Re-orchestration of blood flow by micro-circulations.

Haemoglobin Video Imaging (HVI) demonstrates conjunctival and episcleral blood flow in man with the resolution of a single erythrocyte. A new method for establishing vessel hierarchy in micro-circulations is described, which recognises either delivery or drainage vessels and references vessel order to the capillary. These tools have been used to characterise blood flow.Anterior ciliary arteries show pulsatile variation in diameter. The episcleral arterial circle that they supply has functional apices with pulsatile flow reversal. Perfusion fields overlap: a single delivery vessel may project to many drainage vessels and vice-versa. Some vascular pathways remained inactive throughout a 1 min angiogram.Small conjunctival delivery vessels have laminar flow, but advancing luminal constrictions are often observed within the blood column. Laminar flow is lost in low-order drainage vessels where erythrocytes aggregate, but quickly recovers, new striae being added to the blood column at each confluence. Aqueous forms a discrete column, which centralises in episcleral drainage vessels.There is strong evidence that the luminal constrictions in small delivery vessels propel blood by peristalsis: they form spontaneously, remote from bifurcations; a single vessel may have multiple constrictions; they truly narrow the lumen, rarely contributing volume to post-capillary venules; they can proceed faster than the vessel contents; they never enter the drainage system; the trailing edges of erythrocyte boluses usually taper. They are rhythmically aligned with cardiac systole.While blood is transported to the periphery by the heart, it is actively transferred through tissues by peristalsis in small delivery vessels.

Completeness of reporting of diagnosed HIV-infected hospital inpatients.

To assess the completeness of human immunodeficiency virus (HIV) reporting among hospital inpatients whose records listed diagnostic codes for HIV infection but who did not meet the 1987 AIDS case definition, we conducted a statewide hospital study of admissions between January 1, 1986 and December 31, 1990. Of the 396 HIV-infected hospital inpatients identified, 313 (79%) had been reported to the State HIV Registry. HIV reporting was less complete for patients who were older and/or were blood product recipients. Of the 313 reported patients, 189 (60%) had been reported prior to their first hospital admission. Temporal improvements were noted in the completeness of HIV reporting among the hospital patients (1986: 65%; 1987: 81%; 1988: 64%; 1989: 82%; 1990: 86%; Chi square for linear trend 9.6, p < 0.01) and prior to their first hospital admission (1986: 31%; 1987: 34%; 1988: 49%; 1989: 64%; 1990: 72%; Chi square for linear trend 26.6; p < 0.01). Women were more likely than men to be reported prior rather than during or after their first hospital admission (71% vs. 55%; p < 0.01). Of the 155 patients with CD4+ T-lymphocyte test results, 41 had CD4+ counts < 200 mm3 and met the 1993 but not the 1987 AIDS case definition. In South Carolina most (79%) diagnosed, hospitalized, HIV-infected patients had been reported to the State HIV REgistry, with improvements in reporting occurring over time. Findings suggest that the 1993 AIDS case definition will improve our ability to monitor severe morbidity related to HIV.

Retinoic acid induced differentiation and commitment in HL-60 cells.

Human leukemic HL-60 cells are an established model for studies of differentiation induction. Retinoic acid (RA), 2 x 10(-6) M, was used to induce terminal differentiation, assayed as nitroblue tetrazol reduction (NBT) and expression of monocytic surface antigens, which were detected by monoclonal antibody Leu M3. In addition, transferrin receptor expression and the number of S + G2 + M-phase cells were determined. With a 12-hr RA incubation, only a decrease of transferrin receptor expression was found, with no change in other parameters. At least 96 hr RA incubation was necessary to induce terminal differentiation, with most cells being positive for NBT and M3. Cells induced with RA for 12 hr and subsequently recultured in liquid culture gradually expressed the differentiated phenotype and lost transferrin receptor expression. The number of S + G2 + M-phase cells in the cultures decreased drastically. After 12 hr RA exposure and 120 hr reculture without RA, the differentiation profile was comparable to that of cells that had been induced with RA for 96 hr. In reculture for up to 120 hr there was no evidence of loss of viability or regrowth of possibly residual undifferentiated cells. From these studies, we conclude that HL-60 cells become committed to terminal differentiation after half a generation-time exposure to RA and remain committed for at least six generation times.

Cerebral vasculitis--recognition, diagnosis and management.

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.

Hereditary C1q deficiency and systemic lupus erythematosus.

We describe a 27-year-old women with systemic lupus erythematosus, C1q deficiency and cytomegalovirus retinitis. She suffered from severe SLE, with cutaneous and CNS involvement, and died of CNS disease aged 28. Review of 29 other published cases of C1q deficiency shows that SLE in these patients is often severe (five with CNS disease, ten with glomerulonephritis). The results of autoantibody studies in this and another patient with C1q deficiency and SLE are presented--both patients had autoantibodies to the extractable nuclear antigens, Sm, RNP and Ro, and one patient had high titres of antibodies to dsDNA. One of the patients had previously been treated with fresh frozen plasma, and antibodies to C1q were present in his serum. Homozygous C1q deficiency is associated with a very high prevalence of severe SLE with the full panoply of autoantibodies characteristic of this disease.

Computer assisted analysis of fluorescein videoangiograms.

The efficient analysis of fluorescein videoangiograms requires immediate access to any frame in a video sequence and complete control over the time base during replay. It should also be possible to compare any two frames by rapid subtraction or to subtract any phase of the study from the remaining sequence. A program that performs all these tasks has been written for a low priced desk-top microcomputer. This should facilitate the clinical introduction of fluorescein videoangiography.

Low dose fluorescein angiography of the conjunctiva and episclera.

By reducing the dose of injected fluorescein its leakage from conjunctival and episcleral capillaries has been minimised. These vessels have been demonstrated with great clarity, and the venous circulation, previously obscured by extravascular fluorescein, has also been revealed. The anatomy of the anterior segment vessels, and the blood flow within them, has been studied in eight normal subjects. The anterior ciliary arteries feed an anterior episcleral arterial circle that has superficial and deep components. This supplies the anterior conjunctival and episcleral circulations, the limbal arcades, and the iris arterioles. Where the superficial arterial circle is deficient, isolated vessels emerge from the deep segments of the circle to supply the episcleral plexus and conjunctival arterioles. Watershed zones between the anterior and posterior territories of the conjunctival and episcleral circulations overlap. They may fluoresce up to 30 seconds after the anterior ciliary arteries. The scope of this technique and the implications of these findings are discussed.

Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease.

The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out of 10 patients had symptoms of systemic vasculitis on presentation; seven had renal impairment; three had chest x-ray abnormalities. Autoantibodies against neutrophil cytoplasmic determinants (ANCA) were present in all cases. In seven patients the scleritis responded well to pulsed immunosuppressive therapy followed by long term oral steroids and cyclophosphamide. Oral steroid therapy alone failed to control severe disease. Corneoscleral disease was not a cause of visual loss. It is important to realise that inflammatory corneoscleral disease may be the presenting feature of a severe systemic vasculitis.

Critique: external comparison of conceptual nursing models.

Research by Jacobson on development of a semantic differential for external comparison of conceptual nursing models was reported in 1984. The present article critiques the philosophical stance and the research methods presented in the Jacobson report. Methods of analysis and evaluation of conceptual nursing models are reviewed, and the influences of conceptual nursing models on the structure of the discipline are examined in light of the purposes of the Jacobson study. Issues related to the investigation and use of models in the development of nursing knowledge are discussed.

National serologic survey of measles immunity among persons 6 years of age or older, 1988-1994.

CONTEXT: Measles incidence in the United States is at a record low, and indigenous transmission has been interrupted in each year since 1996, suggesting that measles is no longer endemic. A national estimate of measles immunity and an understanding of predictors of measles susceptibility are essential for assuring sustained elimination of endemic disease. OBJECTIVE: To assess patterns of immunity and to determine predictors of susceptibility to measles. DESIGN/SETTING: Sera and data on participants from the third National Health and Nutrition Examination Survey (1988-1994) (NHANES III) were examined. NHANES III was a cross-sectional survey of a representative sample of the civilian, noninstitutionalized population of the United States. POPULATION: 20,100 persons 6 years of age or older were tested for measles-specific immunoglobulin G (IgG) antibody by an enzyme immunoassay. MAIN OUTCOME MEASURE: Participants with serum positive for measles antibody were considered protected or immune to measles disease. RESULTS: Prevalence of measles immunity was 93%. Nearly all persons (99%) born in the prevaccine era (before 1957) were immune. Immunity declined among persons born in the vaccine era (after 1956) to 81% among those born in 1967-1976, and increased again to 89% among those born in 1977-1988. Among persons born in the vaccine era, independent predictors of measles susceptibility varied by birth cohort and included birth in the United States, residence in a noncrowded household, residence in a nonmetropolitan area, and, among males, non-Hispanic white and Mexican American race/ethnicity. Among adults 17 years of age or older, additional predictors of susceptibility included living at or above the poverty line and not currently being married. CONCLUSIONS: Population immunity among persons 6 years of age or older is very high; however, as many as 15 million persons across the United States may lack humoral immunity. While it is unclear that the susceptible population can support continuous, indigenous transmission of measles, providers should follow current recommendations to evaluate the measles susceptibility of patients born in the vaccine era and vaccinate eligible patients.

Avoiding surgery for thyroid eye disease.

In thyroid eye disease, autoimmune inflammation of orbital musculature and fat increases the bulk of the orbital contents. Orbital tension rises and patients stratify according to the ease with which their globes can proptose. Restriction of proptosis is associated with optic nerve compression and visual loss; exophthalmos, with corneal damage. Ocular motility is affected, initially by muscle inflammation; late in the disease, by fibrosis. Extraocular factors, including thyroid endocrine disturbance, antigen release, infections, malignancies, and smoking, may trigger and drive the orbital myopathy. The management of thyroid eye disease by the identification and treatment of drives, followed by immunomodulatory therapy, is discussed. Fourteen patients with compressive optic neuropathy were treated with immunomodulation using intravenous methylprednisolone, oral prednisolone, and cyclosporin A, and followed up for a minimum of three years. All recovered their pre-morbid visual acuities and visual fields in both eyes. Severe disturbances of ocular motility also recovered in 30 patients, treated with the same regime. In one subject, ocular motility normalised with intravenous steroids and cyclosporin A, but no oral prednisolone. Morbidity from the treatment was low. Immunomodulation is a rational and successful method for managing optic nerve compression and disordered motility in this condition.

Population paradoxes.

PIP: The global population growth rate began accelerating rapidly early this century, passed 1% around 1940, and peaked at around 2.1% in the latter half of the 1960s, when the world's population was about 4 billion. Since then, the growth rate has declined slowly to the present estimate of 1.7%, and now the figure is nearly 5.5 billion. The first population paradox is that the annual increments in global population are still increasing, even though the rate of growth has begun to decline. In the late 1960s the annual increment was about 80 million and the 1992 figures equaled 93.5 million. This annual increment will probably begin to decline before the turn of the century, but will still remain above 80 million until about 2020. Most of these added people will be in the developing countries, (80-90 million every year), most of them in poverty. Demographers now believe that humanity will achieve global replacement-level fertility around the year 2040, given current trends. By 2040 the population will be about 9 billion. They expect an ultimate world population sometime late next century of about 11 billion. The less optimistic scenarios have global replacement-level fertility delayed to 2060, yielding an ultimate population of 12.5 billion. Indonesia is a good example of the optimistic category. It will achieve replacement-level fertility perhaps by the year 2005. In the mid 1970s the annual growth rates were still increasing, peaking at over 2.3%. At that time, Indonesia was growing at 3.5 million people per year. The growth rate is now below 1.7% and, with the population at about 180 million, the annual increments are just 3 million. Indonesia began this century with a population of around 40 million, and will end it with a population around 210 million. Indonesia's ultimate population will be well in excess of 300 million, indicating the force of momentum.^ieng

The circulation of the human limbus.

The superficial circulations of the anterior segment of the human eye have been studied by the following techniques: photographic and video low-dose fluorescein angiography, video-microscopy using red-free light and stereoscopic colour photography. The results are combined to give a dynamic description of the limbal circulation, including its arterial supply and venous drainage.

Patterns of blood flow in episcleral vessels studied by low-dose fluorescein videoangiography.

The blood supply of the ocular anterior segment arises from a saggittal arterial ring composed of the long posterior ciliary arteries, the muscular and anterior ciliary arteries and perforating scleral arteries. This ring supplies coronal arterial circles within and outside the globe. Low dose anterior segment fluorescein videoangiography demonstrates arterial and venous flow, recording its characteristics and direction. Videoangiograms were performed at low and high magnification in 15 normal subjects. Episcleral arteries and veins were distinguishable by the presence or absence of pulsatile flow and by their fluorescence intensity. Arteries usually perfused earlier than veins, and with higher flow velocity. Twenty-five of 40 arteries flowed away from scleral perforations close to the limbus. All 8 veins drained away from the limbus. The communication between two arteries may be demonstrated by a static, pulsating column of non-fluoresceinated blood. This sign arose at a point of scleral perforation, at the junction between muscular and anterior ciliary arteries and in the episcleral anterior circle. It supports the concept of arterial shunting, both in the saggittal plane and in the superficial coronal circle. Perforating scleral arteries lay anterior to the episcleral arterial circle in superior angiograms and posterior to it in inferior studies. Vessels that had been characterised by videoangiography were identified in stereo colour photographs of angiographic fields. Arteries were best distinguished from veins by their high tortuosity and thick walls. Using these photographic characteristics, the distribution of arteries and veins over the rectus muscles was surveyed in 13 subjects. The incidence of arteries is lowest over the lateral rectus muscle. Veins were concentrated in the vertical meridian and were absent over lateral rectus in 8 subjects. Five intra-operative videoangiograms are reported. Retraction of conjunctiva facilitated imaging of the episcleral vessels and demonstrated arterial communication through a shared capillary bed.

The observation of immune complex formation and deposition in the eyes of living rabbits.

Fluorescence microscopy of the conjunctival and episcleral circulations of the rabbit's eye has revealed for the first time the formation and deposition of intravascular and perivascular immune complexes in undisturbed capillaries in vivo. During intravascular immune complex formation, immune aggregates appear abruptly, at a critical antigen/antibody ratio, and embolize to the arterial side of the capillary bed. This is accompanied by a fall in the circulating platelet count. The emboli disperse over the ensuing 120 min. In frozen sections immune aggregates are coarsely granular and intraluminal at the moment they embolize. However, after they disperse, subendothelial granules of antigen can be found. IgG and C3 are associated with both intraluminal and subendothelial antigen. Perivascular immune complex formation is accompanied by an intense inflammatory response, which is absent after the deposition of an intravascular immune precipitate. The mechanism by which immune complexes may accomplish their transition across the capillary endothelium is discussed.

Long-term effectiveness of imagery instructions with retarded persons.

The effects of imagery instructions on paired-associate learning efficiency and on the retention of 16 picture pairs were investigated using two groups of EMR individuals with approximate mental ages of 8 and 11 years, respectively. While facilitated list mastery was obtained under imagery instructions, no facilitation was found for 1-week retention performance. However, in learning a new list immediately following the retention task, those individuals who had received imagery instructions during original learning continued to exhibit facilitated learning. These results extend previous work.