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Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (P<0.01) increase in the ratio of choline-containing compounds to N-acetylaspartate (Cho/NA) in the left cerebellum in boys with DMD compared with control boys. There was no change in the creatine/NA ratio and a significant increase (P=0.03) in the Cho/creatine ratio, suggesting that the change in Cho/NA ratio was due to an increase in choline-containing compounds; this increase has been previously observed in the brain of the murine model of DMD, the mdx mouse. No significant changes were observed in spectra obtained from left frontal lobe in DMD compared to controls. We also observed a significant association between Cho/NA in the left cerebellum, and the performance of DMD boys on the Matrix Analogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.

Background: Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain., Methods: We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age., Findings: We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men., Interpretation: We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Objective: Our purpose was to determine the prognostic significance of human papillomavirus deoxyribonucleic acid in cervical cancers., Study Design: The polymerase chain reaction was used to detect human papillomavirus deoxyribonucleic acid types 6, 11, 16, 18, 31, 33, 52, or 58 in tumors from 148 patients (equal numbers of whom were disease free or had relapses) surgically treated for stage IB or IIA cancers in a major Australian hospital. Cox regression modeling was used to assess the effect of human papillomavirus status on tumor recurrence, taking into account patient age, clinical stage, histologic node status, and type of tumor., Results: Seventy of 74 (95%) of the recurring tumors and 62 of 74 (84%) of the nonrecurring tumors were human papillomavirus deoxyribonucleic acid positive. The rates of positivity of types 16 and 18 were 64% versus 31% in the recurrers and 65% versus 14% in the nonrecurrers. Human papillomavirus type 18 positivity was associated with a greater risk of recurrence than was type 16 positivity (hazard ratio 1.8; p = 0.03). Clinical stage, nodal metastasis, and young age (< or = 35 years) also had adverse effects on relapse (hazard ratio for each approximately 2)., Conclusion: Human papillomavirus type 18 positivity is a risk factor for tumor recurrence in surgically treated cervical cancer.

Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.

A radiolabelled monoclonal antibody that reacts with human breast cancer was injected into the web space of each hand in eight women with breast cancer, and the axillae were scanned 16-24 h later. Scans were positive in seven axillae with palpable lymph nodes and in two axillae with impalpable lymph nodes (metastases later confirmed by needle aspiration). The scan was negative in one axilla with a palpable mass, and here no tumour cells were obtained on needle aspiration. In a man with axillary lymphoma, no specific binding of antibody was observed. This technique could lead to earlier and more precise diagnosis of lymph node metastasis in patients with breast cancer.

Two monoclonal antibodies (mAb) to colorectal cancer were produced using a novel immunization technique. This involved immunizing mice with whole serum obtained from patients with cancer of the colon (three with metastatic disease) and resulted in antibodies which were reactive with colonic tumor tissue by immunoperoxidase testing. Two mAbs (O-1, I-1) were isolated which were non-reactive with normal tissue and with tissues obtained from subjects with benign disease but were reactive with 34/50 (formalin-fixed) colon carcinoma specimens. Further testing on cell lines and other malignant tumors suggested both mAbs detect carcinoembryonic antigen (CEA) as their reactivities were similar to a known anti-CEA antibody, and they reacted with CEA in a solid-phase radioimmunoassay. The two mAbs were found to react with the same or closely associated epitopes on CEA by competitive tests. As the anti-CEA antibodies were made to serum (rather than tissue) CEA, it was possible that unique, highly specific mAb has been produced, particularly as there was a selective reaction of the mAbs for malignant but not normal tissues. A serum test with mAb I-1 was developed which detected raised serum CEA levels in 3/24 patients with benign colonic lesions, 7/19 patients with pancreatic cancer, 5/25 patients with colonic cancer but not in 20 normal individuals. There was direct correlation between these results and a commercially available CEA test kit.

C57BL/6J mice, age 6-8 weeks were inoculated intracerebrally with brain homogenate from mice previously infected with the 139A strain of scrapie; control mice were identically treated with brain homogenate from non-infected normal mice. The activities of choline acetyltransferase (CAT), acetyl cholinesterase (AChE), and glutamic acid decarboxylase (GAD) were determined in the forebrain and hindbrain of these animals after 67, 126 and 151 days post-inoculation. There were no significant differences in the activities of CAT and GAD between scrapie and control mice at early, middle or late stages of the disease in the scrapie-infected animals; there was an about 20% decline in AChE activity in the scrapie brain.

We studied 71 patients with 12-hour Holter monitoring to determine if the incidence and complexity of ventricular arrhythmias in symptomatic coronary artery disease patients were related to the extent of left ventricular dysfunction. Their average age was 51 years, and each had cardiac catheterization within 3 months of study. Thirty-six patients had left ventricular aneurysms, 10 had normal left ventricular angiograms and 25 had left ventricular hypokinesis or akinesis without dyskinesis. The patients with aneurysms had significantly more heart failure, prior infarction, cardiomegaly and impaired ejection fractions. The mean premature ventricular contractions per hour for the aneurysm patients was 34 +/- 52, 3 +/- 5 for those with normal left ventricles, and 11 +/- 24 in the remainder. Complex premature ventricular contraction were noted in 50% of the aneurysm patients, in 10% of the patients with normal left ventricles and in 23% of the patients with hypokinesis or akinesis. Ventricular arrhythmias increase with greater left ventricular wall motion abnormality in patients with symptomatic coronary artery disease.