Biomedical subjects
R Gregory
Publications and source records attributed to R Gregory.
The post-irradiation lower motor neuron syndrome neuronopathy or radiculopathy?
It is not known whether the post-irradiation lower motor neuron syndrome results from radiation damage to motor neuron cell bodies or from damage to the nerve roots of the cauda equina. We studied six cases who had presented with testicular neoplasms, subsequently undergoing irradiation that encompassed inter alia para-aortic nodes with co-irradiation of the distal spinal cord and cauda equina. A predominantly motor disorder affecting the legs ensued after variable and often prolonged latencies (3-25 years). However, all patients also developed mild sensory features either initially or on prolonged follow-up. Sural sensory nerve action potentials (SNAPs) were normal in five. Mild sphincter symptoms occurred in three of five surviving cases after a mean of 7.9 years. MRI showed gadolinium enhancement of the cauda equina in two of three patients. The first reported neuropathological study, uncomplicated by metastatic disease, of the conus and cauda equina was performed in one patient who died. This showed a radiation-induced vasculopathy of the proximal spinal roots, with preservation of motor neuronal cell bodies and spinal cord architecture. These clinical, radiological, neurophysiological and pathological findings all point to a predominantly, but not exclusively, motor radiculopathy affecting the irradiated portion of the cauda equina proximal to the dorsal root ganglia. Radiation exposure exceeded 40 Gy both in our series and in previous reports. The natural history of this disorder is one of relentless deterioration occasionally punctuated by 1-2-year periods of stability. Post-irradiation lumbosacral radiculopathy is a more accurate name for this condition.
p53 gene therapy in vivo of herpatocellular and liver metastatic colorectal cancer.
Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers. Colorectal cancer is leading cause of cancer mortality in the United States, whereas hepatocellular cancer is the leading worldwide cause of cancer death; the liver is a primary site of morbidity in both diseases. Because systemic tumor suppressor gene therapy is currently not feasible, we have chosen to develop a regional form of such therapy directed at primary or metastatic liver neoplasms. Gene replacement therapy with p53 is a promising new strategy to treat advanced human cancers.
Persistent serratus anterior paralysis after fracture of an anterior cervical bone graft.
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Why isn't sociology a science?
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Progressive myoclonic ataxia associated with coeliac disease. The myoclonus is of cortical origin, but the pathology is in the cerebellum.
We report four patients with a progressive myoclonic ataxic syndrome and associated coeliac disease. The onset of the neurological syndrome followed the gastrointestinal and other manifestations of coeliac disease while on a gluten-free diet, in the absence of overt features of malabsorption or nutritional deficiency. The condition progressed despite strict adherence to diet. The neurological syndrome was dominated by action and stimulus sensitive myoclonus of cortical origin with mild ataxia and infrequent seizures. Plasmapharesis and immunosuppressive treatment were tried in two patients but were not beneficial. Post-mortem examination of the brain in one case showed selective symmetrical atrophy of the cerebellar hemispheres with Purkinje cell loss and Bergmann astrocytosis, and with preservation of the cerebral hemispheres and brainstem. Coeliac disease should be considered in the differential diagnosis of all patients presenting with a progressive myoclonic ataxic syndrome.
Spontaneous intracranial hypotension.
The clinical features and radiological appearances of spontaneous intracranial hypotension are described in three patients and the medical literature is reviewed. Awareness of this condition and its differentiation from more sinister meningitic processes is important to avoid unnecessary invasive investigations and to allow prompt diagnosis and effective treatment.
Excessive secretion of insulin precursors characterizes and predicts gestational diabetes.
Using assays that specifically measure insulin, intact proinsulin, and 32,33 split proinsulin, we examined the beta-cell secretory response to an oral glucose tolerance test (OGTT) in 64 women with gestational diabetes mellitus (GDM) and 154 pregnant normoglycemic control subjects of comparable age and body mass index. Women with GDM were characterized by a lower 30-min insulin increment (40.8 [34.9-47.6] vs. 58.6 [53.6-64] pmol insulin/mmol glucose, P < 0.001; geometric mean [95% confidence interval]) and a higher plasma insulin level at 120 min (702 [610-808] vs. 444 [400-492] pmol/l, P < 0.001). 32,33 split proinsulin levels were elevated in GDM patients in both fasting (9.1 [7.3-11.4] vs. 6.7 [6.0-7.5] pmol/l, P < 0.02) and 120-min (75.2 [62.9-90.0] vs. 52.2 [46.7-58.3] pmol/l, P < 0.001) samples, respectively. Intact proinsulin levels were significantly elevated at 120 min in the women with GDM (21.3 [18.1-25.1] vs. 14.8 [13.4-16.3] pmol/l, P < 0.001). Thus, the qualitative abnormalities of insulin secretion in GDM patients (low 30-min insulin increment, high 120-min plasma insulin, and elevated 32,33 split proinsulin) are similar to those seen in nonpregnant subjects with impaired glucose tolerance. To determine whether measures of proinsulin-like molecules (PLMs) might assist in the prediction of GDM, women who had a 1-h glucose level of > 7.7 mmol/l after a 50-g glucose challenge at 28-32 weeks' gestation had insulin and PLMs measured in the 1-h sample.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of basal lamina in Schwann cell glycolipid biosynthesis.
Schwann cells that are deprived of axonal contact switch their glycolipid metabolic pathway from primarily galactocerebroside (GalCe) synthesis to the formation of glucocerebroside (GlcCe) and its homologs. The removal of axonal influence has a dual effect on Schwann cell phenotype; they lose the ability to assemble both myelin and basement membrane. To determine whether a loss of basement membrane directly affects glycolipid expression, we have examined lipid biosynthesis in Schwann cells which were allowed to interact with axons of dorsal root ganglion neurons but which were deprived of the ability to assemble basal lamina. These Schwann cells resemble those from myelinating nerve in that they synthesize a large amount of galactohydroxycerebroside. This suggests that axon contact, even in the absence of basement membrane, is sufficient to induce the GalCe metabolic pathway.
Peripheral neuropathy as a presenting feature of type 2 diabetes: a case-controlled study.
The characteristics and outcome of 68 newly diagnosed Type 2 diabetic patients who presented with clinically evident peripheral neuropathy were compared with matched controls who had no neuropathy at diagnosis. All subjects (34 male) whose median age was 68 (range 47-89) yr were identified from a computerized diabetes register and presented in 1982-1990. The groups were compared at diagnosis for haemoglobin A1, body mass index, blood pressure, smoking, and alcohol consumption, and for co-existent coronary and peripheral vascular disease. Mortality and morbidity were recorded to March 1991. Significantly more patients with neuropathy had co-existent peripheral vascular disease: 24(35%) compared to 6(9%) controls (p = 0.0021). Twenty (30%) of those with neuropathy and no controls had retinopathy at diagnosis, which was sight-threatening in 10. Seven (10%) with neuropathy but no controls presented with foot ulcers, one requiring limited amputation. Two more patients with neuropathy and one control subsequently developed foot ulcers resulting in one or more amputation in each group. Twenty-one (31%) of those with neuropathy and 14 (21%) controls died (p = 0.2109). In conclusion more diabetic patients with clinically evident peripheral neuropathy at diagnosis have peripheral vascular disease than matched patients without neuropathy. It is likely that macrovascular disease either exacerbates or causes the neuropathy in this group of patients. They are at high risk of developing foot ulceration and high priority should be given to foot care in planning their management.
A hint of risk: tradeoffs between quantitative and qualitative risk factors.
Risk-perception research plays an active role in discussion of risk-management alternatives. However, little guidance is provided regarding how public concerns should be weighed against other sources of cost and benefits. This paper reports the results of two experiments that measure tradeoffs among cost (in dollars), a quantitative risk measure (number of deaths or injuries), and several qualitative characteristics associated with perceived risk. Most subjects were willing to make the requested trade. However, the perceived risk information led others to reject the proposed technology.
Quantitation of satellite cell proliferation in vivo using image analysis.
A nonisotopic, double fluorescence technique was developed to study myogenic satellite cell proliferation in posthatch turkey skeletal muscle. Labeled satellite cell nuclei were identified on enzymatically isolated myofiber segments using a mouse monoclonal antibody (anti-BrdU) followed by fluorescein-5-isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibody. Myofiber nuclei (myonuclei+satellite cell nuclei) were counterstained with propidium iodide (PI). The myofiber segment length, myofiber segment diameter, and the number of PI and FITC labeled nuclei contained in each segment was determined using a Nikon fluorescence microscope, a SIT video camera and Image-1 software. Data collected by three different operators of the image analysis system revealed 5.0 +/- 1.4 satellite cell nuclei per 1000 myofiber nuclei and 5284 +/- 462 microns3 of cytoplasm surrounding each myofiber nucleus in the pectoralis thoracicus of 9-week-old tom turkeys. BrdU immunohistochemistry coupled with the new approach of PI staining of whole myofiber mounts is an effective combination to allow the use of an efficient semi-automated image analysis protocol.
Coexistence of hereditary motor and sensory neuropathy type Ia and IgM paraproteinemic neuropathy.
A patient with minimal motor dysfunction dating from early childhood developed more rapidly progressive distal weakness and positive sensory symptoms due to peripheral neuropathy in the fourth decade of life. DNA analysis showed the partial duplication of chromosome 17p associated with hereditary motor and sensory neuropathy type Ia. In addition, the patient had an IgM paraproteinemia and the typical morphological features of IgM paraproteinemic neuropathy on nerve biopsy.
Progressive sensory nerve dysfunction in amyotrophic lateral sclerosis: a prospective clinical and neurophysiological study.
Sensory nerve function was determined in 19 patients with amyotrophic lateral sclerosis (ALS), using a battery of clinical and neurophysiological tests. This assessment was repeated on 12 patients after intervals of 6-18 months. Twelve controls were also studied. In the ALS group, only 2 patients had noticed mild sensory symptoms and none had sensory signs. Between successive studies the vibration thresholds increased, but not to a significant degree. ALS patients showed a significant fall in amplitude of the sensory nerve action potentials in the median, radial, and sural nerves (P < 0.04); sensory nerve conduction velocity did not alter. The median nerve somatosensory evoked potential N19 latency showed a highly significant increase (P < 0.008). Significant subclinical deterioration in sensory nerve function occurs in ALS, and parallels the progressive motor decline. Neuronal degeneration in ALS is not restricted to motor neurons.
Bovine and human NPH insulins as T cell immunogens.
The aim of this study was to assess the immunocompetence of T cells from patients with poorly controlled diabetes with respect to Candida albicans antigen and to compare the relative immunogenicity of human insulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins. T-cell proliferation was measured in vitro in response to C. albicans, bovine and human insulin, bovine and human NPH and protamine in 17 patients with newly-diagnosed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (non-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin. The following results were found: Baseline responses to C. albicans (as a recall antigen) were similar for patients and controls despite marked hyperglycaemia in the patients. No patient had a response greater than mean + 2 S.D. of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies. Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) patients treated with bovine NPH responded to bovine and human insulin after 6 months, of whom one responded exclusively to human. In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to protamine. It was concluded that there is no evidence of T-cell immunosuppression in poorly-controlled diabetes or of T-cell autoimmunity to insulin in newly-diagnosed type 1 diabetes. Treatment with bovine NPH insulin immunizes T cells to insulin, but human NPH does not.(ABSTRACT TRUNCATED AT 250 WORDS)