Axonal damage in the spinal cord of multiple sclerosis patients detected by magnetic resonance spectroscopy.

Axonal damage is a major factor contributing to permanent disability in patients with multiple sclerosis (MS); it has been extensively investigated in the brain using magnetic resonance spectroscopy (MRS). In this study, MRS was used to investigate the degree of neuronal damage in the cervical spinal cord in MS. Spectra were acquired from spinal cord and brain in 11 patients with MS (expanded disability status score [EDSS], range 2.5-7.0) and 11 controls. Brain lesion volume and spinal cord cross-sectional area were measured. Concentration of the neuronal metabolite N-acetyl-aspartate ([NAA]) was reduced in the spinal cord in MS patients relative to controls (reduced by 32%, P < 0.05), indicating significant neuronal damage. Additionally, the spinal cord was significantly atrophied in MS patients (15%, P < 0.001). No significant reduction in brain [NAA] was seen in the MS group. There were no correlations between clinical measures and cord atrophy or brain lesion volume on MRI; however, spinal cord [NAA] correlated with the cerebellar subscore of the neurological assessment (P < 0.005), while brain [NAA] correlated with disease duration (P < 0.05). MRS demonstrated cellular damage within the cord over and above the tissue atrophy seen by MRI. Combining MRI and MRS may therefore give a more complete picture of neurodegeneration in the spinal cord.     

Rapid determination of trisomy 18 parental origin using fluorescent PCR and small tandem repeat markers: case reports

Trisomy 18 is the second most common genetic defect after trisomy 21, almost 90% of which are due to additional chromosome from the mother. The parental origin of the additional chromosome can, if required, be determined by two methods: karyotyping, which takes several weeks; or, more recently, by polymerase chain reaction (PCR) which is often problematic. Fluorescent PCR of small tandem repeats (STRs) can determine the parental origin in the majority of cases within 5 h. Although the incidence of paternal origin is known for both trisomy 21 and trisomy 18, this technique can rapidly determine the parental origin in cases where there is insufficient samples to perform conventional tests. Determining parental origin by these methods may also have clinical significance in the diagnosis of chromosomal translocations or in the diagnosis of genetic disease using linkage analysis.     

Applications of magnetic resonance spectroscopy to diagnosis and monitoring of mitochondrial disease

Magnetic resonance spectroscopy (MRS) can now be performed on routine high-field clinical magnetic resonance imaging systems. Over the last decade it has provided several useful insights into the pathophysiology of mitochondrial disorders. More recently, the feasibility of applications to clinical diagnosis and monitoring have been demonstrated. Exciting new work suggests that carefully supervised physical conditioning in conjunction with sodium dichloroacetate administration can markedly enhance both biochemical measures of aerobic metabolism and functional performance of patients with mitochondrial myopathies.

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Sommario La risonanza magnetica spettroscopica (MRS) può oggi essere effettuata di routine in apparecchi clinici di risonanza magnetica. Nell'ultima decade essa ha fornito importanti informazioni nella patofisiologia dei disordini mitocondriali. Più recentemente sono state dimostrate le sue possibilità di applicazione nella diagnosi clinica e nel monitoraggio di pazienti neurologici. Nuovi ed interessanti studi suggeriscono che un allenamento attentamente supervisionato in congiunzione con trattamento con dicloroacetato è capace di migliorare i parametri biochimici e la performance di pazienti con miopatie mitocondriali.

     

A one-year series of pediatric emergency department wheezing visits: the Hawaii EMS-C project.

During a 12-month period ending on November 30, 1988, data were collected on 2468 pediatric patients with wheezing who visited a pediatric ED. Cohort characteristics included: sex (64% male, 36% female), history of prematurity (12%), evidence of concurrent infection (82%), taking theophylline (35%), taking beta adrenergics (60%), taking cromolyn (6%), and taking corticosteroids (4%). The hospitalization rate was 10.5%. Seasonal variations, weather, air quality, and infections appeared to have significant effects on the daily variation of wheezing exacerbations. Initial oxygen saturation (OSAT) correlated with disease severity as measured by hospitalization risk and the number of bronchodilator treatments required in the ED. A suggestion for categorizing the treatment of asthma based on past history is proposed. Using this system in conjunction with pulse oximetry, wheezing severity and appropriate therapy can be more objectively determined.     

Genomic fingerprints of Staphylococcus aureus of bovine origin by polymerase chain reaction-based DNA fingerprinting.

Staphylococcus aureus (n = 75) isolated from mammary secretions of cows with subclinical and clinical mastitis from several geographic locations in the USA were examined using polymerase chain reaction-based DNA fingerprinting. DNA fingerprints were produced using a synthetic oligonucleotide primer (5''GTAACGCC3'') to produce a distinct spectrum of amplified DNA fragments facilitating a high degree of resolution for differentiating S. aureus strains. PCR-based DNA fingerprinting grouped the 75 S. aureus isolates into 19 distinct profiles. The technique differentiated closely related strains within and between geographic locations. Findings suggest that certain types are found across geographic regions suggesting a common clonal type. Within herd data suggest heterogeneity among subclinical and clinical isolates of S. aureus strains. Compared to existing typing methods, PCR-based DNA fingerprinting is easy to perform and interpret. Use of PCR-based DNA fingerprinting may allow for a more detailed investigation of the epidemiology of S. aureus mastitis in dairy cows.     

Radiotherapy for palliation of locally advanced prostatic carcinoma.

Some patients present with distressing symptoms due to locally advanced prostatic carcinoma which may be refractory to hormonal manipulation and/or surgical treatment. Over an 8-year period 26 patients received local palliative radiotherapy for recurrent bleeding and lower urinary outflow tract obstruction. All were treated with conventional external beam radiotherapy and all but 2 obtained useful palliation of symptoms, especially those with recurrent bleeding. We also found that radiotherapy could be given to the majority of patients on an out-patient basis in 2 or 3 fractions. This was well tolerated and there were few side effects.     

CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.     

Stabilization of phage T4 lysozyme by engineered disulfide bonds.

Four different disulfide bridges (linking positions 9-164, 21-142, 90-122, and 127-154) were introduced into a cysteine-free phage T4 lysozyme at sites suggested by theoretical calculations and computer modeling. The new cysteines spontaneously formed disulfide bonds on exposure to air in vitro. In all cases the oxidized (crosslinked) lysozyme was more stable than the corresponding reduced (noncrosslinked) enzyme toward thermal denaturation. Relative to wild-type lysozyme, the melting temperatures of the 9-164 and 21-142 disulfide mutants were increased by 6.4 degrees C and 11.0 degrees C, whereas the other two mutants were either less stable or equally stable. Measurement of the equilibrium constants for the reduction of the engineered disulfide bonds by dithiothreitol indicates that the less thermostable mutants tend to have a less favorable crosslink in the native structure. The two disulfide bridges that are most effective in increasing the stability of T4 lysozyme have, in common, a large loop size and a location that includes a flexible part of the molecule. The results suggest that stabilization due to the effect of the crosslink on the entropy of the unfolded polypeptide is offset by the strain energy associated with formation of the disulfide bond in the folded protein. The design of disulfide bridges is discussed in terms of protein flexibility.