Predictive Value of the GLIM Criteria in Chinese Community-Dwelling and Institutionalized Older Adults Aged 70 Years and Over.

OBJECTIVES: The Global Leadership Initiative on Malnutrition (GLIM) has recently published criteria for classifying malnutrition. This study investigated the associations between malnutrition and adverse outcomes, and identified which component(s) of the GLIM criteria is/are risk factor(s) of adverse outcomes in Chinese older adults. DESIGN: A prospective cohort study of Chinese older adults in a healthy ageing study. SETTING: Participants' place of residence. PARTICIPANTS: Community-dwelling and institutionalized Chinese older adults aged ≥70 years living in Hong Kong. MEASUREMENTS: Malnutrition at baseline was classified according to selected GLIM criteria. Adverse outcomes including poor self-rated health, functional limitation (Barthel Index), falls, frailty (FRAIL scale), hospitalization and mortality were assessed after a 3-year follow-up. Associations between malnutrition and components of selected GLIM criteria (weight loss, low body mass index (BMI), low muscle mass and disease burden) and each adverse outcome were examined using adjusted binary logistic regression and Cox proportional hazards model. Odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) are presented. RESULTS: Data of 1576 community-dwelling (45.5% female, 78.1±6.5 years) and 427 institutionalized (69.6% female, 85.5±6.4 years) older adults were included at baseline. Among community-dwelling older adults, malnutrition was associated with frailty (n=899, OR: 2.44, 95% CI: 1.05-5.70) and mortality (n=1007, HR: 1.37, 95% CI: 1.12-1.66). No association was found for other outcomes. Among institutionalized older adults, malnutrition was not associated with any outcomes. Low BMI and low muscle mass were risk factors of frailty; while weight loss was a risk factor of mortality in community-dwelling older adults. Weight loss and disease burden were risk factors of mortality among institutionalized older adults. CONCLUSION: The association between malnutrition and frailty and mortality was observed in community but not in institutional settings. Further studies are required to draw more definitive conclusions on the use of GLIM criteria in institutional settings.

Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis.

BACKGROUND: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, and temporal lobe necrosis is observed in about 7% of patients after radiotherapy. Although some studies reported that these patients demonstrated cognitive impairment after radiotherapy, it is still unclear if the cognitive deficits are related to the radiation exposure or the radiation-induced necrosis. OBJECTIVE: To compare the cognitive function of patients with and without temporal lobe necrosis after radiotherapy for nasopharyngeal carcinoma. METHODS: A comprehensive neuropsychological battery was administered to 53 patients with nasopharyngeal carcinoma who had completed their radiotherapy at least 1 year previously. As evidenced by magnetic resonance imaging, 31 patients developed necrosis after treatment. Thirty-one age- and education-matched individuals were recruited as normal control subjects. RESULTS: Whereas the performance of patients without temporal lobe necrosis was similar to that of normal control subjects, patients with temporal lobe necrosis demonstrated significant impairment on tests of verbal (P<.001) and visual memory (range, P<.001 to P =.03), language (range, P<.001 to P =.01), motor ability (P =.02), planning (P =.02), cognitive ability (P =.007), and abstract thinking (range, P =.009 to P =.04). However, the performance of patients with necrosis on tests of general intelligence (range, P =.08 to P =.15), attention (range, P =.06 to P =.55), and visual abilities (range, P =.06 to P =.47) was not significantly different from that of normal control subjects and patients without necrosis. CONCLUSIONS: Radiotherapy for nasopharyngeal carcinoma seemed to have adverse but insignificant effects on the cognitive functions of the patients. However, for patients who developed temporal lobe necrosis after radiotherapy, memory, language, motor ability, and executive functions were significantly impaired, although their general intelligence remained relatively intact.

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogues of trimethoprim.

A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.

A series of nine 2,4-diamino-5-[6-( or 7-)quinolylmethyl]pyrimidines has been prepared by condensations of quinolinecarboxaldehydes with beta-anilinopropionitriles, followed by treatment with guanidine. All compounds has basic or methoxy substituents at the 2- or 4-positions of the quinoline ring. All of the 6-quinolylmethyl derivatives were highly inhibitory against Escherichia coli dihydrofolate reductase (DHFR), provided that an 8-substituent was present in the quinoline ring. Those compounds that had basic substituents in the 2-position of the quinoline ring were also highly specific for bacterial dihydrofolate DHFR, relative to a vertebrate counterpart. Protonation on the quinoline ring nitrogen is a possible cause of specificity.

Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.

The recent increase in fungal infections, especially among AIDS patients, has resulted in the need for more effective antifungal agents. In our search for such agents, we focused on developing compounds which inhibit fungal dihydrofolate reductase (DHFR). A series of 25 5-(arylthio)-2,4-diaminoquinazolines were synthesized as potentially selective inhibitors of Candida albicans DHFR. The majority of the compounds were potent inhibitors of C. albicans DHFR and much less active against human DHFR. High selectivity, as defined by the ratio of the I50 values for human and C. albicans DHFR, was achieved by compounds with bulky and rigid 4-substituents in the phenylthio moiety. For example, 5-[(4-morpholinophenyl)thio]-2,4-diaminoquinazoline displayed a selectivity ratio of 540 and was the most selective inhibitor synthesized to date. Substitution in the 2- or 3-position of the 5-phenylthio group provided only marginal selectivity. 6-Substituted-5-[(4-tert-butylphenyl)thio]-2,4-diaminoquinazolines showed potent activity against the C. albicans enzyme but were equally active against human DHFR. Most of the selective compounds were also good inhibitors of C. albicans cell growth, with minimum inhibitory concentration values as low as 0.05 microgram/ mL.

X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.

X-ray crystallographic analysis of 5-(4'-substituted phenyl)sulfanyl-2,4-diaminoquinazoline inhibitors in ternary complex with Candida albicans dihydrofolate reductase (DHFR) and NADPH revealed two distinct modes of binding. The two compounds with small 4'-substituents (H and CH3) were found to bind with the phenyl group oriented in the plane of the quinazoline ring system and positioned adjacent to the C-helix. In contrast, the more selective inhibitors with larger 4'-substituents (tert-butyl and N-morpholino) were bound to the enzyme with the phenyl group perpendicular to the quinazoline ring and positioned in the region of the active site that typically binds the dihydronicotinamide moiety of NADPH. The cofactor appeared bound to DHFR but with the disordered dihydronicotinamide swung away from the protein surface and into solution. This unusual inhibitor binding mode may play an important role in the high DHFR selectivity of these compounds and also may provide new ideas for inhibitor design.

2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.

A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship (SAR) studies suggested that a meta substituent, particularly a meta methyl substituent, invariably increased antiviral activities. However, optimal antiviral activities were manifested by compounds where both meta groups in the arylsulfonyl moiety were substituted and one of the substituents was a methyl group. Such a disubstitution led to compounds 3v, 3w, 3x, and 3y having IC50 values against HIV-1 in the low nanomolar range. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. However, they showed a lack of activity against the K103N and Y181C mutant viruses. The elucidation of the X-ray crystal structure of the complex of 3v (739W94) in HIV-1 reverse transcriptase showed an overlap in the binding domain when compared with the complex of nevirapine in HIV-1 reverse transcriptase. The X-ray structure allowed for the rationalization of SAR data and potencies of the compounds against the mutants.

Galpha(14) links a variety of G(i)- and G(s)-coupled receptors to the stimulation of phospholipase C.

1. The bovine Galpha(14) is a member of the G(q) subfamily of G proteins that can regulate phospholipase Cbeta isoforms but the extent to which Galpha(14) recognizes different receptor classes is not known. 2. Galpha(14) was cotransfected with a variety of receptors in COS-7 cells, and agonist-induced stimulation of phospholipase C was then measured. 3. Activation of the type 2 but not type 1 somatostatin receptor in cells coexpressing Galpha(14) stimulated the accumulation of inositol phosphates; functional expression of both subtypes of somatostatin receptors was determined by the ability of somatostatin to inhibit cyclic AMP accumulation. 4. Among the three opioid receptors (mu, delta, and kappa), only the delta receptor was capable of stimulating IP formation when coexpressed with Galpha(14) in COS-7 cells. 5. A panel of G(i)- and G(s)-linked receptors was screened for their ability to stimulate IP accumulation via Galpha(14). The adenosine A(1), complement C5a, dopamine D(1), D(2) and D(5), formyl peptide, luteinizing hormone, secretin, and the three subtypes of melatonin (mt1, MT2, and Xenopus) receptors were all incapable of activating Galpha(14), while the alpha(2)- and beta(2)-adrenoceptors were able to do so. 6. Galpha(14)-mediated stimulation of phospholipase Cbeta was agonist dose-dependent. These data demonstrate that although Galpha(14) can interact with different classes of receptors, it is much less promiscuous than Galpha(15) or Galpha(16).

The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani.

Several alkyl phosphorylcholines and related derivatives were tested against Leishmania donovani amastigotes in mouse peritoneal macrophages in vitro and ED50 values were determined in the range of 1-12 microM. The three alkyl phosphorylcholines tested against L. donovani in BALB/c mice were active, an ED50 of 12.8 mg/kg/day X 5 was ascertained for one compound, but an alkyl phosphorylethanolamine was inactive.

Effect of ABO blood group mismatching on corneal epithelial cells: an in vitro study.

AIM: To determine, in vitro, the effects of blood group ABO mismatching on corneal epithelial cells. METHODS: Corneal epithelial cell cultures were established from 32 human cadaver donor eyes. Epithelial cells (100 microl of 4 x 10(2) cells per microl) were incubated for 4 hours with antibodies against blood group antigens A, B, and AB, with and without complement. Cell lysis was assayed by a chemiluminescent assay using Cytolite reagent. Live cells, remaining after incubation, were counted in a scintillation counter. The blood group of the donors was determined retrospectively, in a blinded manner. RESULTS: Retrospective tracing of donor blood groups was possible for 20 donors. In all cases the blood group corresponded with that suggested by the cell lysis assay. Significant cell lysis was observed when known A group cells were incubated with anti-A and anti-AB antibody, B group cells were incubated with anti-B and AB antibody, and AB group cells were incubated with anti-AB antibody. Lysis occurred only in the presence of complement. No lysis of O group cells was observed with any of the antibodies. In all cases, lysis was observed only with neat (serum) antibody concentrations. CONCLUSIONS: Blood group ABO mismatching results in significant lysis of corneal epithelial cells. The antibody concentration required for lysis equals that found in serum. Such levels of antibody are unlikely to be achieved in tears and/or aqueous. This may offer an explanation for the conflicting reports of the studies on the effect of blood group matching on corneal grafts. The variability in the outcome may reflect the levels of antibodies gaining access to the corneal cells and not the mismatching alone.

Idiopathic cervical dystonia: Report of discordance in a pair of monozygotic twins.

The gene for idiopathic torsion dystonia (ITD) has been located on chromosome 9q32-34. It remains controversial whether cervical dystonia (CD) is genetically determined or not. A previous report of a concordant expression of CD in a pair of monozygotic twins suggested a genetic role. We report discordance in a pair of monozygotic twins, one presenting with adult-onset idiopathic CD with duration of disease for 7 yr, while the other co-twin remained normal. Family history was negative for dystonia. The pair of twins spent all their life in the same environment. This argues against the role of genetics in the etiology of CD.

The magic angle phenomenon in tendons: effect of varying the MR echo time.

Increased signal intensity on magnetic resonance (MR) imaging of tendons arising from the magic angle phenomenon is well recognized. This study aimed to evaluate the effect of varying the echo time (TE) upon tendon signal intensity, and to determine if a modified TE value produces acceptable T1 and proton density (PD) weighted images. Fresh bovine tendons were imaged in a 1.5 T MR scanner using spin echo (SE) T1 and PD weighted sequences and utilizing a number of different coils. For each set of sequences, the tendon was orientated at 55 degrees to the main magnetic field (B0) and imaged using constant TR and incremental TE values. Signal intensity was measured on images at each TR/TE value and compared with the signal intensities of tendons orientated at 0 degree to B0, obtained using minimum TE values. This experiment was repeated with a 1.0 T MR scanner and utilizing a spine coil. The Achilles tendon of a human volunteer was similarly imaged using a general purpose flex coil. For bovine and human tendons orientated at 55 degrees to B0, the signal intensities decreased exponentially with increasing TE. A critical TE value exceeding 37 ms, for each sequence, reduced the signal intensities to the levels obtained with the tendons orientated at 0 degree to B0, such that the magic angle phenomenon could be avoided. Although there was variability of the signal intensities with different coils, the critical TE value remained constant and the anatomical clarity was not degraded. The critical TE value was unaltered using two MR scanners of different field strengths.

Lumbar spine magnetic resonance imaging: comparison between fast spin echo proton density and spin echo T1 axial scans.

Spin echo (SE) T1 axial scans are routinely obtained in magnetic resonance imaging of the lumbar spine in many centres. This study directly compared matched SE T1 and fast SE (FSE) proton density (PD) axial scans. Both SE T1 and FSE PD axial scans of the lumbar spine were obtained in 116 consecutive patients. The imaging parameters (field-of-view, slice thickness, interslice gap, number of excitations and matrix size) and scan levels were identical for each pair of sequences. At two selected levels, L4/5 and L5/S1, various structures were independently graded by two observers. In 232 lumbar levels analysed, the bone marrow, epidural fat, disc, extradural nerve root and facet joint were equally well seen on both sequences by both observers (combined mean grades of 2.93-2.99). The thecal sac was marginally better depicted on FSE PD than on SE T1 images, with mean grades of 2.96 and 2.88, respectively. The psoas muscle was adequately visualized for diagnostic purposes on both sequences (mean grades of 2.30-2.32). The cauda equina were better seen on FSE PD (mean grade 1.92) than on SE T1 (mean grade 1.00) images. In conclusion, FSE PD scans are comparable to and may potentially replace SE T1 axial MR scans of the lumbar spine.

Acute vertebral body compression fractures: discrimination between benign and malignant causes using apparent diffusion coefficients.

Diffusion weighted MRI was performed on patients with acute vertebral body compression. The usefulness of the apparent diffusion coefficient (ADC) in differentiating between benign and malignant fractures was evaluated. A total of 49 acute vertebral body compression fractures were found in 32 patients. 25 fractures in 18 patients were due to osteoporosis, 18 fractures in 12 patients were histologically proven to be due to malignancy, and 6 fractures in 2 patients were due to tuberculosis. Signal intensities on T(1) weighted, short tau inversion recovery (STIR) and diffusion weighted images were compared. ADC values of normal and abnormal vertebral bodies were calculated. Except for two patients with sclerotic metastases, benign acute vertebral fractures were hypointense and malignant acute vertebral fractures were hyperintense with respect to normal bone marrow on diffusion weighted images. Mean combined ADCs (ADC(cmb); average of the combined ADCs in the x, y and z diffusion directions) were 0.23 x 10(-3) mm(2) s(-1) in normal vertebrae, 0.82 x 10(-3) mm(2) s(-1) in malignant acute vertebral fractures and 1.94 x 10(-3) mm(2) s(-1) in benign acute vertebral fractures. The differences between ADC(cmb) values were statistically significant (p<0.001). The ADC is useful in differentiating benign from malignant acute vertebral body compression fractures, but there may be overlapping ADC values between malignant fractures and tuberculous spondylitis.

Rapid spontaneous resolution and redistribution of acute subdural hematoma in a patient with chronic alcoholism: a case report.

We report a case of a 54-year-old man who had documented traumatic acute subdural hematoma. He suffered from a transient episode of confusion and a follow-up CT scan of brain 6 h after the initial scan showed resolution and redistribution of the subdural hematoma. In this case report, we review the literature for the underlying pathophysiology of this uncommon phenomenon.

Late temporal lobe necrosis in patients with nasopharyngeal carcinoma: evaluation with combined multi-section diffusion weighted and perfusion weighted MR imaging.

Late temporal lobe necrosis is a well-known and serious complication in patients with nasopharyngeal carcinoma (NPC) following radiotherapy. Owing to the close proximity to the skull base, the medial temporal lobes are inevitably included in the target volume of irradiation. Patients with NPC provide a unique opportunity in study of delay radiation effect in normal human brain. The objective of this study was to evaluate late temporal lobe radiation injury by combined multi-section diffusion weighted and perfusion weighted MR imaging. We prospectively studied 16 patients with typical clinical symptoms of late temporal lobe necrosis or other abnormalities in the temporal lobes incidentally detected by conventional MR imaging. All patients had a previous history of radiotherapy for histologically proven NPC. Conventional T1- and T2-weighted images, fast gradient echo with echo-planar diffusion-weighted and perfusion-weighted MR imaging were performed. Apparent diffusion coefficient (ADC) map and relative cerebral blood volume (rCBV) map were computed via commercially available software. MR diffusion and perfusion images were then analyzed and graded by two independent observers with focusing on the diffusion and perfusion mismatch. The temporal lobe lesions displayed marked high diffusion on the ADC map. The rCBV map also revealed marked hypoperfusion in these temporal lobe lesions in all patients. The areas of abnormality on the rCBV map were significantly larger than the lesions on the ADC map in 14 patients (observer 1) and 13 patients (observer 2). Since late temporal lobe necrosis is probably caused by damage of the endothelium of vessels and ischemia, perfusion and diffusion mismatch might imply injured tissue but potentially salvageable brain tissue. A mismatch may be potentially used to predict the response to treatment in-patients with late temporal lobe necrosis.

Determining the lumbar vertebral segments on magnetic resonance imaging.

STUDY DESIGN: A study to test the ability of an additional cervicothoracic localizer scan to decrease interobserver discrepancy in the identification of vertebral segments in magnetic resonance imaging of the lumbar spine. OBJECTIVES: To investigate whether lumbar vertebral segments can be identified correctly from lumbosacral magnetic resonance localizer scans, the degree of interobserver discrepancy, and the value of an additional cervicothoracic localizer scan. SUMMARY OF BACKGROUND DATA: In magnetic resonance imaging of the lumbar spine, it may be difficult to identify transitional lumbosacral vertebral segments. METHODS: The sagittal and coronal lumbosacral localizer scans of 141 consecutive patients referred for magnetic resonance imaging of the lumbosacral spine were reviewed independently by two radiologists with the aim of locating the L5 vertebra. An additional sagittal cervicothoracic localizer scan also was performed in each case. The final study group consisted of 129 patients. The L5 vertebra was identified by counting caudally from C2 using the sagittal cervicothoracic and lumbosacral localizer scans. In the 54 most recently studied patients, cod liver oil capsule surface markers were placed near the thoracolumbar junction to quantify any marker shift between the two sagittal localizer scans. RESULTS: The lumbar segments could be identified consistently by counting caudally using cervicothoracic and lumbosacral localizer scans. Using sagittal lumbosacral localizer scans alone, the lumbar vertebral segments could be identified correctly in only 80.2% of patients. Coronal lumbosacral localizer scans produced similar results (82.2%). The accuracy fell to 77.9% when using a combination of both sagittal and coronal lumbosacral localizer scans. There was a 11.6% interobserver discordance in assessment of these levels. Lumbosacral transitional vertebrae were identified in 17 patients (13.2%), including 8 sacralized L5 and 9 lumbarized S1 vertebrae. Apparent surface-marker shift between cervicothoracic and lumbosacral localizer scans was insignificant, averaging only 1.9 mm (range, 0.0-5.6 mm). CONCLUSIONS: The addition of a cervicothoracic localizer scan in magnetic resonance imaging of the lumbosacral spine is highly recommended.

Hypertrophic olivary degeneration following surgical excision of brainstem cavernous hemangioma: a case report.

Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubo-olivary pathway. It is distinguished from other types of neuronal degeneration in that hypertrophy, rather than atrophy, takes place in the neurons in the inferior olivary nucleus. Prior to the invention of Magnetic Resonance Imaging (MRI), HOD was difficult to be detected, and a firm diagnosis could only be made at autopsy. We present a case of bilateral HOD following surgical excision of a cavernous hemangioma in the brainstem. The literature and imaging findings of this uncommon condition are reviewed.