Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study

The objective of this study was to analyse the temporal course of the jugular venous-arterial gradient of S-100B protein after severe head injury and the correlation between the absolute concentrations of serum S-100B protein and outcome, CT findings, and clinical variables. Fifteen patients were included in this pilot study. All patients were treated according to a standard therapy protocol targeted to maintain cerebral perfusion pressure. The serum concentration of S-100 protein was measured daily for five consecutive days after injury by a monoclonal two site immunoluminometric assay. Nine patients showed favourable and six unfavourable outcome after 6 months with a mortality rate of 33% (five patients). The mean gradient between jugular venous and arterial blood was 8.2% (p<0.05). Patients showing an unfavourable outcome had significantly higher jugular venous or arterial S-100 values compared with those with a favourable outcome (jugular venous S-100B 2.78 microg/l v 1.22 microg/l, p<0.05; arterial S-100B 2.48 microg/l v 1.19 microg/l, p<0.05). All patients with an initial or secondary increase in S-100B value of >2 microg/l were found to have an unfavourable outcome. S-100B was found to be an independent predictor of outcome after severe head injury. The persisting increase of S-100B for three to five days even in patients with favourable outcome and no signs of secondary insults might reflect continuing damage to the blood-brain barrier or ongoing glial cell death.     

Matrix metalloproteinases generate angiostatin: effects on neovascularization

Angiostatin, a cleavage product of plasminogen, has been shown to inhibit endothelial cell proliferation and metastatic tumor cell growth. Recently, the production of angiostatin has been correlated with tumor-associated macrophage production of elastolytic metalloproteinases in a murine model of Lewis lung cell carcinoma. In this report we demonstrate that purified murine and human matrix metalloproteinases generate biologically functional angiostatin from plasminogen. Macrophage elastase (MMP-12 or MME) proved to be the most efficient angiostatin-producing MMP. MME was followed by gelatinases and then the stomelysins in catalytic efficiency; interstitial collagenases had little capacity to generate angiostatin. Both recombinant angiostatin and angiostatin generated from recombinant MME-treated plasminogen inhibited human microvascular endothelial cell proliferation and differentiation in vitro. Finally, employing macrophages isolated from MME-deficient mice and their wild-type littermates, we demonstrate that MME is required for the generation of angiostatin that inhibits the proliferation of human microvascular endothelial cells.     

Isolation of the genomic clone of the rhesus monkey beta-amyloid precursor protein

In the evaluation of CTS, electromyography of various myotomes as well as proximal and distal muscles remains quite useful in helping to assess other clinically suspected differentials such as plexopathy, systemic neuropathies, radiculopathies, and proximal nerve entrapments. With regards to T-EMG specifically, it can provide information regarding axonal loss; however, it only crudely estimates relative severity and prognosis. These are better and less painfully determined by nerve conduction studies. The addition of nerve conduction studies to the clinical assessment gives one the ability to diagnose, determine severity and prognosis, and determine best management. The addition of T-EMG in typical cases of CTS causes excess pain and adds little to the information already gained. Therefore the author suggests that T-EMG be reserved for atypical or unusual presentations when additional information is needed such as when nerve conduction studies cannot be performed or when the pathology is potentially aggressive causing significant axonal injury over a short time.     

Mad King George: the impact of personal and political stress on mental and physical health

Both historians and psychiatrists have tried to explain the recurrent attacks of mental and physical illness experienced by King George III of Great Britain. Although the porphyria hypothesis is widely accepted, this diagnosis assumes that the king's breakdowns were not precipitated by extreme stress. This assumption was tested using single-case historiometric methods. Biographical data were compiled to form two extensive chronologies of the monarch's life, one for stressful events and the other for pathological symptoms. From this information 22 independent judges reliably assessed fluctuations in stress (total, personal, and political) and health (total, physical, and mental) across 624 consecutive months between 1760 and 1811. The cross-correlations were then calculated for the raw, first-differenced, and prewhitened time series. A consistent tendency appeared for the king's health to deteriorate after increases in stress, most frequently with a 9-month delay. The current study demonstrates the utility of applying quantitative techniques to a psychobiographical debate hitherto examined solely by qualitative approaches.     

Characterization of porphyrin heme oxygenase inhibitors

Recent data suggest that many autoreactive T cells, particularly to tissue-specific self antigens, can escape thymic deletion. The current dogma is that these autoreactive T cells are silenced by the failure of most tissues to provide co-stimulation (signal 2), antigen alone (signal 1) inducing T cell unresponsiveness. However, I propose that activation of autoreactive T cells frequently occurs but autodestruction by effector T cells is tightly regulated. This phenomenon is most evident with lymph node metastasizing tumour cells where the regional lymph node can mount a vigorous response to the invading tumour cells but tumour growth is unimpaired. I suggest that autodestruction is prevented by inhibitory receptors on T cells which recognize class I MHC structures on target cells. These receptors, which I propose deliver 'signal minus 1' to T cells, were recently described on NK cells and a subpopulation of peripheral T cells. They are also strikingly similar to a family of anti-self receptors that my laboratory described on murine T and B cells 15 years ago. In the 'signal minus 1' model, antigen-activated T cells acquire the inhibitory receptors when they become co-stimulation independent and gain the ability to exit lymphoid organs and enter non-lymphoid tissues. Thus, if autoreactive effector T cells encounter autoantigen in tissues they are functionally silenced by inhibitory receptor engagement and signal minus 1 delivery. In contrast, I propose that in response to intracellular infections, cells down-regulate expression of their ligands for inhibitory receptors. Such a model allows infected cells to be selectively eliminated by effector T cells. If correct, the model predicts that effector T cells, whether foreign-antigen- or autoantigen-specific, can selectively respond to infected cells. This apparent 'usefulness' of autoreactive T cells may explain their observed persistence even after an encounter with autoantigen. It is also suggested that signal minus 1 may silence autoreactive B cells specific for tissue-specific cell surface antigens and lack of signal minus 1 may partially explain the vigorous T cell response to allogeneic MHC. Finally, it is hypothesized that, in evolutionary terms, inhibition of autodestruction by the recognition of a 'self marker' and delivery of signal minus 1 is an ancient process which probably emerged in early metazoans.     

Vocal cord dysfunction masquerading as exercise-induced asthma. a physiologic cause for "choking" during athletic activities

Exercise-induced bronchospasm is a common clinical problem that is particularly troubling for patients who engage in strenuous physical activity, such as athletes. When such individuals develop this condition, the associated airway narrowing can materially interfere with performance; however, events other than asthma can also produce these symptoms and their differentiation is essential for proper treatment. The present report describes seven elite athletes with psychogenic vocal cord dysfunction who presented with acute dyspnea during sporting competitions. Although the combination of exertion and wheezing suggested the diagnosis of exercise-induced asthma, the patients' histories were sufficiently unique so as to represent a recognizable syndrome. The patients underwent clinical physiologic evaluations including bronchoprovocations with isocapnic hyperventilation of frigid air, methacholine and/or exercise. Direct laryngoscopy was also performed in some subjects. The findings that differentiated these patients from asthmatics were a lack of consistency in the development of symptoms when exposed to identical stimuli, the onset of breathing difficulties during exercise, and poor therapeutic and prophylactic responses to anti-asthma medications. The clinical impression of a functional disorder was confirmed by bronchoprovocations that demonstrated the variable extrathoracic airway obstruction of vocal cord dysfunction. Patients with atypical exertional complaints require careful clinical and physiologic evaluation. The mere association of exercise and airway obstruction is not sufficient to establish the diagnosis of asthma.     

Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer. Tolerance and outcome

BACKGROUND: Metastatic breast cancer in elderly patients is less often treated with chemotherapy than in younger patients because of concerns related to toxic effects and tolerance. This is especially the case with doxorubicin-containing regimens. METHODS: We conducted a retrospective study of 1011 consecutive patients with metastatic breast cancer treated with doxorubicin-based chemotherapy protocols between July 1973 and July 1984. Age was not an exclusion criterion. Patient characteristics, dose intensity, hematologic-related toxic effects, and the cause of death were analyzed. The Kaplan-Meier survival curves were plotted and tested by the generalized Wilcoxon test. RESULTS: Seven hundred sixty-seven patients aged between 50 and 64 years were identified. While the response rate was higher in the younger group, the overall survival curves were similar for the two groups (P = .06), as well as the time to progression of the disease (P = .15). The dose intensity was comparable between the groups (P = .49), as was the median platelet and white blood cell nadirs. Neutropenic fever occurred in 16% of each group (P = 83), and fever in 12% and 17% of each group, respectively (P = .05). Death from infections occurred in 3.1% and 3.2% of patients in the two groups, respectively (P = .82). CONCLUSION: Patients with metastatic breast carcinoma who are older than 65 years tolerate the acute side effects of doxorubicin-based combination chemotherapy as well as the younger age group. Time to progression of disease and the overall survival are similar for both groups. Doxorubicin-based regimens are safe and effective for patients older than 65 years.     

Meningiomas in the region of the cavernous sinus: a review of 21 patients

OBJECTIVE: To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; > or = 2500 g) Malaysian infants during the first year of life. METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity. RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life. CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.     

AMS 3-piece inflatable penile prosthesis implantation in men with Peyronie's disease: comparison of CX and Ultrex cylinders

PURPOSE: We compared the ability of the CX and Ultrex cylinders to straighten the penis in men who received a 3-piece AMS 700 series inflatable penile prosthesis for erectile dysfunction and erectile deformity due to Peyronie's disease. MATERIALS AND METHODS: The records of 34 and 38 patients receiving devices CX and Ultrex cylinders, respectively, were reviewed. RESULTS: All 34 patients receiving the CX cylinders achieved complete penile straightening with cylinder inflation and bending alone. In 10 of 38 patients receiving the Ultrex cylinders complete straightening with cylinder inflation and bending could not be achieved, and simultaneous corporoplasty was necessary. CONCLUSIONS: Girth expanding CX cylinders have better penile straightening properties than girth and length expanding Ultrex cylinders. We recommend use of CX cylinders for 3-piece AMS 700 series inflatable penile prosthesis implantation in men with Peyronie's disease.