Variability in vibration perception threshold among sites: a potential source of error in biothesiometry

Vibration perception threshold was measured with a biothesiometer by a single observer at both medial malleoli and both big toes in 110 diabetic patients aged 15-65 selected at random and in 64 non-diabetic subjects aged 20-65. The vibration perception threshold showed appreciable individual variation both between contralateral sites and between ipsilateral sites, differing by at least 30% between the big toes in 26 (24%) of the diabetic patients and 16 (25%) of the non-diabetic group. Variability between sites was significantly greater in the diabetics than the normal subjects. The vibration perception threshold exceeded published normal values at one or more sites in 22 of the diabetic patients but at all four sites in only four. The wide variability in vibration perception threshold among sites may be due to the tissue characteristics locally and, in diabetic patients, possibly to asymmetric neuropathy. Biothesiometer readings at single or unilateral sites may be unrepresentative or misleading.     

Painless stress fractures in diabetic neuropathic feet.

We describe two patients with diabetes mellitus and associated neuropathy, who presented with painless foot swelling and no history of trauma. X-Rays revealed recent underlying fractures-in one of a metatarsus, and the other of a proximal phalanx. These were assumed to be ''stress'' fractures unassociated with pain because of the severe sensory neuropathy. Though spontaneous fractures in neuropathic feet have been previously described, they almost always occur in association with Charcot joints, and are usually painful. The differential diagnosis of acute swelling in the foot of a diabetic patient with sensory neuropathy should include stress fracture.     

Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.     

Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy

Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals, but who had not undergone any urodynamic investigations, were found to be unobstructed on urodynamic criteria. A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed. One year post-operatively, 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result. The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment. Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time. This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed. The importance of a screening flow rate is emphasised. All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non-urodynamic selection criteria. We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients. Cystometry does, however, have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy.     

3,3',5'-Tri-O-methylpiceatannol and 4,3',5'-tri-O-methylpiceatannol: improvements over piceatannol in bioactivity

Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) (NSC 365798) has recently been isolated and was subsequently synthesized for NCI tumor panel testing as a new antileukemic natural product from the seeds of Euphorbia lagascae. During the synthesis, a bioactive reaction mixture of several partially O-methylated piceatannol analogues was obtained. This mixture has now been maximized and subjected to bioactivity-directed fractionation, using brine shrimp lethality, to yield 3,3',5'-tri-O-methylpiceatannol (NSC 381281); this new compound has improved stability and better bioactivity in several systems than piceatannol itself. To confirm the structure, 5 was synthesized from vanillin. In addition, the isovanillin analogue, 4,3',5'-tri-O-methylpiceatannol (NSC 381864), another new compound, was synthesized and found to be bioactive.     

Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats.

Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.