphy using indium-111 DTPA: variability in healthy subjects. Oral colon transit scintigraphy using indium-111 diethylene-triamine-pentaacetic acid was performed in 41 healthy subjects (22 females, 19 males) to determine variability with age and sex and to define normal ranges. Repeat studies were performed in 10 females and 9 males to assess intra-subject variability. Females showed slightly but significantly slower colonic transit than men and slightly greater intra-subject variability. There was no correlation between age and colonic transit. The results have implications for the definition of normal ranges.


Electromyography of the pubococcygeus muscles in patients with obstructed defaecation. The function of the pubococcygeus muscles during defaecation straining was compared in 10 women with obstructed defaecation and 12 age-matched control subjects. Video-proctography in each patient showed failure to evacuate the rectum and sagging of the pelvic floor during attempted defaecation. Trans-perineal concentric needle electromyography in the puborectalis muscle and transvaginal electromyography in the pubococcygeus muscle was carried out during defaecation straining and during attempted rectal balloon expulsion. Contraction of the pubococcygeus muscle was observed in 10 of the 12 control subjects and in 2 of the 10 patients with obstructed defaecation (P < 0.005). Virtually equal proportions of subjects in each group showed relaxation or contraction of the puborectalis muscle during straining. There was significant perineal descent on straining in the patient group (P = 0.005). This group of patients with obstructed defaecation showed failure of the pubococcygeus muscles to contract, perhaps due to neuropathic weakness of the muscles. The puborectalis muscle did not cause obstructed defaecation in these patients, and the concept of "paradoxical" contraction of this muscle is questioned.


Conservative and surgical treatment in acute and chronic anal fissure. A study on 308 patients. The aetiology of anal fissure is not fully understood--why some heal spontaneously and others become chronic remains a mystery. In this study we compared surgical and conservative therapy and investigated which surgical procedure is most useful in the treatment of fissure. There were investigated 308 patients, 157 with acute fissure and 151 with chronic fissure. Healing was achieved in 45 +/- 15 days and in 40 +/- 10 days in acute fissures treated conservatively and surgically, respectively, 40 +/- 15 days and 30 +/- 5 days were required to achieve healing in chronic fissure by conservative and surgical therapy, respectively. Manometric tests showed a decrease in resting pressure and maximum voluntary contraction pressure at one month, and an increase towards the pre-operative level at 4 months for both parameters. There were no recurrences at 5 years in 100 patients (50 males and 50 females).


Combined radiation and chemotherapy for epidermoid carcinoma of the anal canal. Between 1985 and 1992, 46 patients with epidermoid carcinoma of the anal canal were treated prospectively by a protocol of combined radiation and chemotherapy with 5-Fluorouracil and Mitomycin C. The survival rate, NED-survival rate and local tumour control rate were 84%, 71% and 83% at 5 years. Anorectal function was retained in 33 of 41 patients (80%). We observed severe acute toxicity including three deaths, but very little late morbidity. The only marginally significant prognostic factor (P = 0.06) for local tumour control was T-stage. NED-survival was significantly affected (P = 0.02) by reduction of chemotherapy during the second course.


Observations on the characteristics of stimulated defaecation in severe idiopathic constipation. A combined manometric and radioisotope study is described which was designed to investigate the motility characteristics of induced defaecation in the colon, rectum and anal canal, in patients with severe constipation. Five women with severe idiopathic constipation, aged 30-45 years, were studied. A multiple channel water-perfused manometric tube was placed colonoscopically into either the whole colon or left colon to monitor pressure activity. In two whole-colon studies, 5.5 MBq 111In DTPA and later 9 MBq 99mTc DTPA were instilled into the colon to monitor the transit of colonic contents in response to two separate stimuli. Motor activity was initiated on both occasions by intraluminal instillation of 5.5 mg bisacodyl. In the whole-colonic studies a right colonic stimulus initiated multiple high-pressure peristaltic waves which traversed the entire length of the colon. The bowel was then refractory to a second stimulus at the splenic flexure. In the five left colonic studies, a stimulus at the splenic flexure produced high-pressure peristaltic waves which proceeded distally, and which included a rise in rectal pressure. The anal canal relaxed simultaneously with the onset of peristalsis high in the left colon, and remained relaxed until the pressure wave reached the anus and bowel content had been expelled. In both types of study high-pressure waves corresponded to the effective transport of radioisotope. The constipated patients showed a coordinated motor response to the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction of the effluent volume in high-output ileostomy patients by a somatostatin analogue, SMS 201-995. Twelve ileostomy patients were given subcutaneous SMS 201-995 therapy (100 micrograms t.d.s. for 5 days) in a randomized placebo-controlled trial. All patients had ileostomies constructed 60 cm proximal to the terminal ileum (proximal ileostomy) following restorative proctocolectomy. SMS 201-995 reduced the daily ileostomy output from 997 +/- 52 g to 736 +/- 28 g, P < 0.05, along with a decrease in daily sodium and chloride excretion (sodium: 92.60 +/- 8.51 to 75.22 +/- 8.64 mEq, chloride: 143.46 +/- 8.54 to 113.60 +/- 15.84 mEq; both P < 0.05). There were no significant changes in the plasma levels of glucagon, C peptide, insulin, renin or aldosterone with SMS 201-995 therapy. Patients developed no severe side effects and reported easier management of the ileostomy and a reduction in thirst. Our results suggest a possible clinical role for SMS 201-995 in the management of proximal ileostomy.


Preoperative hyperthermia combined with chemotherapy and radiotherapy for patients with rectal carcinoma may prevent early local pelvic recurrence. We examined retrospectively the results of hyperthermia combined with irradiation and chemotherapy (HCR) prescribed preoperatively for patients with adenocarcinoma of the rectum. We compared two groups of patients: Group A: 23 were treated surgically between 1986-1988 and received HCR therapy; group B (controls) 48 were treated with surgery alone or surgery plus chemotherapy from 1980-1985. The recurrence rate within 2 years was compared. Although there was a difference in follow-up time, the two groups were comparable with regard to various prognostic factors. The incidences of local recurrence and of lung metastasis were nil in those given the HCR therapy. In group B, however, the incidences were 15% and 10%, respectively. These differences were statistically significant (P < 0.05). The incidence of liver metastasis was much the same between the two groups. All patients tolerated the HCR therapy well except for one with myelosuppression and who refused local hyperthermia because of mild anal pain. There were no other side effects requiring cessation of this treatment. These findings suggest that preoperative HCR therapy for patients with rectal carcinoma decreases the frequency of local recurrence and the likelihood of tumour cell spread during surgical procedures.


Anal fistulas in Crohn's disease: incidence and outcome of surgical treatment. The incidence and prognosis of anal fistulas were investigated in a prospective study comprising 136 patients operated on for Crohn's disease. The incidence of anal fistulas was 27 of 136 (20%), in patients with classical disease 12 of 68 (18%), and in those with Crohn's colitis 15 of 68 (22%). A fistula preceded the intestinal manifestation of the disease in 6 patients. At the time of diagnosis of Crohn's disease anal fistulas were observed in 19 cases, including 3 of the 6 with early onset which had resisted treatment and remained active. Five patients developed anal lesions during the course of the disease, all but 2 in temporal relationship to an intestinal recurrence. Of the 27 patients with anal fistulas, 11 were of the low-anal type, whereas 14 were anorectal. Conventional laying open of the fistula was undertaken in all patients with classical Crohn's disease in close conjunction with resection of the intestinal disease. On local surgical treatment 10 of 12 (89%) healed with preservation of continence. Four recurrent fistulas occurring in conjunction with intestinal recurrence also healed uneventfully. Laying open was undertaken in 11 of the 15 patients with colitis. Healing was obtained in only 4 of these patients. In the remaining 4 severe colitis indicated immediate proctocolectomy. Occurrence of fistulas involved a significant delay in perineal healing after proctectomy. It is concluded that traditional laying open of an anal fistula in patients with classical Crohn's disease is followed by high rate of uneventful healing. In contrast, local surgical treatment of anal fistulas complicating Crohn's colitis is usually unsuccessful.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevention and treatment of osteoporosis. One of the most frequent disorders in American women: a review. This review summarizes basic pathophysiology, epidemiology, classification and theories on the etiology of osteoporoses. Diagnostic, preventative and therapeutic aspects are discussed including the use of hormones and hormone analogues (estrogen, progestins, calcitonins, anabolic steroids), calcium, fluoride, bisphosphonates, vitamins D and their metabolites and the recently proposed "coherence therapy". Reference is made to new compounds under study including imidazoquinazolinones, methylxanthines and benzothiophenes.


A statistical study on clinical findings of solar keratosis. Clinical findings were studied in 50 patients with 53 lesions of solar keratosis encountered during the 15 year period from 1977 to 1991. The majority of these cases were evident in the over-sixty age group (average 62.2 years). A greater proportion were females. Most lesions were observed on the face; especially on the cheek, and from the outer eyelid to the temple. The erythematous type (desquamative-keratotic) lesion was the most evident. With the exceptions of the years 1979 and 1991, no remarkable increase in the number of patients was noted during the 15 year period.


A statistical study on histopathologic findings of solar keratosis. We examined histopathologic data from 50 patients with 53 lesions of solar keratosis encountered over the past 15 years (1977 to 1991). The epidermis showed acanthosis, uneven epidermal dyeing properties, disorderly arrangement of the basal cells, atypia of the nucleus, mitotic figures and hyperpigmentation of the basal layers. The dermis showed actinic elastosis, cell infiltration mainly consisting of the lymphoid cells, and incontinentia pigmenti histologica. Among histologic types, the hypertrophic type was the primary example.


Relation between serum uric acid and angiographically defined coronary artery disease in postmenopausal women. Serum uric acid (UA) levels were studied in 40 postmenopausal women and 57 men, almost matched for age and body mass index (BMI) and undergoing coronary angiography. For women, the mean value of UA increased as the number of coronary arteries with > or = 50% stenosis increased. Its value was significantly higher (p < 0.05) in a three-vessel disease group than that of a group without stenosis. No significant changes were seen in men. However, the increase in UA for postmenopausal women was statistically (p < 0.05) correlated with serum triglyceride levels. Possibly, UA is not an independent coronary risk factor. However, elevated UA levels may suggest the prevalence of severe coronary artery stenosis for postmenopausal women.


Treatment of chronic cerebrovascular disease in elderly patients with pentoxifylline. A placebo-controlled, randomized, double-blind study was conducted to assess the efficacy and safety of pentoxifylline in 80 patients with symptoms of vascular dementia. Efficacy was assessed using neuropsychologic tests. With regard to the primary efficacy criteria, absolute changes in the active treatment group were more pronounced in both the protocol and endpoint analysis than in the placebo group. Compared with the placebo group, differences were statistically significant for the active treatment group. Similar changes were reported in a post-hoc defined subgroup of patients displaying "stepwise deterioration," an essential criterion of multi-infarct dementia (MID). Medication was generally well-tolerated. The present study shows that pentoxifylline is suitable for the symptomatic treatment of vascular dementia.


Serum levels of lipids and apolipoproteins in angiographically assessed coronary artery disease in Japanese patients. Serum total cholesterol (T-CHO), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) values were determined in 143 Japanese subjects undergoing coronary angiography. Among the factors measured, T-CHO, TG, apo B and C-III levels were significantly higher in patients with coronary artery disease (CAD) than in those without CAD. The HDL-C/T-CHO ratio was also significantly lower in patients with CAD. Although no parameters show differences between the group without CAD and the group of single vessel disease, T-CHO and apo B were significantly higher in the groups with double and triple vessel disease, and TG and apo C-III were also higher in the group with triple vessel disease compared with the normal group. Furthermore, the HDL-C/T-CHO ratio was significantly lower in the double and triple vessel groups, and HDL-C was lower only in the triple vessel group. The results indicate that changes in these parameters suggest a high likelihood of multiple vessel disease, and that an increase in TG and apo C-III levels is also one of the important indicators for CAD even in Japanese patients.


Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators. Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.


Helicobacter pylori and peptic ulcer diseases: prevalence and association with antral gastritis in 210 patients. Evidence is accumulating that Helicobacter pylori infection plays a major contributory role in peptic ulcer disease [Duodenal Ulcer (DU) and Gastric ulcer (GU)] and non-ulcer dyspepsia (NUD). We, therefore, studied prospectively 210 consecutive patients with upper gastrointestinal symptoms (62 DU, 38 GU and 110 NUD) to determine the prevalence of H. pylori infection and to investigate their association with histological gastritis. Using endoscopic biopsy of the gastric antrum for diagnosing H. pylori infection by Campylobacter-like Organism (CLO) test, histology or bacteriology, the overall prevalence of H. pylori was 63.3 per cent. When H. pylori infection was related to diagnosis, DU had the highest prevalence rate of H. pylori infection (66%), GU and NUD were less frequently associated with H. pylori infection (55% and 44% respectively). We found a close association between H. pylori infection and histologically antral gastritis, in that 72.7, 61.7, and 62.6 per cent of the DU, GU and NUD patients with antral gastritis (respectively) had H. pylori infection. In contrast, none of these patients seen with normal antrum had H. pylori infection. We also found that the prevalence of H. pylori in our patient series was not age related. Of the three procedures used to demonstrate H. pylori, the CLO test and histological staining method gave the highest yields of 84.9 and 79.6 per cent respectively, and bacteriology in only 44.3 per cent, we conclude that the prevalence of H. pylori infection in Thai patients with upper gastrointestinal symptoms is high. H. pylori infection commonly occurs in the patients with antral gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.


The impact of routine preoperative electrocardiogram in patients age > or = 40 years in Srinagarind Hospital. A 12 lead electrocardiogram (ECG) has been recommended for adult patients before operations involving general or regional anesthesia. However, there is a growing consensus that it is of little benefit and ECG should be done only in selected subsets of patients with cardiac signs and symptoms or older patients. We prospectively surveyed 1,013 patients before operation, 395 patients were 40 years or more, ECG abnormalities were present in 130/395 (32.9%), significant ECG abnormalities in 31/395 (7.9%) and ECG with management change in 10/395 (2.5%). Old or questionable myocardial infarction were found in 8 (4.0%) and acute ischemia or injury in 4 (2.0%). The frequency of ECG abnormalities increased with age in males but not in females. Abnormal physical examination could predict only 20 per cent of abnormal ECG. The variables which could predict ECG abnormalities were age and irregular pulse. The frequency of ECG abnormalities, significant ECG abnormalities and ECG abnormalities which led to management change in those patients with normal physical examination were 31.7, 6.4 and 2.2 per cent respectively. In conclusion we propose that preoperative ECG may be indicated in both men and women aged > or = 40 years.


Gore-Tex cruciate ligament reconstruction in athletes. This prospective study evaluated the athletes with chronic instability of the knees using the expanded polytetrafluoroethylene (PTFE) prosthetic ligament as a substitute for the ACL and PCL preoperatively and at regular intervals during the post-operative period. Thirty Gore-Tex ACL and four Gore-Tex PCL reconstruction were performed. All patients had chronic instability of the knee joint for a duration of one month to five years (average 15.7 months). There were thirty-one males and three females, most of them were football players (63%). The average follow-up was 23 months postoperation. Ninety-seven per cent of the patients had satisfactory results. Objectively the instability pattern was improved in 97 per cent of the knees and subjectively, no pain persisted post operatively. Rejection occurred in one patient. The results indicated excellent stability of the affected knee joint. However, longevity of the prosthesis under the wide variety of loading conditions in athletes remains to be determined by continuing clinical study.


A common source foodborne outbreak of E1 Tor cholera following the consumption of uncooked beef. In July 1988, an outbreak of cholera with 71 culture-confirmed cases of biotype El Tor, serotype Ogawa, occurred in a non-endemic area in Mae Sot district, Tak province. Fifty-two cases had diarrhea and 19 had asymptomatic cholera infection. No cases died. Epidemiological investigation revealed a significant association between cholera infection and the consumption of uncooked beef. Increased risk of cholera infection was observed when the incriminated beef was kept at room temperature and consumed later without cooking. The beef was possibly contaminated with V. cholerae O1 from an infected butcher who may have contracted the disease from his foreign worker who was found to have asymptomatic cholera infection. Early detection of the outbreak and rapid identification of transmission source permitted prompt appropriate control measures which, therefore, prevented the outbreak from spreading to other communities. As outbreaks of foodborne diseases, including cholera, have been reported frequently after the consumption of raw food in many parts of Thailand, preventive educational efforts should be directed towards modifying the traditional behavior patterns of consuming raw food among these Thai people.


Elderly bed-blockers in a Thai teaching hospital: is it a problem? Elderly patients suffer from a wide range of chronic disabling diseases and social problems. These conditions often lead to increased lengths of hospital stay for acute medical and surgical problems--"bed-blocking". By means of a one-day census of all inpatients at Chulalongkorn Thai Red Cross Hospital the number and reasons for continued hospital stay of all patients, classified by age (less than 60, and 60+ years), were measured. Of 191 medical inpatients surveyed, 34 per cent were 60 years and over. More older than younger patients were still in hospital for non-medical reasons (35% vs 21%, Chi-square = 4.89, p < 0.01). Durations of hospital stay were longer for older patients: median stay 8 and 11 days respectively for those less than 60 and those 60+ years. Early discharge of disabled elderly people to their families was achieved by vigorous social work, thus reducing the extent to which elderly patients become bed-blockers. Further demographic trends, coupled with a breakdown of the extended family structure, will make bed-blocking a very likely problem. The present patterns of care may lead to poor long-term outcomes for the elderly.


Corneal involvement in acrodermatitis enteropathica: a case report. A case of acrodermatitis enteropathica occurred with corneal changes consisting of superficial punctate lesions, nebulous subepithelial opacities and linear epithelial erosions. These manifestations exacerbated intermittently whenever the patient ran out of her oral zinc sulphate therapy, but regressed and disappeared when she resumed her medication.


Direct epidural morphine injection during lumbar discectomy for postoperative analgesia. A double-blind controlled study was done on 42 patients to test the analgesic activity of epidural morphine after lumber laminectomy for single level disc herniation. Sixteen patients received 3 mg preservative-free morphine. Twenty-six patients received normal saline. The patients given epidural morphine had a longer postoperative pain-free period (6.28 vs 2.37 hours) and needed less postoperative analgesia (0.2 vs 0.9 times for paracetamol, and 0.16 vs 0.51 times for morphine). Epidural morphine injection under direct vision during discectomy operation is an effective and safe method for postoperative pain relief.


Scanning electron microscopic study on dendritic cells and fibroblasts in connective tissue. Perfusion fixation and intravascular resin injection were used to study in situ the cells of superficial fascia (loose connective tissue) of the rat limb by scanning and transmission electron microscopy. These procedures enabled us to differentiate fibroblasts, representative cells of the connective tissue and so-called "dendritic cells," the other cellular constituent of the tissue, known as possible antigen presenting cells. "Dendritic cells" were amoeboid with some spatular processes by which the cells clung to the collagen fiber bundles. The fine structures characteristics of macrophages; they contained abundant primary and secondary lysosomes and expressed factor XIIIa in their cytoplasm. Fibroblasts, on the other hand, were attenuated, sheet-like cells whose edges were juxtaposed closely to collagen and elastic fibers, and were further anchored by microfibrils. The cells were usually interconnected to each other with gap junctions, thus producing a cellular network in the connective tissue.


Ultrastructure of intracellular membranous system and intracellular transport of asialoglycoproteins in rat hepatocytes. The ultrastructure of the intracellular membranous system in rat hepatocytes was observed three dimensionally with a scanning electron microscope using the aldehyde prefix osmium-dimethyl sulfoxide-osmium method. Intracellular organelles were clearly observed in three dimensions, and direct connection of tubular structures with the bile canalicular membrane was clearly seen. The transcellular pathway of asialoglycoproteins in isolated cultured rat hepatocytes was also investigated, by affinity cytochemistry, using gold-conjugated asialofetuin, under a transmission electron microscope. Gold particles were clearly seen not only in vesicles, endosomes and lysosomes, but also in the tubular structures. These results suggest that the tubular structures in rat hepatocytes directly participate in the transcellular transport of macromolecules. In addition, the frequent connections of tubular structures with the bile canalicular membrane indicate that these structures around the bile canaliculus may supply membrane components to the bile canalicular membrane.


Immunogold localization of ribulose-1,5-bisphosphate carboxylase/oxygenase in developing proplastids of dark-grown wax-rich cells of Euglena gracilis. Wax-rich cells of Euglena gracilis Z grown in the dark without agitation were subjected to freeze-substitution procedures in electron microscopy, which gave intact images of wax accumulated as globules in the cytoplasm. The proplastids in these wax-rich cells were shown to contain no extensive internal structures. When these cells were transferred to an inorganic medium containing ammonium salt and aerated in the dark the specific activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) increased concurrently with the development of a prolamellar body and a rudimentary pyrenoid. When cell sections were labeled with antisera prepared against RuBisCO subunits followed by protein A-gold, gold particles (RuBisCO) were localized in a narrow peripheral region between the plastid envelope and the prolamellar body during an earlier phase of the dark incubation of cells. Subsequently, immunogold particles were concentrated over the rudimentary pyrenoid formed at a site adjacent to the prolamellar body, while the stroma was only slightly labeled with gold particles. It was postulated that the small subunits of RuBisCO made in the cytoplasm combined with the plastid-made large subunits to form the holoenzyme at the peripheral region near the prolamellar body before transfer to the rudimentary pyrenoid.


Scanning electron microscopy of proteoglycans in metaphyseal cartilage. Alcian blue (AB) was used for scanning electron microscope investigations on metaphyseal cartilage. In the pericellular area three-dimensional network connecting the cell membrane surface to the lacunar wall is evident. The network is formed by very long rod-like filaments about 50 nm thick. The segments may be interpreted as the proteoglycans (PGs) of the pericellular area. In the pericellular area in hypertrophic and degenerative zones, the rod-like segments are closely connected to "chain granules" which are the morphological expression of Ca-P non crystalline compounds. The rod-like segments are not at all evident either in glutaraldehyde-osmium fixed fragments or in predigested-(streptococcal hyaluronidase and chondroitinase) AB stained ones. It is concluded that AB is a good method to detect the three-dimensional spatial disposition of cartilage PGs.


Natural surfactant for neonatal respiratory distress syndrome in very premature infants: a 1992 update. Natural surfactant (Surfactant TA, Survanta, CLSE, SF-RI 1, Curosurf and human surfactant obtained from amniotic fluid) therapy for RDS in very premature infants has been evaluated in 17 controlled clinical trials. Uniformly intratracheal surfactant administration caused a decreased intensity of mechanical ventilation during the first hours (reduced inspiratory pressure, reduced oxygen requirements) as an immediate effect of surfactant administration. Metanalysis reveals barotraumatic pulmonary complications mainly, pneumothorax and pulmonary interstitial emphysema to occur less frequently in surfactant-treated infants in virtually all trials; an increased incidence of survival without bronchopulmonary dysplasia following surfactant treatment was observed in 10 controlled clinical trials. The incidence of other complications of prematurity (intracranial hemorrhage, patent ductus arteriosus and necrotizing enterocolitis) was unchanged following natural surfactant treatment. Dosing of natural surfactant is still under investigation, however recent data indicate that the initial dose should not be less than 100 mg/kg b.w. and retreatment should be given to infants with unsatisfactory response (i.e. fraction of inspired oxygen (FiO2) > 40%). Timing of surfactant treatment still remains controversial. Prophylactic treatment shortly following birth has been compared with rescue-treatment, i.e. surfactant administration to infants suffering from manifest RDS in most studies 4-8 h after birth. Conflicting data from 5 controlled trials may be interpreted as follows: prophylactic treatment seems to be favourable for extremely premature infants (GA < or = 26 weeks) and rescue treatment seems to be adequate for infants of 27-30 weeks of gestation. Intratracheal surfactant instillation in very premature infants did not result in an improved lung function for 24 h to 48 h in all patients. Ten--25% of study infants were reported to be "non-responders", i.e. infants without sustained decrease in oxygen requirements (i.e. FiO2 > 40%). Various factors may be operative including congenital bacterial infections (sepsis or pneumonia), lung hypoplasia and cardiac failure. Inactivation of surface properties of natural surfactant caused by a leakage of proteins across the alveolar-capillary membrane was observed in experimental and clinical studies. Current investigations focus on a combination of postnatal steroids and surfactant treatment to improve lung function and outcome in "non-responders". As long as any controlled clinical studies are being published, this approach remains experimental. Up to now, any controlled clinical trials have been performed to assess different modes of artificial ventilation (e.g. high frequency oscillating ventilation versus conventional ventilation) combined with surfactant therapy. Data obtained from premature animals given natural surfactant indicate any advantage with respect to gas exchange and lung histology to result from high frequency ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)


Protein C activity in severely ill newborns with congenital heart disease. Levels of protein C functional activity were studied in twenty-nine full-term infants with symptomatic congenital heart disease, who presented in the neonatal period. Protein C levels on admission ranged from < 10% to 61% (mean 37.7% S. D. 14.1%). Eight of the twenty-nine babies had protein C levels between 1.5 and > 3.0 S. D. below the normal neonatal mean with no parental evidence of familial deficiency. Of these infants with low protein C two developed thrombotic complications and four had evidence of coagulation factor consumption. Critically ill infants were over-represented in the group with low protein C. Severely ill newborn infants with protein C at or below the lower limit of the normal neonatal range may be at increased risk of either a consumptive coagulopathy or major thrombosis.


Onset of spontaneous labor and changes in E2 and progesterone levels--possible interrelation. Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy. This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone (E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternal serum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 +/- 24.5 mg/ml verus 177.3 +/- 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor.


Salbutamol infusion to treat neonatal hyperkalaemia. Salbutamol infusion, 4 micrograms/kg in 5 ml of water infused for 20 minutes, was given to treat hyperkalaemia (potassium level > 6.0 mmol/l) in 10 critically ill preterm infants (median gestational age 26 weeks). Seven infants had acute renal failure, two had persistent metabolic acidosis without renal failure and the remaining infant had a combination of acute renal failure and persistent metabolic acidosis. No infant developed a tachycardia or became hyperglycaemic in response to the infusion. Seven of the 10 infants ultimately died but this was at a mean of 9 days following the infusion and as a consequence of complications due to their extreme prematurity or major congenital abnormality. In response to the infusion the potassium level fell in 7 infants with acute renal failure by a median of 1.1 mmol/l (range 0.7-1.8) at one hour but in the three infants with a persistent metabolic acidosis, the potassium level continued to rise. We conclude that salbutamol infusion achieves, without side-effects, at least a temporary reduction in hyperkalaemia in preterm infants with renal failure, but not metabolic acidosis. Its effect is of sufficient duration to allow ample time for definitive therapy to be instituted and thus may be a useful alternative for infants in whom the possible hypoglycaemic side-effects of glucose and insulin should be avoided.


Increased inorganic sulfate concentrations in amniotic fluid. We assayed inorganic sulfate by ion chromatography in 49 amniotic fluid samples from pregnancies of 14 to 38 weeks gestation. In second trimester samples (14 to 26 weeks gestation), amniotic fluid sulfate concentrations (317 +/- 22 mumol/L, mean +/- SE; n = 32) were not different from previously reported maternal serum values but were significantly lower (p < 0.001) than in the third trimester (693 +/- 42 mumol/L; n = 16). In third trimester samples, sulfate concentrations were significantly correlated with creatinine and uric acid but not chloride, suggesting that renal excretion may be the major source of the amniotic fluid sulfate in the late stages of gestation.


Accelerated lung maturation following maternal steroid treatment in infants born before 30 weeks gestation. A meta-analysis was performed of 9 controlled trials of maternal beta-/dexamethasone treatment in which the incidence of RDS in infants born before 30 weeks gestation was reported. A significant decrease could be shown in 250 immature infants. The number of cases was to small for analysis of lower gestational ages or for the demonstration of a reduction in mortality. In a separate study of 135 infants born before 30 weeks gestation tracheal aspirate phospholipid analysis was performed using thin layer chromatography. 64 of them had been exposed prenatally to steroids. Significantly more of these infants had a mature L/S ratio > or = 2.7 (p < 0.02) and prenatal glucocorticoid treatment was associated with a markedly increased survival rate (odds ratio 2.4, p < 0.02). We conclude from the meta-analysis of the literature and from the findings of our study, that accelerated lung maturation follows prenatal steroid treatment with a reduction in RDS-incidence even in very immature fetuses. Consequently it would be appropriate to administer glucocorticoids combined with tocolysis since this has been shown to be beneficial for those women threatening to deliver prematurely at less than 30 weeks gestation.


The effect of thyroxine and corticosteroids upon amniotic fluid fluorescence polarization: a randomized controlled study. The efficacy of glucocorticoid and intra amniotic thyroxine therapy on fetal lung maturity were compared in a randomized prospective clinical trial. Eighty two patients received either intra amniotic thyroxine (n = 36), or intra muscular Dexamethasone (n = 46). The Fluorescence Polarization (FP) of amniotic fluid measured prior to and one week following treatment were similar in the two groups. The rate of decrease in FP value per unit of time (dFP/dt) was identical in the T4 and corticosteroid treated patients and the proportion of immature FP values obtained was similar in the two groups. The effect of thyroxine therapy was more pronounced in pregnancies above 33 weeks gestation. Intra amniotic thyroxine therapy appeared to be as effective as glucocorticoids for the enhancement of fetal lung maturity. This therapeutic modality may be of particular use on pregnant subjects in whom a relative contra indication for the administration of steroids exists.


t-PA activity and antigen in the newborn and infant. Concentrations of tissue plasminogen activator (t-PA) activity and t-PA antigen in blood obtained from neonates were investigated in order to elucidate a fibrinolytic condition of the neonates and compare with that of the infants and children. The t-PA activity was measured by bioimmunoassay using monoclonal antibody (SP-322), which bound with an epitope nonintervening with active site of t-PA. The t-PA antigen was detected by ELISA using the same monoclonal antibody (SP-322). As a result, t-PA activity in blood from the newborn baby increased to 0.97 +/- 0.48 IU/ml at the second to the fifth day, and decreased gradually to the baseline levels of healthy adult until 15 years old. The t-PA antigen level was increased from the seventh day. These results suggests that t-PA activity in blood from the neonates may be higher concentrations than those from the infants, children and adults.


Computerised cardiotocography following vibro-acoustic stimulation. To study the effect of vibro-acoustic stimulation (VAS) to the mean fetal heart rate (FHR), period of high and low FHR variation, overall variation (msec and bpm) and short term variation (msec). In a prospective study 17 pregnant women between 34-42 weeks gestation admitted to antenatal ward for obstetric complications two 60 min FHR recording was carried out with an interval of 30 min in between recordings. On a random basis the fetus was stimulated by a vibro-acoustic stimulator for 5 sec at the beginning of one of the two 60 min FHR recordings. Automated analysis of the FHR, tocodynamometry, and maternal perception of fetal movements was done by a commercially available computerized programme (System 8000). It was possible to obtain the two 60 min recordings with signal loss of < 10% in 12 out of 17 patients. No changes were observed when the FHR parameters for 60 min after VAS was compared with the control period. When analyzed in segments of 0 to 10, 11 to 20, 20 to 40 and 41 to 60 min the mean baseline FHR was significantly higher after VAS during the first 10 minutes compared with any 10 or 20 min segment of the control period or any such segments 10 min after VAS. Concomitantly the overall variation and short-term variation was significantly lower during the first 10 minutes following VAS (p < 0.05) compared with the parameters in the corresponding periods during the control period.(ABSTRACT TRUNCATED AT 250 WORDS)