Cognitive predictors of health behaviour in contrasting regions of Europe.

Four important health behaviours--dietary fat avoidance, regular exercise, smoking and alcohol consumption--were assessed by questionnaire, together with measures of risk awareness and beliefs about the importance of each behaviour for health, in comparable samples of young adults from eight countries: Belgium, England, Germany, Hungary, Ireland, Poland, Portugal and Spain. Results from 3223 men and 3930 women were analysed. Substantial differences in the prevalence of behaviours were identified, but no country consistently showed the most or least healthy profile across behaviours. Women tended to smoke and drink less than men and attempted to avoid dietary fat to a greater extent, while men exercised more than women. Ratings of the importance of behaviours for health were high, while risk awareness showed wide variations, with lower scores from samples in southern and eastern Europe. Across countries, few associations were observed between the prevalence of behaviour and either mean belief ratings or risk awareness. However, in comparisons of people who did and did not perform each behaviour, beliefs were consistently associated with practice. In multiple regression, beliefs about the importance of the behaviour for health independently accounted for 11.3 per cent of the variance in exercise, 18.9 per cent of the variance in smoking and 4.5 per cent of the variance in alcohol consumption. The association between beliefs and dietary fat avoidance was also substantial. In contrast, the relationships between risk awareness and behaviour were mixed. People who avoided dietary fat were more aware than others of the health risks of fat. But non-smokers were less aware than smokers of the risks of smoking, and people who drank regularly were more aware of the dangers of alcohol than were non-drinkers. The results are discussed in the context of the contribution of health psychology to European health promotion.


Post-traumatic stress disorder: the history of a recent concept.

This review describes the history of PTSD in relation to military psychiatry, physiology, and crisis theory. It appears that the consequences of psychic trauma are often underestimated and mental health services often fail to provide adequate care. PTSD may be explained as an initially adequate reaction to danger, which becomes pathological if it does not disappear after the danger is gone. The authors argue in favour of better psychiatric intervention after traumatic events and better care for trauma victims.


Suicide in psychiatric patients: risk and prevention.

The prevention of suicide requires an understanding of protective as well as risk factors, and the recognition of high-risk groups. Factors which increase the risk in patient populations include previous parasuicide, recent relapse or discharge, features of mental state (depression, psychosis), social circumstances (isolation, unemployment), and demographic characteristics (male sex, young age). Protective factors are under-researched but are likely to lie in the nature of psychiatric care. Consequently, community care may affect suicide by altering the level of protection at critical periods in an episode of illness. The clinical prevention of suicide should therefore be a priority for community services, and the relationship between suicide and mental health care should be researched by a national process of monitoring.


A selective review of child psychiatric syndromes with a somatic presentation.

This review focuses on 'aches and pains' and conversion syndromes as a basis for the description of psychological factors and mechanisms of relevance for the somatisation of distress in childhood and which may contribute to medical help-seeking for children. The characteristic pattern of associated psychological factors includes child personality features; academic concerns; family health problems; and styles of family interaction. Further research is required to explore in more depth the nature of these factors, the mechanisms that mediate the development of severe handicapping problems, and effective interventions.


The psychosocial impact of HIV infection in gay men. A controlled investigation and factors associated with psychiatric morbidity.

This study aimed to establish the prevalence of psychosocial problems in gay men with HIV infection, and to identify factors associated with psychological morbidity. The study was a cross-sectional controlled investigation, which included 24 HIV seropositive and 25 seronegative gay men. Outcome measures included current psychological status and psychiatric history; coping and health beliefs; and social and sexual functioning. Seropositive subjects had worse scores on the PSE total score, and greater sexual difficulties. There were also differences in health beliefs and coping. Psychological morbidity was associated with hopelessness, previous psychiatric illness, symptomatic HIV disease, and low self-esteem.


The burden of schizophrenia on the family. A study from Nigeria.

The burden of schizophrenia on rural and urban Nigerian families was studied using a standardised questionnaire. Rural families experienced more burden; however, the difference was significant only in respect of financial burden. Rural families of schizophrenics were shown to be more prone to minor psychiatric morbidity than urban families. Policies should be instigated to reduce such burden.


The influence of ethnicity and family structure on relapse in first-episode schizophrenia. A comparison of Asian, Afro-Caribbean, and white patients.

There is overwhelming evidence that the outcome for people with schizophrenia in Western industrialised countries is inferior to that of those living in the Third World. Extended family structures, greater opportunities for social reintegration, and more positive constructions of mental illness have been offered as possible explanations for this effect. The Asian community in the UK retains many of these features as well as strong links with native cultures of origin. The issue arises as to whether similar differences in outcome may be observed in the UK. An exploratory study was undertaken, examining the early progress of schizophrenia in a first-episode sample (n = 137), and based on systematic examination of case-note data. A lower rate of relapse/readmission in the first 12 months after discharge was found in the Asian (16%) as compared with white (30%) and Afro-Caribbean (49%) patients. Available evidence suggested that speed of access to care, living with a family, and employment may account for this effect. Medication compliance may have contributed to differences in relapse between white and Afro-Caribbeans but was not a factor influencing the low rate among Asians. The limitations and strengths of case-note studies are discussed at length, and it is concluded that a prospective study is warranted and would be highly instructive.


Comparison of quality of life with standard of living in schizophrenic out-patients.

Standard of living reflects the objective dimension of how well the basic needs of life are met, while quality of life is the patient's own subjective view of well-being and satisfaction with her/his life. Sixty-one schizophrenic out-patients completed self-report inventories and participated in interviews about quality of life and standard of living. When living standards were met by a well functioning social service system, patients' perceptions of their quality of life and their standard of living appeared to be independent. Subsequent analyses revealed that 'inner experiences' was one quality-of-life domain frequently reported as unsatisfactory. Moreover, differences in quality of life were found across patients' age, education, and work status.


Expressed emotion in staff working with the long-term adult mentally ill.

Staff-patient relationships in long-term settings were examined in 35 staff and 61 patients. Measures were also taken of the staff's general health, their coping style in relation to work events, and job satisfaction. A range of ratings of EE was evident in staff descriptions of patients under their care. Strain and criticism in the relationship were not associated with identified stressors in the workplace, or the general health of the carer. When patients were grouped according to high-EE and low-EE interviews, there were no significant differences in their symptoms. Criticism was associated with other patient characteristics, including aggressive and attention-seeking behaviour, underactivity, and limited social interaction. The findings have implications for staff training and for the maintenance of optimal staff-patient relationships in services supporting severely disabled patients.


Change in locus of control following admission in adolescent in-patients.

A multidimensional measure of children's perception of control was administered to 56 adolescents before and after admission. Different sources of control ('internal', 'powerful others' and 'unknown') were analysed by domain (sphere of behaviour) and outcome ('success' or 'failure'). There were changes across domain and outcome for all three sources of control with significant changes away from 'powerful others' and 'unknown' control. The trend towards internality was also evident in significant changes in the adolescents' perceptions in the 'general' domain and for a 'success' outcome. Changes towards 'internal' source of control were associated with higher cognitive ability, whereas changes away from 'powerful others' were most marked in girls, and changes away from 'unknown' were greatest in the older adolescents. These preliminary observations may help us understand beneficial effects of in-patient care and plan strategies for sustained change in these patients.


Deliberate self-poisoning and self-injury in adolescents. A study of characteristics and trends in Oxford, 1976-89.

In Oxford during the late 1970s and early 1980s a decline in rates of deliberate self-poisoning and self-injury in older female teenagers was followed by a steady increase between 1986 and 1989. Rates for male adolescents and young female adolescents remained relatively stable throughout 1976-89. Applying the Oxford rates to England and Wales suggest a total of 18,000-19,000 hospital-referred cases per year. While self-poisoning with minor tranquillisers and sedatives has declined, there has been a marked increase in paracetamol self-poisoning, such that by 1988-89 it was involved in 48.3% of overdoses. Relationship difficulties were the most frequent problems faced by these adolescents, especially the females, with unemployment and alcohol and drug problems also being common, especially in males, but psychiatric disorders relatively rare. Substantial proportions of the adolescents, especially the males, were not living with either relatives or friends, and had a history of violence or a criminal record. The annual rate of repetition of attempts, which was 8.9% overall, was higher in adolescents not admitted to the general hospital, and in females not referred to the hospital psychiatric service. Adolescent attempted suicide clearly continues to be a major health problem for which both effective preventive and therapeutic strategies are badly needed.


Methodological issues in using a polydiagnostic approach to define psychotic illness.

Although a polydiagnostic approach to the definition of psychotic disorder provides many advantages to the researcher, there are also disadvantages. A comparison between several different sets of operational criteria using the OPCRIT computer program on a consecutive series of 397 psychotic subjects is described. The results show that although current diagnostic procedures are generally reliable, such approaches can still only supplement skilled clinical judgement, and there remain many pitfalls for the unwary.


Cardiac vagal tone in generalised anxiety disorder.

The aim of the present study was twofold: firstly, to determine cardiac vagal tone in subjects with generalised anxiety disorder directly, using an invasive pharmacological method; and secondly, to test whether the non-invasive method of measuring the amplitude of respiratory sinus arrhythmia (RSA) gives a reliable estimate of cardiac vagal tone in this form of anxiety disorder. Comparison of baseline physiological measures of anxious and control subjects revealed that cardiac vagal tone and heart rate were not different in the two groups of subjects, whereas length of the respiratory cycle and amplitude of respiratory sinus arrhythmia were reduced in the former group. Because of the higher respiratory rates of anxious subjects, the RSA method was found to underestimate cardiac vagal tone in generalised anxiety disorder.


Can autism be detected at 18 months? The needle, the haystack, and the CHAT.

Autism is currently detected only at about three years of age. This study aimed to establish if detection of autism was possible at 18 months of age. We screened 41 18-month-old toddlers who were at high genetic risk for developing autism, and 50 randomly selected 18-month-olds, using a new instrument, the CHAT, administered by GPs or health visitors. More than 80% of the randomly selected 18-month-old toddlers passed on all items, and none failed on more than one of pretend play, protodeclarative pointing, joint-attention, social interest, and social play. Four children in the high-risk group failed on two or more of these five key types of behaviour. At follow-up at 30 months of age, the 87 children who had passed four or more of these key types of behaviour at 18 months of age had continued to develop normally. The four toddlers who had failed on two or more of these key types of behaviour at 18 months received a diagnosis of autism by 30 months.


An empirical study of delirium subtypes.

Using a structured instrument, 325 elderly patients admitted to a general hospital for an acute medical problem were evaluated daily in order to detect symptoms of delirium. Patients were scored for 'hyperactive' or 'hypoactive' symptoms, and then the 125 patients with DSM-III delirium were rated as 'hyperactive type' (15%), 'hypoactive type' (19%), 'mixed type' (52%), or 'neither' (14%). There were no statistically significant differences between the groups with respect to age, sex, place of residence, or presence of dementia. These definitions of subtypes should be studied further.


Mentally ill sex offenders. The experience of a regional secure unit.

Sex offenders suffering from psychotic illness formed an important small group of a regional secure unit's patients. Ten of the 11 such offenders had a diagnosis of schizophrenia. There was a complex relationship between their mental illness and offending.


Pisa syndrome mistaken for conversion in an adolescent.

We present a case of acute dystonia in an adolescent, with features that fit the description of the Pisa syndrome. The symptoms developed postoperatively, in a non-psychiatric setting, following administration of antiemetic medication, and the phenomenon was misdiagnosed as a conversion disorder. This case reinforces previous reports cautioning against misinterpretation of dystonic reactions as functional disorders, especially in children and adolescents.


A female monozygotic twin pair discordant for transsexualism. Some theoretical implications.

A 13-year-old girl was referred because of sexual identity problems. There was no mental illness or neurological abnormalities. As her twin sister had no sexual identity problems, it appears that transsexualism is not transmitted by a simple genetic mechanism.


Neuroleptic malignant syndrome and diabetic keto-acidosis.

A patient suffering from schizophrenia developed diabetic keto-acidosis and NMS after treatment with neuroleptics. The combination of two uncommon complications of treatment with neuroleptics proved fatal.


A real-time approach to spoken language processing in aphasia.

The study is based on an on-line investigation of spoken language comprehension processes in 25 French-speaking aphasics using a syllable-monitoring task. Nonsense syllables were presented in three different conditions: context-free (embedded in strings of nonsense syllables), lexical context (where the target nonsense syllable is the initial, medial, or final syllable of real three-syllable words), and sentence context. This study builds on an earlier one that explored the relationship between the acoustic-phonetic, lexical, and sentential levels of spoken language processing in French-speaking normals and gave evidence of top-down lexical and sentential influence on syllable recognition. In the present study, aphasic patients from various diagnostic categories were classified as high (N = 13) or low (N = 12) comprehenders. The results show that low comprehending aphasics make no use of sentence information in the syllable-recognition task. As for top-down effect at the single word level that is observed in normal listeners. However, a subgroup analysis shows that the Broca's are the only high comprehending aphasics who perform in the same way as normal listeners; this sets them apart from the anomics and conduction aphasics.


Impairment of inflectional morphology and lexical storage.

The present study investigates the repetition, comprehension, and production abilities of three French-speaking agrammatic aphasics on stimuli that require attention to the inflectional markers of number, gender, and tense. Two sets of experiments were conducted within a Strong Lexicalist framework. The results suggest that morphological deficits can manifest themselves at distinct levels of grammar, the lexical and the postlexical. The internal morphological structure and idiosyncracies of lexical items were found to have an effect on aphasic performance. A proposal of a differentially organized lexical storage reflecting the particularities of the French verbal system is put forth. The storage hypothesis suggested for verbs is extended to other lexical items.


Allocation of attention, reading skills, and deafness.

Brannan and Williams (1987) found that poor readers cannot successfully utilize parafoveal cues to identify letter targets. Whether a similar deficit in the use of cue information occurs in deaf poor readers and whether it is only specific to processes that capture attention automatically were investigated in congenitally deaf young adults classified as poor or good readers and hearing controls classified as good readers. Subjects were presented with central or parafoveal cues that varied in cue validity probability, followed by letter targets presented to the left or right of fixation. The reaction time data analyses showed significant main effects for cue type and cue location and significant interactions among cue type, cue location, cue validity probability, and visual field. No significant main effect or interactions involving groups were found. These results raise the possibility that reading difficulties associated with deafness do no involve a deficit in the visual attentional system of deaf people. They also confirm that parafoveal cues are more effective than central cues in capturing attention.


Can residual lexical knowledge concern word form rather than word meaning?

We described a patient with a dramatic deficit of both word comprehension and naming but with good preservation of visual pictorial semantics. On word-picture matching, his performances were slightly better than expected based on the observed lexical semantic disorder; in addition, the patient, who maintained good preservation of his underlying phonology, showed a tendency to point to the picture phonologically related to the target. In order to interpret these data, we advanced the hypothesis that the patient, in spite of his virtually complete inability to name, would be able, in a word-picture matching task, to "covertly" (i.e., preverbally) retrieve the name from the picture and to use this name to attempt a match with the phonological form of the stimulus word. This mechanism, that we called "phonological" comprehension, would allow the identification of the correct target and would explain the choice of the phonologically related foil that was sometimes selected.


Rapid automatized naming and gesture by normal and language-impaired children.

This study investigates whether language-impaired (LI) children show deficits in rapid automatized naming and whether RAN performance is specific to verbal output (or to rapid motor output in general). A total of 67 LI and 54 age-matched control children were tested with the Rapid Automatized Naming (RAN) test (Denckla & Rudel, 1976) and with a manual version of the RAN (RAN-manual) in which subjects were required to provide a nonverbal, pantomime response. Subjects also completed tests of rapid oral and manual sequencing skills and standardized tests of reading ability. Each subject was tested at 4, 6, and 8 years old. The results showed that LI children perform significantly poorer on both versions of the RAN than age-matched controls. Correlations between RAN scores and tests of reading ability were significant for normal and LI subjects and were particularly high for 8-year-old LI children. RAN-manual scores also correlated with 8-year-old LI children's reading scores. Further, RAN and RAN-manual scores for the LI children correlated significantly with these children's manual sequencing abilities, whereas this was not the case for the control subjects. These findings suggest that LI children's rapid sequential processing deficits are not limited to verbal output, but also generalize to other motoric domains.


Morphologic agrammatism following a right hemisphere stroke in a dextral patient.

There is evidence of two major components of grammatic function in the brain: (1) morphologic, probably based in the postcentral perisylvian cortex, encompassing the selection of individual words and inflectional endings according to the rules of grammar; and (2) syntactic, probably based in the frontal lobes, encompassing construction of the overall structure of a sentence (syntax) to match the concept being considered. We present a stroke patient with impaired morphology but, unlike Broca's aphasics, relative sparing of syntax. He omitted 43% of articles, 40% of complementizers, 20% of pronouns, 27% of semantically marked prepositions, 43% of purely grammatic prepositions, and 22% of auxiliary verbs, but his average sentence length was 9.8 words and 64% of his sentences contained embedded clauses. He frequently intermingled two sentences to convey a given concept, juxtaposing words in grammatically unacceptable ways. This intermingling may represent either a grammatic "conduite d'approche," or a failure of the filtering function of a defective morphologic processor. His great difficulty in completing syntactic frames suggests that a more general form of the processes underlying grammatic morphology may play an important role in phrase structure generation.


Effects of semantic context and event-related potentials: N400 correlates with inhibition effect.

Two experiments investigated the modulation of event-related brain potentials (ERPs) by semantic context. A prime-target pair was visually presented in each trial of a lexical decision task. For word targets, three types of relatedness conditions were employed: (1) Related word condition (e.g., school-teacher); (2) Neutral word condition (e.g., [symbol: see text] - number); (3) Unrelated word c((e.g., hospital-potato). In Experiment 1, the reaction time for unrelated targets was longer than that for neutral targets (inhibition effect) which was longer than that for related targets (facilitation effect). The N400 amplitude in the unrelated targets was larger compared to those in the related and neutral targets, which did not differ. In Experiment 2, where only the facilitation effect was obtained, the N400 amplitude did not differ among conditions.


Why are kana words named faster than kanji words?

Feldman and Turvey (1980) found that colors conventionally written in kanji (a logo-graphic script) are named slower than are the unconventional kana (a syllabic script) transcriptions of the kanji color words. This surprising finding was attributed to the closer relation of kana to phonology, which is consonant with the general dual-route theory. However, the present study has shown that kanji numerals are named faster than are the corresponding kana numerals. A hypothesis involving selection difficulty inherent in most kanji is presented to explain those apparently conflicting results. Some implications for further research on the kanji versus kana issue are also discussed.


Interhemispheric dissociation of expressive and receptive language functions in patients with complex-partial seizures: an amobarbital study.

Bilateral intracarotid amobarbital procedures (IAP) were performed in 144 patients with medically intractable complex-partial seizures. As a result of language testing, 29 patients (20.1%) were found to have bilateral language representation to different degrees. In four (2.8%) of these patients--all right-handers with early onset of epilepsy and/or evidence of early brain damage--there was strong evidence of an interhemispheric dissociation of expressive and receptive language functions. Two of these patients had circumscribed temporal foci (one left, one right), and receptive language functions were represented in the hemisphere contralateral to the focus. One patient with a right frontal focus showed left-hemisphere dominance for expressive functions, while the fourth patient exhibited left-hemisphere dominance for receptive functions associated with a right temporo-parietal focus. It is argued that in these four cases the circumscribed functional and/or structural impairments have led to a shift of the anatomically associated language functions to the opposite hemisphere (rather than to neighboring regions of the same hemisphere). These findings substantiate the hypothesis that in special circumstances the anterior (expressive) language area can be located in one hemisphere and the posterior (receptive) area in the other.


Contribution of articulatory rehearsal to short-term memory: evidence from a case of selective disruption.

We describe a brain-damaged patient with disturbed articulatory rehearsal in whom all predictions derived from a working memory model were fulfilled. The patient showed a reduced verbal span, no word-length effect on immediate recall in both the visual or the auditory modalities, no phonological similarity effect in the visual modality, and no effect of articulatory suppression. A slowed overt articulation rate provided independent evidence for disrupted articulatory rehearsal. The other components of working memory, the visuospatial scratch-pad, phonological storage system, and central executive, were functional. The selectivity of the deficit can be taken as evidence for the specific role of articulatory rehearsal in working memory.


Sensitivity to inflectional morphology in aphasia: a real-time processing perspective.

The present study investigates Broca's aphasics' sensitivity to morphological information in an on-line task. German is used as the test language because it is highly inflected. Results from two word monitoring experiments show first that Broca's patients like normal controls are sensitive to the presence of a contextually incorrect inflection. Contrary to normals, they are, however, not sensitive to the absence of an obligatory inflection even when its presence is syntactically highly constrained. Second, they reveal that Broca's aphasics are only sensitive to the presence of an incorrect inflection when it functions as a marker of lexical category (noun vs. verb) and not when it functions as a diacritical marker (second person singular vs. third person singular). The results are taken as evidence for the claim that Broca's aphasics are impaired in the ability to process the full syntactic information encoded in closed class elements in a fast, automatic, and obligatory way.


Could an autonomous syntax module have evolved?

Darwinian evolution necessitates a contribution to reproductive fitness. Recent studies of aphasia and Parkinson's disease show that functional syntactic ability involves neural structures that also are involved in speech motor control and nonlinguistic cognition. The evolution or presence of an autonomous syntax module is, therefore, implausible.


[Experimental method for the definition of intercalation of compounds in DNA].

Intercalation of aromatic compounds into DNA can be appreciated by using, in a complementary way, fibre X-ray diffraction and measurement of variations of the fibre dimensions. The different behaviours resulting from an actual intercalation or an association of small molecules into the DNA grooves can be distinguished by this experimental method which provides significant results for proflavine, ethidium bromide, a platinum compound, 9-aminoacridine and ellipticine.


[Quantitative determination method of nucleic acids by enzymatic amplification (PCR method) to saturation].

We describe here conditions under which the enzymatic amplification of DNA using the polymerase chain reaction (PCR) is quantitative, even when the amplification reaction is run to saturation. DNA in the sample to analyze is co-amplified with known quantities of an internal standard, namely a DNA molecule whose sequence or length differs from that of the sample DNA by only a few base pairs. The two amplification products are detected as run-off products elongated from one or several additional labelled, primers. The ratio between the two signals provides a precise estimate of the amount of specific DNA in the sample to analyze.


[Demonstration of prolactin messenger RNA after amplification in the brain in rats].

By means of immunocytochemistry, a central neuronal network containing a prolactin-like substance has been described in the rat. In order to demonstrate the synthesis of this peptide in these cells, we examined the presence of prolactin messenger RNA (PRL mRNA) in several brain samples including the pituitary gland. Amplification of the PRL mRNA was performed by the polymerase chain reaction technique, followed by southern blotting and hybridization with a specific oligonucleotide. Results showed the presence of the expected cDNA (468 bp) in the hypothalamus. Another cDNA with a lower molecular weight was also observed.


Marketing dentistry: a pilot study in Dudley.

This study was an attempt to persuade non-users or irregular users of dental services to change their behaviour and visit the dentist more regularly. The task was divided into two main parts. One was a promotion campaign undertaken in the Borough of Dudley in the West Midlands and the other a professional development programme for the dentists practising in the same area. The professional development campaign was designed to make the practitioners aware of the barriers to dental care which are perceived by patients. It was undertaken through a series of workshops on various aspects of practice development and promotion to which the staff of all the dental practices in Dudley were invited. Thirty-nine out of a total of forty-one accepted the invitation and attended some or all of the programme. In addition to the workshops members of the research team visited each of the participating practices regularly to discuss aspects of the programme and to record progress. The practitioners had varied attitudes to marketing and varied learning styles, and therefore they had different expectations of the nature and purpose of professional development. The majority attended solely to learn about the promotion campaign. There were also varying perceptions of patient recruitment and retention. None saw this as a serious problem. However, even before the new National Health Service contract for general dental practitioners there was the growing realisation that in the future there would be competition between practices and that this could be a reason for considering recruitment and the retention of patients more carefully. This was considered by many of the dentists, but not all, to be a problem of patient behaviour, linked with a degree of fatalism, and that nothing much could be done about it. There was a reluctance to change and the fear of the risks involved led a number of the general dental practitioners to identify and emphasise the difficulties in making new developments rather than their benefits. Only one quarter of the practices made any changes and they tended to prefer quick solutions rather than basic development. The experience gained in this part of the study indicated that in the future professional development should be considered in terms of the dentist's perception of the costs and the benefits; direct costs, opportunity costs, and the prospect of effecting change.(ABSTRACT TRUNCATED AT 400 WORDS)


Sulfite-containing Canadian pharmaceutical products available in 1991.

To compile an inclusive list of Canadian pharmaceutical products available in 1991 that contained sulfites. Written and oral responses from 94 pharmaceutical companies selected from the 1989 Compendium of Pharmaceuticals and Specialties. A list of sulfite-containing pharmaceutical products was compiled from data supplied by the 90 responding companies. Companies whose products contained no sulfites were separately identified. Sulfites are present in many pharmaceutical products and are one of many excipients and additives that have been reported to cause severe adverse reactions. The provided list should be a useful aid for health care practitioners when prescribing pharmaceutical products for sulfite-sensitive patients.


Cytosol and serum ferritin in breast carcinoma.

This study was undertaken to determine tissue and serum ferritin levels in different stages of breast carcinoma. Eighty-nine cases have been evaluated, the groups investigated being breast carcinoma, benign breast disease and healthy controls. Ferritin levels in both the sera and the tissue cytosols were measured by an enzyme immunoassay method, while total proteins were assayed by Lowry's procedure and the ferritin concentrations given in ng ferritin/mg cytosol protein. No significant difference has been determined for serum ferritin between any of the groups studied, while the tissue cytosol ferritins were found to be 91.6 +/- 50.9, 565.0 +/- 48.3, 142.7 +/- 93.3, 683.3 +/- 212.9 and 655.5 +/- 100.4 ng/mg cytosol protein for the benign, malign (global), malign (stage I), malign (stage II) and malign (stage III) groups, respectively. The differences between the malign groups and the benign group were found to be highly significant (P < 0.001) except for the stage I subgroup, which was fairly significant (P < 0.05). A sensitivity of 90% was evaluated for tissue cytosol ferritin in breast carcinoma, the 'intra-patient' sensitivity being 100%. In conclusion, we state that tissue ferritin is more valuable than serum ferritin as a tumour marker of diagnosis for breast carcinoma.


Early manifestations of induced prostate tumors in Lobund-Wistar rats.

Lobund-Wistar (L-W) rats are susceptible to spontaneous and induced metastasizing prostate cancer. In the search for the initial site of tumor development in the induced disease, rats at risk were examined periodically to acquire this information. In the course of 12 months after the onset of the induction of prostate cancer in L-W rats, 14 of 40 rats (35%) developed visible tumors in the anterior and in the dorso-lateral lobes of the gland. The prostate tumors appeared at 7 months and thereafter. Two of the tumor-bearing rats had developed, in addition, a visible neoplasm in the seminal vesicle. None of the rats with small early tumors had developed visible metastatic tumors, which were manifested in rats with large tumors.


Formation of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in male Fischer-344 rats.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) is known to induce colon tumors in male Fischer-344 rats. Using 32P-postlabeling assays, we have examined PhIP-DNA adduct formation in various organs and white blood cells (WBCs) of the male Fischer-344 rat 24 h after a single oral dose of 0, 0.5, 5 or 50 mg PhIP/kg. Three PhIP-DNA adducts were detected in WBCs and in all organs, except in the liver and stomach which had only two adducts. The extent of adduct formation was dose-related, but at 0.5 mg/kg no adducts could be detected in any of the organs. At 50 mg/kg, adduct levels, expressed as relative adduct labeling values (RAL x 10(7), or adducts per 10(7) nucleotides assuming complete labeling) were highest in the large intestine (5.66), followed by WBCs (5.04), stomach (1.44), small intestine (1.32), kidney (1.16), liver (0.67) and lungs (0.52). It is concluded that orally administered PhIP forms high levels of specific DNA adducts in the large intestine, the target organ in PhIP carcinogenesis in the male Fischer-344 rat, and that the high level of adducts in WBCs indicates that significant amounts of the ultimate carcinogenic form of PhIP are present in the circulation.


Liposuction surgery and autologous fat transplantation.

Since the importation of liposuction surgery into the United States more than a decade ago, we have witnessed a number of major technique changes and practice trends occur. One of us (L.M.F.) was the first dermatologic surgeon to undergo the "lipsuction experience" (Paris, 1977) under the tutelage of Giorgio and Arpad Fisher and Pierre Fournier, and another (R.S.N.) the first to undergo training with Yves Illouz (also Paris). All three co-workers have served on teaching faculties of both the International and American Societies for Dermatologic Surgery, the American Society of Liposuction Surgery, and the American Academy of Cosmetic Surgery, have performed many hundreds of procedures, and have lectured/published on this subject on repeated occasions. We recognize certain vital changes and expansions have occurred during the past decade, and share our impressions of these with you.


N-ethyl-N-nitrosourea induced brain tumors in rats monitored by nuclear magnetic resonance imaging, plasma proton nuclear magnetic resonance spectroscopy and microscopy.

Characteristic slow growing brain gliomas were induced in rats by a single subcutaneous injection of N-ethyl-N-nitrosourea (ENU) within 24 h of birth. A parallel control group of rats was injected with saline. Seven treated rats developed gliomas within 2 years. Periodic nuclear magnetic resonance imaging (MRI) of the brain in 3-mm slices at 1.5 Tesla and monthly plasma sampling for proton magnetic resonance spectroscopy (MRS) at 360 MHz were started 6 months after the injection of ENU. In the MRS experiments, the Fossel index, average of the line widths of the methylene and methyl peaks at 360 MHz, was determined from half-line widths of methyl and methylene peaks at 0.8 ppm and 1.3 ppm. In five of the ENU injected animals that developed histologically verified brain tumors, these were also observed by MRI without contrast agents. There was no consistent correlation between the imaged tumors and the Fossel index obtained through MRS during the course of the study where repeated observations were performed on individual animals, nor was there any consistent statistical difference in the Fossel index between ENU-treated and control animals. The results of this study demonstrate that slowly developing carcinogen-induced brain tumors in rats can be successfully and reliably monitored noninvasively by MRI but not by MRS of plasma.


Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.


Lack of therapeutic effects of platelet activating factor antagonists in WEHI-3B leukemia, human xenotransplanted colorectal and lung cancer and Lewis-lung tumor in vivo.

Four new antagonists of platelet activating factor (PAF) from two different chemical classes (imidazoisoquinolines: SDZ 62-434, SDZ 63-135, SDZ 62-759; imidazopiperidines: SDZ 62-293) were tested for in vivo therapeutic activity in various tumor models including the murine myelomonocytic leukemia WEHl-3B, xenografts of human colon (HTB 38) and lung (HTB 119) cancer cell lines and the murine Lewis-lung tumor. After intraperitoneal (i.p.) injection of 1 x 10(3), 5 x 10(3) and 1 x 10(4) WEHl-3B cells into Balb/c mice, the drugs were given per os (p.o.) or i.p. over 6-14 days. Drug doses were pushed to exceed the lethal dose for 10% of the animals (LD10) and ranged from 1 to 100 mg/kg daily for p.o. treatment and from 1 to 75 mg/kg daily for i.p. treatment. In the xenotransplants and the Lewis-lung tumor experiments, PAF antagonists were given i.p. to nude Balb/c and C57 Black mice after intracutaneous (i.c.) tumor cell inoculation. None of the four compounds induced reproducible prolongation of life span, significant numbers of long term survivors, reduction of tumor size, or delay of tumor growth in any of the therapeutic models. Oral SDZ 62-759 had some activity in experiments in which there was slow WEHl-38 tumor growth in the controls. Toxicity of equivalent drugs doses was higher in the i.p. than in the p.o. schedules.


Changes of DNA methylation in protooncogenes in the process of radiation-induced transformation of mouse m5S/1M cells in vitro.

To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process, methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M. All transformants examined revealed an alteration in DNA methylation in some of the genes, although these changes were variable among them. A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes, whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes. Resultant data indicate that the alteration of DNA methylation is closely related to transformation process, yet how this involvement occurs is complex and remains unclear.


Nitrogen analogues of haematoporphyrin and haematoporphyrin derivative.

The preparation of a number of amines related to haematoporphyrin (HP) and haematoporphyrin derivative (HPD) have been studied and their composition and structure discussed through examination of their 1H, 13C NMR and mass spectral data and other physical properties. In vitro biological studies have been carried out and have shown these amines to have a similar photodynamic efficiency to that of HPD. One of these showed cytotoxic properties at exceptionally low light energy levels.


The induction of ornithine decarboxylase by ornithine takes place at post-transcriptional level in perifused Ehrlich carcinoma cells.

The increase in ODC activity during perifusion of Ehrlich carcinoma cells with 0.5 mM ornithine correlates with an increase in 'de novo' synthetized ODC protein. ODC synthesis was followed by immunoprecipitation of equal quantities of 35S-labelled proteins after 10, 20 and 30 min of labelling. In addition, the rate of 'de novo' protein synthesis is very much elevated in cells perifused with saline buffer supplemented with 0.5 mM ornithine than in cells perifused with the saline buffer only. In spite of the higher specific ODC activity observed in cells perifused with saline buffer plus 0.5 mM ornithine respect to cells perifused with only saline buffer for 3.5 h, no elevation in ODC mRNA was observed when the cells were perifused in the presence of 0.5 mM ornithine.


Antitumor effect and toxicity of two new active-site-directed irreversible ornithine decarboxylase and extrahepatic arginase inhibitors.

The irreversible ornithine decarboxylase and extrahepatic arginase inhibitors (+)-S-2-amino-5-iodoacetamidopentanoic acid (2-AIPA) and (+)-S-2-amino-6-iodoacetamidohexanoic acid (2-AIHA) were evaluated. The LD50 tests were made in rats and mice using both compounds. Rats and mice were treated with either 2-AIPA or 2-AIHA i.p. for a period of 180 days. The treated animals showed a decrease of total serum proteins and increased ALT and AST levels. CK was also modified but inversely related to dose. Protection tests were carried out using L5178Y mouse lymphosarcoma. The mean survival time for each treated group was calculated and the percentage T/C was determined. For 2-AIPA it was 170 and for 2-AIHA it was 210 at 15 mg/kg.


Aphidicolin selectively kills neuroblastoma cells in vitro.

Aphidicolin is a tetracyclic diterpene antibiotic which is known to inhibit the growth of eucaryotic cells by reversible binding to DNA polymerase alpha without significant effect on cell viability in most common human cell lines. We observed that aphidicolin at a concentration of 5 x 10(-7) M kills all cells of four human neuroblastoma cell lines. In contrast, viability of normal human embryonal cells and of human continuous cell lines including HeLa, H9, A549 and Caco-2 was influenced only moderately by aphidicolin. In addition, neuroblastoma cells were killed after treatment with 5 x 10(-7) M aphidicolin in cocultures with normal embryonal cells which continued to proliferate after removal of aphidicolin. These results show that aphidicolin provides an agent which selectively kills neuroblastoma cells in vitro.


Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-C7 cells.

Seven compounds, which included some naturally occurring dietary substances, were tested for their inhibitory effects on growth and metabolism of human leukemic CEM-C1 and CEM-C7 cell lines. Among the active compounds the naturally occurring dietary constituents were found to be the most active. The strongest inhibitory effects were observed with 3',4',5,7-tetrahydroxy-flavone (luteolin) and 4,4'-dihydroxychalcone. 31P-NMR spectra of cells incubated for 24 h with 30 microM of either of these compounds show complete ATP depletion. Also glucose uptake by the cells as measured by 13C-NMR is completely inhibited by these compounds. These results may be relevant to the tumor suppressing activity of bioflavonoids and the role of these compounds in chemoprevention.


The cytotoxic properties of malachite green are associated with the increased demethylase, aryl hydrocarbon hydroxylase and lipid peroxidation in primary cultures of Syrian hamster embryo cells.

Malachite green (MG), an industrial compound and potential environmental health hazard, is highly cytotoxic to mammalian cells in culture. In an attempt to define the biochemical basis, we have compared the cytotoxic effects and morphological alterations shown by MG in Syrian hamster embryo (SHE) cells with the levels of lipid peroxidation and the activities of aryl hydrocarbon hydroxylase, aminopyrine-N-demethylase, superoxide dismutase and catalase. Treatment of SHE cells with MG results into an induction of the mono-oxygenase system, lipid peroxidation and catalase in a dose-dependent way, indicating the formation of reactive free radicals. Accordingly, the possible involvement of reactive free radicals especially hydroxymethyl radicals in the observed high cytotoxicity due to exposure to MG is postulated.


[Present possibilities of prenatal diagnosis of Fabry's disease].

Fabry's disease (angiokeratoma corporis diffusum universale) is an inborn error of metabolism, which is based on a shortage in the cumulation of glycosphingolipids in endothelial and epithelial cells of glomeruli, vascular endothelia and in ganglion cells with subsequent severe organ damage. Heredity is X-linked recessive. In the submitted paper the authors present a case-history of a family where three men were affected and carriership was confirmed in five women. During the first pregnancy one of them a successful prenatal diagnosis was made from cultivated amniotic fluid cells. Chromosomal examination revealed female sex and the levels of the alpha-galactosidase A were established in cultivated cells. A healthy girl was delivered.


[Relation of retinopathy to puberty and sex in insulin-dependent diabetics].

The authors examined by chromatoophtalmoscopy the optic fundus in 302 children and adolescents with insulin dependent diabetes. They classified the findings according to their own classification and selected from the entire number two groups of patients where the common sign was persistence of diabetes for a period of 5-8 years. Group A (n = 32) was, however, formed only by children under 11 years, while group B (n = 35) comprised adolescents aged 16-20 years. In group A the authors found incipient retinopathy in 12.5% children, in group B in 48.6% of the patients (p < 0.005). The degree of retinopathy was also more severe in older subjects. Comparison of the whole group by sex did not reveal a significant relationship (p > 0.05). In the conclusion the authors draw attention to the necessity of careful follow up of the optic finding in child diabetics, in particular during adolescence.


[Evaluation of a peptide preparation (milk) in the care of infants with various gastrointestinal intolerances].

The use of an enteral peptide feed based on hydrolysed whey protein (Pepti Junior, Cow and Gate/Nutricia Ltd.) was evaluated in 17 patients with complex GIT intolerance. Nine post surgical neonates were weaned onto the feed either following a period of parenteral nutrition (8) or after demonstrating intolerance of both breast milk and a lactose-free soy based formula. Eight infants admitted to a gastroenterology ward with multiple protein intolerances were also studied. Patients were fed to their nutritional requirements with the milk containing/100 ml; 67 kcal (280 kJ), 2.0 g protein, 3.7 g fat (50% MCT, 50% vegetable oil) and 6.7 g carbohydrate (98% maltodextrins). Patients were maintained on the feed for 7-45 weeks (mean 21 weeks). Full nutritional support was possible with the new formula in all but 2 children who had jejunostomies; in these patients > 50% of nutritional requirement were supplied by the enteral feed. All patients gained weight (mean 0.16 kg/week) (SD 0.09). With the exception of subclinical selenium deficiency, no abnormalities of haematological, biochemical or vitamin states were observed. Post prandial plasma amino-acid concentrations were within acceptable limits and similar to those reported on standard whey based infant formulae. The feed appeared well tolerated in infants with GIT intolerances with no major complications in long term usage.


[Vaccination in children with neurologic diseases].

The authors explain the main risks of immunization of children with affections of the central nervous system. For practical reasons the diseases are divided into four groups: 1. Perinatal affections and developmental diseases of the CNS. 2. Neurodegenerative and metabolic affections of the CNS. 3. Acquired affections of the CNS. 4. Paroxysmal diseases. The objective of the paper is to reduce the risk of postvaccination complications in children with serious affections of the CNS, while ensuring the contemporary necessary vaccination rate of the population.


[Prevention and reduction of psychological and motor defects in childhood. II. Advantages and risks of longitudinal studies in pediatrics].

The presented investigation characterized the general types of longitudinal projects focused on the long-term follow-up of children in health and disease. First the authors outline briefly the principles and disadvantages of cross-sectional projects. Then follows an account on the methodology of longitudinal projects, evaluation of their advantages and their multiple risks. Approximately 50 years of experience with longitudinal projects indicate that this pretentious research strategy can provide an overall view of developmental trends as regards changes of the health status in the ontogenetic perspective and contribute to the improvement of health care of the child population.


[Hyperechogenic renal pyramids in children].

The authors describe the case-histories of four children with hyperechogenic renal pyramids. These children are followed up at the First Paediatric Clinic in Bratislava.


[Care of foreskin constriction in children].

The suspicion of phimosis is more frequent than it's real occurrence. The diagnosis of phimosis is often used for another nonobstructive conditions of prepuce--conglutination or tight prepuce. The early operation is necessary just in cases of real phimosis, whereas conservative approach is recommended in cases of conglutination and tight prepuce. Physiological development can bring spontaneous improvement in these children. In boys with persisting tight prepuce operation is indicated.


[Broncho-Vax and IRS 19 in the treatment of recurrent respiratory tract inflammation in children].

A group of 80 children with relapsing infections of the respiratory pathways (a minimum of three during the previous period) were investigated during the first year of the investigation (1987-88) with regard to the number and duration of the disease, absence from school, antibiotic consumption and use of bronchodilatating agents. In the subsequent year 1988-1989 the children were divided into a group treated with Broncho-Vaxom, a group treated with IRS 19 and a control group. Before the onset of administration and then every two months functional examinations of the lungs were made in the children. At the beginning of treatment and after its termination some immunological and laboratory values were examined. The effect of treatment was evaluated also subjectively by the parents and physician. Both preparations had a favourable effect on prevention of relapses of respiratory infections. This effects was more favourable after Broncho-Vaxom, in particular in prevention of inflammations of the lower respiratory pathways. IRS 19 eliminates relapses of infections of the upper respiratory pathways sooner.


[The therapeutic effect of tiapride in the treatment of dyskinetic forms of cerebral palsy in children].

The authors administered tiaprid (Tiapridal, Delagrange), to six patients with the dyskinetic form of cerebral palsy, mean dose 11.4 mg/kg/day in three portions. In five instances clinical improvement was recorded, all patients improved as regards tests of practical skills. On the EEG during tiaprid treatment reduction of muscular artefacts was recorded. By means of an original testing device the authors revealed that tiaprid exerts a relatively small influence on the reaction time in response to a light stimulus but that it prolongs significantly the time needed for the motor performance proper. More marked undesirable effects were manifested in one patient (subjectively reported short-term change of sensitivity of the lower extremities and increased amplitude of dyskinesias). The authors emphasize the positive properties of the preparation and recommend tiaprid as the drug of first choice for pharmacological inhibition of extrapyramidal hyperkinesias in patients with the dyskinetic form of cerebral palsy in children.


[Outdoor camp schools from the aspect of mental hygiene].

A survey by means of questionnaires revealed a positive attitude of parents and teachers to outdoor schools of children from nursery and primary schools. While parents prefer three-week stays, teachers are definitely in favour of two-week stays. As far as the subjective experience of children is concerned, analysis of the answers of a total of 1200 primary school children (answers classified by sex, age and period of outdoor school) proved the primary correlation with age and thus also with the level of adaptation mechanisms. The position is most pretentious for pupils of the first and second form of primary schools who must overcome two types of new stresses: separation from parents and demands of the teaching process. Boys are at greater risk than girls as their risk of psychic subdeprivation is greater than in girls. Special care must be devoted maladjusted who in the teachers opinion account for 4% of primary school children and 1.7% nursery school children.


The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism.

We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men. T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity. Five endurance-trained athletes and five sedentary controls (mean +/- SD VO2 max = 48.2 +/- 7.1 vs 23.2 +/- 4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function. Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non-compartmental analysis. When normalized for lean body mass, all kinetic parameters were 25-38% greater in the athletic group compared to controls (P < 0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r = +0.69 to +0.79; P < 0.05). Metabolic clearance rate was positively correlated to a non-significant degree. These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance-trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical conditioning.


Subtle changes in serum thyrotrophin (TSH) and sex-hormone-binding globulin (SHBG) levels during long-term follow-up after radioactive iodine in multinodular non-toxic goitre.

We investigated possible changes in the pituitary-thyroid axis after radioactive iodine (RAI) treatment of multinodular non-toxic goitre. Consecutive patients with multinodular non-toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment. Twenty-three women with multinodular non-toxic goitre were followed after treatment with RAI. Free T4 index (FT4I), FT3I, free T4, SHBG (immunoradiometric assay), and a third-generation TSH assay (chemiluminetric assay) TSH were measured. Three weeks after RAI treatment TSH had decreased and SHBG increased (P < 0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P < 0.01) and gradual decrease in SHBG (P < 0.02). No changes in FT4I, FT3I, or free T4 were found. A third-generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non-toxic goitre. We demonstrated that changes in the pituitary-thyroid axis continue for a long time after RAI treatment of multinodular non-toxic goitre. These patients should be followed up in order to detect possible late hypothyroidism.


Genetic linkage studies of X-linked hypophosphataemic rickets in a Saudi Arabian family.

OBJECTIVE, PATIENTS AND DESIGN: X-linked hypophosphataemic rickets (HYP) is the most common inherited form of rickets and the gene causing this disorder has been localized to Xp22.3-p21.3 by linkage studies of affected families of Northern European origin. In addition, the locus order Xpter-(DXS207-DXS43,DXS197)-HYP-DXS41-X cen has been established and the flanking markers are useful for the presymptomatic diagnosis of HYP. However, a recent study indicates locus heterogeneity and this may hinder the use of the flanking markers for presymptomatic diagnosis in additional families and in particular those from different populations. We have therefore investigated one Saudi-Arabian family (13 affected and six unaffected members) with hypophosphataemic rickets for linkage to these and other X-linked markers. A total of 17 cloned human X chromosome sequences identifying restriction fragment length polymorphisms were used to localize the mutant gene causing this disorder in the Saudi Arabian family. Nine (four from Xp and five from Xq) of the 17 X-linked DNA probes proved informative and linkage was established between HYP and the DSX41 locus, peak LOD score = 4.22 (recombination fraction, theta = 0.00). A positive peak LOD score of 2.32 (theta = 0.05) was also obtained between HYP and the DXS207 locus. Thus, the HYP gene in this Saudi Arabian family is linked to two of the four flanking markers which demonstrated linkage in families of Northern European origin. We conclude that the X-linked hypophosphataemic rickets gene in a Saudi Arabian family is located in the Xp22.3-p21.3, a region where this gene has previously been mapped by linkage studies of families of Northern European origin. Our studies have not demonstrated locus heterogeneity, so the flanking markers for HYP previously established in the families of Northern-European origin will be useful in the genetic counselling and presymptomatic diagnosis of this disorder in the Saudi Arabian family.


Normal pattern of parathyroid response to blood calcium lowering in primary hyperparathyroidism: a citrate clamp study.

The objective of the present study was to elucidate the parathyroid responsiveness by measurements of blood ionized calcium and serum intact parathyroid hormone (PTH) concentrations, before and during trisodium citrate induced hypocalcaemia. Sixteen patients with primary hyperparathyroidism and 32 healthy volunteers. Blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level for 2 hours by blood ionized calcium controlled trisodium citrate infusion. Serum PTH(1-84) was measured by an immunoradiometric assay. In patients and controls, baseline measurements of blood ionized calcium were 1.39 +/- 0.07 vs 1.24 +/- 0.04 mmol/l (mean +/- SD) (P < 0.001) and of serum PTH (1-84) 9.7 +/- 5.4 vs 3.2 +/- 1.1 pmol/l (P < 0.001). During a trisodium citrate clamp, serum PTH(1-84) rose to a maximal concentration after 5-10 minutes in both groups, the patients to 2-10 times baseline, whereas controls rose to 4-7 times baseline values. In both groups the peak of serum PTH(1-84) declined to a steady state concentration around 2-4 times baseline. In conclusion, adenoma cells seem to react in almost the same way as normal parathyroid cells. They respond to initiation of hypocalcaemia by the release of preformed PTH(1-84), and continue to secrete increased amounts of PTH(1-84) during the maintenance of relative hypocalcaemia. The increased baseline concentrations of blood ionized calcium and serum PTH(1-84) and the serum PTH(1-84) response during blood ionized calcium lowering all suggest a shift upwards in the calcium set point.


The effect of morphine and naloxone administration on plasma oxytocin concentrations in the first stage of labour.

We investigated the effect of an opiate (morphine) and an opiate antagonist (naloxone) on the maternal secretion of oxytocin in the first stage of labour. Patients were randomized to receive either morphine 5 mg (n = 9), naloxone 1.2 mg (n = 10) or sterile water (n = 9) which was injected intravenously. Healthy women in the first stage of labour between 3 and 6 cm dilated with no prior analgesia or oxytocin administration were recruited for the study. Peripheral maternal oxytocin levels were measured by radioimmunoassay for 15 minutes before and 15 minutes after administration of the assigned substance. Sampling was at 2.5 minute intervals. Significant reduction in the mean oxytocin concentration was found in the patients who received morphine (-2.62 pmol/l/sample) but no change was found in the naloxone group (+0.57 pmol/l/sample) when compared with controls (+0.64 pmol/l/sample). Maternal oxytocin secretion is inhibited by exogenous opiates in the first stage of labour while an effect of opiate antagonism was not demonstrated.


A randomized double blind placebo controlled trial of the effects on bone metabolism of the combination of nafarelin acetate and norethisterone.

We observed the effects on bone metabolism of the addition of different doses of oral norethisterone during treatment with the GnRH agonist nafarelin (Synarel, Syntex). Ninety-four women with a subjective complaint of heavy menstrual blood loss or objective evidence of endometriosis received intra-nasal nafarelin 400 micrograms daily for 6 months and also received, in a randomized, double blind manner, either 0.7 mg (n = 24), 1.4 mg (n = 23) or 2.45 mg (n = 23) of oral norethisterone or placebo (n = 24) daily. Follow-up was continued for a further 6 months after treatment. Thirty-one patients (33%) left the study prematurely and three patients were non-compliant with the study drug. By 6 months significant increases in urinary calcium/creatinine ratio were seen, compared to baseline, in the nafareline and placebo (P = 0.001, n = 14), 0.7 mg (P = 0.04, n = 13) and 1.4 mg norethisterone groups (P = 0.009, n = 17) but not in the nafarelin or 2.45 mg norethisterone groups (P = 0.72, n = 16). Densitometry of the spine, however, showed decreases at 6 months in all groups: 6.14% (P = 0.0004, n = 11), 5.46% n = 0.0006, n = 13), 3.93% (P = 0.008, n = 14) and 4.04% (P = 0.004, n = 16) for the groups receiving nafarelin and placebo, nafarelin and norethisterone 0.7, 1.4 and 2.45 mg respectively. Six months after stopping nafarelin, with or without norethisterone, bone mass was not different from baseline. The concomitant daily use of up to 2.45 mg of norethisterone does not eliminate the bone demineralization seen during GnRH agonist therapy with nafarelin in premenopausal women.


The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects.

We have investigated the late GH rise occurring 3-5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects. Placebo or 75 g oral glucose was given to the normal subjects 3 hours before 120 mg oral pyridostigmine or placebo. Four tests were carried out at random. (0 min) + placebo (180 min); test 2: glucose (0 min) + placebo (180 min); test 3: placebo (0 min) + pyridostigmine (180 min); test 4: glucose (0 min) + pyridostigmine (180 min). We studied eight normal subjects (four male and four female), ages 19-29 years, body mass indices 18-22 kg/m2. Plasma glucose and serum GH concentrations were measured for 6 hours after oral glucose or placebo administration. Pyridostigmine treatment significantly enhanced the GH releasing effect of prior (3 h) oral glucose. Late GH peak obtained by oral glucose loading rose from (mean +/- SEM) 17.4 +/- 4.6 to 37.2 +/- 9.0 mU/l (P < 0.05) after pyridostigmine, while GH peak following placebo plus pyridostigmine was 12.4 +/- 2.0 mU/l (P < 0.05 vs glucose plus pyridostigmine). The analysis of GH area under curves (AUCs) in the second phase of the tests (180-360 min) confirmed that glucose plus pyridostigmine released a greater amount of GH (4128 +/- 764 mU/l/3h) than glucose (1694 +/- 494 mU/l/3h, P < 0.001) or pyridostigmine alone (1292 +/- 150 mU/I/3h, P < 0.001). Pyridostigmine, an indirect cholinergic drug likely to inhibit somatostatin secretion from the hypothalamus, enhanced the late GH releasing activity of oral glucose. There is evidence that glucose suppresses plasma GH initially by increasing hypothalamic somatostatin release. This would result in an increase in the pituitary stores of GH. We propose that the delayed GH rise after oral glucose occurs when there is a fall in hypothalamic somatostatinergic tone; this is further reduced by the administration of pyridostigmine. At this time the pituitary stores of GH are released as a consequence of resumption of hypothalamic GHRH activity. This leads to the late GH rise.


Characterization of big, big prolactin in patients with hyperprolactinaemia.

The present study was designed to characterize the clinical findings of patients with macroprolactinaemia (sustained hyperprolactinaemia where the predominant form of prolactin is of large molecular size) and to further assess the bioactivity and structure of big, big prolactin (BB-PRL). The patients with macroprolactinaemia were identified by the domperidone test and by gel filtration of their serum samples. The bioactivity of sera and fractions containing BB-PRL was evaluated and the fractions analysed by affinity chromatography and electrophoresis. Eleven patients with hyperprolactinaemia in whom BB-PRL was the predominant form (group 1) were studied. Sera were also examined from eight patients with prolactinomas (group 2). Thirty-one first-degree relatives from patients in group 1 were screened for macroprolactinaemia. Prolactin in the sera and fractions was measured by radioimmunoassay (RIA), immunoradiometric assay (IRMA) and Nb2 cell bioassay (Nb2 BA). The distribution of BB-PRL was also investigated after protein A Sepharose chromatography, immunoprecipitation, SDS-PAGE and Western blotting. (1) Seven out of 11 patients in group 1 had galactorrhoea, menstrual disturbances or both; (2) the ratio Nb2 BA/RIA in whole serum was similar to the ratio found in group 2 patients; (3) the ratios Nb2 BA/RIA and Nb2 BA/IRMA in the BB-PRL fractions obtained after gel filtration were significantly lower than in whole serum (P < 0.003); (4) in group 1 patients, RIA estimates of PRL did not correlate either with Nb2 BA or with IRMA, while Nb2 BA and IRMA were correlated. In group 2 patients, RIA and Nb2 BA were correlated (r = 0.881; P = 0.02); (5) 24-86% of BB-PRL reacted as immunoglobulin-bound PRL as demonstrated by protein A Sepharose and by SDS-PAGE; (6) a high percentage of BB-PRL (54, 49 and 43%), was found in three of the serum samples obtained from 31 first-degree relatives of patients in group 1. Macroprolactinaemia must be suspected not only in patients with asymptomatic hyperprolactinaemia but also in women with galactorrhoea and/or menstrual disturbances who have normal responses to PRL stimulating tests. Our results also suggest that the absence of symptoms in these women is not explained by a lower bioactivity of BB-PRL. Instead, we postulate that due to the high molecular weight, BB-PRL does not easily cross the capillary walls. During gel chromatography either a change in the structure of BB-PRL and/or a removal of substances which potentiate the bioactivity of PRL occurs, explaining the lower bioactivity of fractions containing BB-PRL in comparison with the serum. In this study we demonstrated that at least half (range 24-86%) of BB-PRL behaves as an immunoglobulin-bound PRL. Finally, we found that macroprolactinaemia was not genetically transmitted to first-degree relatives in the majority of the cases studied.


High affinity growth hormone binding protein in plasma of patients with acromegaly and the effect of octreotide treatment.

The objective of this study was to investigate the effect of plasma GH-levels on the high affinity growth hormone binding protein (GHBP). We studied plasma samples of eight patients with acromegaly and eight age and sex matched healthy subjects. Patients with acromegaly were treated with octreotide administered by continuous subcutaneous infusion. Levels of growth hormone binding protein (GHBP) were measured in plasma samples before therapy and 3, 6 and 12 months after starting treatment. During this period, octreotide was administered in doses of 300-800 micrograms/day. The mean dose per patient over the study period ranged from 300 to 575 micrograms/24 h. The GHBP levels of patients with acromegaly were compared with those in the healthy subjects. Bound and free 125I-GH in plasma were measured using FPLC gel chromatography on a Superose 12 column, after an overnight incubation period. The binding data were used for a Scatchard plot analysis. Wilcoxon's signed rank test was used for statistical analysis. We found lower GHBP levels in acromegalic patients (P = 0.01) than in the control subjects. Octreotide treatment resulted in IGF-I levels < 300 micrograms/l in four patients. In these patients GHBP levels increased. We conclude that growth hormone binding protein levels are down regulated in acromegaly, indicating an important role for GH in the regulation of this protein.


Oncogenous osteomalacia and malignancy.

An example of oncogenous osteomalacia is described in association with the rate mesenchymal chondroblastoma. The tumour was characterized with a variety of immunohistochemical antibodies which confirmed its mesenchymal origin. Despite several surgical excisions of local recurrence, plasma 1,25-dihydroxyvitamin D3 concentrations (off treatment) indicate continued tumour activity and the continuing need for vitamin D therapy. This case and two others briefly discussed illustrate some of the difficulties in diagnosis and in achieving a cure in cases of oncogenous osteomalacia. Oncogenous osteomalacia in association with any malignant tumour is rare, there being eight previously recorded cases. Details of these cases are briefly reviewed for comparison. Despite undoubted malignancy our patient has survived 30 years from presentation indicating the benefits of aggressive surgical management.


Pathophysiology of portal hypertension.

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation associated with the development of portosystemic collateral channels, the most important of which are found in lower oesophagus and stomach. Bleeding from these gastro-oesophageal varices represents the major clinical complication and over the last decade there has been considerable interest in the pharmacological management of this condition. The factors underlying the development and maintenance of portal hypertension and the pathogenesis of variceal rupture are as yet not fully understood. Whilst an increase in portal vascular resistance, as a consequence of liver disease, appears to be the primary event in the majority of cases, increasing attention has focused on the potential importance of enhanced circulating levels of vasoactive compounds coupled with a proposed reduction in vascular sensitivity to endogenous vasoconstrictors. Consequently, portal hypertension is now being more widely considered as a multi-organ disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development and maintenance of portal hypertension and considers the pathogenesis of variceal bleeding.


The role of endoscopic sclerotherapy in the management of esophageal varices.

Endoscopic sclerotherapy of esophageal varices has gained worldwide popularity. There is a consensus that sclerotherapy is an effective treatment for temporarily controlling acute variceal hemorrhage. Sclerotherapy has no place in the routine prophylaxis before the index bleed. The role of long-term sclerotherapy to prevent rebleeding is debatable. It is our bias that once patients with cirrhosis suffer a variceal hemorrhage, they should be considered for liver transplantation. If they are not suitable candidates for transplantation and have mild to moderate hepatic dysfunction, then portosystemic shunting provides definitive secondary prophylaxis against rebleeding. Sclerotherapy should be reserved for patients with advanced decompensated cirrhosis.


Surgical therapy of acute esophageal variceal hemorrhage.

Options for the management of patients with acute variceal hemorrhage must be compared for their ability to stop bleeding and prevent rebleeding, for their safety, and for their impact on hepatic reserve. Pharmacologic treatment may stop bleeding in up to 50% of patients, but cannot prevent rebleeding. Balloon tamponade controls bleeding in 90% of patients but is only transiently effective and may cause complications. Immediate sclerotherapy may stop acute bleeding and may provide chronic control with repeated treatments. However, patients who fail to respond to such measures must be submitted for surgical intervention. Emergency portosystemic shunt or esophageal transection represent the current procedures of choice for these patients. Surgery may also prove more cost effective than repeated sclerotherapy as primary therapy in a select group of patients with a high risk of rebleeding. Ultimately, however, primary pharmacologic therapy or hepatic transplantation to correct the pathophysiology underlying the esophageal variceal hemorrhage must be developed and refined if the natural history of this disease is to be substantially altered.


Endoscopic esophageal sclerotherapy: long-term results of the elective procedure.

Chronic endoscopic esophageal sclerotherapy represents a primary technique for the prevention of recurrent bleeding in cirrhotic patients who have already experienced one variceal bleeding episode. 131 patients with portal hypertension and a history of esophageal variceal bleeding underwent endoscopic sclerotherapy. 74 of these patients constituted a subgroup which was singled out for special analysis. In these patients, treatment had been started after conservative management of an acute bleeding episode had stopped the bleeding and follow-up data for at least 6 months were available. 90.5% of these patients had nonalcoholic etiology for their portal hypertension. 60.8% of patients developed recurrent varices and 11.1% had recurrent bleeding from esophageal varices. The bleeding risk index, calculated as the number of hemorrhages/patient/months of follow-up, correlated strongly with the number of previous hemorrhages and inversely with hepatic reserve (Child's class). The bleeding risk index decreased tenfold after sclerotherapeutic obliteration of varices. These data suggest that chronic elective endoscopic sclerotherapy may play a primary role in the management of patients who have bled from esophageal varices.


Bleeding esophageal varices: today's role of portosystemic shunts.

Emergency portosystemic shunting has once again become a significant option in the management of bleeding esophageal varices and portal hypertension. The decision to perform such a shunt and the choice of shunt procedure requires a rational assessment of the pathophysiology and hepatoportal hemodynamics of the patient's disease and the manner in which it is anticipated that the selected procedure may alter portal flow. Since shunt surgery may interfere with hepatic transplantation, the patient's suitability as a future transplant recipient must also be considered in choosing a shunt procedure. Furthermore, if a shunt is to be performed on an emergency basis to control acute bleeding, this procedure must be done before the patient's condition deteriorates sufficiently to represent a prohibitive surgical risk.


Distal splenorenal shunt--premise, perspective, practice.

Despite progress in our understanding and management of patients with portal hypertension, the long-term control of variceal bleeding remains a significant challenge. With further clarification of the underlying pathophysiology and technological advances that have facilitated progress in both diagnosis and treatment, the goal of safe, selective management of patients presenting with variceal hemorrhage is closer to realization. While a variety of non-operative therapies have been advocated, shunt surgery remains the most reliable and durable method of controlling the portal hypertension and the bleeding. More than 20 years ago, Warren and Zeppa introduced the concept of selective shunting to prevent recurrent variceal hemorrhage. The distal splenorenal shunt (DSRS) was advocated as an approach that could selectively decompress the esophageal and gastric varices (resulting in effective bleeding control) while maintaining prograde portal flow (presumably leading to a lower incidence of post-shunt encephalopathy and hepatic failure). While the hemodynamic basis for the DSRS remains valid, its selectivity is neither uniform nor durable and this shunt is neither applicable nor effective in all patients bleeding from varices. It remains, however, appropriate and safe therapy in selected cirrhotic patients with variceal hemorrhage. With careful pretreatment assessment (in the context of the advances that have occurred in both operative and anesthetic management), the DSRS retains an important role in the management of patients with variceal bleeding.


Interventional treatment of portal hypertension.

For many years now, percutaneous transhepatic and transjugular approaches to the portal vein have been applied by gastroenterologists and radiologists for diagnosis and therapy. In patients with variceal bleeding these techniques were used to obliterate the varices, and have provided the knowledge for further developments, such as the creation of an intrahepatic portosystemic shunt by balloon dilatation of the needle tract between the portal vein and a hepatic vein. The recent development of expandable vascular stents has led to improvements in the efficiency and long-term patency of interventional shunts, and justified their clinical application. The rationales for this new approach to the treatment of portal hypertension are its relative safety, even in Child C patients, and the disabilities such as rebleeding or aggravation of hepatic encephalopathy of other current treatments. Since the first clinical application of the transjugular intrahepatic portosystemic stent-shunt in January 1988, the technique has been improved considerably, and the frequency of its application is increasing rapidly. This article attempts to summarize the current state of knowledge of this interventional technique, which will soon have its place among the various methods of treating portal hypertension.


Calcium pyrophosphate deposition disease: description in defleshed skeletons.

The osseous appearance, skeletal distribution, and distinguishing features of calcium pyrophosphate deposition disease (CPPD) were delineated in a population of 2906 contemporary defleshed skeletons. The limitations of routine x-ray and clinical examination were transcended in this study of defleshed bones. The nature of the disease was clearly identified and preconceived notions (based on the "shades of black and white" of the conventional x-ray technique) were examined on the basis of the actual osseous impact. Epidemiologic assessment of this disease allowed it to be distinguished from rheumatoid and other erosive forms of arthritis. Analysis of the "pseudo-rheumatoid" subgroup of CPPD provided clear criteria for distinguishing the disease from rheumatoid arthritis. Characterization of the nature and epidemiology of osseous alterations in a contemporary skeletal population permitted the development of a standard for recognition of CPPD in skeletal populations and for clarification of the nature of associated pseudo-erosions.


Non-Hodgkin's lymphoma and Sjögren's syndrome. An immunopathological study of 113 patients.

One hundred and thirteen patients with untreated non-Hodgkin's lymphoma were evaluated for Sjögren's syndrome (SS) using clinical and biological parameters, and a minor salivary gland biopsy. Concomitant immunophenotyping for T and B cells, and kappa and lambda chains was performed on both minor salivary gland and lymphomatous tissues. Patients with a positive focus score on examination of their minor salivary gland biopsy had a second biopsy, when possible, at the end of induction therapy. Fourteen of the 113 patients had SS according to the Greek criteria, and 4 of these 14 patients had an identical monotypic infiltrate in both their minor salivary gland and lymphomatous tissues. In all four cases this infiltrate disappeared from both locations when the lymphoma was in complete remission (CR). The 10 other patients with criteria for SS had a mixed infiltrate which persisted unchanged when the lymphoma was in CR. Among the 99 patients without SS, 12 had a positive focus score and an identical monotypic infiltrate in both their minor salivary gland and lymphomatous tissue. This infiltrate disappeared from both locations when the lymphoma was in CR. Among the remaining 87 patients, 82 had no minor salivary gland infiltrate, and 5 had a positive focus score with mixed lymphocytic infiltrate. Long term follow up and a large cooperative study are needed to better understand the immunopathologic lesions of patients of this latter type.


Rheumatoid arthritis associated with high levels of immunoglobulin a: clinical and biological characteristics.

We measured the serum immunoglobulins in 191 patients with rheumatoid arthritis (RA) over an 8-month period, looking for a relationship between high IgA levels, disease activity, and clinical and biological features. Twenty-nine patients with a polyclonal hyperimmunoglobulin A (IgA) (15.2%) above 5 g/l constituted group A. A control group of 29 randomized RA patients with normal IgA levels was studied over the same period (group B). The mean serum IgA concentration was significantly elevated in group A: 6.6 +/- 1.8 g/l versus 2.8 +/- 0.9 g/l in group B (p < 0.01). In group A, microscopic haematuria occurred in 20.7% of the cases, as against 3.4% from group B (p < 0.05). Furthermore, the incidence of unilateral sacroiliitis and of arthritis of the distal interphalangeal joints was significantly increased in group A (41.4% and 34.5%, respectively) against 6.9% and 3.4% in group B (p < 0.01) and this correlated with a high IgA serum level (p < 0.01). On the other hand, neither disease activity nor the biological parameters of inflammation were influenced by the level of IgA. Patients with RA associated with high levels of IgA are characterized by a significant increase in the incidence of distal interphalangeal arthritis, unilateral sacroiliitis and microscopic haematuria. These clinical and biological features could define a distinct subgroup of patients with RA.


Lymphocyte subpopulations in an experimental model of axial and peripheral enthesiopathies.

We report a study of lymphocyte subsets in experimental arthritis induced in Wistar Furth rats by native human type II collagen and muramyl dipeptide. This experimental arthritis shares similarities with both the spondyloarthropathies and rheumatoid arthritis. Peripheral blood T lymphocytes, primarily the CD4+ cells (p = 0.01), were lower in arthritic rats than in the controls, although the difference in the CD4/CD8 ratio was not statistically significant. Splenic CD4 cells were significantly (p = 0.03) more numerous in arthritic rats, while the numbers of MHC class II positive cells (p = 0.002) and kappa-bearing B-cells (p = 0.0004) were significantly lower. Determination of peripheral blood and spleen lymphocytes subsets could therefore be used for the assessment of arthritis and for the evaluation of therapeutic agents. Thymic T-cell differentiation does not appear to be impaired in this model. These results differ from the peripheral blood disturbances described in the active stages of human rheumatoid arthritis and are more similar to those reported in ankylosing spondylitis patients. However, the absence of alterations in the Peyer's patches suggests that pathogeneic mechanisms involving mucosal areas and exogenous intestinal antigens are not reproduced in this model.


Specificity analysis of antibodies to single-stranded micrococcal DNA in the sera of normal human subjects and patients with systemic lupus erythematosus.

To evaluate the properties of antibodies to bacterial DNA in the sera of normal human subjects (NHS) and patients with systemic lupus erythematosus (SLE), the effects of ionic strength and pH on their binding to single-stranded DNA (ssDNA) from Micrococcus lysodeikticus (MC) were measured. By ELISA, antibodies to MC ssDNA in NHS showed greater activity at high ionic strength (0.2-1.0 M) than antibodies in lupus sera. Similarly, antibodies in NHS had higher activity at pH 9 than lupus anti-DNA. Competition binding assays indicated, moreover, that NHS anti-DNA showed greater inhibition by DNA than lupus anti-DNA at comparable inhibitor concentrations. Together, these results suggest that antibodies to MC ssDNA in NHS and SLE sera may differ in their mode of interaction with bacterial DNA and that NHS can generate high avidity antibodies to at least certain DNA determinants.


Effect of adjuvant-induced arthritis on bone mass in rats and its prevention by non-steroid anti-inflammatory drugs (NSAIDs).

The effect of two propionic acid derived drugs, ketoprofene and butibufene, on the prevention of osteopenia due to adjuvant-induced anti-inflammatory arthritis, was studied in groups composed of 10 rats each. Another group of 10 rats was treated with a placebo and 20 non-treated rats served as controls. Once arthritis was evoked, propionic acid derived drugs were administered at equivalent doses, in the form of a local cream applied on the foot where arthritis was induced. The placebo group was treated with the cream without propionic acid derivatives. Rats were sacrificed at the end of the study and the femurs where arthritis was induced were dissected. Bone densitometry studies were conducted with double energy X-ray on these bones to calculate the bone mass. Bone mass was higher in the group treated with ketoprofene (p < 0.025) than in the butibufene and placebo-treated groups, and these 3 groups showed lower values than the control (p < 0.001). These results suggest that propionic acid derivatives can prevent the osteopenia induced by inflammation and the subsequent lack of limb use, an effect which may be related to its analgesic and/or anti-inflammatory effects. In addition, this may serve as a good model for the indirect measurement of the effectiveness of analgesic and/or non-steroid anti-inflammatory drugs in experimental animals.


Anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with neuro-Behçet's syndrome.

Anticardiolipin antibodies of the IgG, IgM and IgA isotypes and soluble IL-6 were measured in paired serum and cerebrospinal fluid samples from five patients with neuro-Behçet's syndrome. Another five patients with non-inflammatory neurological diseases were also studied as a control group. Anticardiolipin antibodies, especially the IgM isotype, and IL-6 were highly elevated in the cerebrospinal fluid of patients with neuro-Behçet's. Levels of both IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid dropped after disease activity subsided. These results suggest that the increase in IgM isotype anticardiolipin antibodies and IL-6 in cerebrospinal fluid may be involved in the immune response of neuro-Behçet's within the central nervous system. Serial measurements of IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid may be useful in evaluating disease activity in neuro-Behçet's.


Antiphosphatidylethanolamine antibody as the sole antiphospholipid antibody in systemic lupus erythematosus with thrombosis.

A previously healthy 34-year-old woman, was diagnosed as having systemic lupus erythematosus (SLE), with membranous glomerulopathy which improved rapidly. Neither lupus anticoagulant nor anticardiolipin antibodies were detected in her plasma. After three months of total remission, she developed a severe pulmonary thromboembolism for which no specific biological cause was found. Her plasma was analysed for different antiphospholipid antibodies: lupus anticoagulant and anticardiolipin antibodies were again negative. Using an ELISA prepared with either five different anionic phospholipids or zwitterionic phosphatidylethanolamine, solely an anti-phosphatidylethanolamine IgG was discovered in her plasma. In lupus patients, the presence of antiphospholipid antibodies is now well recognized as a high risk factor for repeated thrombosis and/or recurrent abortions. This case suggests that the presence of antiphosphatidylethanolamine antibody should be investigated in cases of unexplained thrombosis in SLE, where the usual clinical and biological investigations have failed to shed light.


Antiphospholipid syndrome in a child with trisomy 21: the relationship between anticardiolipin G antibodies and the von Willebrand factor.

A young child with trisomy 21 developed severe multiple arterial thromboses in a three-phase clinical course which proved fatal. The episodes were characterized by high levels of both IgG anticardiolipin antibodies and the von Willebrand factor. The data suggest that there is a relationship between these two elements and the clinical events which followed.


The effect of intravenous immunoglobulin on lymphocyte populations in children with Kawasaki syndrome.

High dose intravenous immunoglobulin (IVIG) is extremely effective therapy for Kawasaki syndrome (KS), but the mechanism of action remains unknown. The present study was performed to determine the effect of IVIG on lymphocyte populations and lymphocyte activation markers in 15 children with KS. Following IVIG, there was a decrease in the percentage of CD19 cells and an increase in the percentage of CD8 cells, but there was no change in the proportion of CD3 or CD4 cells. Moreover, there was no change in the percentage of activated CD4 or CD8 cells, as measured by HLA DR and interleukin-2 receptor expression after IVIG therapy. These results indicate that IVIG is effective treatment for KS via mechanisms other than the direct modulation of T cell activation markers.


Elastolytic activity of human monocytes: rheumatological aspects.

Activation of human monocytes in rheumatic disorders includes the production of substances active in immunologic interactions, inflammatory responses, and tissue remodelling. This review discusses the cell surface-related elastolytic activity of live human monocytes, as determined by a newly developed elastin assay. Elastase activity was not found to be depressed by patient treatment with glucocorticoids or slow-acting disease modifying drugs nor enhanced by phagocytosis, but was increased by immune complexes in vitro and in patients with rheumatoid arthritis or giant cell arteritis. The leucocyte elastase content seems to be influenced by systemic factors before the monocytes are released into the blood. The enzyme expression of elastase is determined by local factors acting after the cells have left the circulation. Monocyte expression may therefore be a link between immune activation and proteolytic activity.


Family violence: a letter to my doctor.

The epidemic of family violence in America is widespread, deadly and complex. Even the very young, the very old and pregnant women may be safer on the streets than in there own homes, according to a recent article in the AM News. The cost to our society is staggering. And you, as physicians, are on the front lines, daily confronting the effects of this national crisis. Approximately every third patient you see is a victim of family violence. Your patients' bruises, fractures and other injuries are often symptoms of a far more sinister disease. The patient needs your help. As doctors, you are being asked to treat not just the symptoms but also the underlying cause--to look below the surface to the illness beneath. As healthcare professionals you are being asked to take the lead in helping society eradicate this devastating epidemic and restore the health of our families through these individual lives. In a letter to you, her trusted doctor, the following profiles a victim of abuse.


Spinal and somatic growth in patients with juvenile chronic arthritis treated for up to 2 years with deflazacort.

We previously reported a double-blind controlled trial of Deflazacort vs Prednisone in patients with Juvenile Chronic Arthritis who had required corticosteroid therapy for at least one year. This paper presents further results on an additional 11 patients, making 26 altogether, who were treated for one year with deflazacort. Fourteen of these went on to a second year of deflazacort treatment. As previously reported, the relative rate of spinal bone mineral growth in the first year was greater for the spinal bone mineral content than for the body surface by about 70%. In the second year of treatment spinal bone mineral continued, with wide variations, to grow at the same or a very slightly greater rate. However, somatic growth recovered so that there was no significant difference between the relative growth rates in the spinal bone mineral and the body surface area in year 2 (P = 0.78). Deflazacort therapy appears to permit appropriate growth of the spine in relation to the rest of the body against a background of variable growth impairment due to the disease process and the treatment required to control it.