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Biomedical subjects

C Singer

Publications and source records attributed to C Singer.

At least 55 records · Page 3Linked to original sources

Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I.

Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. This multicenter, double-blind, placebo-controlled study used two 10-hour clinical evaluations to compare the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg tid) with placebo in patients with Parkinson's disease (PD) experiencing motor fluctuations from levodopa/carbidopa. One hundred fifty-one patients completed the study. Clinical evaluations lasting 10 hours were performed on day -1 and day 42 using United Parkinson's Disease Rating Scale motor subscale and "on/off" and dyskinesia assessments every 30 minutes. Tolcapone significantly reduced "off" time an average of 40% and increased total "on" time by about 25% at all dose levels, as compared to placebo treatment. Levodopa/carbidopa dosage and frequency were significantly reduced. Tolcapone was well tolerated, with patients experiencing typical dopaminergic side effects that could be reduced or eliminated by lowering levodopa/carbidopa dosages. Tolcapone was effective at prolonging the clinical benefit of levodopa and reducing total levodopa requirements in PD patients with motor fluctuations.

Aged↗

Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia.

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Adult↗

Fatty and fibroglandular tissue volumes in the breasts of women 20-83 years old: comparison of X-ray mammography and computer-assisted MR imaging.

OBJECTIVE: A method for segmenting MR images of the breast was applied to determine fatty and fibroglandular tissue volumes in breasts of women in different age groups. The results were compared with subjective assessments of breast density from X-ray mammograms in the same patients. MATERIALS AND METHODS: Two experienced mammographers assessed the percentage of fat in the breasts of 40 women who were 20-83 years old. MR images were obtained on a 1.0-T scanner equipped with a bilateral receive-only breast coil. Images were acquired using a three-dimensional T1-weighted gradient-echo sequence with a 1.25 x 1.4 x 2.5 mm resolution. On average, breast parenchyma appeared in 30 images in each breast. Image segmentation was based on a semiautomated, two-compartmental (fatty and fibroglandular tissue) model that accounts for partial volume effects. To validate the accuracy of the MR imaging segmentation technique, we performed a phantom study using an identical imaging sequence. RESULTS: The accuracy of the MR imaging segmentation of the phantom was of the order of 2%. In our subjects, fat content was 42.5% +/- 30.3% (mean +/- SD) on mammography versus 66.5% +/- 18% on MR images. Although we found a significant correlation (r = .63) between the two techniques, mammography poorly differentiated breasts containing less than 45% fat. When our analysis included only dense breasts (i.e., those containing less than 75% fat on MR images), the correlation coefficient decreased to .34. The largest discrepancies between mammography and MR imaging occurred in breasts that had 60-80% fat as measured on MR imaging. CONCLUSION: Fatty and fibroglandular tissue can be differentiated on MR images of the breast with high precision and accuracy, therefore allowing assessment of breast density. The conclusions of researchers who used mammographic density patterns should be reassessed.

Adipose Tissue↗

Internal tremor in patients with Parkinson's disease.

Although sensory symptoms were not originally described in Parkinson's disease (PD), in recent years it has been increasingly recognized that painful sensations and paresthesias occur in approximately 40% of patients. It has been our observation that PD patients often describe a sensation of internal tremor, a feeling of tremor inside the chest, abdomen, arms, or legs that cannot be seen. We investigated the prevalence and characteristics of internal tremor by administering a questionnaire to 100 consecutive patients with PD and 50 age-matched controls seen in our movement disorders center. A sensation of internal tremor was present in 44% of this sample of PD patients and in 6% of the control population (p < 0.0001). The presence of internal tremor was unrelated to Unified Parkinson's Disease Rating Scale score, Hoehn and Yahr stage, duration of disease, or the presence of observable tremor. The frequency of other sensory symptoms (aching, tingling, burning) was higher in the PD patients with internal tremor (73%) than in those without (45%; p = 0.005). Internal tremor is associated with anxiety in 64% of patients (p < 0.0001). It was described as uncomfortable and was unrelieved by antiparkinsonian medication in three quarters of patients. A sensation of internal tremor is commonly reported by PD patients and should be recognized as a useful diagnostic factor in PD.

Aged↗

Once-daily aminoglycoside therapy: potential ototoxicity.

Current data indicate that once-daily aminoglycoside therapy is as efficacious as traditional multiple daily dosing and equally or less toxic. Our experience with once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients) occurrence of documented ototoxicity after prolonged aminoglycoside exposure.

Aged↗

Malignant breast epithelium selects for insulin-like growth factor II expression in breast stroma: evidence for paracrine function.

Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-II-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast. We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.

Breast↗

The challenge of vancomycin-resistant enterococci: a clinical and epidemiologic study.

BACKGROUND: Vancomycin-resistant enterococci have been recovered with increasing frequency from hospitalized patients. Risk factors, mode of nosocomial transmission, extent of colonization in hospitalized patients, and treatment options for these organisms have not been completely delineated. METHODS: We studied 53 patients (group A) with vancomycin-resistant enterococci isolated from various clinical specimens and also surveyed for vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile toxin assays (group B). Stool specimens submitted for identification of bacterial pathogens and stool specimens from hospital employees were also analyzed for vancomycin-resistant enterococci. RESULTS: Seventy-six isolates of vancomycin-resistant enterococci were recovered in group A. Five of these patients harbored vancomycin-resistant enterococci on admission. Fifty-three of 289 group B stool specimens submitted for C. difficile toxin assays yielded vancomycin-resistant enterococci. Cephalosporins and vancomycin were the most common antimicrobial agents received by both groups of patients. Enterococcus faecium isolates were more resistant than Enterococcus faecalis isolates to antimicrobial agents. All isolates exhibited high-level aminoglycoside resistance and were not beta-lactamase producers. There were at least 15 different molecular clones of E. faecium and three of E. faecalis. Vancomycin-resistant enterococcal bacteremia was associated with a 100% in-hospital mortality rate. CONCLUSIONS: Multidrug-resistant and vancomycin-resistant enterococci have become important nosocomial pathogens that are difficult to treat. Vancomycin-resistant enterococcal bacteremia was associated with a poor prognosis. We found a high rate of colonization in patients with suspected C. difficile toxin colitis. Judicious use of vancomycin and broad-spectrum antibiotics is recommended, and strict infection control measures must be implemented to prevent nosocomial transmission of these organisms.

Adult↗

The use of pramipexole, a novel dopamine (DA) agonist, in advanced Parkinson's disease.

We evaluated the efficacy, safety and tolerability of a new dopamine D-2 receptor agonist, pramipexole [(S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzathiazol-dihydro chloride], as adjunctive therapy in patients with advanced Parkinson's disease (PD). Twenty-four PD patients with motor fluctuations were treated in an 11 week prospective, single-blind parallel-group, placebo-controlled trial. The pramipexole treated group experienced a significant improvement in "off" time functioning as measured by the activities of daily living portion of the United Parkinson's Disease Rating Scale. In addition, the active treatment group was able to reduce total levodopa dose by 30% (p < 0.05). Pramipexole was well tolerated and the side effects reported were typical of other dopamine agonists. We conclude that pramipexole has antiparkinsonian effects which make it potentially useful in the treatment of motor fluctuations in PD.

Aged↗

Late presentation of congenital muscular torticollis: use of MR imaging and CT scan in diagnosis.

A 17-year old boy presented with a 10-year history of progressive head tilt to the right. Bilateral posterolateral cervical pain was mild and he was fully functional. The right sternocleidomastoid (SCM) muscle was prominent without rotation of the head to the left. The SCM had a cord-like consistency on palpation. Magnetic resonance (MR) and computed tomography (CT) scan imaging of the neck musculature suggested fibrous tissue within the substance of the muscle. This was histopathologically confirmed when the right SCM was surgically explored and resected. Congenital muscular torticollis is usually seen in newborns, infants, and children but may also present in adolescence and young adulthood. It should be included in the differential diagnosis of cervical dystonia as one of the nondystonic causes of abnormal head posture. Combined use of MR and CT scan of neck muscles may be of help in the diagnosis.

Adolescent↗

Gait abnormality in essential tremor.

Essential tremor (ET) has been described as a monosymptomatic disorder. In reports describing large series of patients with ET, there are rare patients who exhibit a noticeable gait disorder. However, we have observed that patients with ET and normal gait often exhibit an abnormality of tandem gait. To investigate this observation, we examined whether a gait disorder was present in 36 consecutive patients (mean age 69) with ET. We employed a tremor rating scale that scored tremor amplitude, location, and disability. In all patients, gait and tandem gait were separately evaluated. Eighteen of 36 patients (50%) exhibited tandem gait abnormalities in the presence of a normal narrow-based gait compared to 11 of 40 age-matched controls (28%) (p < 0.05). Abnormality of tandem gait was more frequently present in older ET patients and those with > 5 years of disease duration. No relationship was found between presence of tandem gait abnormality and gender, tremor severity, head involvement, or positive family history. The finding of a tandem gait abnormality in 50% of ET patients suggests that cerebellar dysfunction may be important in its pathophysiology.

Aged↗