Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus-induced vascular disease.

Fundamental issues remain unresolved regarding the possible contribution of viruses to vascular pathology, as well as the role of the immune system in regulating these processes. Here we demonstrate that infection of mice with gamma-herpesvirus 68 (gammaHV68) provides a novel model for addressing these issues. Interferon-gamma receptor-deficient (IFNgammaR-/-) mice died weeks to months after gammaHV68 infection from a severe large-vessel panarteritis. GammaHV68-infected B cell-deficient and normal weanling mice exhibited milder large-vessel arteritis. Immunohistochemical analyses demonstrated gammaHV68 antigen in arteritic lesions and revealed a striking tropism of gammaHV68 for smooth muscle cells. These studies demonstrate that IFN-gamma is essential for control of chronic vascular pathology induced by gammaHV68 and suggest gamma-herpesviruses as candidate etiologic agents for human vasculitis.

Writing, dictating, and speaking letters.

It is commonly assumed that dictation requires a long time to learn, but authors eventually dictate much faster than they write. Performance results now show that novice dictators can learn in a few hours to dictate with the speed and quality with which they write. However, they do not think they perform this well. Dictators with years of experience are from 0 to 25 percent faster than novices, depending upon the complexity of the letters. Planning time is about two-thirds of composition time, regardless of the method of composition.

Sequential study of C reactive protein in neonatal septicaemia using a latex agglutination test.

The usefulness of serial study of C reactive protein in the early detection of neonatal septicaemia was evaluated in a neonatal unit using a commercially available latex agglutination slide test as a rapid screening method and electroimmunoassay as a reference method for C reactive protein determination. A positive latex test was obtained in 11 infants with verified septicaemia (positive blood culture), two infants with clinically evident infection but without bacteriological confirmation, one infant with recurrent chest infection due to Pseudomonas aeruginosa, and one infant who showed signs of birth asphyxia with meconium aspiration, but was not infected. Positive latex test results correlated with raised concentrations of C reactive protein, measured by immunoassay. In some instances, however, concentrations of C reactive protein in excess of 12 mg/100 ml gave weaker agglutination results in the slide test, which could be interpreted as negative results. In a sequential study of the infected infants, 6.3% of the values recorded on a slide test were false negatives. In contrast, false positive values were observed on a slide test in 1.9% of 27 non-infected infants. The higher percentage of false negative values may be due to the presence of excess antigen in the sera of some infected children. It is suggested that the latex test should be carried out on suitable dilutions of serum. Although the slide test may reliably indicate infection at an early stage in neonates, the C reactive protein response is non-specific, as seen in a non-infected infant who showed signs of birth asphyxia with meconium aspiration. Provided the non-specific nature of the C reactive protein response is recognised, the latex test may be a useful serum measurement for early diagnosis of neonatal septicaemia of the newborn. The test has the advantage of being performed easily, quickly, and cheaply.

The effect of external load on torque production by knee extensors.

The kinematics of the knee joint are load-dependent; the length of the lever arm of the extensor mechanism and the pathway of the instant center of rotation vary with external load. This study was conducted to determine if the maximum extensor torque-generating capacity of the knee joint is dependent on the distance from the knee joint at which the external force resisting extension is located. Maximum isometric extensor torques were measured at 90 and 30 degrees of knee flexion while the distance from the knee joint to the resisting force was varied. Our results demonstrated that the subjects generated larger maximum extensor torques, at both 90 and 30 degrees of knee flexion, when the external resisting force was positioned farther distal to the knee joint. This increase was as large as 50 per cent with the knee at 30 degrees of flexion.

The effect of lateral meniscectomy on motion of the knee.

With the use of a five-degrees-of-freedom testing apparatus, we studied changes in the motion of the knees of cadavera after isolated resection of the lateral meniscus, with section of the anterior cruciate ligament and resection of the medial meniscus. Primary anterior and posterior translations were not affected by lateral meniscectomy. When lateral meniscectomy was done in addition to resection of the anterior cruciate ligament, anterior translation did not increase compared with that measured after isolated section of the anterior cruciate ligament. However, when the means of the paired differences in anterior translation were compared, a significant increase was found. This differed from the results after excision of the medial meniscus and section of the anterior cruciate ligament; in that situation, medial meniscectomy resulted in significantly more anterior translation.

Studies of Visual Inspection.

This paper describes the results of four experiments in a series aimed at understanding and improving visual inspection in general and of small integrated circuits (i.e. 'chips') in particular. Stimuli consisted of chips that, although electrically sound, contained visual anomalies. The first experiment found that the modal duration of eye fixations of trained inspectors was about 200 msec. The most accurate inspectors made the fewest eye fixations and were the fastest. The second experiment evaluated the performance of inspectors at one of the many sequential stages of chip inspection and found that 23% of the chips containing anomalies were accepted, whereas only 2% of the chips without anomalies were rejected. When the same chip was judged more than once by an individual inspector the consistency of her judgment was very high whereas the consistency between inspectors was somewhat less. The third experiment showed that variation by a factor of six in inspection speed led to variation of less than a factor of two in inspection accuracy. The fourth experiment showed that inspection via a ground glass screen is only a little worse than the usual method of looking through a binocular microscope. This was true even though the inspectors had no previous experience with the screen.

Serial study of C reactive protein in neonatal septicaemia.

Serial C reactive protein concentrations were assayed by electroimmunoassay in 41 infants. Values in most of the non-infected infants were below 0.3 mg/dl, the lower limit of detection of C reactive protein by electroimmunoassay. Eleven of 12 infants with proved sepsis (positive blood cultures) had significantly raised concentrations and one infant with recurrent pseudomonas chest infection had a raised C reactive protein concentration. High C reactive protein concentrations were also found in infants with suspected infection. Successful treatment was followed by a decrease in the C reactive protein concentration. Total white blood cell count was not as appropriate as C reactive protein determination in the early identification of bacterial infection in the newborn.

Morphofunctional evaluation of fibrin glue versus microsuture nerve repairs.

Complications of microsuture repair of peripheral nerves include mechanical trauma, foreign body reaction, impairment of vascularity, and possible obstruction to successful sprouting. In addition, there are occasions when it is virtually impossible to perform a suture repair because of limited exposure and/or very fine structures, such as are encountered in pediatric cases. These situations have continued to provide the impetus for evaluating alternative methods of nerve coaptation. Recently, the use of tissue glue has gained in popularity as a technique for sutureless nerve repairs. We decided to test the efficacy of fibrin glue repair versus microsuture coaptation in the rat sciatic model. The repair sites were assessed for tensile strength, by quantitative morphometry, and by electrophysiologic studies. Tensile strength findings revealed that at two, four, and eight weeks after surgery, there was no significant difference between the two repair techniques, although there was a trend toward a stronger hold in the microsuture repairs. Electrophysiologic recordings revealed that conventional microsuture repairs had significantly faster conduction velocities, larger area under the curve, and higher peak amplitudes. The onset and peak latencies were comparable, revealing that the axonal quality of at least a certain number of axons was similar electrically. Axonal counts both proximal and distal to the repair showed no significant difference, although there was an overall suggestion of superiority in the number of myelinated axons in the suture repair.

Is laser nerve repair comparable to microsuture coaptation?

Efforts to improve functional recovery following nerve injury and repair have included studies of sutureless repairs. The rat sciatic nerve was used as an experimental model to compare the efficacy of laser nerve repairs with standard microsuture repairs. Electrophysiologic (Compound Action Potential), quantitative morphometric, and behavioral (toe spread) measurements were used for assessment, and tensile strength of the repairs was also determined. Electrophysiologic studies showed that microsuture-repaired nerves had significantly faster conduction velocities, but the areas of the waveforms and peak amplitudes showed no significant differences between the two repair groups. Axon counts revealed significant differences in the suture group proximal to the repair site, contrasted with laser repairs. Toe spread evaluations, carried out at three day intervals, demonstrated a significant difference between the two methods of repair in only three out of 22 test dates: in these isolated cases, the suture group measurements were superior. The tensile strength findings confirmed that, at four days, microsuture repair was significantly stronger but thereafter, there was no difference between the two nerve repair techniques.

Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children.

In the past year, ten infants have been admitted to hospital with a new or previously unrecognised disorder, characterised by an acute onset of encephalopathy, fever, shock, watery diarrhoea, severe disseminated intravascular coagulation, and renal and hepatic dysfunction. Seven of the infants died. No specific causative agent has been identified, but preliminary studies suggest that the pathophysiology of the disease may involve release of proteolytic enzymes (such as trypsin) into the circulation, with destruction of the microcirculation.

Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumours.

Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.