A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio.

BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy. MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1-C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression. RESULTS: The maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10-13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10-7; maximally compressed level: P = 1 × 10-11; caudal: P = 1 × 10-4), correlations (modified Japanese Orthopedic Association score; rostral: -0.52; maximally compressed level: -0.59; caudal: -0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (-0.45) and sensory (-0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10-13; area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.

Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability.

BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

Oscillometry and direct blood pressure: a comparative clinical study during deliberate hypotension.

Oscillometry using an automatic monitor was compared with invasive blood pressure monitoring in 21 patients scheduled for surgery under general anaesthesia with deliberate hypotension. Six ranges of mean blood pressure measurements were studied, two of which were hypotensive. An excellent correlation was found between the two methods (systolic: r = 0.94; mean: r = 0.93; diastolic: r = 0.88) but there was a large variability among individual subjects. For systolic, diastolic and mean intra-arterial readings above an approximative value of 10.64 KPa (80 mmHg), the oscillometric monitor was found to underestimate blood pressure. Inversely, it was found to overestimate blood pressure for intra-arterial readings under the approximative value of 10.8 KPa (80 mmHg). We conclude that the non-invasive monitor represents a good trend estimation of the invasive radial blood pressure technique, but that wide inter-individual variability and the overestimation of blood pressure below an approximative value of 10.64 KPa (80 mmHg) precludes interchange of techniques when absolute values are considered, especially during controlled hypotension. However, oscillometry could represent a better estimate of central aortic pressure.

[Comparison of masked and endogenous depression using psychometric scales, endocrinological markers and pharmacological responses. Masked depression versus endogenous depression]. / Comparaison de la dépression masquée et de la dépression endogène à l'aide d'échelles psychométriques, de marqueurs endocrinologiques et de réponses pharmacologiques. Dépression masquée versus dépression endogène.

Masked depression refers to a concept of a phenomenological state, either endogenous or psychogenic where somatic symptoms replace sadness: Thirty patients were evaluated by RDC (22 endogenous and 8 masked depressions) wherein in the latter dysphoria was replaced by a nonreactive persistent somatic complaint. They were rated on Beck and Hamilton Depression Scales, on Hamilton and Trait-State Anxiety Scales and the NOSIE. All patients presented with insomnia, anorexia, loss of weight, diminished libido and anhedonia. Initial ratings were similar for both diagnostic groups except for a significantly higher agitation factor and lower retardation in masked depression. Although 59.9 percent of the subjects are positive on the dexamethasone test, only 1 masked depression did not suppress secretion of cortisol. After a randomized 30-day drug trial where patients were assigned to Clomipramine or Desipramine, patients in both groups show significant improvement on rating scales but diagnostic group drug treatment interaction exists on anxiety and agitation criteria.

[Diagnosis of inflammatory sacroiliitis. Comparison of complementary examinations]. / Diagnostic des sacro-iliites inflammatoires. Comparaison des examens complémentaires.

In order to test the sensitivity of different techniques in the diagnosis of sacroiliitis, we have made a prospective and non-controlled study of 22 patients using standard radiography of the sacroiliac joint; conventional tomography and axial scintigraphy (calculation of an ISI sacroiliac index). The normal upper limit of the sacroiliac index (1.42) was studied in parallel, using a group of 63 control subjects. Correlation between the radiological examinations was average, but was very poor between radiology and scintigraphy. Conventional tomography and calculation of the sacroiliac index were of equal value diagnostically. Clear images of juxta-articular geodes were seen during scanning, but were not taken into account in the diagnosis. They may represent the onset of larger erosions and need to be verified.

Bioavailability, pharmacokinetics, and clinical effects of an oral preparation of etoposide.

Bioavailability of an oral preparation of the antineoplastic drug etoposide (VP-16) was studied in 13 patients with advanced malignancies. An initial pilot study involving three patients suggested that approximately 50% of an orally administered dose was absorbed. Ten additional patients were randomized to receive either 100 mg/m2/day iv or 200 mg/m2/day orally. Three weeks later, the alternate dose schedule was administered. Plasma samples were assayed for VP-16 using a high-pressure liquid chromatography technique. Comparison of the area under concentration-time curves (C X t) revealed that 17%-72% (mean, 52%) of an orally administered dose was absorbed. Absorption was less than 40% for only one patient. For oral and iv preparations, mean peak plasma VP-16 concentrations were 9.6 and 13.0 micrograms/ml, mean alpha-half-lives were 0.96 and 0.82 hour, mean beta-half-lives were 7.2 and 6.8 hours, mean C X t values were 75.9 and 75.3 mg/L/hour, mean plasma clearances were 1.44 and 1.45 L/hour/m2, and mean extrapolated volumes of distribution were 15.2 and 16.9 L/m2, respectively. The half-life for oral absorption was 0.44 hour and peak plasma concentrations were noted 0.5-3 hours after oral drug administration. Granulocyte count nadirs tended to be lower in patients with high C X t values and low plasma clearance values. Granulocytopenia was dose-limiting. Gastrointestinal toxicity was extremely mild. We recommend doses of oral VP-16 of 800 mg/m2/course over 3-5 days for patients with a moderate amount of prior treatment. It is probable that previously untreated patients will tolerate a higher dose and that heavily pretreated patients will require a lower dose.

Comparative esophageal and anorectal motility in scleroderma.

Esophageal and anorectal pressures were recorded in 26 patients (4 men and 22 women) with scleroderma. Eleven patients suffered from a localized form of the disease and 15 from progressive systemic sclerosis. The latter only had marked functional abnormalities in esophageal and anorectal motility. Mean resting pressure at the lower esophageal sphincter of patients with progressive system sclerosis and controls was, respectively, 6 +/- 2 and 25 +/- 1 mmHg (p less than 0.001); mean closing pressure was 5 +/- 5 and 48 +/- 3 mmHg (p less than 0.001); coordination of opening the lower esophageal sphincter with the oncoming contraction in the distal esophagus was 0% and 68% +/- 5% (p less than 0.001); and relaxation (fall of the lower esophageal sphincter pressure to resting levels in the stomach) was 18% +/- 12% and 98% +/- 1% (p less than 0.001). The rectoanal inhibitory reflex was of lesser amplitude than normal in 74% of patients with progressive system sclerosis and was absent in 13%. Quantitative analysis demonstrated a significant reduction in response to rectal distention with 20 or more ml of air (p less than 0.001). There was a correlation between the amplitude of the lower esophageal sphincter relaxation and the amplitude of the rectoanal inhibitory reflex in response to rectal distention with 30-50 ml of air (p less than 0.05 to p less than 0.025). Our data show that in systemic sclerosis, anorectal motility is as frequently abnormal as esophageal motility.

Adjuvant arthritis: influence of the adjuvant volume and composition on the established arthritis.

Adjuvant arthritis remains an interesting model for the evaluation of therapeutic agents and for the study of inflammatory mechanisms. The severity and time course of the primary nonspecific inflammation and of the induced polyarthritis are influenced by the composition and volume of the injected adjuvant. The injection of complete adjuvant produces always an oedema which is much greater than the sum of the oedemas induced by mineral oil or mycobacteria alone. In Lewis rats, highly susceptible to adjuvant arthritis, the intensity of the induced lesions increases with the injected oil volume and for equal volumes is maximal with 500 micrograms of Mycobacterium butyricum. In the injected paw the specific immune character of the inflammation is more important when a small volume of adjuvant is used and is maximal for 500 micrograms of mycobacteria in 0.1 ml of mineral oil.

Constipation with colonic inertia. A manifestation of systemic disease?

Transit of radiopaque markers was delayed in the ascending colon of 51 females and 3 males treated for severe idiopathic constipation. Onset of symptoms was between age 10 and 20 in more than half of the patients. Eighteen percent had previously undergone unnecessary laparotomy for large bowel pseudoobstruction. Stool frequency ranged from 1 stool every three days to 1 every 2 months. Twenty-six percent suffered from fecal incontinence. In addition, 30% had orthostatic hypotension and 15% galactorrhea of idiopathic origin. Patients had a higher than normal anal pressure (P less than 0.001). They all had a rectoanal inhibitory reflex, but it was abnormal in 76%. In the upper esophageal sphincter, resting pressure was higher (P less than 0.02), and coordination poorer (P less than 0.05) than in normal control subjects. Incidence of spontaneous tertiary contractions in the body of the esophagus was greater than normal (P less than 0.03). In the lower esophageal sphincter, resting pressure was lower (P = 0.001) and gastroesophageal gradient weaker (P = 0.05). Closing pressure of the sphincter was lower (P less than 0.001) and coordination less adequate (P less than 0.02). After subcutaneous injection of 0.035 mg/kg bethanechol, urinary bladder intraluminal pressure increased by over 15 cm H2O in 31% of patients but never did in controls, and average maximal pressure was greater (P less than 0.025). Time taken to reach peak pressure was shorter (P less than 0.01). This study provides evidence that patients who suffer from constipation with colonic inertia also have abnormal function in other hollow viscera.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of gastrointestinal microbleeding caused by aspirin, fenbufen, and placebo.

Fifty volunteers, randomly divided into five groups, received placebo, fenbufen, or aspirin at dosages used in treating osteoarthritis and rheumatoid arthritis (fenbufen, 600 or 900 mg daily; aspirin, 3.6 g daily) for 28 days. Following radioactive chromium labeling of red cells in each subject, stool specimens were collected weekly for determination of blood loss by radioisotope procedure. Statistical analyses demonstrated no significant differences in gastrointestinal microbleeding between subjects who received fenbufen (600 or 900 mg daily) and those who received placebo. Conversely, there were significant (p less than 0.01) differences in microbleeding between subjects given aspirin and those given either dosage of fenbufen or placebo.

Iatrogenic lesions of the upper airway in the newborn.

A retrospective study of 140 babies who survived the first week of life and who had endotracheal intubation showed that 65 of them had either or both of the following complications of endotracheal tube therapy: (a) Collapse of one or more lobes with the tube in place or within the first two days following extubation and lasting less than 24 hours. When collapse lasted more than 48 hours, it often required repeated intubation for tracheal cleansing. The right lung, especially its upper lobe, was predominantly affected. (b) Tracheal lesions and nasal necrosis. A statistical comparison with intubated babies of similar age without complications showed the following factors to predispose to lobar collapse: younger gestational age, maximal high oxygen concentration administered, and prolonged duration of intubation. The results of endotracheal tube cultures bore no relation to the complication rate.

Nuclear androgen receptors of human prostatic tissue--a quantitative histological study.

The objective of this study was to determine the nuclear dihydrotestosterone (DHT) nuclear receptors content in tissues of normal prostate, benign prostatic hypertrophy (BPH), and prostatic cancer. We also attempted to correlate this with the histological pattern of these tissues. Specimens were obtained from five normal subjects, 24 BPH, and 19 prostatic cancer patients. Nuclear receptors content was determined. All histological sections were reviewed by three independent pathologists. The criteria for the quantitative analysis were the degree of cellularity and the stromal content. The mean receptor content was not significantly different between neoplastic tissue (52.6 fmol/mg protein) and hyperplastic tissue (38.9 fmol/mg protein). The number of binding sites in normal prostatic tissue was 8.5 fmol/mg protein. The correlation between the degree of cellularity and DHT receptors showed no significant difference for both BPH, as well as prostatic cancer. Similar results were obtained when stromal content was compared.

Phagocytosis of sodium urate and calcium pyrophosphate crystals by leukocytes of gouty, pseudogouty and health donors.

The initial rates of oxygen consumption and of glucose oxidation via the hexose monophosphate shunt were measured during the phagocytosis of sodium urate and calcium pyrophosphate microcrystals. By applying the kinetics of an enzyme-catalyzed reaction, the affinity of the polymorphonuclear leukocytes for crystals, Km, and the maximum rate, Vmax, were determined. When the comparisons are made between the two kinds of crystals, the differences in Vmax are always significant (p less than 0.02). The lesser phlogistic properties of pyrophosphate crystals stem probably in part from different crystal-protein interactions. The influence of the donor is less marked. Part of the weakly depressed phagocytic activity observed with pseudogouty PMN may be attributed to antiinflammatory drugs.

The gastric antisecretory effects of clofibrate in the rat.

The object of this study was to explore the effect of clofibrate on gastric secretion. The volume and the total acid output of Shay-treated rats (pyloric ligation) was studied after intragastric, intraduodenal, intramuscular and intraperitoneal administration of clofibrate. The experimental model was a factorial (3 X 4) random block design. The treatment factor had 3 levels: water, oil and clofibrate. The route of administration factor had 4 levels: intragastric, intraduodenal, intraperitoneal and intramuscular. The data were analyzed by analysis of variance. Compared to the control group (water and oil) the intraduodenally and intraperitoneally administered clofibrate produced a statistically significant (p less than 0.001) reduction in the volume and total acid output. The intragastric and intramuscular groups did not show a statistically significant reduction on the gastric secretion. It is concluded that clofibrate acts systemically rather than locally to reduce gastric secretion.

Radiographic evaluation of the symptom-producing adenoid.

Adenoid hypertrophy has several variable symptoms. In this study, symptoms were divided into minor and major. A lateral radiograph of the nasopharynx was performed in 114 patients to study the superior and antroadenoid diameters. With proper statistical analysis, a correlation was made between the various clinical groups (scores) and the adenoid measurements. Our results support Hibbert's findings that the antroadenoid width is a better indicator of the symptom-producing adenoid than adenoid mass measurements with their loosely defined norms. A thorough history and physical examination remain paramount in the diagnosis and management of adenoid hypertrophy.