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Lipoprotein[a] or Lp[a] is a cholesterol-rich plasma lipoprotein that is associated with increased risk for cardiovascular disease. To better understand this association we determined the amount of apo[a] and apoB as possible estimates for Lp[a] and low density lipoprotein (LDL) accumulation in atherosclerotic lesions and in plasma, from patients undergoing vascular surgery, using specific radioimmunoassays for apolipoprotein[a] and apolipoprotein B. Apo[a] and apoB were operationally divided into a loosely bound fraction obtained by extracting minced samples of plaque with phosphate-buffered saline (PBS), and a tightly bound fraction obtained by extracting the residual tissue with 6 M guanidine-HCl (GuHCl). We found that 83% of all apo[a] but only 32% of all apoB in lesions was in the tightly bound fraction. When normalized for corresponding plasma levels, apo[a] accumulation in plaques was more than twice that of apoB. All fractions of tissue apo[a], loosely bound, tightly bound, and total, correlated significantly with plasma apo[a]. However, no significant correlations were found between any of the tissue fractions and plasma apoB. If all apo[a] and apoB had been associated with intact Lp[a] or LDL particles, the calculated mass of tightly bound Lp[a] would actually have exceeded that of tightly bound LDL in five cases with plasma Lp[a] levels above 5 mg apo[a] protein/dl. When PBS and GuHCl extracts of lesions were subjected to one-dimensional electrophoresis, the major band stained for lipid and immunoblotted positively for apo[a] and apoB, suggesting the presence of some intact Lp[a] in these extracts. These results suggest that Lp[a] accumulates preferentially to LDL in plaques, and that plaque apo[a] is directly associated with plasma apo[a] levels and is in a form that is less easily removable than most of the apoB. This preferential accumulation of apo[a] as a tightly bound fraction in lesions, could be responsible for the independent association of Lp[a] with cardiovascular disease in humans.

Foam cells in atherosclerotic lesions are derived not only from blood monocytes but also from smooth muscle cells (SMC). To better understand the mechanisms by which SMC may become lipid-laden, we have studied the catabolism by cultured rabbit aortic SMC of LDL derived from atherosclerotic lesions (A-LDL) previously shown to be chemically modified. A-LDL was isolated either from homogenates of atherosclerotic plaques in human aortas by affinity chromatography and gel filtration, or from nonhomogenized extracts of plaque minces by ultracentrifugation and gel filtration. Internalization of A-LDL by SMC or fibroblasts appeared to be mediated primarily via the LDL receptor since: 1) either unlabeled LDL or A-LDL could inhibit the degradation of 125I-labeled A-LDL or of 125I-labeled LDL, 2) the uptake of both A-LDL and LDL, as estimated by their abilities to stimulate cholesterol esterification, was reduced in cells in which LDL receptor expression was down-regulated; and 3) the uptake of both [3H]cholesteryl ether-labeled A-LDL and LDL by normal fibroblasts was significant and could be inhibited by excess LDL, but was negligible in receptor-negative fibroblasts. At saturating concentrations of lipoproteins, maximum cholesterol esterification in SMC was greater for LDL than for A-LDL. Over a 48-h incubation, A-LDL, like LDL, was unable to induce cellular cholesteryl ester accumulation. Cross-competition studies suggested that either the affinity of A-LDL for the LDL receptor was less than that of LDL, or that some particles in A-LDL are not internalized by SMC. The latter alternative was supported by the observations that some A-LDL particles had undergone aggregation, especially at high concentrations, and that aggregated forms of A-LDL or plasma LDL failed to be internalized and degraded by SMC. Collectively, these results are consistent with recognition of some of the A-LDL particles by the LDL receptor, but also suggest that, at least under in vitro conditions, A-LDL is unlikely to induce lipid accumulation in SMC resulting in SMC-derived foam cells.

Three hundred and fifty-five prostitutes working in The Gambia were enrolled in a study of retroviral infections. Eight-seven (24.6%) were infected with HIV-2 only, two (0.6%) with HIV-1 only, four (1.1%) had sera showing double HIV-1/HIV-2 reactivity, and 37 (10.4%) were seropositive for HTLV-I. After allowing for socioeconomic and serological variables in a multivariate analysis, HIV-2 infection was associated with serological evidence of a previous episode of syphilis [a rapid plasma reagin (RPR) positive/Treponema pallidum haemagglutination assay (TPHA) positive; odds ratio (OR) = 2.18, 95% confidence interval (CI) = 1.19-3.98], with having antibodies against Haemophilus ducreyi (OR = 2.05, 95% CI = 0.89-4.70) or against HTLV-I (OR = 2.17, 95% CI = 0.91-5.19). HIV-2-seropositive prostitutes were three times more likely [17 out of 78 (22%) versus 15 out of 219 (7%), P less than 0.001] to have generalized lymphadenopathy than those who were seronegative. These data suggest that genital ulcer diseases may facilitate the transmission of HIV-2, and that HIV-2 rapidly induces the appearance of generalized lymphadenopathy in a substantial proportion of infected individuals.

We report a new technique of transcranial magnetic stimulation of the motor cortex to measure conduction within central motor pathways of 67 patients with cervical spondylosis or disk herniation. There were upper motor neuron signs in 34 patients (51%) and x-ray evidence of cervical cord compression in 44 (66%). Muscle action potentials (MAPs) to cortical stimulation were abnormal in 84% of patients with, and 22% of those without, radiologic signs of cervical cord compression. Median nerve somatosensory evoked potentials were altered in only 25% of patients. The frequency of MAP alterations correlated with upper motor neuron signs. In 5 (11%) of the 44 patients with x-ray evidence of cervical cord compression, subclinical cord compression was disclosed by cortical stimulation. In 10 patients restudied 3 months after surgical decompression, normalization of central motor conduction time did not occur, indicating permanent damage to the cervical cord.

Mother-to-child infection with HIV-2 is thought to be rare, and there have been few previous reports of transmission by this route. Reports of morbidity associated with HIV-2 infection in children are also rare. We describe eight children born to mothers who were infected with HIV-2; five developed AIDS, and three were still seropositive at 17-49 months of age. The only apparent route of HIV-2 transmission was from mother to child, except for one child who had been transfused. Three of the children with AIDS died, all having decreased CD4+ lymphocytes and mitogen responses. Further studies are needed to determine the prevalence and natural history of mother-to-child transmission of HIV-2.

A variety of different cholesterol-rich particles with different physical and chemical structures can be isolated from human atherosclerotic lesions. Many of these particles are internalized in an unregulated fashion by macrophages in culture, leading to lipid loading of these cells. However, the in vivo relevance of this uptake is still uncertain. In this overview, we have summarized data obtained primarily in our laboratory on low density lipoprotein (LDL)-like particles (A-LDL) and large cholesterol-rich droplets isolated from human atherosclerotic lesions. Based on our studies, we propose a variety of different mechanisms of uptake. A-LDL can be internalized by the LDL receptor or the scavenger receptor on macrophages in culture; the latter uptake mechanism can lead to lipid loading. In addition, at high concentrations A-LDL can undergo aggregation, possibly due to intermolecular cross-bridging by aldehydes released during oxidation of these particles. The aggregates are subsequently internalized by macrophages by phagocytosis, a process which appears to be independent of the LDL or scavenger receptor. By contrast, arterial smooth muscle cells do not take up these aggregates. Large cholesteryl ester-rich particles isolated from human lesions, and derived from LDL that had been degraded by hydrolytic enzymes in the extracellular space of the arterial wall, or from inclusions released from lysed foam cells, are also internalized via phagocytosis by macrophages in culture. Since some of these particles contain apoliproteins and/or proteins that are ligands for receptors on macrophages, initial receptor-mediated binding may precede and facilitate subsequent phagocytosis in some cases. Uptake of the diverse group of cholesteryl ester-rich particles in plaques can induce lipid loading of macrophages and therefore may lead to further growth of the atherosclerotic plaque.

The aim of this study was to test the efficacy of nocturnal oximetry as a means of continuous recording of SaO2 in the identification of apnoeic events in the recognition of non-apnoeic desaturation. The oscillations of SaO2 in relation to successive periods of apnoea during the course of the sleep apnoea syndrome (SAS) or with apnoeic episodes in patients with chronic airflow obstruction (BPCO) or restricted disease, were identified using a new delta index quantifying the variations of SaO2 during the night. 26 successive patients in whom there was an indication for nocturnal oximetry were included in a prospective study comparing nocturnal oximetry and polysomnography during 34 nights. In the apnoeic patients we found a strong correlation (r = .85. p. less than .01) between the apnoeic period and the delta index. In BPCO the number of apnoea was correlated with the delta index (r = .96. p. less than .01). A minimal threshold of the delta index fixed at 1.5 was satisfactory for detecting apnoea if the initial SaO2 was less than 93%. The value of the adequate for affected detection ought to be fixed at .8 (95% sensitivity) when the initial SaO2 was greater than 93%. A detection of apnoeic events thus seems possible by this method.

Neurophysiologic mechanisms responsible for parkinsonian rigidity are poorly understood. In any case, they have to fit all the clinical data which are first reviewed before discussing 2 theories which are proposed to interpret rigidity. The first theory postulates that increased resistance to mobilization is due to hyperactivity in a long loop reflex pathway which originates at the neuromuscular spindles and relays in the motor cortex. This theory is based on the largely accepted finding that, in parkinsonian patients, M2 response is increased when a voluntary movement is abruptly stopped. Although popular this hypothesis is far from explaining all the clinical facts, namely that rigidity is equal in extensor and flexor, proximal and distal muscles. Based on a reflex set by primary afferent discharges, it is incompatible with the lack of rigidity reinforcement after faster passive mobilization. The second theory rests on data obtained from electrophysiological studies of some spinal interneurones. Both IA and IB inhibitory interneurones are functionally modified but not in the same direction. While the IA inhibitory interneurone is facilitated, the IB inhibitory interneurone is less active. Disappearance of autogenic inhibition can explain rigidity at rest and the tonic stretch reflex. In addition, interneurones intervening in the flexor reflex disclose a modified excitability. It is possible to interpret these facts by postulating an abnormal influence transmitted through descending reticulospinal pathways. This abnormal influence would result from modified activation of reticular nuclei by afferents projecting from the basal ganglia. Such a hypothesis is open to experimental testing through the startle reaction. The latter facilitates the H reflex by the reticulospinal pathways, the influence of cortex--if any--being negligible.(ABSTRACT TRUNCATED AT 250 WORDS)

A series of 123 patients suffering traumatic spondylolisthesis of the axis is reported. This lesion is associated with extension and axial loading injury, and there is a high incidence of injuries of the face or scalp and of associated fractures of the upper cervical spine. There is a low incidence of neurological injury, which seems paradoxical in the presence of what appears to be gross instability, but protection from extremes of flexion and extension may be adequate treatment. Union is usual regardless of displacement. Traction is a safe means of treatment, but early waking in a halo support reduces time in hospital without jeopardizing the result. Operation is needed only for chronic instability with or without pain, and anterior interbody fusion of C2--3 is than preferred in order to preserve rotation at the atlanto-axial joints.

The authors describe their experience with two cases of congenital Trypanosoma brucei-gambiense trypanosomiasis treated with orally administered difluoromethylornithine. The first case tolerated well his treatment (35 days of DFMO) and has probably been definitively cured. The second case, already in a desperate condition upon admission, died after only 4 days of difluoromethylornithine (DFMO). The authors hypothesize that difluoromethylornithine (DFMO) may be the drug of choice for congenital trypanosomiasis because of its good absorption by the oral route, its ability to penetrate the cerebrospinal fluid especially in presence of meningeal inflammation and its activity against Trypanosoma brucei-gambiense.

In a prospective randomised trial, 620 patients who had Trypanosoma brucei gambiense trypanosomiasis with central nervous system involvement were treated either with prednisolone plus melarsoprol or with melarsoprol only. 598 patients were evaluable: morbidity and death associated with melarsoprol-induced encephalopathy was reduced in patients who were given prednisolone. The two groups did not differ either in the incidence of other complications of melarsoprol therapy or in relapse rate after melarsoprol therapy. The cost of prednisolone would be outweighed by savings on the treatment of encephalopathies in such patients.

The authors relate their experience of integrating screening for African human trypanosomiasis (AHT) caused by T.b. gambiense in a network of multi-purpose health centres at Nioki, Zaire. Since 1983 the health centre nurses have been trained in the laboratory techniques for AHT screening and have been given the essential equipment (microscope, slides, coverslips). The strategy used was that of passive screening of patients who came of their own accord to the health centre: systematic palpation and aspiration of lymph nodes, and examination of wet and/or thick blood films from patients with AHT-like symptoms (fever not responding to antimalarials, headache for over a week, somnolence, arthralgias, pruritus, weight loss). When a trypanosome was detected, the patient was referred to the hospital for confirmation and lumbar puncture. From 1983 to 1987 the proportion of new cases detected by the health centres rose from 0% to 31.1%, while the returns of the mobile teams diminished as the disease regressed. Nevertheless, only 22.1% of the new cases detected by the health centres had normal CSF, as opposed to 64.8% of the new cases detected actively by the mobile teams. These two approaches therefore seem to be complementary: 83% of the new cases detected by the health centres were diagnosed on lymph node aspirates and/or wet films, and it is likely that better use of thick blood films could improve the performance of the health centres.(ABSTRACT TRUNCATED AT 250 WORDS)

26 patients with arseno-resistant Trypanosoma brucei gambiense trypanosomiasis were treated with difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, given intravenously, then orally. There was rapid disappearance of trypanosomes in the cerebrospinal fluid (CSF), gradual decrease of CSF lymphocytosis, and parallel improvement in central nervous system status. Side-effects, including diarrhoea, anaemia, and hair loss, were common but tolerable and reversible. 5 patients died during or shortly after treatment. None of the 21 patients who completed therapy has had a relapse during the 6-30 month follow-up.

Hanging, a common method of execution, began in antiquity and continues to this date. Unfortunately, the exact cause of a victim's demise was not always obvious, and many victims died as the result of asphyxiation from the hangman's noose. In the latter part of the 19th century, scientific curiosity led to autopsy studies of the cervical spine; Paterson in 1890 first described the lethal lesion. Experimental work in 1913 demonstrated that when the hangman's knot was placed beneath the chin, death rapidly occurred because of a traumatic spondylolisthesis of the second cervical vertebra. This knot placement then became standard as the most efficient method of execution. It was not until the mid-20th century that the similarity between judicial and civilian injury was recognized. The reports were infrequent, and most of the pars interarticularis fractures resulted from automobile accidents in which the victim was thrown forward and struck his or her face against the windshield which caused sudden violent hyperextension. The similarity between civilian and vehicular injuries was recognized in 1965 by Schneider who, together with his associates, reported eight cases; it was this group who introduced the term "hangman's fracture". Garber presented his thoughts on this subject, noting that there was a difference between the forces generated by judicial hanging and those caused by motor vehicle accidents and other similar civilian injuries. The former results in axial loading and hyperextension, and, rarely, in flexion or axial loading. Since the lesion occurs at the pars interarticularis of C2, Garber suggested that a more appropriate term might be traumatic spondylolisthesis of the axis.

A reduction of flexor carpi radialis H reflex size was produced by submotor threshold stimulation of the radial nerve. This reduction reflects reciprocal inhibition exerted by the inhibitory IA interneuron. The effects of contralateral movements on IA reciprocal inhibition were studied in eight normal subjects. Active contralateral arm movement appeared to significantly increase the degree of reciprocal inhibition without affecting the unconditioned reflex. A minor enhancement of reciprocal inhibition was also noted after passive mobilization. Results are discussed in terms of contralateral segmental afferent fibers influencing IA interneuronal excitability. They strongly suggest that contralateral muscular IA afferents may reinforce reciprocal inhibition in man.

A retrospective review of 262 consecutive cervical spine fractures revealed that 41 (16%) were odontoid fractures. Twenty patients were younger than 40 years of age (19 fractures were the result of a motor vehicle accident), whereas 19 fractures occurred in subjects older than 60 (13 were the result of a fall). Fractures were of the Anderson-D'Alonzo Types I (one patient), II (19 patients), and III (21 patients). Significant displacement was present in 31 patients. Anterior and posterior displacement occurred equally, but most of the anterior fractures were seen in patients younger than 40, and the majority of the posterior fractures occurred in those older than 60. Primary fusion was performed in 12 cases. Conservative management was used in 26. Three patients died (one from a spinal cord transection and two from other injuries). In the conservatively treated group, the average time to healing was 12 weeks, but the overall nonunion rate was nine out of 26 (7/13 Type II, 2/13 Type III fractures). The halothoracic jacket was poorly tolerated in patients older than 75 years of age. If daily supervision is not possible, early C1-2 fusion or treatment in an appropriate brace seems superior in the elderly patient.

The authors have reviewed their experience with a combination of pentamidine and suramin for Trypanosoma Brucei - Gambiense trypanosomiasis, in order to determine the limit of cerebrospinal fluid (CSF) normality. Among 341 patients with a cerebrospinal fluid (CSF) showing 1-3 white blood cells/millilitre treated with this combination of drugs, there were 30 relapses (8.8%); among 66 patients with a cerebrospinal fluid (CSF) showing 4-5 white blood cells/millilitre, they found 9 relapses (13.6%). This difference was not statistically significant. Therefore, combination of pentamidine- was not statistically significant. Therefore, a combination of pentamidine/suramin remains an acceptable treatment for Trypanosoma brucei-gambiense sleeping sickness patients having 1-5 white blood cells/millilitre in their cerebrospinal fluid (CSF).

During the last 35 years, nursing knowledge has known a surge in its development. Following the evolution of the scientific world, nursing first embraced the logical empiricist perspective of discovering and knowing. Historicism and, more recently, critical social theory have been explored as alternative ways of making knowledge in nursing. This paper discusses the evolution of nursing knowledge, considering its past and present activities. The authors suggest that a cooperative attitude amongst nurses, and a coexistence of various paradigms of knowledge development characterize the future of nursing. Nursing knowledge should be understood as a stage in its evolution and growth. The result of this process will never be a final static body of knowledge. Knowledge expansion will be encouraged through a process of integrating components from different research traditions, such that a multidimensional understanding of phenomena will be realised.

Traumatic spondylolisthesis of the axis is classified either as Type 1, an undisplaced fracture involving the posterior elements only, or Type 2, a displaced fracture involving the posterior elements plus the anterior structures. This classification is the basis of a rational treatment program. Neurologically, not one in a series of 42 patients was made worse by the proposed program of treatment. All fractures healed per primam without operative intervention. There was no evidence of late instability. The incidence of spinal cord and nerve root involvement was low although the incidence of associated trauma, particularly head trauma, was extremely high.

Twenty-five patients with arseno-resistant Trypanosoma brucei gambiense sleeping sickness were treated with oral nifurtimox, 12-17 mg/kg/d for 60 d. During treatment, trypanosomes disappeared from the cerebrospinal fluid (CSF) of 7/7 patients; the CSF infections; leucocyte was significantly lower at the end of treatment than before it was begun (pre-nifurtimox: 124.2 (+/- 149.3) per microliter; post-nifurtimox: 11.9 (+/- 12.1) per microliter; P less than 0.001). Nifurtimox was well tolerated, with gastro-intestinal disturbances in 6 patients and a reversible cerebellar syndrome in 2 patients. Among the 19 patients seen at least once at follow-up, 12 (63%) relapsed. The other 7 patients have been followed for 3-18 months, and the CSF remained completely normal in 4 of them. This study confirms that nifurtimox has some activity against T.b. gambiense, but a daily dosage higher than 15 mg/kg/d will be necessary to achieve cure of most patients.