Dr John Thomson (1847-1909). Pioneer surgeon, military surgeon and a founder of St John Ambulance in Australia.

Surgeon John Thomson (1847-1909), a Scot who made his life's work in Queensland, was a pioneer surgeon, radiologist and bacteriologist, and one of the founders of the St John Ambulance movement in Australia and the Railway Ambulance Corps. He was variously President of the British Medical Association (Queensland Branch), the Medical Board of Queensland, the Medico-Ethical Association, and the Intercolonial Medical Congress, which was held in Brisbane in 1899. A pioneer military surgeon in this country, he was the foundation Principal Medical Officer (as Surgeon-Major) of the Queensland Ambulance Corps within the Queensland Defence Force. His advocacy for a university north of Sydney was one of the factors which led to the foundation of the University of Queensland, a body which honoured him by the establishment of the John Thomson Lectureship, which for half a century was its most prestigious public oration. The life and times of this singular doctor exemplify one small class of pre-Federation medical pioneers whose professional outreach established a number of voluntary organisations which have blossomed in Australian society to the present day.


Electrocution in Western Australia, 1976-1990.

To describe the epidemiology of electrical fatalities in Western Australia between 1976 and 1990. Data for the study were gathered from hospital records, autopsy reports and findings from State Energy Commission and coronal investigations. Information that was abstracted included age, sex, occupation, voltage, history of incident and autopsy findings. There were 104 victims. Death occurred most frequently in young men exposed to low voltage current during summer, and nearly half the fatalities occurred in the workplace. Water was present in up to 52% of fatalities. Without exception, all victims developed a lethal arrhythmia at the time of exposure to the electric shock, which usually resulted in death at the scene. When a victim is exposed to a fatal electric shock, the lethal arrhythmia occurs at the time of electrocution and is just as likely to occur at home as in the workplace. Electrical fatalities can be prevented largely by the use of residual current devices.


Beyond the Barcoo--probable human tropical cyanobacterial poisoning in outback Australia.

To determine the cause of a disease known variously as "Barcoo fever, Barcoo spews, Barcoo sickness", or simply "the Barcoo", once prevalent in outback northern and central Australia. Comparison of the recorded symptoms with those of known infectious diseases and gastrointestinal illness; consideration of the epidemiology, including times and places of occurrence and the population affected. The disease had features of a toxic rather than an infectious illness and had the characteristics of poisoning by toxic cyanobacteria (blue-green algae). In particular the symptoms were similar to those shown to be due to the hepatotoxin of the tropical cyanobacterium Cylindrospermopsis raciborskii (Woloszynska). Poisoning by cyanobacterial toxins was once widespread in outback northern Australia and toxic cyanobacteria must still be present in many areas. Although not reported and probably not diagnosed as such, the disease still occurs in mild form. Widespread illness does not occur but individuals still experience symptoms similar to those described a century ago. Precautions are necessary to prevent algal contamination or proliferation in domestic or communal water supplies.


The potential for teratogenicity of vitamin A and its congeners.

To review the evidence for teratogenic potential associated with the use of vitamin A and synthetic retinoids in Australia. Relevant indexed journal articles and standard drug information reference texts were identified by Medicine and library search. Information was also obtained from the Australian National Perinatal Statistics Unit. We summarised human and animal data relating to the teratogenicity of vitamin A derivatives and synthetic retinoids, including case reports documenting systemic effects from topically administered drugs, pertinent information relating to the clinical pharmacokinetics and adverse effects of these compounds, and the approved and potential indications for the use of these agents. Extensive experimental evidence points to the teratogenicity of natural and synthetic retinoids in animals. Data confirming an effect in humans are not as good. Nevertheless case series, case reports and some epidemiological data regarding isotretinoin suggest that synthetic retinoids are similarly teratogenic in humans. Although there are extensive guidelines and legislation dealing with the use of these compounds in the United States and Australia, the potential for teratogenicity induced by vitamin A still exists. This is because retinoids and vitamin A continue to be prescribed for women of child-bearing potential and documented evidence from the United States reveals that not all prescribers comply with recommendations that minimise the risk of malformations. Non-prescription forms of vitamin A are available without a pregnancy hazard warning, and potentially teratogenic amounts are available from dietary sources. There exists a potential for teratogenicity in association with the use of both synthetic and natural retinoids in Australia. Monitoring systems currently in place in this country may not detect these malformations should they occur.


Munchausen syndrome by proxy--a cause of preterm delivery.

To present the first case of Munchausen syndrome by proxy involving self-induced preterm delivery. A 27-year-old Caucasian woman induced antepartum haemorrhage and rupture of membranes with a knitting needle at 26 weeks' gestation, leading to delivery of the infant. This "prenatal child abuse" led to a prolonged intensive care stay, extensive treatment and subsequent bronchopulmonary dysplasia. As the child recovered from the effects of extreme prematurity, he became a victim of fabricated illness and recurrent smothering episodes. After the diagnosis of Munchausen syndrome by proxy was made, the child was removed from the mother and he has since enjoyed good health. Self-induction of antepartum haemorrhage can lead to preterm delivery and may be recognisable by certain clinical parameters. The victim of self-induced preterm delivery, if survival ensues, may be subject to further abuse.


Open air rock concert: an organised disaster.

To describe the planning and implementation of health care provision at a mass gathering, and to describe the conditions treated at such an event. When approximately 93,000 fans gathered outdoors in Sydney's Centennial Park, a natural reserve, for Australasia's largest ever outdoor rock concert, there was an obvious potential for medical disaster. At most disasters or mass gatherings, accurate patient numbers and details are not available, but an organised patient data collection system allowed the case load at this event to be clearly defined. This showed that 450 patients were attended to by the first aid teams. Triage identified 36 of these as having conditions serious enough to require admission to the medical area. Seven of these patients were ultimately transferred to hospital. A brief practical outline is provided of the medical planning for the concert, detailing the staff and equipment, how to avoid potential problems, the use of voluntary organisations, and specific site organisation. Key points in the medical planning, organisation and practicalities, especially those which are vital to any disaster response, are highlighted. Solutions to recurrent problems experienced by medical personnel involved with mass gatherings or disasters are suggested. The lack of practice in implementing a multiple casualty or disaster plan may be remedied by organised responses to mass events.


Telephone-related lightning injury.

To review reported telephone-related lightning injuries, outline the mechanisms of injury and suggest treatment strategies. Cases notified to Telecom Australia and an extensive search of the literature. There is a dearth of literature on telephone-related lightning injury. Some reports note it in passing, others describe single incidents. Case reports from Australia provide detail sufficient for review, and the general principles which govern management of such injuries are presented. Telephone-related lightning injury is not rare. Practitioners should be aware of the uniqueness of lightning injury and the complexity of its assessment. A research program aimed at further elucidation of the detail of this injury is proceeding.


Platypus envenomation--a painful learning experience.

To describe in detail for the first time, the clinical course and medical management of a significant human envenomation by the Australian platypus (Ornithorhynchus anatinus). A 57-year-old man was envenomated via two spur wounds to the right hand from each hind leg of a male platypus. Pain was immediate, sustained, and devastating; traditional first aid analgesic methods were ineffective. On admission to hospital, narcotics administered intravenously, both intermittently and by infusion, provided inadequate analgesia. A right wrist block was dramatically effective. After the blockade narcotic analgesic support was required for several days. The patient spent six days in hospital, and the envenomated area remained painful, swollen and with little movement for three weeks. Significant functional impairment of the hand persisted for three months, the cause of which is uncertain. Male platypus venom remains largely unstudied. It produces savage local pain and marked local swelling, but no apparent tissue ischaemia. No antivenom is available; in its absence the only effective analgesia appears to be regional nerve blockade, when the envenomation site and available skills permit. Immobilisation assists.


There's a worm in my eye.

To report a case of an unusual worm infestation of the eye. A 28-year-old veterinary surgeon complained of the intermittent appearance of a worm in her eyes. Her previous camping travels in west and central Africa suggested the diagnosis of Loa loa, which was confirmed on surgical removal of the worm from beneath the conjunctiva. Laboratory investigations showed peripheral blood eosinophilia, negative thick blood film examinations for microfilariae and positive results of filarial serology. The worm was removed intact after incision of the overlying conjunctiva. Diethylcarbamazine was prescribed and the patient remained asymptomatic in the subsequent 12 months. The sighting of a worm in the eye is rare in Australia and usually occurs in immigrants or returned travellers. Loa loa is the most common offending species and is identifiable and treatable.


Lead poisoning from Indian herbal medicine (Ayurveda)

To present a case of lead poisoning following ingestion of Indian herbal medicine. A 37-year-old man presented with a history of abdominal pain, anorexia and malaise. He had recently returned from a trip to India where he had been taking two different herbal tonics. Investigation revealed low-grade hepatitis and normocytic anaemia with prominent basophilic stippling. The blood lead concentration was high, and analysis of the herbal tablets revealed a very high lead content. The patient required narcotic analgesia for abdominal pain and was treated with chelation therapy with calcium ethylenediaminetetra-acetate (calcium EDTA) for five days which resulted in a high urinary excretion of lead and resolution of his symptoms over a period of several days. Lead poisoning in Australia is usually the result of chronic industrial exposure, but practitioners should be aware of the possibility of poisoning from other domestic sources such as unglazed pottery, cosmetics and herbal remedies, especially those from Asia and India, in which lead may be present in high concentration. Patients from Asia who present with unexplained anaemia or abdominal symptoms should be asked about exposure to such sources.


Prenatal cocaine exposure in the laboratory mouse: effects on maternal water consumption and offspring outcome.

Pregnant mice were given 50 mg/kg cocaine HCl (1% solution, sc) once daily from gestation days 7 through 18 (sperm positive = day 0; term = day 19). Pair-fed and untreated control groups were also used. The pregnant cocaine-treated females showed normal weight gain and food consumption but had significantly increased water consumption. The cocaine-treated group had a significant increase in embryonic resorptions but no significant effects on stillbirths or postnatal mortality. The offspring of cocaine-treated females had significantly reduced birth weights and postnatal weight gains up to the age of 28 days. There was also a delay in their ear opening but not in other maturational milestones. Increased water consumption following cocaine treatment has been reported by other studies. We speculate that cocaine has a diuretic effect. We discuss the implications of this effect during pregnancy.


The effects of prenatal exposure to phenytoin and other anticonvulsants on intellectual function at 4 to 8 years of age.

Twenty phenytoin exposed children between 48 and 99 months of age had an evaluation of behavior and intelligence by a single examiner who was unaware of exposure status. The controls were 98 children identified at birth as having three or more minor anomalies. None of the children evaluated were mentally retarded. In both, a case-by-case comparison and a comparison of the two entire groups, the phenytoin-exposed children had significantly lower scores for both Performance IQ (PIQ), Full Scale IQ (FSIQ), and Visual Motor Integration Test (VMIT). Similar abnormalities have been found in studies of animals exposed to phenytoin in utero. These results suggest that the teratogenic effects of phenytoin may include an effect on cognitive function.


Prenatal exposure to cocaine. I: Effects on gestation, development, and activity in Sprague-Dawley rats.

Sperm-positive Sprague-Dawley rats received one of four treatments for 20 days beginning within 24 hours of conception. One group received subcutaneous injections of 15 mg/kg cocaine twice daily (Cocaine-D); a second group received 15 mg/kg cocaine twice daily for two consecutive days at 5-day intervals (Cocaine-I); a third group received normal saline twice daily (Saline); and a fourth group received 1.5 mg/kg amfonelic acid (AFA), a dopamine reuptake inhibitor, once daily. Cocaine-D, Cocaine-I, and AFA dams were fed ad lib. An attempt was made to pair-feed the Saline dams with the Cocaine-D dams; however, the Saline dams did not eat as much as the Cocaine-D dams which resulted in dams in all groups essentially eating ad lib. The Cocaine-D pups showed a slightly delayed righting behavior and neophobia at 30 days of age, as evidenced by hypoactivity during the first 15 min of a 6-h activity test. The Cocaine-I pups were hypoactive during the 3-h dark phase of the 6-h activity test when tested at 30 days of age. These effects did not occur in the offspring exposed to AFA, a potent dopamine uptake inhibitor and CNS stimulant which indicate that one or more other sites for cocaine action may combine for its effects on the developing fetus.


A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol.

Attentional behavior was examined in one hundred twenty-six 72-month-old children for whom prenatal exposure to marihuana, cigarettes, and alcohol has previously been ascertained. Discriminant Function Analysis revealed a dose-response association between prenatal cigarette exposure and impulsive behavior as manifest on poorer performance on a response inhibition task and increased errors of commission on a sustained vigilance task. Performance on a series of memory tasks particularly those requiring verbal recall was also negatively associated with maternal cigarette use. Prenatal marihuana habits were associated with increased omission errors in the vigilance task, possibly reflecting a deficit in sustained attention. In addition, Discriminant Function Analysis revealed a dose-response relationship between prenatal marihuana use and a higher rating by the mothers on an impulsive/hyperactive scale. Relatively low levels of maternal alcohol consumption was related to decreased impulsive responding both in the response inhibition task and in terms of the mothers' perception of the child's behavior. The multifaceted approach of examining attentional behavior was essential to reveal the differential associations with the three prenatally used drugs. The implications of the observations and how the findings relate to and extend the existing literature is discussed.


Sociodemographic factors modifying the effect of environmental lead on neuropsychological development in early childhood.

A long-term prospective cohort study was conducted to examine the association between prenatal and postnatal exposure to environmental lead and childhood neuropsychological development. The possible interactive effects of blood lead and some covariates on early development were explored in this study. Our data suggest that gender of the child modifies the effect of lead on the neuropsychological development during early childhood. At the ages of 2 and 4 years, girls appear to be more sensitive than boys to the neuropsychological effects of lead. However, there is no significant modification of the effect of lead by some other covariates, such as parental smoking, socioeconomic status, home environment, birth weight, and the kind of infant feeding. Evidence of interactions between environmental lead exposure and other covariates in the causation of neuropsychological deficits in childhood underscores the desirability of considering both main effects and interactions in this area of research. Such effects, if confirmed, may have implications for public health intervention strategies.


Combining individual and family treatment: guidelines for the therapist.

Successfully combining individual and family treatment for psychosis-prone outpatients who live with their families is a process of keeping the needs of the patient and the family in balance. The therapist has to respond to each in an even-handed way that preserves an alliance with both. Through guidelines and case reports, this chapter describes how to maintain that balance. The therapist-patient relationship is the core of treatment and keeps the clinician's focus squarely on the individual needs of the patient. In keeping with that focus, the therapist encourages self-determination on the patient's part and sets up opportunities for the family to communicate directly with the therapist in front of the patient, rather than surreptitiously behind the patient's back. In keeping with a collateral emphasis on the family, the therapist involves the family regularly and early in the course of treatment, respects the family's knowledge of the patient, puts that knowledge to use, and works with the family to deal promptly and effectively with incipient emergencies. The therapist knows that it is not only the therapist but also the family who stimulate a patient to change. The therapist, building on whatever strengths the patient and family possess, enlists the family as an ally in promoting and bringing about therapeutic progress.


Comparison of two weeks versus one week of prenatal ethanol exposure in the rat on gonadal organ weights, sperm count, and onset of puberty.

Sprague-Dawley dams from Harlan Ind. (Indianapolis, IN) were administered a fortified ethanol liquid diet containing 35% ethanol derived calories for two weeks (E-2) beginning on day 7 or one week (E-1) beginning on day 13 of gestation and continuing through parturition. Control dams were pair-fed an isocaloric liquid diet containing no ethanol during these periods or remained on lab chow and water. E-2 dams consumed an average of 13.52 g ethanol/kg bwt during the first week of exposure (days 8-14) and 12.50 g ethanol/kg bwt the second week (days 14-20). E-1 dams consumed significantly less than E-2 dams during the second week (9.75 g/kg; p < 0.0001). Although the lower consumption in E-1 dams led to a significant decrease in maternal weight gained during the few days of pregnancy compared to E-2 dams, birthweights of E-1 offspring were significantly heavier than those of E-2 offspring (p < 0.05). No effect of ethanol was detected on anogenital distance at birth in either sex. Puberty was delayed in female offspring of both E-1 and E-2 dams (p < 0.01) as measured by age of vaginal opening. These data suggest that the primary teratogenic actions of ethanol in the rat on fetal growth, as well as delayed puberty in females, occur in the last week of gestation. In adult E-2 males, testis weight was significantly heavier than all other groups when indexed to body weight. No effect of prenatal ethanol exposure was observed on the indexed weights of prostate, epididymis, or seminal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


Prenatal ethanol effects on reward efficacy for adult mice are gestation stage specific.

We previously reported that adult mice exposed to ethanol throughout gestation (G5-17) responded slower than controls on reinforcement schedules which required large numbers of responses per unit of food, i.e., high fixed ratio (FR) schedules. The primary finding of the present study was that ethanol exposure during the last 5 days of gestation (G12-17) is sufficient to produce this effect whereas a similar exposure early in gestation (G5-10) is not. Both male and female mice exposed to ethanol late in gestation responded slower than either lab chow or pair-fed controls, and the effect was similar to that of mice exposed to ethanol throughout gestation (G5-17) in our earlier study. Thus, developmental events occurring late in gestation are important for the reduced reinforcing efficacy of food for prenatal-ethanol-exposed mice. In addition, the present experiment established the comparability of the sucrose and lab chow controls on this task. The results of the present study and our previous report are compatible with the hypothesis that the reduced responding on high FR schedules exhibited by prenatal-ethanol-exposed mice reflects a reduction in the efficacy of food reward. It is possible that the reduction in reward efficacy is due to altered development of neuronal systems functionally related to reward which develop late in gestation.


Prenatal exposure to cocaine. II: Effects on open-field activity and cognitive behavior in Sprague-Dawley rats.

Pregnant rats received subcutaneous injections of 15 mg/kg of cocaine twice daily (Cocaine-D), twice daily for two consecutive days at 5-day intervals (Cocaine-I), 0.9% saline (Saline) twice daily, or 1.5 mg/kg amfonelic acid (AFA) daily from gestational days 1-20. Offspring were tested for: rates of spontaneous alteration at postnatal days (PND) 32, 35, 40, and 45; acquisition and retention performance on a water maze task beginning at PND 30 and 60; entrance into and activity in an open-field apparatus at PND 60 and 180. The Cocaine-D offspring were less likely than Control offspring to enter the open field when tested at PND 60. The Cocaine-I offspring were hyperactive in the open-field apparatus when tested at PND 60. The drug treated offspring did not differ from the Saline control animals on all other measures. The failure of the Cocaine-D animals to enter the open field is consistent with neophobic behavior that we have observed before in rats exposed in utero to cocaine.


Infertility: psychotherapeutic issues.

In supportive therapy with infertility patients, the clinician tries to relieve dysphoria and enhance self-esteem. Dynamically informed supportive interventions are designed to decrease guilt that may relate to past sexual activities, sexually related diseases, or abortions. These interventions should also be empathetic, promote optimism and reality testing, help with problem solving, allow catharsis and ventilation, decrease feelings of isolation and loneliness, educate and clarify, and praise and encourage where appropriate. Mental health clinicians have an important role to play in the treatment of these patients, provided they learn enough about the psychology of the experience of infertility and about the technology utilized in its treatment. As the number of people seeking treatment for infertility grows, the need for skilled therapists for this population will grow at a parallel rate.


Prenatal cocaine and alcohol exposures affect rat behavior in a stress test (the Porsolt swim test).

Prenatal cocaine and alcohol exposures have been associated with a variety of adverse effects ranging from subtle neurobehavioral abnormalities to major malformations. In this study, we used the Porsolt swim test to assess the effects of prenatal cocaine and alcohol exposures on stress-related behavior. Pregnant Long-Evans rats were injected daily with 80 mg/kg cocaine HCl (SC) or 6.2-6.5 g/kg ethyl alcohol (PO) from gestation days 7-20 with half the dose given in the morning and the other half in the afternoon. Pair-fed and ad lib control groups were also used. One male offspring from each litter was evaluated in the Porsolt swim test at the age of 120 days. The alcohol and cocaine groups were less immobile (i.e., struggled more to escape) than the controls. These results suggest that prenatal exposure to either alcohol or cocaine can adversely affect behavior in stressful or fearful situations.


RNA editing in trypanosomes. The us(e) of guide RNAs.

Guide RNAs are encoded in maxicircle and minicircle DNA of trypanosome mitochondria. They play a pivotal role in RNA editing, a process during which the nucleotide sequence of mitochondrial RNAs is altered by U-insertion and deletion. Guide RNAs vary in length from 35 to 78 nucleotides, which correlates with the variation in length of the three functionally important regions of which they are composed: (i) a 4-14 nucleotide 'anchor' sequence embedded in the 5' region, which is complementary to a target sequence on the pre-edited RNA downstream of an editing domain, (ii) a middle part containing the editing information, which ranges from guiding the insertion of just one U into one site to that of the insertion of 32 Us into 10 sites, and (iii) a 5-24 nucleotide 3' terminal oligo [U] extension. Moreover, a variable uridylation site creates gRNAs containing a varying segment of editing information for the same domain. Comparison of different guide RNAs demonstrates that, besides the U-tail, they have no obvious common primary and secondary sequence motifs, each particular sequence being unique. The occurrence in vivo and the synthesis in vitro of chimeric molecules, in which a guide RNA is covalently linked through its 3' U-tail to an editing site of a pre-edited RNA, suggests that RNA editing occurs by consecutive transesterification reactions and is evidence that the guide RNAs not only provide the genetic information, but also the Us themselves.


In vitro reconstitution of U1 and U2 snRNPs from isolated proteins and snRNA.

In this paper we describe a method for preparing native, RNA-free, proteins from anti-m3G purified snRNPs (U1, U2, U4/U6 and U5) and the subsequent quantitative reconstitution of U1 and U2 snRNPs from purified proteins and snRNA. Reconstituted U1 and U2 snRNPs contained the full complement of core proteins, B, B', D1, D2, D3, E, F and G. Both the U1 and U2 reconstituted particles were stable in CsCl gradients and had the expected buoyant density of 1.4 g/cm3. Reconstituted RNP particle formation was not competited by a 50 fold molar excess of tRNA, as determined by gel retardation assays. However, U1 and U2 particle formation was reduced in the presence of an excess of cold U1 or U2 snRNA demonstrating a specific RNA-protein interaction. U1 and U2 snRNPs were also efficiently reconstituted in vitro, utilizing proteins prepared from mono Q purified U1 and U2 snRNPs. This suggests that for the assembly of snRNPs in vitro no auxiliary proteins other than bona fide snRNP proteins appear to be required. The potential of this reconstitution technique for investigating snRNP assembly and snRNA-protein interactions is discussed.


Identification and typing of members of the protein-tyrosine phosphatase gene family expressed in mouse brain.

Protein-tyrosine phosphatases (PTPases) form a novel and important class of cell regulatory proteins. We evaluated the expression of PTPases in mouse brain by polymerase chain amplification of cDNA segments that encode the catalytic domains of these enzymes. Degenerate primer pairs devised on the basis of conserved protein motifs were used to generate a series of distinct PCR-derived clones. In this way, murine homologues of the human PTPases LRP, PTP beta, PTP delta, PTP epsilon and LAR were obtained. Corresponding regions in their catalytic domains were used to reveal the evolutionary relationships between all currently known mammalian PTPase protein family members. Phylogenetic reconstruction displayed considerable differences in mutation rates for closely related PTPases.


Effect of delta-lysin on the phase transitions of lipid assemblies.

X-ray small-angle diffraction, differential scanning calorimetry (DSC), and temperature scanning densitometry (TSD) were used to study the effect of delta-lysin on the phase transitions of lipid assemblies from 1,2-0-dixehadecyl-sn-glycero-3-phosphocholine (DHPC). The experiments were carried out in excess of water in a temperature range of 0-55 degrees C, and at low peptide concentrations between 10(-4) and 10(-2) moles peptide per mole phospholipid. The incorporation of delta-lysin into lipid assemblies alters the lipid structure without significant changes on the temperatures of phase transition from gel to liquid crystalline phase. The temperature of the main transition was nearly unaffected. A reduction in the transition volume of the lipids with increasing concentrations of delta-lysin was observed. The minor changes in these parameters were interpreted as long-range structural changes caused by the peptide incorporation. The results are discussed in terms of the concept of cooperative phase transition of entire clusters occurring within a membrane implying that relative stable domains of gel phase, and liquid crystalline phase co-exist.


Nucleotide sequence of a pregnancy-specific beta 1 glycoprotein gene family member. Identification of a functional promoter region and several putative regulatory sequences.

The pregnancy-specific beta 1 glycoprotein (PSG) genes encode a group of heterogeneous proteins produced in large amounts by the human syncytiotrophoblast. Their expression seems to be regulated at the transcriptional level during normal pregnancy. In the present work, we isolated from a human placental library a 17 kb genomic fragment corresponding to a member of the PSG multigene family. DNA sequence analysis of 1190 nucleotides upstream of the translational start and of the first intron, revealed the presence of several putative regulatory sequences. In a transient chloramphenicol acetyltransferase expression assay, 5' flanking sequences within 123 nucleotides upstream to the first major transcription initiation site, functioned as a strong promoter in COS-7 cells. Meanwhile, sequences 5' further upstream had the ability to abolish this promoter activity. The sequence analyzed did not contain any obvious TATA-like boxes or G+C-rich regions, suggesting the existence of unique promoter elements implicated in transcription initiation and regulation of this PSG gene family member.


Autoantibodies to nucleolin cross-react with histone H1 in systemic lupus erythematosus.

IgM autoantibodies to nucleolin and histone H1 are strongly associated in the serum of patients with systemic lupus erythematosus. IgM eluted from immobilized nucleolin specifically stained histone H1 blotted to nitrocellulose; conversely, IgM eluates prepared from immobilized histone H1 stained nucleolin blots. We conclude that the linkage of anti-nucleolin and anti-histone H1 autoantibodies in SLE is due, at least in part, to immunologic cross-reactivity between these two autoantigens, which share certain similar structural features.


Refined definition of the 56K and other autoantigens in the 50-60 kDa region.

Alteration of the acrylamide:bisacrylamide ratio in the SDS-polyacrylamide gel used for Western blotting strongly improved the unambiguous detection of antibodies against 50-60 kDa autoantigens present in autoimmune patient sera. The relative migration of Ro52, the 56K autoantigen and calreticulin increased with reduced acrylamide:bisacrylamide ratios in contrast to that of Ro60, La and Jo-1. These analyses indicated that these six autoantigens correspond to six distinct polypeptides. Further analyses using recombinant calreticulin showed that (i) the 56K autoantigen is neither identical nor related to calreticulin and (ii) calreticulin is not a Ro autoantigen. A series of experiments designed to better characterize the 56K autoantigen showed that (i) the antigen is not detectable in fixed cells, presumably due to masking of the epitopes; (ii) about equal amounts of the antigen were recovered in nuclear and cytoplasmic cell fractions after enucleation of the cells; (iii) the 56K autoantigen is not stably associated with either RNA or other proteins.


Effect of deletions 5' to the translation initiation sequence on the expression of an mRNA in animal cells.

To learn if an mRNA.18S rRNA interaction or a special secondary structure in the mRNA start region is essential for translation in eukaryotic cells, we constructed recombinant plasmids with the SV40 early promoter 5' to part of the Escherichia coli tufB-lacZ gene. Deletion of bases potentially complementary to the 18S rRNA highly increased the transient beta-galactosidase expressed in transfected CHO cells. Deletion of bases that fostered formation of potential hairpins with the mRNA 5'-terminus or altered the structure of the coding region reduced beta-galactosidase activity suggesting that these features of the mRNA secondary structure may be essential for initiation of translation. Computer aided analysis of the potential structure of 290 mRNAs suggests these are conserved features of the initiation region.


Engagement of the TcR/CD3 complex stimulates p59fyn(T) activity: detection of associated proteins at 72 and 120-130 kD.

Engagement of the T cell antigen-receptor complex (TcR/CD3) induces the rapid tyrosine phosphorylation of a spectrum of substrates whose modification is crucial to the activation process. Although CD4-associated p56lck and TcR/CD3-associated p59fyn(T) could account for this cascade, TcR/CD3 driven stimulation of p59fyn(T) activity has not been demonstrated. In this study, we confirm in Brij 96 based buffers that p59fyn(T) can be co-purified in association with the TcR/CD3 complex, and further demonstrate that antibody-induced cross-linking of TcR/CD3 on the cell surface results in a dramatic increase in the detection of receptor associated kinase activity. This results in an increased phosphorylation and detection of TcR/CD3-p59fyn(T) associated zeta (16-21 kD), p72 (72 kD) and p120/130 (120-130 kD) chains. A distinction between increased recruitment and/or activity of p59fyn(T) was not possible due to the fact that receptor associated p59fyn(T) could not be detected by immunoblotting. However, an alternative approach using membrane vesicles demonstrated an anti-CD3 mediated induced increase (2-5-fold) in the phosphorylation of the fyn kinase. Augmented catalytic activity was accompanied by p59fyn(T) labelling at the autophosphorylation site Tyr420, consistent with stimulated fyn catalytic activity, as well as the phosphorylation of polypeptides at 18-20 (TcR zeta), 31, 90 and 130 kD. Stimulation of fyn activity implicates this kinase as a mediator of the tyrosine phosphorylation events originating from the TcR/CD3 complex.


Localization and characterization of the carbohydrate-binding site of the porcine lymphocyte mannan-binding protein.

Mannan-binding proteins found in the liver and serum of several vertebrate species are supposed to play an important role in the intracellular transport of glycoproteins, as well as in several protective reactions including complement activation and elimination of various pathogens. To study these protective functions at molecular level it is necessary to understand the fine oligosaccharide specificity and mutual relation among various forms of these soluble lectins. We have isolated mannan-binding protein as peripheral membrane proteins of porcine lymphocytes. This lectin was purified to homogeneity and shown to possess many properties in common with the well studied rat liver proteins (mol. mass, subunit composition and general organization of the molecule). Binding studies performed with three series of defined oligosaccharides (high mannose, hybrid type, and complex) on native lectin molecules as well as isolated carbohydrate-binding domains revealed distinctive features of this mannan-binding protein, including its impaired ability to bind the oligosaccharide ligand after reduction and decyclization at core N-acetyl-D-glucosamine 1.


Expression of the V(D)J recombinase gene RAG-1 is tightly regulated and involves both transcriptional and post-transcriptional controls.

The V(D)J recombinase activating genes, RAG-1 and RAG-2, are coexpressed only in immature lymphocytes, and are sufficient and necessary for V(D)J recombination to occur in non-lymphoid cells. In order to examine control mechanisms operative in the regulation of RAG-1 and RAG-2, we have studied the pattern of expression of these genes in human pre-T cells, pre-B cells, and thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA); an agent which mimics some of the lymphocyte maturation changes seen in vivo. The expression of RAG-1 and RAG-2 was tightly controlled in a rapid, yet very complex, manner with both positive and negative control elements operating. Treatment of immature lymphocytes with TPA caused the specific and rapid elimination of steady-state RAG-1 and RAG-2 RNA. Nuclear run-on assays showed that TPA completely repressed the transcription of RAG-1 within 30 min. In addition to repressing the transcription of RAG-1, TPA treatment caused the rapid and specific degradation of RAG-1 transcripts by decreasing the apparent half-life of RAG-1 mRNA more than two-fold. As judged by cycloheximide treatment of cells, the effects of TPA were not dependent on new protein synthesis. A labile transcriptional repressor, separate from the TPA-associated repression of transcription, was also active in cells transcribing RAG-1 and RAG-2 RNA. After depletion of this labile repressor by cycloheximide treatment, steady-state RAG-1 and RAG-2 RNA levels, and their transcription rates, were elevated four- to six-fold; but were still susceptible to elimination by TPA treatment. Treatment of pre-T CEM cells with interleukin-2, or theophylline (an agent that increases intracellular cAMP) resulted in a two-fold increase in RAG-1 RNA suggesting that lymphokines, either independently or through second messengers, may modulate RAG-1 and RAG-2 expression. The complex, rapid and precise regulation of RAG-1 and RAG-2 expression is consistent with the view that it is necessary for the cell to tightly regulate V(D)J recombinase levels; lower expression may result in inefficient recombination of Ig/TCR genes, whereas increased expression may lead to recombination errors that are deleterious to the cell.


Evidence for immunodominance between closely related epitopes in the selection of T cell repertoire: hierarchy of T cell epitopes in a repeating sequence.

In a protein antigen the number of epitopes that are presented by the MHC molecules to the T cells is generally limited. This phenomenon of immunodominance determines the T cell response to a given antigen. To understand the molecular basis of epitope selection we have analysed the hierarchy of T cell epitopes in a repeating synthetic polypeptide antigen Poly 18, Poly EYK(EYA)5 in the mice of H-2d haplotype. Because of its repeating nature, all the potential epitopes of Poly EYK(EYA)5 generated as a result of antigen processing will have extensive sequence overlap, therefore, providing an excellent system to investigate the molecular basis of T cell peptide epitope selection in vivo. We have synthesized a series of 12 and 15 amino acid peptides to mimic these epitopes. In H-2d mice Poly EYK(EYA)5 elicits T cell clones that optimally react with 15 amino acid peptides EYK(EYA)4 and/or (EYA)5. Similar results were obtained when related 12 amino acid peptides EYK(EYA)3 and/or (EYA)4 are used. (EYA)5 reactive T cell clones appear to be very heterogenous and much larger in number than EYK(EYA)4 reactive clones. (EYA)5 reactive clones could be elicited by at least three short Poly-18 derived epitopes (EYA)4, EYK(EYA)3 and (EYA)3EYK while EYK(EYA)4 reactive clones elicited only by the EYK(EYA)3 epitope. However, we observed the dominance of (EYA)5 reactive clones even when EYK(EYA)3 was used as an immunogen and this could be related to the degeneracy of their antigen specificity. Our earlier antigen competition studies suggest that (EYA)5 does not compete with EYK(EYA)4 epitope in binding to I-Ad. Therefore, there is no intramolecular competition between these epitopes to activate T cells. The epitope (EYA)3EYK appears to be subdominant since it can elicit Poly EYK(EYA)5 specific T cells upon immunization but does not appear to be part of Poly EYK(EYA)5 repertoire. Peptides such as (EYA)2EYKEYA or EYAEYK(EYA)2 with lysine substitution in the middle of the sequence were non immunogeneic. Similar results were obtained when the larger 15 amino acid peptides were used as antigen. Another level of epitope immunodominance is seen when substituted peptides of the two immunodominant epitopes are used. Some of these epitopes have potential to be part of the Poly 18 repertoire but they are greatly under represented when intact Poly 18 is used as antigen. The unusual hierarchy observed for immunodominance in these overlapping epitopes of EYK(EYA)5 sequence suggest a bias in the selection of T cell repertoire based upon the crossreactivity between potential epitopes generated as a result of antigen processing.


Role of inter-heavy and light chain disulfide bonds in the effector functions of human immunoglobulin IgG1.

The role of inter-heavy and light chain disulfide bonds in the effector functions of human IgG1 was investigated. This was accomplished by mutating appropriate sites in IgG1 such that the disulfide bond pattern now resembled that of IgG4. The effector functions of the mutant antibody were then compared to native IgG1 and IgG4. The antibody-dependent cell cytotoxicity activity was completely abolished in the mutant and the complement-dependent cytotoxicity assay was reduced fifteen-fold. The results suggest that the inter-heavy and light chain disulfide bond pattern of an antibody molecule play a role in its effector functions.


Molecular analysis of human immunoglobulin V lambda germline genes: subgroups V lambda III and V lambda IV.

Three human immunoglobulin V lambda germline genes have been isolated: two from the V lambda IV subgroup and one from the V lambda III subgroup. The V lambda III gene and one of the V lambda IV genes appear to be functional (each being utilized in at least two expressed V lambda genes), despite deviations from the reported consensus sequences in their promoter TATA-box and recombination signal sequence elements. The other V lambda IV gene is a pseudogene. Of the 20 human V lambda germline genes characterized to date, 45% are pseudogenes or vestigial genes.


Highlights of controversial issues in anaesthetic reactions.

This chapter will first briefly deal with some of the controversial issues surrounding allergic reactions to anaesthetics. Other points which appear to be of fundamental importance and which need further investigation will also be mentioned. Readers are referred to other chapters for further information on some of the issues.


[Plasmids for biodegradation of 2,6-dimethylpyridine, 2,4-dimethylpyridine, and pyridine in strains of Arthrobacter].

Arthrobacter crysallopoietes strain KM-4 degrading 2,6-dimethylpyridine and strain KM-4a degrading both 2,6-dimethylpyridine and pyridine, Arthrobacter sp. KM-4b degrading 2,4-dimethylpyridine were isolated from soil. Arthrobacter crystallopoietes KM-4 and Arthrobacter sp. KM-4b contain 100 Md plasmids pBS320 and pBS323. Arthrobacter crystallopietes KM-4a harbours a 100 Md and 80 Md plasmids. Plasmid curing and conjugation transfer results confirm that these plasmids are involved in degradation of 2,6-dimethylpyridine, 2,4-dimethylpyridine and pyridine. A mutant with lost ability to degrade 2,6-dimethylpyridine was isolated during the growth of strain KM-4 rifR at 42 degrees C. Electrophoretic analysis of the plasmid from temperature sensitive mutant revealed the deletion the size of 26 Md from pBS320 plasmid.


[Induction of the SOS-like system in Rec-mutants of Bacillus subtilis].

Influence of the recE1, recB2, recB3, recB19, recF15, recF18, recL16, recM13 and recM27 mutations of the induction of the SOS-like system component, i. e. the RecE protein of Bacillus subtilis was studied by RIA-dot-blot method in UV-irradiated or treated by nalidixic acid cells. These agents caused a significant increase in the wild type (rec+) cells but did not stimulate the RecE synthesis in the rec mutants tested. The two exceptions were recB2 and recF18 mutants treated by nalidixic acid. The tsi23 mutation caused thermoinduction of phi 105 bacteriophage in the rec+ genetic background while no prophage particles were induced in the recE, recF, recL, recM mutants. The data suggest that the genetic damage of several rec genes including recB, recE, recF, recL and recM can block induction of the SOS-like system of Bacillus subtilis.


[Structure of ends of linear plasmid N15].

The complete structure of the pins on the ends of the linear plasmid N15 (telomers) has been defined for procaryotic organisms for the first time. The ends of the plasmid DNA contain the short nonideal inverted repeats (the size of 28 nucleotide bps) differing in only two nucleotide pairs.


[Structure of a region in the genome of bacteriophage N15, necessary for formation of hairpins at ends of the linear plasmid prophage].

A fragment containing telRL site of bacteriophage N15 has been cloned in the vector plasmid pUC19. The nucleotide sequence of a small region from EcoRV-PstI fragment has been defined by Maxam-Gilbert technique. The analysis of the obtained sequence has shown the telRL site to be a nonideal palindrome (the size of 56 nucleotide ops) in which two nucleotide pairs differ in the positions 12 and 14 on both sides of the palindrome centre. The DNA region with alteration of purines and pyrimidines (GC) surrounded by AT-rich regions: 5'-ATTATACGCGCGTATAAT-3'--in the symmetry centre of palindrome is characteristic of the telRL site structure. This characteristic of the region may play a key role in recognition of the site by the specific enzyme at formation of linear prophage-plasmid during lysogenization.


[Cloning the asd and lysC genes from Cornyebacterium glutamicum].

Plasmids carrying an asd gene from a mutant. S-(2-aminoaethyl)-L-cysteine resistant strain of Corynebacterium glutamicum were selected from a clonoteque constructed on a plasmid cloning vector pSL5 by complementation of asd mutation in Escherichia coli. Evidence has been obtained that the cloned chromosomal DNA fragment contains also a complete sequence for feed-back-resistant aspartokinase lysC gene.


[Analysis of deletions in the dystrophin gene by the multiplex amplification method in patients suffering from Duchenne's muscular dystrophy].

Multiplex polymerase chain reaction was carried out with the material from 68 patients suffering from Duchenne muscular dystrophy in Moscow and Leningrad clinics. Six pairs of oligoprimers were used. Deletions were detected in the material from 22 patients. A new type of deletion was found. Data on deletion frequencies and spectrum were compared with the results published by other authors.


[A new R-plasmid from Yersinia pseudotuberculosis].

Yersinia pseudotuberculosis strain 140-P isolated from soil in the Far East was found to harbour an R-plasmid different from the plasmids that had been isolated from the bacteria previously. A new R-plasmid pLD140 is conjugation proficient and codes for the cellular resistance to streptomycin, tetracycline and sulfonamides. The plasid belongs to incompatibility group IncP. Its restriction endonucleases BamHI and SalI profile is different from the ones of the plasmids belonging to the RP4 family.


Discrepancy between self-reported and actual caloric intake and exercise in obese subjects.

Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet--low total energy expenditure and underreporting of caloric intake--in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic effects of food and exercise. Low energy expenditure was thus excluded as a mechanism of self-reported diet resistance. In contrast, the subjects in group 1 underreported their actual food intake by an average (+/- SD) of 47 +/- 16 percent and overreported their physical activity by 51 +/- 75 percent. Although the subjects in group 1 had no distinct psychopathologic characteristics, they perceived a genetic cause for their obesity, used thyroid medication at a high frequency, and described their eating behavior as relatively normal (all P < 0.05 as compared with group 2). The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis.


Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.


[Plasmids from bacilli related to BAcillus subtilis].

The basic structural and functional properties of natural bacilli plasmids are analyzed in this review. Bacilli plasmids are mostly cryptic, but some are found to have selective markers. Small plasmids replicate by rolling-circle mechanism, however, the replication of large plasmids is likely to occur by the theta-mechanism. Plasmid structures involved in replication are analyzed. The bacilli plasmids are stable. They are promising material for vector construction.


Sympathetic overactivity in patients with chronic renal failure.

Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/- 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.


Asthma.

There is an active inflammatory process in the airways of patients with asthma, even when the patients are asymptomatic. Some of the types of cells involved in this process possess the necessary biologic activities to produce many of the pathophysiologic features of asthma, but the underlying mechanisms have not yet been elucidated. Reducing the severity of the inflammatory process appears to be a reasonable goal of therapy, with potential long-range implications for the morbidity of asthma. Whether this theoretical benefit will be realized awaits further observation.


Transient ischemic attack (TIA) secondary to subdural hematoma.

Subdural hematomas many sometimes clinically resemble Transient Ischemic Attacks (TIA's). We present three cases which were initially evaluated for, diagnosed as having and were treated for TIA's, but later were found to have subdural hematomas. As in case one, patients with subdurals may have antecedent head trauma which they may or may not recall. Patients presenting with symptoms resembling TIA's need a complete neurologic evaluation. The differential diagnosis for TIA's includes arteriosclerotic extracranial vascular disease, cardiac emboli, migraine, seizure disorder, and mass lesions. Since the prognosis and treatment differs one needs to determine the etiology of the symptoms before treatment is initiated. Specifically, other diagnoses must be excluded prior to anticoagulation therapy, as evidenced by case 2.


Resources for medical decision-making in situations of high uncertainty.

The high standards of medical practice rest on the assumption that a physician's competence equips him or her to act on a patient's behalf. The conundrum created by medical uncertainty regarding the patient's diagnosis or the appropriate course of treatment seldom receives attention in the medical literature. This article highlights how the age-old medical ideal of beneficence, the modern concept of probabilities, the added dimension of treatment modification based on patients' preferences, and a compassionate disposition operate as competence-supporting tools in high uncertainty medical situations.


[Subacute sclerosing panencephalitis (SSPE) in women during pregnancy].

Four women with SSPE during pregnancy were observed. The influence of pregnancy on the course of illness was in all patients unfavourable: the disease exacerbated, what could be explained by physiological immunosuppression connected with gestation. Delivery (in three cases by sectio caesarea) had no beneficial influence on the fatal course of SSPE. In two cases intrauterine necrosis of foetus took place in the 8th and 20th week from the beginning of SSPE. In other two cases healthy children were born. One of them does not exhibit any neurological abnormalities during the first 5 years of life.


[IgG1-IgG4 subclasses in the cerebrospinal fluid and blood serum and their synthesis in the central nervous system in multiple sclerosis].

IgG1, IgG2, IgG3 and IgG4 subclasses were detected in cerebrospinal fluid and sera from 32 patients with MS. The CSF levels of IgG1 and IgG3 subclasses in MS patients were significantly higher than those of controls. There were no statistical differences between the values of IgG subclasses in MS and control sera. The IgG1 and IgG3 indices were significantly higher in MS patients than in controls showing that among four IgG subclasses IgG1 ang IgG3 were synthesized in the central nervous system of patients with MS. The elevation of IgG1 and IgG3 indices in MS patients was found more frequently (in about 90% of patients) than the elevation of the general IgG index (in 72% of patients).


[Results of prospective 24-hour EEG studies of patients after cranio-cerebral injuries].

In 26 patients 24-hour cassette EEG recording and routine EEG records were taken between 6 and 35 days and again between 6 and 12 months after craniocerebral trauma. Neurological examination and CT of the head demonstrated cerebral concussion in 11 cases and brain contusion in 15 cases. Early after trauma routine EEG was abnormal in 5 cases (19.2%) exclusively in those with brain contusion, and 24-hour EEG recording was abnormal in 16 cases (61.5%), including 7 with cerebral concussion and 9 with brain contusion. In the second half year after trauma 24-hour EEG was normal in 5 cases (19.2%) which had previously abnormal records, and abnormal EEG changes appeared in 6 cases (23.1%) with previously normal findings. Seizure activity was found in the first weeks after trauma in 9 (34.6%) 24-hour recordings. In the second half year after trauma seizure activity was no longer present in 2 cases, but appeared in 6 other cases. Thus 24-hour recording between 6 and 12 months after trauma demonstrated seizure activity in 50% of all patients. In 2 of them epileptic fits developed. The study shows that repeated 24-hour EEG recording after craniocerebral trauma may be important in early detection of patients who are at risk of epilepsy development.


[Clinical symptoms and the CT image of neoplasm metastases to the brain].

On the basis of 149 CT examinations of cases of brain metastases the neurological symptoms and signs were analysed in relation to the character of the metastasis and the extent of oedema. Stroke beginning of clinical manifestations, loss of consciousness, seizures and neurological syndromes were evaluated.


[Ischemic stroke in patients under 50 years of age with special reference to its etiology and risk factors].

Eighty-four patients with ischaemic stroke aged 18-50 years were analysed. They had been treated in the years 1985-1989. Forty-five of them were followed up. In a high proportion of cases stroke was a result of thrombosis. Many risk factors were found in this group, mainly hypertension. In most cases stroke was serious, in several cases post-stroke epilepsy and poly-infarction dementia developed.


[Neuropathological analysis of 8 cases of clinically diagnosed Reye syndrome].

Authors discuss the possible etiopathogenesis of Reye syndrome (RS) on the base of eight own cases presented in this paper and others previously described. The febrile infection was observed on the beginning of the disease in all actually analysed cases and was followed by symptoms of acute damage of liver and brain. The central nervous system lesions present the changes increasing with time from brain oedema to the necrosis of nerve tissue. The oedematous changes could be recognized as a principal cause of unconsciousness and even of coma in RS. When the etiology of RS remain unknown the clinico-pathological observations of such cases incline to formulate three questions: Is an genetically conditioned background necessary which facilitate toxic or infectious factors to induce the RS? Is the etiology of RS only genetically conditioned? Is an specific viral infection the cause of RS?


[Arteriovenous malformations of the dura mater].

The authors present two cases of dural arteriovenous malformations treated in Dept. of Neurosurgery, Warsaw Medical School. The main clinical problems of this type of AVM are discussed.


[Risk factors of leukemic infiltration in patients with acute myeloblastic leukemia].

On the basis of clinical neuropathological evaluation of 48 patients with acute myeloblastic leukaemias the authors analyse the risk factors of leukemic infiltrations developing in the brain. The investigations revealed that the distinct dissemination of leukemic cells in blood is the most important risk factor of such infiltrations. The risk increases significantly in older patients. Survival time and maintenance of high leukocytosis do not intensify the risk of leukemic infiltrations in the brain.


[Use of transcranial Doppler ultrasonography for evaluation of intracranial pressure].

Transcranial Doppler (TCD) studies are very useful for the evaluation of intracranial pressure changes. The most informative for the TCD increase diagnosis are the diastolic pressure decrease and increase of two computed indices: pulsatility index (PI) and resistance index (RI). Single measurements can be misleading and therefore, monitoring of neurosurgical intensive care patients is suggested. Additional information is provided by TCD studies in cerebral blood flow autoregulation tests. The usefulness of TCD in brain death diagnosis is discussed also.


Astrocyte-endothelial interaction: physiology and pathology.

The blood-brain barrier of higher vertebrates is formed by the layer of endothelial cells lining the brain microvessels. The close anatomical association between endothelial cells and perivascular astrocytic end feet suggests cooperation between these cell types in forming and maintaining the blood-brain barrier. This review considers evidence from grafting experiments, developmental studies and culture models of the brain endothelium, concerning the inductive influences acting on the endothelium, and from endothelial cells acting on perivascular astrocytes. Examples from pathology and neurotoxicology which may involve breakdown of induction are also considered.


[A case of congenital muscular dystrophy with changes in the white matter of the brain].

A case of cerebro-muscular disease is reported in a 5-year-old girl with normal mental development. The changes resembled those in Fukuyama dystrophy, but the clinical picture differs from that dystrophy in normal mental development and absence of other pathological changes in the central nervous system.


Glioma heterogeneity in vitro: the significance of growth factors and gangliosides.

Despite renewed attempts by the WHO at updating the system of classification for brain tumours, most of the dynamic biological processes which underlie both the morphological appearances which form the basis for such systems and the malignant potential of gliomas remain an enigma to the neuropathologist. One feature recognized in human gliomas is their phenotypic and genotypic heterogeneity. Such cellular heterogeneity seen in the histological section is retained in vitro, at least during early passage. It is proposed that this heterogeneity is important in the growth and maintenance of the tumour and may be related to the activity of growth factors and gangliosides. Such molecules may not only influence the histoarchitecture of glial neoplasms but may also determine malignant progression and invasive potential. Moreover, there may be an intimate relationship between growth factors and gangliosides constituting an intricate feedback mechanism upon which the biological progression of gliomas depends.


The inflammatory response in the CNS.

In recent years it has been recognized that cells of the mononuclear phagocyte lineage, macrophages and microglia, are a major component of gliosis. We review here studies on the kinetics of the myelomonocytic response to acute excitotoxin induced neuronal degeneration and following the injection of endotoxin (LPS) into the parenchyma of the central nervous system. These studies have shown that the kinetics of myelomonocytic recruitment to the parenchyma of the central nervous system is quite unlike that of other tissues; the polymorphonuclear cells are largely excluded and monocytes are only recruited after a delay of several days. The unusual nature of the inflammatory response in the central nervous system needs to be considered when drawing parallels with the acute inflammatory response in other tissues.


[Intramedullary metastatic tumor. Case report].

An extremely rare case of intramedullary spinal cord metastasis (Carcinoma solidum metastaticum) is presented. No primary tumour was found. The authors discuss diagnostic and therapeutic problems of treatment in such cases.


Transplanted cultured type-1 astrocytes can be used to reconstitute the glia limitans of the CNS: the structure which prevents Schwann cells from myelinating CNS axons.

Transplantation of different glial cells into areas of demyelination made in the adult rat spinal cord allows insights into the cell-cell interaction necessary to reconstruct a glial environment around demyelinated axons. Such studies have shown that type-1 astrocytes are central to the exclusion of Schwann cells from areas of glia-free demyelination. However, for these cells to be established in a manner which prevents Schwann cell remyelination of CNS axons, cells of the O-2A lineage are also required. If cultures of isogeneic rat type-1 astrocytes and mouse O-2A cells are transplanted into lesions made in non-immunosuppressed animals. Schwann cell remyelination is limited and extensive oligodendrocyte remyelination is achieved. This paradigm creates a model of immune mediated demyelination in which the immune response is not primarily directed at oligodendrocyte specific epitopes.


Genes coding for proteins in central nervous system myelin.

There has been considerable interest recently in a genetic component as a causative factor in multiple sclerosis, but the identity of putative susceptibility genes is unknown. In the past decade, the primary amino acid sequences of the four proteins making up 90% of the protein content of central nervous system myelin (proteolipid protein, myelin basic protein, 2',3'-cyclic nucleotide-3'-phosphohydrolase, and myelin-associated glycoprotein) have been determined in several species. Additionally, the structural genes coding for these proteins have been analysed and their human chromosomal localization determined. We have been analysing these genes for possible variants conferring susceptibility to multiple sclerosis. Recent results have shown that cholera and pertussis toxin substrates and low molecular-weight GTP-binding proteins are also present in central nervous system myelin. This implies the presence of signal transducing systems whose purpose is currently obscure. The emerging picture of central nervous system myelin is of a complex dynamic structure composed of many more proteins than was previously thought.


[Spontaneous cerebrospinal rhinorrhea--report of 2 cases].

The authors present 2 cases of non-traumatic, so called "spontaneous" rhinorrhea. The pathological mechanism of CSF nasal fistula and operation methods are discussed.


Pathology of the central nervous system in patients infected with the human immunodeficiency virus (HIV): a report of 252 autopsy cases from Brazil.

The central nervous system (CNS) was studied in 252 HIV-infected patients from the States of Rio de Janeiro and São Paulo in Brazil, the regions with the highest incidence of AIDS in the country. We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases. There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or tumours. Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections. The most frequent was toxoplasmosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%). Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7%. Other opportunistic and HIV associated lesions were present in a limited number of cases and there were also vascular and non-specific lesions. Our study confirms the high frequency of CNS lesions in HIV infected patients. They are morphologically similar to those previously described. However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV-associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio-economic factors.


Morphological spectrum, distribution and clinical correlation of white matter lesions in AIDS brains.

This paper analyses the histopathological characteristics and the topographical distribution of 'pure' HIV-associated white matter lesions of the brain in 18 AIDS patients at autopsy; it includes a time-controlled correlation of neuropathology to clinical staging of the AIDS dementia complex. Three distinct lesion types can be delineated: 1 Vacuolar myelin damage (n = 15) in the hemispheric and interhemispheric white matter, in projection fibre tracts, and in intracerebral segments of cranial nerves III, VII, and VIII; 2 Angiocentric foci (n = 14), disseminated randomly in the white matter; 3 HIV leukoencephalopathy (n = 14), as previously defined, seen predominantly in the hemispheric white matter. As a sole lesion type, HIV leukoencephalopathy is found in two cases, while vacuolar myelin damage and angiocentric foci always occur in combination with one or both other types of pathology. Patients with advanced AIDS-dementia complex consistently show severe and combined white matter pathologies at autopsy. We conclude that, in addition to the previously defined features of diffuse HIV leukoencephalopathy, vacuolar myelin damage and angiocentric foci are significant and frequent components of white matter pathology in AIDS autopsies. This reflects the multitude of pathogenetic factors which co-operate in damaging the brain in AIDS. The advanced AIDS dementia complex correlates with the combined and severe white matter lesions.


Late effects following central nervous system radiation in a pediatric population.

Between 1970 and 1986, 120 children with central nervous system malignancy were treated with radiation therapy. These included 44 low-grade astrocytomas, 11 high grade astrocytomas, 32 medulloblastomas, 15 ependymomas/ependymoblastomas, 3 primitive neuroectodermal tumors and 8 pineal tumors. Seven children were treated without biopsy. Fifty-one treated children were evaluated for the effects of therapy on growth, endocrine function, IQ and hair regrowth. Mean height was 1.5 standard deviations below the mean height for the patient's age at study (range 0-5.7). Height was significantly less in patients receiving radiation to the pituitary and those with somatomedin-C deficiency. Height was also decreased with whole CNS radiation and spine dose > 20 Gy but not to a significant degree. Pituitary radiation in any dose increased the chance of endocrine deficiency (p = 0.004) and 21 of 51 patients had somatomedin-C deficiency. Mean IQ was 92.7 (+/- 18.8), with a slight trend toward decreased IQ with increasing whole brain dose of radiation. Hair regrowth was complete in 20 of 46 evaluated patients, diminished regrowth occurring with increasing volume and dose of radiation. No difference in the measured late effects could be detected with respect to age at treatment, sex, histology or location of tumor.


Cerebro-spinal fluid eosinophilia in shunt infections.

Hypereosinophilia has been detected in the CSF of 22 patients in a series of 81 cases of shunt infection. It was related with the evolution of the sepsis. Its persistence at the end of treatment appeared to predict later complications, septic or obstructive, and it could be the sign of latent infection. HE might be the result of a specific reaction directed against the infected material, but a non-specific process cannot be eliminated.


Cerebral blood flow velocity and failure of autoregulation in neonates: their relation to outcome of birth asphyxia.

Using the continuous wave Doppler technique, we examined the pulsatility index (PI) of the anterior cerebral artery in 14 asphyxiated infants. We also measured the blood pressure (BP) and fontanel pressure (FP) and calculated the cerebral perfusion pressure (CPP). According to the neurological prognosis, we divided the 14 infants into two groups and studied correlation of each factor. In the good-prognosis group (n = 11), PIs are within normal limits. There is a negative correlation between BP, CPP and PI, suggesting that the autoregulation of cerebral blood flow has been lost. On the other hand, there is no significant correlation between BP, CPP and PI in the poor-prognosis group (n = 3). These infants are thought to have lost the autoregulation, but their cerebral blood flow is not pressure-passive. Not only BP but also brain edema, vasodilation, and possibly other factors may contribute to determine the cerebral blood flow. Concerning FP, no remarkable correlations are found between two groups. It is therefore very important to monitor the PI, BP, FP in asphyxiated infants even if the degree of asphyxia is mild.


Transventricular endoscopic investigation and treatment of suprasellar arachnoid cysts.

Three children with a suprasellar arachnoid cyst and characteristic neuropathological signs are presented. Through the use of CT scanning and NMR imaging the location, volume and attenuation factors of these cysts can be documented. Stereotactically guided endoscopic exploration of the third ventricle region with visualization and manipulation of the cyst have been performed. This technique should be considered a safe and accurate alternative to craniotomy.


Severe type Hunter's syndrome. Polysomnographic and neuropathological study.

The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea.


Disturbance of GABA metabolism in pyridoxine-dependent seizures.

In an infant with typical pyridoxine-dependent seizures, CSF GABA level, was determined before treatment with pyridoxine. Before onset of treatment, level of GABA in CSF was highly lowered (16 pmol/ml), pyridoxine level in serum was within normal range. Immediately after application of 80 mg pyridoxine fits stopped and the EEG was without seizure activity. The data substantiate previous findings in brain tissue from a patient with pyridoxine-dependent seizures. They are proof of a disturbed GABA metabolism in pyridoxine dependent seizures.


Congenital caudal spinal atrophy: a case report.

An infant presented at birth with symmetrical flaccid paraparesis limited to lower legs and feet, and involving the proximal and distal muscle group. Limitation of the ankle joints was noticed. There were no sensory deficits to painful stimuli and no evidence of loss of sphincter control. Muscle CT revealed severe muscle atrophy in the pelvis and lower limbs, and electromyographic study of the bilateral hamstrings showed polyphasic giant potentials. Motor and sensory nerve conduction velocities were within normal limits, and the spinal MRI showed no structural abnormalities in the cord and the lower spine. These features suggest a congenital segmental abnormality at the anterior horn cell level in the lumbosacral spinal cord, which we propose to call "congenital caudal spinal atrophy".


Proton NMR spectroscopy of Canavan's disease.

Proton Nuclear Magnetic Resonance (NMR) spectroscopy was used to quantitatively determine cerebral N-Acetyl Aspartate (NAA) concentrations in four patients with Canavan's disease and in four age-matched control subjects. Macroscopic NAA concentrations (mumol/gm wet weight) were not found to be significantly different from controls. Reduced levels of choline and creatine were observed in all patients, and increased levels of lactate and inositol in the eldest three patients.


Hereditary progressive dystonia with diurnal fluctuation (Segawa's syndrome)--an unusual case.

A young girl with hereditary progressive dystonia with diurnal fluctuation or Segawa's syndrome, completely handicapped and confined to a wheelchair between the age of 5 and 9, revealed an unusually slow response to levodopa. The ability to walk returned only after 12 to 14 months of treatment. Apart from peculiarities of behaviour due to longstanding immobility and ensuing parental overprotection, there were no psychological or mental abnormalities. Other organic diseases were ruled out. A series of regular follow-ups over the course of 7 years was performed. While residual and irregular day-to-day variation of functional capacities almost disappeared after conversion to a preparation with a decarboxylase inhibitor, some mild neurological abnormalities and a slight choreic hyperkinesia persisted with doses providing functional results. The patient today leads an almost normal teenage life and has performed well in school.


Severe adverse reaction to carbamazepine: significance of humoral and cellular reactions to the drug.

Hypersensitivity to carbamazepine is a well-known phenomenon. The involvement of several organ systems including liver, kidney, bone marrow and other organs have been described. We have observed a 7-year-old boy who had been treated with carbamazepine for seizures. After 10 days of treatment he developed a severe illness with skin rash, high fever, lymphadenopathy, hepatosplenomegaly and lymphopenia. Only slightly decreased complement components and increased complement split products but no circulating immune complexes were demonstrable on admission. Anti-carbamazepine antibodies, T-cell-activation and a significant T-cell reactivity against carbamazepine were found, indicating specific hypersensitivity. Complete recovery was observed after discontinuation of the drug and steroid treatment.


Magnetic resonance imaging of progressive hydrosyringomyelia in two patients with meningomyelocele.

Two patients who postoperatively developed extensive multiseptated hydrosyringomyelia following surgical repair of a lumbal meningomyelocele are reported. Since MRI has been available, an increasing number of reports showed that MRI is useful in the diagnosis of hydrosyringomyelia. Hydrosyringomyelia can be considered as a dysraphic lesion. Etiology and pathogenesis of hydrosyringomyelia are still not fully understood. Probably arachnoidal adhesions and cord tethering in both patients may be potential factors in producing cystic degeneration of the underlying structure secondary to ischemia.


Behavioural effects of two dipeptides L-phenyl alanyl-L-arginine (Phe-L-Arg) and L-phenyl alanyl-D-arginine (Phe-D-Arg) after intracerebroventricular or intrathecal injections in mice.

L-phenylalanyl-L-arginine (Phe-L-Arg) and L-phenylalanyl-D-arginine (Phe-D-Arg), dissolved in a physiological saline were injected intrathecally into the lateral brain ventricle, and their behavioural as well as analgesic effects in mice were determined. It was found that a 100 nM dose of either peptide intracerebroventricularly (i.c.v.) injected induced an increase in the locomotor activity and a convulsive effect, whereas the same dose if injected produced a significant analgesic effect. It has been concluded that Phe-L-Arg and Phe-D-Arg have significant but different central effects in mice.


Prenatal stress alters the hypothalamic levels of methionine-enkephalin in pup rats.

We examined hypothalamic Methionine-enkephalin levels in offspring (postnatal day 10) from stressed female rats in different period of gestation: Group 1, restraint stress day 2 through 6; group 2, restraint stress day 7 through 11; group 3, restraint stress day 12 through day 16 and group 4, restraint stress day 2 through day 16. The hypothalamic levels of Methionine-enkephalin (134.37 +/- 6.19 pg/mg) in the offspring of stressed females from day 2 to day 6 of gestation were significantly (p < 0.001) higher than that obtained in the control group (100.66 +/- 10.13 pg/mg). Similar results were obtained in groups 2 and 3. However, in rat pups from females stressed during 15 days of gestation (group 4) the hypothalamic levels of Methionine-enkephalin (96.5 +/- 6.33 pg/mg) were similar to that obtained in the control group (101.5 +/- 5.15 pg/mg). These results suggest that acute prenatal stress alters the endogenous opioid activity in offspring with possible resultant effects on developmental processes.


Structure-activity studies on the effects of atrial natriuretic peptide, brain natriuretic peptide and their analogs on fear-motivated learning behavior in rats.

Our previous studies have demonstrated that rat atrial natriuretic peptide (rANP 1-28) and porcine brain natriuretic peptide (pBNP 1-32) administered into the lateral brain facilitate the consolidation of a passive avoidance response and delay the extinction of an active avoidance response in fear-motivated learning in rats. To study the structure-activity relationships in the same learning processes, the effects of several fragments related to ANP and BNP were investigated following their intracerebroventricular administration to rats. The following peptides were studied: rANP 1-28, rANP 5-28, rANP 5-27, rANP 7-23 (ring), rANP 17-23, hANP 10-28, hANP 15-28, hANP 20-28, hANP 1-28, pBNP 1-32 and pBNP 7-32. The peptides were used in equimolar concentration. Two of the peptides studied, ANP 20-28 and ANP 17-23, were ineffective on the extinction of active avoidance behavior and on the consolidation of passive avoidance learning. They exhibited similar actions. The results showed that small fragments of ANP and BNP can carry the biological activity of ANP and BNP on the central nervous system (CNS). It is likely that the biological active center for ANP lies between amino acids 15 and 23 and it is suspected that the ring structure is not absolutely important for the CNS activity.


The presence of neuropeptides in GABAergic and cholinergic rat cerebrocortical synaptosome sub-populations.

GABAergic and cholinergic synaptosomes from rat cerebral cortex were isolated by a magnetic immunoaffinity technique, i.e. immunomagnetophoresis. These subpopulations were extracted and subjected to radioimmunoassay for four neuropeptides: Neuropeptide Y (NPY); vasoactive intestinal peptide (VIP); substance P (SP); and somatostatin (SRIF). In each of the sub-populations three of the four peptides were enriched in the sorted fraction compared with the mother fraction with respect to the cytosolic marker lactate dehydrogenase (LDH). In the GABAergic sub-population the order was SP > SRIF > NPY > or = VIP whilst in the cholinergic sub-population they were enriched in the order VIP > or = NPY > SP > SRIF. The presence of NPY has not previously been reported in cortical cholinergic neurons.


The NMDA-receptor antagonist dizocilpine (MK-801) suppresses the memory facilitatory action of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) has been shown to improve memory both in animal amnesia models and in humans. In an earlier study we have found that respiratory stimulant action of TRH is mediated through the N-methyl-D-aspartate (NMDA) receptors. Since brain NMDA receptors are implicated in neuronal plasticity, we have investigated whether the non-competitive NMDA antagonist dizocilpine antagonizes the memory-facilitatory action of TRH. TRH (5 mg/kg i.p.) increased passive avoidance scores in the rats in both memory retention and retrieval tests. Dizocilpine (0.2 mg/kg i.p.) caused no significant performance changes. However, it completely blocked the improvement of retention caused by TRH and reversed its effect on retrieval. We conclude that the facilitatory effect of TRH on avoidance retention and retrieval may be mediated by NMDA receptors.


Grade II and grade III hypothyroidism in rapid-cycling bipolar patients.

Thyroid function was evaluated in 10 rapid-cycling bipolar patients who had previously responded to lithium treatment. Five patients had grade II and 1 patient had grade III hypothyroidism as determined by thyrotropin-releasing hormone tests. Treatment with thyroxine in addition to lithium significantly decreased the intensity and frequency of rapid cycling episodes.


Acutely administered haloperidol-induced pattern changes of regional cerebral blood flow in schizophrenics. Observation from subtraction of brain imaging with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime.

Changes in regional cerebral blood flow in brain images with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime before and after intramuscular injection of haloperidol (0.08 mg/kg) were studied in 5 medicated subjects in their twenties, consisting of 5 schizophrenics and 1 patient with histrionic personality disorder, by a subtraction method of brain images. The haloperidol injection induced two types of perfusion pattern change; in 2 of the schizophrenics, a relative hypoperfusion in the frontal lobes in the images prior to injection was converted to a relative hyperperfusion. In the other 3 schizophrenics and in the patient with histrionic personality disorder, the slight left hemispheric dominance was changed to a marked right hemispheric dominance. The results indicate that haloperidol affects perfusion patterns in schizophrenics.


Twenty-four-hour beta-endorphin secretory pattern in Alzheimer's disease.

A chronobiological study was carried out in 6 male patients (67-71 years), suffering from Alzheimer-type dementia (ATD) and 6 male patients (52-74 years) suffering from multi-infarct dementia (MID), to evaluate their 24-hour beta-endorphin and cortisol secretory patterns. Six healthy male adults (28-37 years) and 6 healthy elderly male subjects (78-84 years) constituted the control groups. Blood samples were drawn every 4 h from 8.00 to 20.00 h and every 2 h from 24.00 to 6.00 h. Mean 24-hour beta-endorphin levels were significantly (p < 0.05) higher in the ATD patients (39.2 +/- 1.5 ng/l) than in the other groups (33.8 +/- 1.1, 30.1 +/- 1.6 and 33.2 +/- 1.1 ng/l in the elderly subjects, the adults and the MID patients, respectively). The circadian rhythm was absent in the ATP patients, in the elderly subjects and the MID patients. No differences in plasma cortisol circadian rhythm were observed among the four groups. Our data indicate that changes in circulating beta-endorphin concentrations and circadian pattern may be due to the aging process.


Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


Tricyclic antidepressant plasma levels after fluoxetine addition.

After a review of a pharmacokinetic interaction between tricyclic antidepressants (TCA) and fluoxetine the authors report their own data. They confirm the existence of an interaction of TCA with fluoxetine, in clinical practice, but the fluoxetine was not associated in all cases with a marked increase of TCA plasma levels. The increase appeared especially high with clomipramine (n = 4) and imipramine (n = 3), and lower or dose-dependent with amitriptyline (n = 4). The pharmacokinetic change did not induce side effects in the patients, even when the total TCA plasma level increased to 965 (clomipramine) or 785 (imipramine) ng/ml. The authors then discuss the clinical implication and the possible mechanism of action.


Thyroid hormone correlates of sensation seeking and anxiety in healthy human females.

The present study explores the relationships among a number of personality measures (the Sensation-Seeking Scale, SSS; the State-Trait Anxiety Inventory, and the Susceptibility to Punishment Scale) and some parameters of the pituitary-thyroid axis. The study was carried out on a group of 37 physically and mentally fit female volunteers, none of whom had a personal history of psychiatric or endocrinologic illness. The subjects were controlled for the menstrual cycle. The most relevant result was a significant negative relationship between the SSS score and plasma basal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Interaction between T4 and TSH levels with trait anxiety was also observed.


Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.

The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.


Effect of carbamazepine treatment on EEG changes induced by different cortical activation patterns in newly referred epileptic patients.

Sixteen epileptic patients suffering from focal epilepsy who underwent antiepileptic drug treatment with carbamazepine (CBZ) for the first time were studied. The EEG was recorded at rest with eyes closed, during blocking reaction (BR), fixation (FIX) and mental arithmetic tasks. The computerized EEG study, performed before and after CBZ therapy, utilized spectral analysis. Data underwent statistical evaluation through Anova and correlation analysis. The parameters evaluated were the mean frequency and the mean absolute and relative power. The results have shown that after CBZ treatment there is a decrease in the alpha reactivity during BR and FIX, while a significant increase in beta activity was observed during all tasks. The effect of CBZ therapy on EEG activity during cortical activation patterns are discussed.


Where have all the captains gone? A comparison of active and reserve MC ranks and ages, Vietnam to Desert Storm.

An analysis of ages and ranks of hospital-based physicians in one area of the Persian Gulf War was used for a comparison with similar data from the Vietnam War. Mean age in the latter was 33.4 years; rank was Captain (0-3.24). In Desert Storm, mean age and rank significantly increased to 46.0 years and close to Lieutenant Colonel (0-4.73), respectively. The large proportion of Reserve Component Physicians (75%) in the Persian Gulf War is the probable explanation for these findings. Medical Corps recruitment and retention problems may result from this most recent war and pose potential threats to success in future U.S. conflicts.


Ten leadership steps to a smooth facility upgrade.

Leading a medical treatment facility (MTF) through the construction phases of a major upgrade, repair, or any sizable facility project is a challenging and complex endeavor. The Executive Staff can make the process easier on everyone and ensure the final product is in tune with the MTFs needs by taking positive leadership actions. This article describes the effective actions discovered during a 2.5-year-long total MTF upgrade of the 52 Tactical Fighter Wing (TFW) Clinic. These actions involved promulgating a broad systems view of the process, establishing philosophies and criteria, promoting team work, involving customers, and building consensus among the staff.


A descriptive analysis of urine cultures: pure versus mixed isolates.

Out of 5,670 urine cultures performed in 1989, 1,448 positive cultures with unique results were analyzed. Of these 1,448, 67% were pure cultures, and 50% had at least one isolate with a colony count greater than 100,000 colony forming units/ml. Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus, and diphtheroids were more likely (p < 0.01) to occur in mixed than pure culture, while Escherichia coli was more likely to occur in pure than mixed culture. The most common organism combinations were diphtheroids-coagulase negative Staphylococcus (30 cultures), E. faecalis-coagulase negative Staphylococcus (28), E. faecalis-P. aeruginosa (13), K. pneumoniae-P. aeruginosa (9), and E. coli-P. aeruginosa (9).


A descriptive study of mentoring relationships experienced by Army nurses in head nurse or nursing supervisor roles.

Mentoring relationships experienced by Army Nurse Corps officers in head nurse or nursing supervisor roles were examined via a survey questionnaire. Findings indicate that career development relationships are occurring among these nurses, but less than half of the relationships consist of mentoring. Nursing supervisors comprised the largest group of career developers, while head nurses were the second most likely group to assist with the development of a novice nurse. Approximately half of the nurses indicated that the career development relationship had a "substantial" influence on their personal lives, and a "very great" influence on their professional lives.