Detection of Borrelia burgdorferi in ticks by species-specific amplification of the flagellin gene. We developed a polymerase chain reaction (PCR) that specifically amplifies a fragment of the flagellin gene (fla) of Borrelia burgdorferi, the causative agent of Lyme disease. This fla target, amplified with nested primers, was conserved among all 80 strains of B. burgdorferi tested. Strains examined included cultures from ticks, humans, and rodents from major B. burgdorferi-endemic regions of the United States and parts of Europe and Asia. Templates from B. hermsii, B. parkeri, B. turicatae, and B. coriaceae were not amplified, nor were eukaryotic DNAs from three tick genera. Several host DNAs potentially present in a tick blood meal also were not amplified. Approximately six B. burgdorferi per PCR reaction could be detected by ethidium bromide staining of amplified DNA. Colony-raised Ixodes dammini were used to evaluate the method. One infected nymph in a pool of 40 ticks was routinely detected. The specificity of the assay for detecting B. burgdorferi-infected ticks in pools was 94% (29 of 31). This protocol should prove useful for assessing infection rates in other putative arthropod vectors.


Serodiagnosis and screening of canine visceral leishmaniasis in an endemic area of Corsica: applicability of a direct agglutination test and immunoblot analysis. For effective control of visceral leishmaniasis caused by Leishmania infantum in the Mediterranean area, the detection of infected dogs is of utmost importance. To assess the suitability of a direct agglutination test (DAT) and immunoblot analysis in serodiagnosis and screening of infected dogs under field conditions, a study was performed on 113 dogs in an endemic area of Corsica. Twenty one of 22 parasitologically confirmed cases were correctly diagnosed by both tests, and 100% specificity was found when 11 dogs with other diseases were examined. Interestingly, eight of 80 apparently healthy dogs from the same area were found to be parasite-positive by the DAT test as well as by the immunoblot. Although both tests were equally sensitive and specific, based on both the feasibility of its application in field conditions and ease of performance, we consider the DAT to be more suitable for serodiagnosis and large-scale screening of infected dogs.


The population dynamics in mosquitoes and humans of two Plasmodium vivax polymorphs distinguished by different circumsporozoite protein repeat regions. The population dynamics of two Plasmodium vivax polymorphs were studied over a two-year period in a village in a hyperendemic area of Papua New Guinea in both the mosquito and human populations. Strains of P. vivax were distinguished by different circumsporozoite (CS) protein repeats, the VK210 (classic) and the VK247 (variant) polymorphs. In 1986, 34% of P. vivax CS protein-positive mosquitoes were of the VK247 type. Although the proportion of P. vivax sporozoite antigen-positive mosquitoes compared with all sporozoite-positive mosquitoes did not change from 1986 to 1987, the proportion of P. vivax-positive mosquitoes of the VK247 polymorph decreased significantly from 34% to 11% (5 of 45) in 1987. In 1986, 61% (47 of 77) of humans tested had IgGs that recognized the VK247 CS repeat, while only 26% (22 of 84) had IgGs that recognized the VK210 CS repeat. The observed fluctuation in the proportion of the two P. vivax CS protein polymorphs recorded in the mosquito population from 1986 to 1987 is consistent with a hypothesis of selection by humoral immune pressure on the VK247 strain.


Treatment of patients with recrudescent falciparum malaria with a sequential combination of artesunate and mefloquine. A sequential combination of artesunate followed by mefloquine was evaluated prospectively in 24 patients with acute recrudescent falciparum malaria. The sequential combination was used to minimize possible side effects and to take advantage of the ability of artesunate to rapidly clear parasitemia and the prolonged effect of mefloquine to clear residual parasites. All patients had experienced one or more treatment failures with one or more courses of the following drugs (administered alone or in combination): quinine, tetracycline, mefloquine, artesunate, and sulfadoxine/pyrimethamine. Sequential treatment with artesunate (600 mg over five days) followed by mefloquine (750 mg and 500 mg six hours apart) cured all 24 patients. Each patient was followed for 28 days and 10 were observed for at least 35 days without clinical or parasitologic evidence of recrudescence. Fever and parasite clearance times after treatment with the sequential combination were 32.8 +/- 19.3 hr (mean +/- SD) and 40.0 +/- 16.2 hr, respectively. Susceptibility testing of selected parasite isolates indicated that all of the isolates tested were resistant to one or more antimalarial drugs. These results suggest that sequential treatment with artesunate followed by mefloquine is effective and well-tolerated in patients with recrudescent falciparum malaria.


Use of an enzyme-linked immunosorbent assay to detect anti-adherence protein antibodies in sera of patients with invasive amebiasis in Cairo, Egypt. We used enzyme-linked immunosorbent assay (ELISA) to detect IgG antibodies to the Entamoeba histolytica galactose-inhibitable adherence protein in the sera of 50 uninfected controls, 50 cases with asymptomatic cyst passage, 100 patients with amebic colitis, and six patients with amebic liver abscess from Cairo, Egypt, and in 50 healthy controls from the United States. When the mean + 3 SD value above that of the controls from the United States was used as a criterion for a positive ELISA result, 100% of those with invasive amebiasis, 80% of those with asymptomatic infection, and 64% of the Egyptian controls had anti-adherence protein antibodies. However, when the mean + 2 SD value of Egyptian control sera (optical density = 0.094) was used as the criterion for positivity, 33 (89%) of 37 sera from individuals with invasive amebiasis having symptoms for at least one week were antibody positive, in contrast to only 12% of asymptomatic cyst passers (P < 0.01). In a highly endemic area such as Cairo, Egypt, detection of serum anti-adherence protein antibodies by ELISA may have greatest diagnostic use in patients with symptomatic invasive amebiasis of greater than one week duration.


A clinical and epidemiologic study of 292 cases of lance-headed viper bite in a Brazilian teaching hospital. The records of 292 patients who were admitted to a teaching hospital from 1984 to 1990 in Uberlandia in southeastern Brazil after being bitten by snakes of the genus Bothrops were retrospectively surveyed. The patients were from 42 municipalities in three states of Brazil. Most (42%) bites occurred between 4:00 PM and 10:00 PM. Fourteen percent of the bites occurred in the month of April. In 54 (18%) of the cases, the snakes were captured and identified as belonging to the following species: B. moojeni (29), B. neuwiedi (18), and Bothrops species (7). A diagnosis was made based on clinical findings in 238 (82%) cases. The lower limbs were the commonest site of bite (74%). The median time interval between bite and admission to the hospital was 3 hr. Fang marks were recorded in 58% of the cases and swelling was recorded in 82%. Clotting time was greater than 15 min in (142 of 264) 54% of the cases. A tourniquet was used on 44 cases. The mean +/- SD dose of specific antivenom used was 187.48 +/- 93.44 mg. The complications that occurred included abscess formation in 18% of the cases, necrosis in 16%, and renal failure in 5%. Amputation was performed in three (1%) cases. The case fatality rate was also 1% (three cases). When all cases were analyzed, the chi-square test for trend showed an increased susceptibility of renal failure with age (P < 0.04). Clotting time greater than 15 min was associated with the development of abscesses (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Perianal mass and recurrent cellulitis due to Enterobius vermicularis. A unique case of enterobiasis presenting as recurrent cellulitis and a perianal mass in a six-year-old girl is reported. Complicated perianal lesions due to Enterobius are unusual. Only 10 previous cases are known, with unclear pathogenesis in most of them, although mucosal breaches and perianal crypt or gland entry have been postulated. The association of the mass in this case with a deep crypt, and the histopathologic finding of squamous epithelium focally surrounding the granulomatous reaction to the Enterobius eggs suggest that the worm entered the perianal tissues via a crypt. Local secondary bacterial infection can cause significant morbidity. Surgical excision of such granulomatous mass lesions is necessary in symptomatic or complicated cases.


Pyridinoline, a mature collagen cross-link, in fibrotic livers from Schistosoma mansoni-infected mice. The amount of pyridinoline, a cross-linking amino acid found in mature collagen, was measured in murine liver for a period of up to 40 weeks following Schistosoma mansoni infection. The pyridinoline level (expressed as pmol per 100 micrograms of liver) markedly increased in the course of murine schistosomiasis, and the number of pyridinoline residues per collagen molecule was also higher in the livers of infected mice than that of control livers. This increase in the extent of intermolecular collagen cross-linking might play a role in the modulation of collagen catabolism as an auxiliary mechanism of extracellular matrix accumulation during fibrogenesis.


The role of IgG antibodies from irradiated cercaria-immunized rabbits in the passive transfer of immunity to Schistosoma mansoni-infected mice. Antibodies of the IgG subclass isolated from the sera of rabbits immunized with cercariae subjected to 50 kilorads of gamma irradiation passively provided partial immunity against Schistosoma mansoni challenge in C57B1/6J mice. These mice exhibited reductions in adult worm burdens of 43-61% compared with recipients of normal rabbit antibodies. Passively transferred IgG antibodies were most effective when given 4-7-days postchallenge; they were less effective when given just before challenge, and were totally ineffective when given 15 days postchallenge. It was also shown that the Fc portion of the IgG molecule was important for passive transfer of immunity. Finally, we observed that although some antibodies from irradiated cercaria-immunized rabbits recognized keyhole limpet hemocyanin (KLH), these KLH cross-reacting antibodies were not necessary for successful passive transfer of immunity. Antibodies from a KLH-immunized rabbit also failed to passively protect mice.


Strongyloides stercoralis infection in IgA-deficient dogs. Two litters of eight-week-old, IgA-deficient pups, each including one normal littermate control, were infected with 5,000 infective third-stage Strongyloides stercoralis larvae per pup. No significant differences between the dogs deficient in serum and mucosal IgA and the normal control dogs were observed in any of the parasitologic parameters measured during the course of infection. The time required to reach patency, the maximum number of larvae shed in the feces, the number of days postinfection at which larval shedding was at its maximum, and the time required to eliminate shedding were similar in the two groups. Once larval shedding ceased, there was no recrudescence, even though serum and fecal IgA were absent or low throughout the seven-month course of the investigation. All dogs remained asymptomatic, with complete blood counts and clinical chemistries within normal ranges. In addition, serum IgM and IgG levels were within the normal range for both groups of infected dogs. All dogs from which necropsy samples were obtained harbored low numbers of adult female worms, some of which were barren. An IgA deficiency apparently does not affect the course or severity of S. stercoralis infection in the dog.


Low immunogenicity of a Plasmodium vivax circumsporozoite protein epitope bound by a protective monoclonal antibody. The repeat region of the Plasmodium vivax circumsporozoite (CS) protein contains 20 copies of the nine-amino acid sequence DRA A/D GQPAG. A monoclonal antibody that passively protects monkeys against sporozoite challenge recognizes a four-amino acid linear sequence AGDR included within this nonamer, but when monkeys were immunized with a vaccine, NS1(81)V20, which contains 20 copies of the nonamer, they failed to produce antibodies to AGDR. To determine if natural exposure to sporozoites induces antibodies to AGDR, we tested sera from 176 individuals from a malaria-endemic area in Flores, Indonesia. Seventy-one percent of the adults had antibodies to the P. vivax repeat region; only 18% had detectable antibodies to AGDR. None of the subjects had antibodies to the P. vivax variant repeat ANGAGNQPG. We next tested sera from six human volunteers immunized with NS1(81)V20 and found that the vaccine, despite inducing antibodies against the nonamer, as it did in the monkeys, did not induce antibodies against AGDR. To further test our ability to raise anti-AGDR antibodies using synthetic peptides, we immunized Aotus monkeys and BALB/c mice with AGDR. Sera from the mice reacted strongly with both AGDR and a recombinant protein containing the 20 copies of the nonamer. Sera from the monkeys reacted only minimally with a protein (VIVAX-1) that contains monomeric AGDR within its sequence. Sera from the mice also bound air-dried P. vivax sporozoites, while sera from the monkeys did not.(ABSTRACT TRUNCATED AT 250 WORDS)


Biochemical characterization and zymodeme classification of Leishmania isolates from patients, vectors, and reservoir hosts in Kenya. A total of 407 Leishmania and other Leishmania-like isolates obtained from patients, other vertebrates, sand fly vectors, and other arthropods from Kenya and other countries were characterized and compared with several World Health Organization and other well-characterized reference strains of Leishmania, Trypanosoma, Crithidia, Herpetomonas, and Leptomonas by cellulose acetate electrophoresis (CAE), using 20 enzyme systems. Analysis of the isoenzyme banding patterns (IBP) of the isolates generated isoenzyme profiles that were resolved as zymodemes and tabulated. Isolates that produced similar isoenzyme profiles in all 20 enzyme systems were placed into a particular Leishmania isoenzyme taxon, with the zymodeme designated numerically as Zn. A total of 66 zymodemes were recorded for the 407 isolates studied. To obviate the need to draw all 66 representative IBP for each of the 20 enzyme systems, the 66 zymodemes (Z1-Z66) were again placed into similarity groups represented by pattern number or Pn. This resulted in 23-50 IBP (Pn) per enzyme system. The highest number of IBP scored was for malate dehydrogenase (MDH) (P1-50) and the lowest score was for glucose-6-phosphate isomerase (GPI) (P1-23). From these different isoenzyme profiles or zymodemes, IBP of 14 (MDH, GPI, nucleoside hydrolase, phosphoglucomutase, malic enzyme, isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, mannose-6-phosphate isomerase, 6-phosphogluconate dehydrogenase, glutamate oxaloacetate transferase/aspartate aminotransferase, glutathione reductase, superoxide dismutase, fumarase, and glyceraldehyde-3-phosphate dehydrogenase) of the 20 enzyme systems were selected for computer-calculated numerical taxonomy. Consistent individual isoenzyme bands with similar relative mobilities of the 14 enzyme systems were scored into groups (allelomorphs, allozymes, or electromorphs) and used in cluster analysis. For each pattern in every profile, the presence of a consistent band was entered as 1 and its absence as 0. A total of 419 allozyme characters (variables) were scored for the 14 enzyme systems. Lastly, all different zymodemes sharing a particular IBP (Pn) within an enzyme system were counted and the total number was shown as a zymodeme frequency (Zf). Final analysis of the CAE isoenzyme profiles and cluster-dendrograms resulted in the identification of several potentially new species and subspecies of Leishmania and other Leishmania-like isolates from patients, sand flies, and animal reservoir hosts collected from Kenya and other locations in Africa. Zymodeme analysis of the Kenyan visceral and cutaneous leishmaniasis isolates resulted in the identification of 11 subpopulations of the L. donovani species complex and six subpopulations of the L. tropica species complex endemic to different geographic areas of Kenya.


Use of genetic polymorphisms detected by the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) for differentiation and identification of Aedes aegypti subspecies and populations. Amplification of random regions of genomic DNA using 10-base primers in the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was used to differentiate and identify mosquito populations based on genetic variation. Genomic DNA was extracted from individual mosquitoes from 11 geographic populations of Aedes aegypti and amplified in PCR reactions using single primers of arbitrary nucleotide sequence. Discriminant analysis of the population frequencies of RAPD fragments produced using three different primers allowed accurate discrimination between the geographic populations in 89% of individuals and between subspecies (Ae. aegypti aegypti versus Ae. aegypti formosus) in 100% of mosquitoes tested. The genetic relatedness of the populations was estimated using three different statistical methods, and unknown populations were correctly classified in a blind test. These results indicate that the RAPD-PCR technique will be useful in studies of arthropod molecular taxonomy and in epidemiologic studies of the relatedness of geographic populations and vector movement.


Papulonecrotic tuberculid. Identification of Mycobacterium tuberculosis DNA by polymerase chain reaction. Sections from 22 formalin-fixed, paraffin-embedded skin biopsies from 12 patients with papulonecrotic tuberculid (PNT) were examined for the presence of Mycobacterium tuberculosis DNA with use of the polymerase chain reaction. All patients had a positive tuberculin skin test and a compatible clinical picture and responded to antituberculous therapy. Histological examination showed the typical morphology of PNT lesions with dermal necrosis surrounded by an ill-formed granulomatous infiltrate. Mycobacterial DNA was detected in 11 of the 22 biopsies. None of the negative controls showed positive DNA identification by amplification. Great care was taken in avoiding false-positive results due to contamination. After reviewing the literature, we believe this is the first time that PNT lesions have been investigated by PCR for the presence of mycobacterial DNA. These findings provide direct proof that mycobacterial products are present in PNT lesions and support the theory that this organism is in some way responsible for the development of PNT.


Immunohistochemical localization of cytokines in nevi. Eight common nevi and 11 dysplastic nevi were evaluated for the presence of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-alpha, interleukin-1-alpha, and interleukin-1-beta by immunohistochemical labelling with highly specific monoclonal antibodies. Basic fibroblast growth factor was abundant in the nevus cells and keratinocytes of nevi. Dysplastic nevus cells on average stained less intensely for basic fibroblast growth factor than did common nevus cells. In both types of nevi, basic fibroblast growth factor was identified in the basement membranes at the dermoepidermal junction and surrounding nevus cell nests and individual nevus cells. Labelling of nevus cells for transforming growth factor-alpha was variable, while there was moderate labelling for platelet-derived growth factor and light labelling for interleukin-1-alpha. Only two nevi, both dysplastic, stained (very faintly) for interleukin-1-beta. It is possible that these cytokines, especially basic fibroblast growth factor, act in autocrine fashion to maintain nevocellular growth and may also contribute to the epidermal hyperplasia and fibrosis frequently observed in nevi.


True histiocytic lymphoma (monocytic sarcoma). The clinical, histological, immunophenotypic, and genotypic characteristics of two cases of cutaneous genuine histiocytic lymphoma are described. Both cases presented as cutaneous lesions. Both patients remain alive and free of disease at 26 and 10 months after the diagnosis and after having been treated with polychemotherapy. Neither peripheral blood nor bone marrow infiltration was detected in either case. Histological and immunophenotypic examination showed dense, diffuse dermic infiltrates of mononuclear cells with positive macrophage-associated markers (CD11c, CD68), and negative T- or B-cell-associated antigens. A germline configuration of both T-cell receptor and immunoglobulin genes was observed in gene rearrangement studies. Although most of the cases that have been diagnosed as histiocytic lymphoma or malignant histiocytosis in the past turned out to be B- or T-large-cell lymphomas, a small number of cases (two in our consecutive series of 350 cases) show characteristics of monocyte-macrophage tumors. We stress the importance of the CD68 marker in the diagnosis of true histiocytic lymphoma, suggest a therapeutic approach based on similarities with monocytic leukemia, and propose the use of the term monocytic sarcoma for this clinicopathological presentation.


Follicular mucinosis in alopecia areata. The pathological features of alopecia areata were described in association with those of follicular mucinosis in the scalp pathology of an 18-year-old woman. The immunohistochemical picture of the inflammatory infiltrate showed a high CD4/CD8 ratio (25:1), which was significantly different from the CD4/CD8 ratio in patients with alopecia areata. The abundance of helper/inducer cells along with the involvement of the upper part of the hair follicles might explain the development of follicular mucinosis in this case. Different possibilities were discussed, but the clinical presentation and the follow-up favored the clinical and pathological interpretation of alopecia areata with incidental findings of follicular mucinosis.


Linear morphea with secondary cutaneous mucinosis. Secondary mucinosis is a common finding in connective tissue diseases, especially in lupus erythematosus and dermatomyositis, but is seen only rarely in morphea. We report the case of a 9-year-old boy who presented with linearly arranged, flesh-colored to erythematous, indurated, very tender plaques on his right arm. He had similar lesions on his midchest and upper back. Histopathology revealed the characteristic findings of morphea and mucin deposition between thickened collagen bundles. This is an unusual case of linear morphea with hyaluronic acid deposition.


Giant cell fibroblastoma with a dermatofibrosarcoma protuberans component. We describe a unique case of giant cell fibroblastoma that contained a component of dermatofibrosarcoma protuberans in the left inguinal region of a 37-year-old man. Our case adds further proof of the close histogenetic relationship between these two tumors.


Merkel cell tumor masquerading as granulation tissue on a teenager's toe. Merkel cell tumor (MCT) typically occurs on the head or neck of elderly patients. A case is presented of a teenage girl with an MCT on her toe. The diagnosis was made 5 years after an ingrown nail on the toe was avulsed. During the interim 5 years, the periungual skin looked like granulation tissue and thus no biopsy was performed. This case of MCT is unique in three aspects: (a) extraordinarily young age, (b) atypical site, and (c) deceptive clinical appearance. Awareness of the possible occurrence of MCT in younger patients and in unusual locations will facilitate earlier diagnosis.


Horace and medicine.

Horace and medicine. The Roman poet Horace, who died 2,000 years ago, achieved fame in his own lifetime as a gentle satirist and writer of odes of inimitable lyrical beauty. Posterity honors him for his solid common sense and the aptness and elegance of his language. This article briefly reviews his life and quotes a number of passages from his works that refer to contemporary medicine and hygiene.


Low platelet gamma-aminobutyrate aminotransferase and monoamine oxidase activities in chronic alcoholic patients. The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) were estimated in blood platelets from 25 male chronic alcoholics and from 27 healthy male volunteers without histories of alcohol abuse. Based on clinical criteria, the alcoholics were classified into type 1 or type 2 alcoholism. The activity of GABA-T was found to be lower both in type 1 and type 2 alcoholics than in healthy volunteers. With regard to MAO, the platelet activity was found to be significantly lower only in type 2 alcoholics in concordance with previous reports. No significant correlation was found between the activities of GABA-T and MAO in the blood platelets of healthy volunteers. The inhibitory effect of 400 mM ethanol on the platelet MAO activity increased with decreasing concentrations of the substrate phenylethylamine. The degree of inhibition of ethanol on the platelet MAO activity, however, did not differ significantly between alcoholics and controls.


Techniques to enhance compliance with disulfiram. Pharmacodynamic benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if medicational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, and patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed.


Family history, alcohol use and dependence symptoms among young adults in the United States. Drawing upon data from the National Longitudinal Survey of young adults, this paper examines the effects of family history of alcoholism and current alcohol use by the young adults. A multivariate analysis of the data from the study indicates that there are both main and interaction effects of family history and current alcohol use on dependence symptoms among the young adults.


Do women develop alcoholic brain damage more readily than men? Chronic alcoholism is related to brain damage (i.e., volume changes) in both men and women. There is an open question whether the brains of women are more vulnerable than those of men to alcohol toxicity. The present follow-up study focuses on a direct comparison of sex-related differences in alcoholic brain shrinkage and its reversibility. In a prospective design, a random sample of 65 alcoholics of both sexes (51 males and 14 females) was studied. Computerized tomography brain scans before and after a 6-week inpatient treatment program with controlled abstinence revealed a significant re-expansion of the brain as assessed by linear measurements. By controlling for moderating variables such as age, mean daily alcohol consumption, liver dysfunction, etc. the degree of brain shrinkage was found to be similar in men and women despite significantly shorter ethanol expositions in the women. These findings corroborate the hypotheses of other investigators about basic biological differences between the two sexes as to the effects of alcohol. The hypothesis of an enhanced vulnerability of women to acute and chronic complications of alcoholism is supported.


Serum type I collagen propeptide and severity of alcoholic liver disease. We assessed the relationship of serum type I collagen propeptide concentrations with various severity indices of alcoholic liver disease, including clinical and morphological severity, the amount of alcohol consumption, and the serum levels of other components of connective tissue. The serum concentration of the carboxyterminal propeptide of type I procollagen (PICP) was measured with a new radioimmunoassay that is devoid of a crossreaction caused by type III procollagen-derived fragments. A significant correlation was found between serum PICP and the Combined Clinical and Laboratory Index (CCLI) (rs = 0.58, p < 0.001) and the Combined Morphological Index (CMI) (rs = 0.57, p < 0.01). However, PICP was elevated less frequently than serum type III collagen propeptide (PIIINP), type IV collagen or laminin, and the correlations with the latter three parameter with both the CCLI (PIIINP: rs = 0.80, type IV collagen: rs = 0.80; and laminin: rs = 0.81) or CMI (PIIINP: rs = 0.75, type IV collagen: rs = 0.72; and laminin rs = 0.61) were all stronger than that of PICP. Furthermore, although during a follow-up period of 6 months, the mild or moderately drinking patients had a significant decrease in PIIINP and the heavily drinking patients had no improvement. PICP was, however, found to improve in both the mild and heavy drinkers. These results point to differences in handling of type I and type III collagen propeptides in alcoholic liver disease. The latter appears to be a more sensitive indicator of disease severity, presence of alcoholic hepatitis, and the amount of alcohol intake.


DSM-III-R and proposed DSM-IV alcohol abuse and dependence, United States 1988: a nosological comparison. The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV (options 1 and 2) diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-III-R and DSM-IV diagnoses of alcohol abuse and dependence combined were remarkably similar. However, disaggregation of abuse and dependence diagnoses showed that there were major discrepancies between the classification systems. Reasons for these discrepancies are discussed in terms of differences in the number of diagnostic criteria and the content of the DSM-III-R and DSM-IV abuse and dependence categories, the requirement for physiological dependence in DSM-IV classifications, the relationship between the abuse and dependence categories, and the impact of the duration criteria.


Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.


Prolonged QT interval in alcoholic autonomic nervous dysfunction. QT prolongation on electrocardiography is related to sudden cardiac death and is frequently found in alcoholics. We studied QT prolongation in relation to the function of cardiac autonomic nerves assessed by the coefficient of variation of the R-R interval (CVRR) in three age-matched groups of men: 32 alcoholics with autonomic nervous dysfunction (AN), 32 alcoholics without AN, and 32 healthy controls. The QTc interval and CVRR were measured at rest on the 30th day of abstinence, when electrolyte imbalance had disappeared. Subjects with arrhythmia, conduction abnormality, cardiomegaly, ischemic heart disease or diabetes mellitus were excluded. A CVRR of less than 80% of standard predicted value was judged to represent AN. In alcoholics, QTc correlated negatively with the ratio of CVRR to its standard value (r = -0.49, p < 0.0001). The incidence of QTc prolongation was higher in alcoholics with AN (46.9%) than in alcoholics without AN (21.9%, p < 0.05). QTc prolongation was not observed in healthy controls. The QTc interval was significantly (p < 0.01) longer in alcoholics with AN (444 +/- 20 msec) than in alcoholics without AN (426 +/- 17) and in healthy controls (398 +/- 18). These results suggest that alcoholism causes dysfunction of the autonomic nerves as well as worsening QT prolongation, and this may predispose such patients to sudden cardiac death.


The identification and partial characterization of acetaldehyde adducts of hemoglobin occurring in vivo: a possible marker of alcohol consumption. Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of "fast" hemoglobin. The presence of higher amounts of "fast" Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the "fast" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14C]acetaldehyde (AcH)-Hb was synthesized in vivo for use as a standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides; the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker samples. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake.


Drinking patterns and problems: a comparison of ER patients in an HMO and in the general population. The purpose of this study was to compare drinking patterns and alcohol-related problems and associations of these variables with casualties in an emergency room (ER) population and in the general population from which these patients come. A probability sample of patients seen in all three health maintenance organization (HMO) hospital ERs in one U.S. county (N = 986) and a household probability sample of those living in the same county who reported belonging to the HMO (N = 735) were interviewed. The ER sample was more likely to report consequences related to drinking, less likely to report feeling they should cut down on their drinking, and more likely to report greater use of the ER than the general population sample. Similar associations were found between injured and noninjured in the two samples. These data lend support for the generalizability of findings of associations of alcohol and casualties obtained from ER studies to the larger general population.


Ambient temperature effects on taste aversion conditioned by ethanol: contribution of ethanol-induced hypothermia. Six experiments examined the effects of low (5-10 degrees C), normal (21 degrees C), or high (32 degrees) ambient temperature on conditioned taste aversion and body temperature changes produced by ethanol, lithium chloride, or morphine sulfate. Fluid-deprived rats received five to seven taste conditioning trials at 48-hr intervals. On each trial, access to saccharin at normal ambient temperature was followed by injection of drug or saline and placement for 6 hr into a temperature-controlled enclosure. Exposure to low ambient temperature facilitated, whereas exposure to high ambient temperature retarded acquisition of ethanol-induced conditioned taste aversion. The ability of an alteration in ambient temperature to influence conditioned taste aversion varied as a function of ethanol dose and was related to ambient temperature's effect on ethanol-induced hypothermia. More specifically, strength of conditioned taste aversion was negatively correlated with core body temperature after ethanol injection. Alterations in ambient temperature alone did not affect ingestion of a paired flavor solution in the absence of drug. Moreover, alterations in ambient temperature did not appear to influence conditioned taste aversion by changing ethanol pharmacokinetics. Finally, high and low ambient temperature did not affect development of taste aversion conditioned by lithium chloride or morphine sulfate. The overall pattern of data presented by these experiments supports the hypothesis that ambient-temperature influences strength of ethanol-induced conditioned taste aversion by altering the hypothermic response to ethanol. More generally, these data support the suggestion that body temperature change induced by ethanol is related to ethanol's aversive motivational effects and may be involved in modulating ethanol intake.


Localization of protein-acetaldehyde adducts on cell surface of hepatocytes by flow cytometry. Acetaldehyde, a highly reactive intermediate of ethanol metabolism, has been shown to form adducts with liver proteins (e.g., a cytosolic 37 kDa protein and the microsomal cytP450IIE1) in rats fed alcohol chronically. In this study, flow cytometry was utilized to test for the presence of protein-acetaldehyde adducts (-AAs) on the surface of hepatocytes and immunotransblot was used to detect for the 37 kDa protein-AA in cytosol as was previously described. For flow cytometric analysis, rabbit anti-hemocyanin-AA IgG and fluorescein isothiocyanate-conjugated goat anti-rabbit serum IgG were used as the primary and secondary antibodies to label surface protein-AAs on hepatocytes at 0 degrees to 4 degrees C. After labeling and washing, hepatocytes were fixed with paraformaldehyde-cacodylate and analyzed with a flow cytometer. In an experiment wherein hepatocytes isolated from rats pair-fed liquid diets with and without ethanol were treated by adding both the primary and secondary IgGs, some hepatocytes from both alcohol-fed and control rats exhibited positive fluorescence but no significant difference in fluorescence intensity was noted. In another experiment, hepatocytes were isolated from rats pair-fed cyanamide (a selective aldehyde dehydrogenase inhibitor) with and without ethanol. The number of hepatocytes showing positive fluorescence in the presence of both primary and secondary IgGs was significantly higher in rats fed cyanamide plus ethanol than in rats fed cyanamide only. Of note, the 37 kDa protein-AA could be detected by immunotransblot in liver cytosol of alcohol-fed rats but not in the controls of both experiments with and without cyanamide supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of ethanol and control liquid diets on the hypothalamic-pituitary-thyroid axis of male Fischer-344 rats. The effects of a high dextrose liquid diet containing ethanol and two different control liquid diets on serum and brain thyroid axis hormones and liver and brain deiodinase activities were studied in groups of adult male Fischer-344 (F-344) rats. Rats received either lab chow, ad libitum; a nutritionally complete 10% (w/v) ethanol liquid diet, ad libitum; a volume of either a high carbohydrate (HC) or a high fat (HF) isocaloric control liquid diet equal to the volume of diet consumed by rats given the ethanol diet; or the HC control diet, ad libitum. Consumption of liquid diets was measured daily and body weights recorded every other day throughout the study. Hormones were measured after 2, 4, or 8 weeks and deiodinase activities after 4 or 8 weeks. Also, groups of rats were given the 10% ethanol diet, ad libitum, or pair-fed the HC control diet intermittently for 8 weeks, and thyroid hormones and thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) were determined. Within 2 weeks rats became accustomed to all diets and thereafter weight gain was comparable in all groups. Small differences between serum thyroid hormones of rats fed the ethanol diet and pair-fed HC or HF controls may have been caused by lower T4 secretion in ethanol-fed rats. Marked differences in free and total T4 and T3 between F-344 rats fed liquid diets for 4 or 8 weeks and rats fed lab chow probably resulted from higher liver 5'-deiodinase activity in rats fed liquid diets.(ABSTRACT TRUNCATED AT 250 WORDS)


Tolerance to adenosine's accentuation of ethanol-induced motor incoordination in ethanol-tolerant mice. Our previously published reports have provided data that have supported a functional correlation between ethanol-induced changes in the characteristics of adenosine receptor, adenosine uptake and release in the brain, and ethanol-induced motor incoordination. The present data demonstrated a cross-tolerance between ethanol and adenosine further supporting the hypothesis that brain adenosine modulates the motor impairing effects of ethanol. Mice that received (-)-N6-cyclohexyladenosine (CHA) [0.25 mg/kg/day, intraperitoneally (ip)] for 10 days exhibited marked attenuation (cross-tolerance) to acute ethanol-induced motor incoordination compared with chronic saline (ip) controls. The attenuation of acute ethanol-induced motor incoordination was essentially same in animals that received CHA (25 ng/5 microliters/day for 10 days) by the intracerebroventricular (icv) route as opposed to the controls that chronically received artificial cerebral spinal fluid by the same route. Similarly, tolerance was exhibited to acute CHA (0.125 mg/kg ip and 12.5 ng/5 microliters icv) by animals fed liquid ethanol (19.5 g/kg/24 hr) for 10 days compared with none in the pair-fed sucrose controls. Scatchard plots using cerebellar tissue homogenates from animals given chronic CHA or chronic ethanol indicated no change in Bmax and/or Kd values for CHA binding when compared with CHA binding in tissues from their respective controls. However, a lack of any change in the binding characteristics cannot rule out the involvement of adenosine receptors in the observed cross-tolerance between ethanol and CHA. The results may suggest desensitization of adenosine A1 receptors due to chronic CHA and ethanol as an alternate possible explanation in the development of cross-tolerance between adenosine (CHA) and ethanol.


Proopiomelanocortin messenger RNA is decreased in the mediobasal hypothalamus of rats made dependent on ethanol. It is thought that certain actions of ethanol involve an interaction with endogenous opioids, including proopiomelanocortin-derived peptides such as beta-endorphin. To examine this possibility, we used a sensitive and specific assay for proopiomelanocortin mRNA to obtain an estimate of the activity of the endorphinergic system in the mediobasal hypothalamus and the pituitary of rats exposed for 10 days in an inhalation chamber to either ethanol or water. This protocol causes dependence in the ethanol-exposed group, as demonstrated by the presence of withdrawal seizures after cessation of treatment. While ethanol treatment did not affect proopiomelanocortin mRNA levels in the pituitary, the level in hypothalamus was significantly lower in the ethanol-treated animals than in controls. These results suggest that some effect of ethanol may involve the hypothalamic endorphinergic system.


Membrane biogenesis in the presence of ethanol. To investigate the effect of ethanol on the intracellular transport in gastric epithelial cells, the in vitro system, generating transport vesicles which transfer mucus glycoprotein apopeptide (apomucin) from rough endoplasmic reticulum (RER) to Golgi, was assembled. The vesicles, generated from gastric mucous cell RER microsomes and labeled with [3H]palmitic acid, were isolated from the maternal RER and characterized. The electron microscopy revealed that these RER products consisted of 80 to 100 nm smooth membrane vesicles, while the immunochemical analyses showed that they contain apomucin but were devoid of the characteristic integral proteins of the RER membrane. Incubation of apomucin transporting vesicles with Golgi in the presence of UDP-[3H]galactose resulted in the formation of glycosylated mucin and fusion of the vesicles with Golgi. Formation of ER transport vesicles was dependent on the supply of lipid precursors, and the activity of phosphoglyceride and sphingolipid synthesizing enzymes. In the presence of 60 and 120 mM ethanol, the vesicles were formed, but their lipid composition was modified. The results suggest that ethanol-induced membrane alterations are initiated at the early stages of the membrane biogenesis and are first reflected in the lipid composition of the intracellular transport vesicles.


Regional distribution of low-Km mitochondrial aldehyde dehydrogenase in the rat central nervous system. To clarify the regional capacity of the brain to oxidize biogenic aldehydes and ethanol-derived acetaldehyde, a quantitative immunohistochemical study of the microregional and cellular expression of low Km mitochondrial aldehyde dehydrogenase (mALDH; EC 1.2.1.3) in the rat central nervous system was undertaken, using antiserum raised in rabbit against low-Km aldehyde dehydrogenase purified from rat liver mitochondria. mALDH-specific immunoreactivity (IR) was observed to various extent in the majority of structures in all brain and spinal cord areas. Staining was strong in the extranuclear cytoplasm of neuronal and glial cell bodies but less pronounced in their processes and terminals, the conducting tracts, white matter and neuropile and in blood vessels. Immunostaining density was 2 to 3 times higher in neuronal perikarya as compared with neuropile. mALDH-positive neurons were found in all brain regions, being strongest in the inferior olive and hippocampus stratum pyramidale and weakest in substantia nigra. The percentage of morphologically identifiable ALDH-positive neurons ranged from 40% in the arcuate hypothalamic nucleus to 88% in the cerebellar Purkinje cells. A comparison of the heterogeneous expression of mALDH in various rat CNS regions and cells, as observed in the present study, with the corresponding previously published distributions of the potential acetaldehyde-producing enzymes ADH and cytochrome P450 2E1 indicates major differences, which may help in understanding potential acetaldehyde-mediated CNS effects of ethanol. Knowledge of the regional distribution of high-affinity aldehyde dehydrogenase should also throw light on the neurophysiological role of local regulation of the metabolism of biogenic aldehydes in the brain.


Effect of chronic alcohol ingestion on the binding of high density lipoproteins to rat hepatic membranes: involvement of apolipoprotein E. Feeding alcohol to rats produces high density lipoproteins (HDL) particles that exhibit lowered apolipoprotein (apo) E:apo A1 ratio. In this study, we have carried out experiments to compare the abilities of apo E-deficient HDL particles of the alcohol-fed rat and apo E-sufficient HDL particles of the control rat to bind to hepatic membranes. When rat hepatic membranes were incubated with rat serum HDL of physiological concentrations (< or = 200 micrograms HDL-apo A1/ml), binding of HDL to hepatic membranes showed concentration dependent on HDL-apo A1. Polyclonal antibodies that specifically recognize apo A1 and apo E inhibited HDL binding to hepatic membrane while the antibody against apo AIV did not. The binding of 125I-apo A1-HDL was diminished by adding excess amount of unlabeled HDL to the incubation mixture. Apo E-deficient serum HDL obtained from alcohol-fed rats competed less efficiently against radiolabeled HDL for binding to rat hepatic membrane than normal HDL from control animals. The defect in apo E-deficient serum HDL obtained from alcohol-fed rats can be corrected by preincubation with added purified apo E. We hypothesize that this weaker binding may result in slower degradation of apo E-deficient HDL particles by the liver and in part explains the higher plasma HDL levels found in alcohol-drinking animals.


Diffuse pulmonary infiltrates in hypogammaglobulinemia. This is the first case report of lymphangitic carcinomatosis from adenocarcinoma of the stomach presenting as interstitial lung disease in a patient with CVH. Adenocarcinoma of the stomach occurs with increased frequency and at an earlier age in CVH as compared with the normal population. This diagnosis should be kept in mind during evaluation of patients with CVH. Periodic examinations of stool for occult blood should be performed. Aggressive diagnostic evaluation should be undertaken in any CVH patient with gastric complaints, as well as careful follow-up in patients with pernicious anemia, atrophic gastritis, or achlorhydria with regard to cancer screening.


Evidence of cross-reactivity between olive, ash, privet, and Russian olive tree pollen allergens. In a clinical investigation, 103 Michigan residents with symptoms suggestive of allergic rhinitis or asthma were skin tested with olive (Olea europaea) pollen extract. Nineteen had positive reactions. Since the olive tree is not native to nor grown in Michigan, this study was undertaken to determine whether the skin test reactivity was the result of cross-reactivity among tree pollen allergens. ELISAs were developed to measure olive, ash (Fraxinus americana), privet (Ligustrum vulgare), and Russian olive (Elaeagnus angustifolia) specific IgE antibodies. Inhibition studies were performed to determine whether pollen extracts from each of these tree species could inhibit IgE antibody binding to olive extracts. Eleven of the 19 skin test-positive patients were olive-ELISA positive, eight either were ELISA-positive to ash, seven to privet and ten to Russian olive. There were significant correlations between the ELISA results to olive and each of the other three pollens. The inhibition studies demonstrated that all three of the tree pollens were capable of inhibiting the binding of IgE to olive extract in a dose-response fashion. IgE-immunoblot studies demonstrated several proteins common to olive, ash, and privet. Twelve of the olive skin test-positive patients were contacted and 75% were exposed to one or more of the studied trees in their yards. Five patients had traveled to areas where olive trees are grown. We conclude that there is a high degree of cross-reactivity among allergens from native Michigan trees and from olive trees. This cross-reactivity is the most likely reason for skin test reactivity to olive pollen extract in Michigan.


IgE-mediated inhalant allergy in inhabitants of a building infested by the rice weevil (Sitophilus oryzae). The rice weevil (Sitophilus oryzae) is known as a stored product pest. Occupants living in a factory used previously as a granary and known to be contaminated by the rice weevil developed rhinitis and asthma. To study the role of the potential insect allergens, extracts were prepared from whole body and a grain dust of the rice and grain weevil (Sitophilus granarius). The extracts were coupled to cyanogen bromide-activated paper disks. Skin prick tests (SPT) were performed using common inhalant allergens as well as the insect allergen preparations. In cases of a positive SPT, specific serum IgE to the insect products was measured. Histamine release studies with peripheral leukocytes (HR) and studies using immunoblot techniques were performed. Fifteen of 39 subjects living in the infested rooms demonstrated positive SPT to the extracts of insect origin. Histamine equivalent wheal size induced by the whole body extract of the rice weevil required 3-160 micrograms protein/mL. Five of 15 subjects (with positive SPTs) had elevated specific IgE-levels to the insect material. RAST-inhibition studies indicated cross allergenicity between rice and grain weevils, and also between the frass of both beetles. Five of 15 subjects were positive in the HR assay (Ag30, allergen concentration for 30% HR for the whole body extract: range, 10(-3) to 400 micrograms protein/mL, maximum release: 26% to 89%). IgE binding was detected after SDS-PAGE by immunoblot techniques at different locations: 35-38, 54, 67, 70, and > 94 kD.(ABSTRACT TRUNCATED AT 250 WORDS)


Cough variant asthma: usefulness of a diagnostic-therapeutic trial with prednisone. Cough variant asthma is characterized as a persistent, nonproductive cough with minimal or no wheezing and dyspnea. The diagnosis can be overlooked or misdisagnosed. We describe the severity of cough, the misery of some patients who have this syndrome and the usefulness of a diagnostic-therapeutic trial in ten patients with cough variant asthma. We evaluated ten patients whose chief complaint was persistent nonproductive cough. During the course of evaluation, all patients received a diagnostic-therapeutic trial of prednisone for cough variant asthma after other major causes of cough had been excluded. The duration of cough ranged from 2 months to 20 years. Some patients had significant side effects from coughing including interference with social life, work and sleep, urinary incontinence, stool incontinence, hoarseness, and vomiting. After a diagnostic-therapeutic trial with prednisone, nine patients reported significant improvement of cough in three days. One patient required 2 weeks of therapy for optimal improvement. All were subsequently controlled primarily with inhaled conticosteroids. The diagnosis of cough variant asthma may not be made for a prolonged time. A short course of prednisone as a diagnostic-therapeutic trial can establish a diagnosis and be followed by an effective method of control of cough by inhaled corticosteroids.


Bird antigen persistence in the home environment after removal of the bird. Hypersensitivity pneumonitis (HP) secondary to bird exposure is treated with glucocorticosteroids and avoidance. Despite therapy, symptoms may persist for a prolonged time. Just as cat antigen, Fel d 1, may persist for greater than 20 weeks after cat removal, there may be persistent bird antigen to explain prolonged symptoms in bird HP. It was the intent of this study to determine household distribution and persistence of bird antigen after removal of the bird from the patient's home. The homes of patients with birds were followed serially after bird removal with multiple samples collected using a hand-held vacuum cleaner. Bird antigen levels were determined by an inhibition enzyme-linked immunoassay. In five homes the antigen declined gradually despite extensive environmental control measures, with high levels still detectable at 18 months in one home. This data suggests that high levels of bird antigen can be detected for prolonged periods of time after bird removal and environmental cleanup. The antigen may account for the persistence of disease in some patients with HP. In severe HP, the preferred therapy may be temporary relocation of the patient away from the room in which the bird was housed, in addition to corticosteroids, until the patient's environment is demonstrated to be relatively bird antigen-free.


Comparison of three normal breathing techniques to assess reversibility of airway obstruction. Measurement of forced expiratory volume in one second (FEV1) is generally used to assess airway obstruction. Function tests during normal breathing are used as complementary tests as well as alternatives. Studies have been done comparing the esophageal pressure method with body plethysmography, and respiratory acoustical impedance with body plethysmography. We have not found any other studies comparing all three methods in the same subject. It is not clear whether those tests contribute to the assessment of reversibility of airways obstruction. We addressed the following questions: (1) How does the response of FEV1 to an inhaled beta agonist (400 micrograms fenoterol) relate to the response of lung function tests during normal breathing? (2) Are values obtained with three normal breathing techniques comparable in assessing severity of obstruction? We collected these data in 17 patients. A significant correlation was found between airway resistance measured with any of the three methods. The scatter was large, both before and after bronchodilation. The reversibility by the three methods expressed as absolute values (before and after inhalation) were comparable. In order of preference it appears that acoustical impedance is to be preferred to esophageal pressure because of less discomfort to the patient, and to body plethysmography because of the lower cost of the apparatus. Acoustical impedance can be used to assess acute changes in bronchomotor tone.


Four-year experience with bronchial asthma in a pediatric intensive care unit. Charts of all children with severe acute asthma admitted to the Pediatric Intensive Care unit (PICU) of this hospital between January 1987 and December 1990 were reviewed retrospectively. There were 47 admissions for life threatening asthma to the PICU over this period, representing about 2% of all acute asthma admissions to our hospital. The mean duration of symptoms in these patients before admission was 54 hours. Only 55% of the PICU admissions had received bronchodilators before coming to our hospital emergency room from where they were admitted. From arterial blood gas analysis, 57% of the patients had hypercapnia (PaCO2 > 45 mmHg). All the patients received nebulized salbutamol frequently as well as intravenous aminophylline and hydrocortisone. Mechanical ventilation was used in only 8.5% of the patients. Only two patients developed pneumothorax, neither of whom had been mechanically ventilated, but they did not require surgical intervention for drainage. There was only one death in a patient who was known to have sickle cell anemia and developed sagittal sinus thrombosis. We conclude from our series that the mortality for children with life threatening asthma admitted to PICU is very low if bronchodilators and steroids are used optimally in their management, along with judicious selection of those requiring mechanical ventilation.


Allergy to lysozyme/egg white-containing vaginal suppositories. Seven patients who received a lysozyme, nystatin, and tetracycline containing vaginal suppository because of suspected vaginal infection, developed local or systemic allergic reactions. The coincidence of the symptoms with the repeated use of the suppository as well as skin and lymphocyte transformation tests indicated that the lysozyme in the suppository was responsible for the allergic reactions. This lysozyme preparation contained additional egg proteins, which contributed to the allergic reaction in certain patients: three patients with a previous history of egg allergy and serologic and/or skin test evidence for egg-white sensitization developed the allergic reaction after the first suppository. Four patients had urticaria or anaphylaxis after treatment for at least three days; none of these four patients developed egg allergy. Five of seven individuals had positive skin tests (prick or scratch) to ovomucoid and lysozyme, but none of the patients had lysozyme-specific IgE in the circulation. All seven patients, with or without egg allergy, showed vigorous T cell responses to purified lysozyme and partly to other egg-white proteins in the lymphocyte transformation test, which was absent in controls. Vaginal suppositories that contain lysozyme and other contaminating egg white proteins can either elicit allergic reactions in patients with a preexisting egg white allergy or induce sensitization to lysozyme and other egg white components.


Immediate and delayed type hypersensitivity to malathion. Between December 1989 and June 1990, 1,874 reports of alleged malathion application related illness from repeated spraying of a mixture of malathion corn syrup bait to eradicate a Mediterranean fruit fly infestation in Southern California were received by the Toxics Epidemiology Program of Los Angeles County. Among these complaints were 47 reports of urticaria, 38 reports of angioedema and 213 reports of a nonspecific skin rash. In order to determine whether these alleged skin reactions were the result of an immediate or delayed type of hypersensitivity reaction to malathion or to the corn syrup bait we studied ten subjects referred for testing by the local health department. All ten subjects had no reaction on patch testing. One child exhibited a positive reaction to the bait and one child had irritant reactions to malathion and to the bait. This study documented one case of a possible immediate IgE reaction to malathion bait. Due to the low participation rates in this study, no specific conclusions concerning the rate of sensitivity in the population can be drawn, although it appears that such reactions are uncommon.


Adrenal function of children with bronchial asthma treated with beclomethasone dipropionate. The function of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in nine asthmatic children treated by inhalation of beclomethasone dipropionate (300 micrograms/day) for 12 weeks. The trial was designed as a prospective study. The 24-hour urinary free cortisol, serum cortisol, response to ACTH, and nocturnal serum cortisol followed by 20-minute sampling were measured before and after the study period. No significant changes were found, suggesting that inhaled beclomethasone, in a daily dose of 300 micrograms, does not cause suppression of the HPA axis.


A structured approach to occupational hygiene in the design and operation of fine chemical plant. In order to ensure appropriate occupational hygiene controls can be incorporated in the design and operation of fine chemical plant, a structured scheme has been developed based upon the intrinsic hazard of the materials in use. The scheme provides guidelines for managing the inherent risks to health presented by the operation of such plant, including basic recommendations on the selection and operation of selected plant equipment. Although the scheme has focused on a carcinogenic ranking system for aromatic amines and nitro compounds, with suitable modifications its underlying philosophy and principles should be capable of application to any toxicological scheme for ranking the relative hazard of chemical substances.


Determination of potential dermal exposure during application of crop protection products by boom spraying. The margin of safety is an increasingly important index relating to crop protection products. It relates the available toxicological evidence for the chemical to exposure when the material is used. Determination of potential dermal exposure is an essential element in the calculation of the margin of safety. In the early 1980s a considerable amount of work was done by the British Agrochemicals Association Limited (B.A.A.) on potential dermal exposure. Since that research was undertaken the results obtained have often been used as a model to estimate potential dermal exposure for other crop protection products. This paper presents the findings of a study of potential dermal exposure during boom spraying of an oil-seed rape crop. The conclusions of this study are two-fold. For the application technique studied, the data for mixing and loading generated in the 1980s are inappropriate for prediction of operator exposure and consequent calculation of margin of safety for a product. Also, in future exercises, exposure data should be collected during equipment washing after spraying.


Measurements of the efficiency of respirator filters and filtering facepieces against radon daughter aerosols. The filtration efficiencies of respirator filters and filtering facepieces have been tested against radon daughters in a fluorspar mine. The test method involved the use of sampling filters exposed to natural radon daughters in air filtered by the test respirators. Respirators with a filtration efficiency high enough for them to be considered suitable for use against toxic dusts generally reduced radon daughter levels by 90% or more, though nuisance dust masks were ineffective. The measured penetration of radon daughters through the former types of filter correlated reasonably well with the penetration of 0.1 microns neutralized monodisperse aerosols, and with that of the BS 4400 sodium chloride aerosol, measured in the laboratory. To simulate exposure in working conditions mine air containing radon daughters was drawn through the test filters for 8 h, but their performance was not affected and they were not measurably radioactive as a result.


Exposure to sulphuric acid and sulphur dioxide in the manufacturing of titanium dioxide. An assessment of exposure to sulphuric acid and sulphur dioxide was performed in the French titanium dioxide manufacturing industry. The three plants use the sulphuric acid process, with potential exposure mainly to sulphur dioxide and sulphuric acid. The exposures found were below the French limit values, except for some employees using the Moore filtration process in one plant. For sulphuric acid sampling, a comparison was made between thoracic particulate mass and inhalable particulate mass, from samples taken with a Marple cascade impactor. This comparison shows that the suggested new limit value (0.1 mg m-3 in thoracic particulate mass) would be much more severe than the present one (1.0 mg m-3 with no restriction as to the droplet size).


Developments in occupational health and safety qualifications. Standards of competence for health and safety practitioners are being developed by the Occupational Health and Safety Lead Body (OHSLB) within the overall context of the national changes in vocational training. These changes focus on the development of National Vocational Qualifications (NVQs) and Scottish Vocational Qualifications (SVQs).


European initiatives and the occupational hygiene profession. This paper summarizes the development of occupational hygiene in Europe where the recognition of this profession is still not adequate especially at the political and governmental level. The role of international organizations or associations such as the World Health Organization (WHO) and the International Occupational Hygiene Association (IOHA) is emphasized and illustrated by a few examples. Although not promoting the occupational hygiene profession as such, the European Community is playing a significant role in the development of this discipline by its active policy in the field of health and safety at work. The other relevant actors in this respect are the International Labour Office (ILO) and the dynamic and proficient national societies such as the Italian Association of Industrial Hygienists and the British Occupational Hygiene Society. A few of the most relevant challenges in the development of this indispensable discipline are finally presented. One of the highest priorities is training and education since a profession cannot evolve and continue to grow without fresh blood.


The suitability of the urinary metabolite 1-hydroxypyrene as an index of poly nuclear aromatic hydrocarbon bioavailability from workers exposed to carbon black. Levels of airborne dust have been measured in the breathing zone of five warehouse packers in a carbon black manufacturing plant on consecutive days over 1 week. Post-shift urine samples were collected on individuals over the week and the concentration of the pyrene metabolite 1-hydroxypyrene have been measured. A questionnaire was used to assess the likelihood of potential confounding factors, such as direct exposure to feedstock oil, as well as smoking and diet. The arithmetic mean both of airborne dust and of excreted 1-hydroxypyrene for each individual have been correlated (a) with the constraint that the regression line pass through the origin, and (b) without this constraint. The slope of the regression through the origin was significant and that of the second regression (not through the origin) was not. The statistical test to determine whether excretion on days after Monday was higher than that on Monday itself proved highly significant. The results suggest that 1-hydroxypyrene may be a useful indicator of exposure to the PNAs adsorbed onto carbon black.


Atypical retinitis pigmentosa: a report of three cases. We report three cases of patients with atypical retinitis pigmentosa (RP): sector bilateral, sector unilateral, and inverse. Clinical and functional features of perimetry, color vision testing, adaptometry, electroretinography, fluorangiography, and audiometry are described. One patient had isolated RP; the others had syndromic RP, combined with defective hearing and celiac disease. Two of these patients were followed for three years and one for 13 years. Their disease courses during the period of observation are discussed.


Acute retinal necrosis after chickenpox in a healthy adult. A healthy man had acute retinal necrosis (ARN) two weeks after diffuse varicella eruption. Treatment with acyclovir and corticosteroids was associated with a favorable clinical outcome. To our knowledge, there are no reported occurrences of permanent visual loss or retinal detachment in healthy patients with postvaricella ARN.


Physician participation in a randomized clinical trial for ocular melanoma. One substudy of the Collaborative Ocular Melanoma Study (COMS) is a randomized trial examining surgery versus radiation therapy for ocular melanoma. To understand the perspective of the physician investigators, a survey of the 101 COMS physicians from 29 major institutions in the United States and Canada was completed before randomization of the first patient. A 95% response rate was obtained, and follow-up interviews were conducted with 87% of the physicians. The study found that (1) COMS physicians identified significant differences between incentives and disincentives to participate in any trial compared with participating in COMS, (2) COMS physicians could be differentiated and had a stronger clinical rather than research orientation, and (3) COMS physicians exhibited a high intention to recruit an identifiable subset of eligible patients. These data suggest that continued support of individual investigators and a close examination of incentives and disincentives to physician participation would be useful in enhancing accrual in this study. A follow-up of this group is planned throughout the anticipated ten-year duration of patient recruitment of this COMS trial.


Immunohistochemical staining techniques of intraocular tumors. The peroxidase-antiperoxidase staining technique for the antigens S-100, neuron-specific enolase, and alpha 1-antichymotrypsin (alpha 1ACT) was applied to 57 intraocular tumors: 46 malignant melanomas of the uvea, seven retinoblastomas, and four tumors metastasizing to the eye. The staining characteristics of the different intraocular tumors were compared. Staining for S-100 in a fine-needle aspiration biopsy sample taken from a malignant melanoma of the choroid before enucleation of the globe was attempted. The positive staining of a few cells thus obtained suggested that this technique may be helpful in the diagnosis of melanomas. The alpha 1ACT stain used in this study has not been used previously in ophthalmology to our knowledge. We found 60% of malignant melanomas of the choroid stained positively. Another finding was the staining of the retinal pigment epithelium with alpha 1ACT in 30% of eyes with malignant melanoma of the uvea.


[Synthesis and structure of substituted bromo and nitrobenzyl benzylidene imidazolidinediones and thiazolidinediones]. Synthesis and physico-chemical properties of five bromobenzyl-benzylidene-imidazolidinediones and five nitrobenzyl- or benzyl-benzylidene-thiazolidinediones are described. The microbiological activity of bromobenzyl-benzylidene-imidazolidinediones against microorganisms such as Candida albicans, Neurospora crassa and Mycobacterium smegmatis are evaluated.


[Multiple drug addiction].

[Multiple drug addiction]. The "polydrug use" well known at the USA, has sprayed in France and Europe during the last ten years. Harms of polydrug use were pointed out by some specialized centers. The aim of this work is to emphasize the dangers of the abuse of some drug associations. Animal pharmacology, clinical observations and epidemiology are the main research method involved animal in the study of "polydrug use". These methods are often difficult to perform in elderly persons and in pregnant women. It is not easy to extrapolate from animals to man. The pharmacokinetics of drugs often differs from a species to another. Animal models are nevertheless useful for studies dealing with drug interactions, especially with enzyme metabolism. Clinical studies will be dependent on the ethical questions. Some examples are mentioned. Alcohol use develops in many drug addicts, particularly in those on methadone maintenance. The association of cocaine and other amphetamine-type stimulants with morphinics or cannabis is very dangerous. Other associations are quite frequent including various hypnotics or cough suppressants (even nomorphinic). "Polydrug use" generally increase mortality in drug addicts. The medical profession is not well informed on this subject. Further research must be led on the harmful effects of drug associations and on the reasons leading drug addicts to multiplicate drug associations in an almost epidemic way.


[Skin absorption promotors].

[Skin absorption promotors]. Transdermal penetration of drugs is currently much studied because it presents several attractive aspects, avoiding first past effects and offering means of immediate breaking of the therapeutic in case of hitch. But it must overcome the very efficient hindrance of the epidermal barrier. Few among the molecules have prerequisite structural and pharmacodynamical aspects necessary to this way of penetration. Substances belonging to diverse chemical families enhance sometimes largely this passage; they are named "penetration enhancers". In this review are listed the ideal properties of enhancers, the chemical structure of the currently more used ones, the possible interaction with other components of the formula in the case of TTS and towards the patient.


[Determination of an intrinsic value of diffusion coefficient of active principle in polymeric matrix for the formulation of a controlled release system]. The study of diffusion in a polymeric system often poses difficult experimental problems, notably when the rate of release is determined in a liquid receptor phase which can interact with the system. In this publication, we propose two experimental methods to determine the diffusion coefficient by a gel-gel kinetic release study, in which the receptor is a same gel unloaded initially. The first method is based on the use of radioactive tracers and a multi-channel radioactivity counter to obtain, at different times, the concentration profiles in the diffusion medium. The theoretical model is given for a gel donor with the concentration C0 of diffusing molecules is below or above the solubility Cs. The second method is based on the measurement of the displacement of solubility front during the diffusion within the system in the case C0 > Cs. The theoretical model shows that this displacement is a function of square root of t. For illustration, two experimental determinations of testosterone diffusion coefficient on the one hand in a silisic acid gels and on the other hand in an acrylic acid gels are given.


[Immunoenzymatic assay of dyes used in affinity chromatography of proteins]. Immobilized reactive dyes are frequently used in pseudoaffinity chromatography since it has been evidenced that they could specifically interact with some biologicals of interest, and, as a consequence, be separated and purified by this way. This specificity was so high in some cases, that a single step purification process was possible. In addition to these features, the wide variety of dye molecules available associated to their chemical stability and low cost make possible their use as ligands for industrial applications. Nevertheless, one drawback of the use of dye sorbents for protein purification is the possible leakage of dye molecules, with a risk of biological properties alteration of the purified product. We describe a new quantitative assay method for dyes that could contaminate biologicals separated through special affinity columns. This method based on the specific recognition of dyes by antibodies showed a high specificity and a much better sensitivity than the classical spectrophotometric approaches. It has been applied to the quantification of dyes used in affinity chromatography (Cibacron Blue F3-GA, Basilen Bleue E3-G and Procion Red HE-3B) in the presence of proteins having a special affinity for these dyes. This immunoenzymatic assay is also easily applicable to the detection of leachables from dye affinity columns submitted to drastic regeneration treatments.


Gunshot wounds of the colon: role of primary repair. This is a prospective study of 100 patients with bullet injuries of the colon. Primary repair was performed except in cases of severe colonic damage requiring colectomy or in the presence of disseminated gross peritoneal contamination. Primary repair was performed in 76% with an incidence of abdominal sepsis of 11.8%. The remaining 24% of the patients had a colostomy and the incidence of abdominal sepsis was 29.2% (P < 0.05). Left-sided colonic injuries, multiple colonic perforations, shock on admission, delay > 6 h, more than two associated intra-abdominal injuries, high Injury Severity Score (ISS), and high Penetrating Abdominal Trauma Index (PATI), are not in themselves contraindications for primary repair.


Perianal abscess in children.

Perianal abscess in children. The records of 16 children presenting with a diagnosis of perianal abscess, over a 5-year period, were reviewed. The clinical and microbiological features of paediatric perianal abscesses are similar to those found in adults, although the incidence of associated diseases is higher in paediatric patients. Perianal abscesses in children are best treated by incision and drainage. The presence of an underlying contributing disease should be excluded.


Two types of colorectal carcinoma in Crohn's disease. Fourteen examples of carcinoma developing in the colon or rectum were encountered in a series of 1008 patients with Crohn's disease treated in Aberdeen during the 34-year period, 1955-1988. Seven patients were under 55 years of age at the time of onset of Crohn's disease, and had a long history of the disease before carcinoma supervened. Older patients had short histories and a better prognosis. One squamous carcinoma may have arisen in relationship to a fistula in ano.


Which surgeons avoid a stoma in treating left-sided colonic obstruction? Results of a postal questionnaire. There is now good evidence to indicate that the majority of patients with large bowel obstruction can be safely managed by resection and immediate anastomosis, but have surgeons embraced this policy? A postal survey has been performed to ascertain the opinions of consultant general surgeons within the Wessex region regarding the management of left-sided large bowel obstruction. Of 47 questionnaires sent, 42 replies could be analysed. In patients of good anaesthetic risk, 90% would perform resection with primary anastomosis if the lesion was at the splenic flexure, and 62% would adopt this policy for a rectosigmoid obstruction. In patients of higher anaesthetic risk these figures fell to 71% and 31%, respectively. Surgeons with a gastrointestinal interest were more likely to recommend resection with primary anastomosis. However, this trend reached statistical significance only for splenic flexure and descending colon lesions in good-risk patients. Most surgeons would avoid a stoma in the presence of liver metastases, and only three would be more likely to create a stoma in this situation.


The 'Jaykay' stoma flange cutter.

The 'Jaykay' stoma flange cutter. One of the many difficulties associated with stoma management is that of cutting the hole in the appliance to fit neatly and precisely around the mucocutaneous border. A new stoma flange cutter has been designed which facilitates the cutting or the enlargement of holes in stoma flanges to the exact size required. This equipment may be of use to partially sighted or manually disabled patients as well as to those able patients who would prefer an easier method of cutting the hole in their stoma flange. It may also be of use in operating theatres to enable theatre nurses to cut flanges more accurately and quickly for patients with colostomies, ileostomies or urinary conduits.


A prospective comparison of laparoscopic versus open cholecystectomy. In one surgical unit, 115 patients undergoing cholecystectomy were studied to compare patient recovery, subjective and objective pain experienced and complications after laparoscopic and open cholecystectomy. The data were collected prospectively where allocation to open or laparoscopic cholecystectomy was by consecutive attendance. Laparoscopic cholecystectomy was feasible in 90% of patients presenting with symptomatic gallstones. Compared with the open operation, laparoscopic cholecystectomy was safe with less peroperative and postoperative morbidity, was more cost-effective and was associated with faster patient recovery as documented by less postoperative pain, earlier return to diet, earlier full mobilisation and discharge home. Laparoscopic cholecystectomy is superior to open cholecystectomy and should be available to all patients requiring elective cholecystectomy.


Audit of an oesophageal unit.

Audit of an oesophageal unit. We report an audit of 786 oesophageal procedures, including 53 oesophagectomies, performed during 1990 in a specialist oesophageal unit. Apart from assessing morbidity and mortality, audit allows a review of cost efficiency and justification for certain practices with regard to patient management. The data reported here may provide a framework against which individual surgeons may assess their own results and compare costs of procedures with a similar outcome.


Costs can and must be a component of surgical audit. The cost of running a surgical firm at Addenbrooke's Hospital in Cambridge was assessed over a 1 month period in May 1989. The total of 97,380 pounds was much more than expected for a firm of one full-time and one part-time consultant. It related to the month's workload of 101 admissions, 656 inpatient days, 92 operations and 442 outpatient visits. The derivation of a simple formula enabled individual patient episodes to be costed; from this new data and information stored routinely on the firm's audit system. It has been used to cost patients undergoing procedures commonly performed by the firm and also to illustrate the effect of complicated surgery on resources. Audit has been shown to have potential in a clinician's assessment of his resource use. Its future development in this role is strongly advocated.


Beneficial effects of continuous passive motion after total condylar knee arthroplasty. A randomised, controlled study of the use of postoperative continuous passive motion (CPM) and immobilisation regimen after total condylar knee arthroplasty was performed. CPM resulted in a significant increase in both the early and late range of knee flexion. This increase occurred in both rheumatoid and osteoarthritic patients. The improvement of 10 degrees at 12 months allowed additional important function to be attained. CPM resulted in significantly earlier discharge from hospital. It did not increase the clinical incidence of wound healing problems, nor did it significantly increase the postoperative fixed flexion deformity or the extension lag. CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty.


Activity analysis: measurement of the effectiveness of surgical training and operative technique. All surgical procedures are characterised by a sequence of steps and instrument changes. Although surgical efficiency and training in operative technique closely relate to this process, few studies have attempted to analyse it quantitatively. Because efficiency is particularly important in day surgery and lower third molar removal is a high-volume procedure, the need for which is responsible for particularly long waiting-lists in almost all UK health regions, this operation was selected for evaluation. A series of 80 consecutive procedures, carried out for 43 day-stay patients under general anaesthesia by seven junior staff (senior house officers and registrars: 39 procedures) and four senior staff (senior registrars and consultants: 41 procedures) were analysed. Median operating time for procedures which required retraction of periosteum was 9.5 min (range 2.7-23.3 min). Where these steps were necessary, median time for incision was 25 s (range 10-90 s); for retraction of periosteum, 79 s (range 5-340 s); for bone removal, 118 s (range 10-380 s); for tooth excision, 131 s (range 10-900 s); for debridement, 74 s (range 5-270 s); and for suture, 144 s (range 25-320 s). Junior surgeons could be differentiated from senior surgeons on the basis of omission, repetition and duration of these steps. Juniors omitted retraction of periosteum in 10% of procedures (seniors 23%) and suture in 13% (seniors 32%). Juniors repeated steps in 47% of operations; seniors, 14%. Junior surgeons took significantly more time than senior surgeons for incision, bone removal and tooth excision. No significant differences between junior and senior surgeons were found in relation to the incidence of altered lingual and labial sensation at 7 days. It was concluded that activity analysis may be a useful measure of the effectiveness of surgical training and the efficiency of operative technique.


Clinical evaluation of percutaneous insertion and long-term usage of a new cuffed polyurethane catheter for central venous access. A new, long-term venous access catheter was evaluated in clinical practice and the insertion time, complication rate and prospective follow-up recorded. Fifty novel polyurethane catheters (Cuff-Cath) were inserted in 48 patients, for cytotoxic chemotherapy in 36, long-term total parenteral nutrition in five and miscellaneous indications in seven. All catheters were inserted by a percutaneous technique under local anaesthesia. The mean insertion time was 18 min. There were three insertion complications; failure to cannulate, pneumothorax and malposition. Seven catheters required removal (sepsis in five, subclavian vein thrombosis in two) and one catheter fell out. Total catheter days to date has been 6607 (mean 132, range 18-831 days). Eleven catheters are still in use a mean of 154 days (range 38-490 days) after insertion. Furthermore, a new technique has been described which prevents inadvertent displacement. This new catheter combines the mechanical advantages of polyurethane, together with those of a Dacron cuff. Early results suggest that this catheter may be a useful alternative to silicone catheters of the Hickman/Broviac type for long-term central venous access.


A 5-year review of carotid endarterectomy in a vascular unit using a computerised audit system. BIPAS, a computerised vascular audit has been used to analyse the results of 203 carotid endarterectomies performed over a 5-year period in a vascular unit. In addition, all but two patients have been followed up with regular duplex scans. The indications and surgical techniques have remained similar over the study period though preoperative carotid arteriography is no longer considered essential and intraoperative monitoring with transcranial Doppler insonation is becoming routine. There were six perioperative deaths and 20 postoperative neurological defects. However, only three survivors had any long-term disability. It was not possible to identify any particular patients at high risk of perioperative stroke, although simultaneous major surgery and significant bilateral carotid endarterectomy seemed to be more hazardous. Routine follow-up using duplex scanning identified patients with late occlusion (5%) and restenosis (8%), but only three patients (1.5%) suffered a late stroke. Once the perioperative hazards of death and permanent stroke (4.4% in this series) have been overcome, carotid endarterectomy provides good protection against subsequent stroke.


[The urinary metabolites of niacin during the course of pellagra]. The three main metabolites of niacin have been measured in urine of 10 Mozambican women living in refugee camps in Malawi and displaying clinical symptoms of pellagra. This study, in which a control group was included, showed that the ratio 6PYR/N1MN is well correlated to the occurrence of clinical symptoms of niacin deficiency and constitutes a reliable indicator of vitamin PP status in subjects at risk of this deficiency.


Postprandial pattern of triglyceride-rich lipoprotein in normal-weight humans after an oral lipid load: exaggerated triglycerides and altered insulin response in some subjects. In 13 healthy, male nonsmokers (mean age: 25.7 +/- 2.4 years) with normal fasting triglycerides we investigated postprandial changes of triglycerides in several lipoprotein fractions. After a 12-hour overnight fast they ingested a standardized lipid load (1,017 kcal) including 30,000 IU retinyl palmitate. Postprandially, total triglycerides increased significantly (p < 0.001) to a peak value of 221 +/- 81 mg/dl at 5 h. Two subjects had an exceptionally strong triglyceride response (peak values: 363 and 390 mg/dl). They had the highest levels of retinyl palmitate in the chylomicron and the nonchylomicron fraction, and one of them showed elevated intermediate-density lipoprotein values throughout the test period. In addition, they showed an altered early and an increased late postprandial insulin response. Thus, our data provide evidence that an exaggerated postprandial triglyceride response may point to an increased atherogenic risk even in healthy subjects with normal fasting triglycerides.


Zinc status in anorexia nervosa.

Zinc status in anorexia nervosa. Some aspects of zinc nutritive status in patients suffering from anorexia nervosa were evaluated. Basic anthropometric measurements, Zn levels in serum, urine and hair as well as serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH; Zn-dependent enzymes) and delayed dermal hypersensitivity were tested both in patients and in control subjects. The patients showed higher Zn levels in serum (123%), hair (85%) and urine (215%) than controls, whereas ALP and LDH values were 38 and 21%, respectively, lower than those from the control group. Half of the patients showed hypoergy, and less than 50% of them were able to show a normal immune response. These results suggest that Zn-dependent functions may be impaired in anorexia nervosa as a consequence of Zn unavailability.


Effect of vitamin D deficiency on testicular function in the rat. To study the effect of vitamin D deficiency on testicular function, 30-day-old male rats were put on a vitamin-D-deficient diet. At 120 days of age, the testicular function of these animals was compared with that of rats of the same age group fed, ad libitum, a diet containing vitamin D and rats fed on a restricted amount of diet with vitamin D. In vitamin-D-deficient rats, there was a significant reduction in the total body weight, testicular and epididymal sperm count and testicular glutamyl transpeptidase activity (an index of Sertoli cell function) as compared to control group rats, but there was no difference in the testicular lactate dehydrogenase activity (an index of germ cell function). Histological examination of the testis in vitamin-D-deficient rats revealed a significant reduction in the Leydig cell count along with degenerative changes in the germinal epithelium. Histological examination of the tibia revealed excess of osteoid in vitamin-D-deficient rats only. On the other hand, in undernourished rats given a normal amount of vitamin D, the only significant change was a reduction in total body weight. These results suggest that vitamin D deficiency retards spermatogenesis by interfering with the function of Sertoli and Leydig cells.


Micronutrient status in females during a 24-week fitness-type exercise program. Thiamin, riboflavin, vitamin B6, magnesium, iron and zinc status, assessed from blood samples, was studied during a 24-week fitness-type exercise program. Subjects in exercise (n = 21) and control (n = 18) groups were female university students, aged 18-33 years. Erythrocyte (E) transketolase and glutathione activation coefficient, serum magnesium, zinc and ferritin, blood hemoglobin concentration and mean corpuscular volume were similar in both groups throughout the entire study. E-aspartate aminotransferase activation coefficient (vitamin B6 status) increased (4%) in exercise and decreased (7%) in control groups (p = 0.04), respectively. E-magnesium was stable in exercise but decreased (4%) in control groups (p = 0.004%). E-zinc increased (9%) in exercise subjects but remained stable in controls (p < 0.0001). A marginally altered vitamin B6 status was the only negative change found in exercise subjects.


Comparison of food intakes of selected populations in former East and West Germany: results from the MONICA Projects Erfurt and Augsburg. The intakes of selected food groups in former East and West Germany were compared, based on data from the dietary surveys of the MONICA project Erfurt 1987 and of the MONICA project Augsburg 1984/85. Three-day records from 132 middle-aged men from the city of Erfurt (response 73%) and 3-day records from 424 middle-aged men from the city of Augsburg (response 70%) could be included in the comparison. The differences in the consumption of animal products were rather small. The intake of bread and baked goods, potatoes and cooked vegetables was higher in Erfurt, whereas the intake of raw vegetables was lower. The most striking differences appeared in the consumption of fat.


Effect of the antiprotozoal agent metronidazole (Flagyl) on absorptive and digestive functions of the rat intestine. Metronidazole (Flagyl), an antibiotic commonly used in treating intestinal infections, when administered orally at a dose level of 100 mg/kg body weight daily for 7 days to rats brought about a significant elevation of the uptake of end-product nutrients like D-glucose, L-alanine, L-aspartic acid and L-leucine in the intestinal segments. Brush border membrane-bound hydrolytic enzymes, i.e. sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase levels, were also elevated. Substrate kinetic analysis of the uptake of nutrients as well as the enzymes indicated that the drug increased the maximum of apparent initial velocity, while the substrate affinity constants did not change. Studies of the temperature-dependent parameters of the nutrient uptake and the enzyme activity revealed that metronidazole did not induce any shift in the transition temperature (T(o)) for the uptake but the energy of activation (Ea) was reduced in all the cases except those of maltase and leucine aminopeptidase, which registered an increase in Ea and a marginal shift in T(o), respectively. A significant elevation was seen in the levels of membrane cholesterol, phospholipid, ganglioside and plasmalogen in metronidazole-treated animals, while triglycerides and the non-esterified fatty acids remained unaffected. The effects produced by metronidazole treatment persisted in the animals, which were allowed a recovery period of 7 days after the drug regimen.


Multiple sclerosis in 54 twinships: concordance rate is independent of zygosity. French Research Group on Multiple Sclerosis. In a large population-based multiple sclerosis (MS) sample (n = 7,951), 116 twins were identified (1.4%), of which it was possible to contact 97. In 27 pairs, the twin of the patient with MS was dead. Among the 70 remaining pairs, 16 were excluded because either the index patient or their twin did not accept protocol requirements. The final sample included 54 pairs. Twin zygosity was determined by DNA fingerprint analysis. We found 17 monozygotic pairs and 37 dizygotic pairs. One of the 17 monozygotic pairs (5.9%) and 1 of the 37 dizygotic pairs (2.7%) were concordant for MS. In 42 of the clinically unaffected twins, magnetic resonance imaging (MRI) of the brain was performed, and 9 scans were classified as indicative of MS. Three of these 42 patients had abnormal visual-evoked potentials, but all 3 had normal MRI scans. The overall proportion of pairs in which the co-twin had some form of clinical, radiological, or electrophysiological abnormality was approximately 30%; this proportion was independent of zygosity.