Mannosidosis: an unusual cause of a deforming arthropathy

We report on a case of a deforming arthropathy in a young man with a lysosomal storage disorder. A 31-year-old man with a known diagnosis of mannosidosis presented with a painful swollen right elbow. Radiographs of his right elbow showed a disorganised joint with multiple fragments resembling the appearances of a neuropathic joint. This case provides further evidence that a deforming arthropathy may occur as part of the spectrum of skeletal abnormalities seen in mannosidosis. Received: 17 November 1999 Revision requested: 13 December 1999 Revision received: 6 March 2000 Accepted: 9 March 2000     

Induction of CYP1A in the beagle dog by an inhibitor of kinase insert domain-containing receptor: differential effects in vitro and in vivo on mRNA and functional activity.

Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A.     

Artery and vein separation using susceptibility-dependent phase in contrast-enhanced MRA

In magnetic resonance angiography, contrast agents are frequently used to help highlight arteries over background tissue. Unfortunately, enhancing veins hamper the visualization of arteries when data are collected over a long period of time after the arterial phase of the contrast agent. To overcome this problem, we have developed a novel imaging and postprocessing method that is capable of eliminating veins by utilizing the susceptibility difference between veins and surrounding tissue. This method was applied in the peripheral vasculature where the vessels are predominantly parallel to the main field and where the blood oxygen level-dependent effect is most pronounced. Results are presented for both long (15.8 msec) and short echo times (7.8 msec) and for sequential and centrally reordered acquisition schemes. The short echo scan approach appears to be the most promising, making it possible to obtain good suppression of the venous signal even when the timing is not perfect or when repeat scans are necessary.     

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.     

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety)

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.     

Effect of operative volume on morbidity, mortality, and hospital use after esophagectomy for cancer

OBJECTIVE: We sought to evaluate the effect of operative volume, hospital size, and cancer specialization on morbidity, mortality, and hospital use after esophagectomy for cancer. METHODS: Data derived from the Health Care Utilization Project was used to evaluate all Medicare-reimbursed esophagectomies for treatment of cancer from 1994 to 1996 in 13 national cancer institutions and 88 community hospitals. The complications of care, length of stay, hospital charges, and mortality were assessed according to hospital size (>/=600 beds vs <600 beds), cancer specialization (national cancer institution vs community hospital), and operative volume (esophageal [>/=5 Medicare esophagectomies per year vs <5 Medicare esophagectomies per year] and nonesophageal operations [>/=3333 cases per year vs <3333 cases per year]). RESULTS: Mortality was lower in national cancer institution hospitals (4.2% [confidence interval, 2.0%-6.4%] vs 13.3% [confidence interval, 4.2%-26.2%], P =. 05) and in hospitals performing a large number of esophagectomies (3. 0% [confidence interval, 0.09%-5.1%] vs 12.2% [confidence interval, 4.5%-19.8%], P <.05). Multivariate analysis revealed that the independent risk factor for operative mortality was the volume of esophagectomies performed (odds ratio, 3.97; P =.03) and not the number of nonesophageal operations, hospital size, or cancer specialization. Hospitals performing a large number of esophagectomies also showed a tendency toward decreased complications (55% vs 68%, P =.06), decreased length of stay (14.7 days vs 17.7 days, P =.006), and decreased charges ($39,867 vs $62, 094, P <.005). CONCLUSIONS: These results demonstrate improved outcomes and decreased hospital use in hospitals that perform a large number of esophagectomies and support the concept of tertiary referral centers for such complex oncologic procedures as esophagectomies.     

Antibiotic resistance in clinical isolates of Pseudomonas aeruginosa in Jamaica.

OBJECTIVE: To assess antibiotic resistance in clinical isolates of Pseudomonas aeruginosa in Jamaica, and to obtain baseline information on the presence of this important pathogen. METHODS: A total of 51 isolates of Pseudomonas aeruginosa, obtained from 162 clinical specimens from major hospitals and laboratories in seven parishes in Jamaica, were analyzed between May and August 2002. Isolates were tested against 18 different antibiotics by a disk diffusion method. RESULTS: Organisms were cultured from wound swabs (56%), high vaginal swabs (10.5%) and ear swabs (42.5%). Overall, the highest percentage rates of resistance were found for cefaclor (100% of all isolates), nalidixic acid (82.4%), kanamycin (76.5%), and trimethoprim/sulfamethoxazole (56.9%). Resistance rates were 25.5% or lower for tobramycin, gentamicin and polymyxin B, cefotaxime, ciprofloxacin and norfloxacin, piperacillin, carbapenems and amikacin. Forty-one isolates showed intermediate sensitivity to most of the antipseudomonal antibiotics, and the remaining 10 isolates were resistant to eight or more antibiotics. The multiresistant isolates, most of which were hospital isolates, were all resistant to tetracycline, nalidixic acid and trimethoprim/sulfamethoxazole, and highly (80%-90%) resistant to kanamycin, ciprofloxacin and norfloxacin. CONCLUSIONS: This study confirms that antibiotic resistance in this clinical pathogen is emerging in Jamaica, and suggests that due care must be taken in hospital settings to adequately diagnose pseudomonal infections and prescribe the antibiotic treatment most effective in preventing the increase in multidrug resistant organisms.     

Measurements of preferred walking speed in subjects with central and peripheral vision loss

BACKGROUND: Previous mobility studies have used Preferred Walking Speed (PWS) in order to determine the walking efficiency in terms of the Percent Preferred Walking Speed (PPWS) of visually impaired adults. PWS has been measured in previous studies using the sighted guide (SG) and non-sighted guide (NSG) techniques. This study compared the NSG, SG and string (ST) (subjects walked by holding on lightly to a cardboard tube attached to a piece of string) techniques of measuring PWS in visually impaired subjects. METHODS: Forty visually impaired subjects with central and peripheral vision loss were recruited. PWS was measured using the NSG, SG and ST techniques. For each technique, PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20-m corridor. RESULTS: There were no significant differences in PWS using the SG, NSG and ST techniques. CONCLUSION: For assessing walking efficiency, either the SG, NSG or ST technique could be employed when measuring PWS in visually impaired subjects.