The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat

Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (<10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types – clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.     

Atrial Flutter with 1:1 Atrioventricular Conduction Caused by Propafenone

We describe a case of 1:1 atrial flutter in a patient with coronary disease taking propafenone. In atrial flutter, the atrial rate is usually about 300 beciis/min with 2:1 AV conduction and a ventricular rate of 150 beats/min. Class IA antiarrhythmic drugs, especially quinidine and disopyramide, may cause 1:1 AV response because they reduce atrial rate and are vagolytic. However, propafenone is a Class IC agent and has no anticholinergic properties, and the occurrence of 1:1 AV conduction at a rate of about 250 beats/min is an important side, effect that, although uncommon, should be recognized.     

Thermodynamic stability of wild-type and mutant p53 core domain

Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn²⁺ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.     

Associations between soil lead and childhood blood lead in urban New Orleans and rural Lafourche Parish of Louisiana.

This study evaluates associations between soil lead concentrations (SPb), age of housing, and blood lead levels (BPb) of children in metropolitan New Orleans and Lafourche Parish, Louisiana. The database includes over 2,600 SPb and 6,000 BPb samples paired by their median values and pre-1940 housing percentages for 172 census tracts. Associations were evaluated with Fisher's exact test and Spearman's rho test and modeled with the least sum of absolute deviations regression. Census tracts with low SPb are associated with new housing, but census tracts with high SPb are evenly split between old and new housing [Fisher's exact test, p = 8.60 X 10(-13) for the percentage of housing built before 1940 (percent pre-1940 housing) versus SPb]. The p-value for SPb versus BPb is 12 orders of magnitude stronger than the p-value for percent pre-1940 housing versus BPb. Census tracts with low BPb are associated with new housing, but census tracts with high BPb are split evenly between old and new housing (Fisher's exact test, p = 1. 67 X 10(-12) for percent pre-1940 housing versus BPb). Census tracts with high SPb are associated with high BPb and census tracts with low SPb are associated with low BPb (Fisher's exact test, p = 3.18 X 10(-24) for BPb versus SPb). The Spearman's rho test of the association of SPb and BPb in Orleans and Lafourche Parishes yielded a p-value of 6.12 X 10(-24). The least sum of absolute deviations regression model of the data is BPb = 1. 845 + 0.7215 (SPb)0.4. A comparison of the modeled BPb versus observed BPb has an r(2) of 0.552 and a p-value of 2.83 X 10(-23) that this relation was due to chance. If blood lead in children is more closely associated to soil lead than to the age of housing, then primary lead prevention should also include soil lead.     

The role of ultrasound in the diagnosis of a large, rapidly growing, thyroid mass.

The value of ultrasound in the diagnosis of a large rapidly growing thyroid mass was assessed in a study of 42 patients with a large (> 3 cm) rapidly growing (< two months) solitary mass. Haemorrhage into a thyroid nodule was present in 31 patients and thyroid malignancy in 11. Ultrasound of haemorrhage into a thyroid nodule revealed a large cystic mass in all 31 patients containing internal debris (22), septations (three), or a combination of both (six). The malignant causes of a large rapidly growing mass were lymphoma (two), anaplastic carcinoma (four) and metastasis (five). Ultrasound of these thyroid malignancies revealed a mass with a smooth, well-defined margin and strikingly low homogeneous echogenicity in all cases. Patients with thyroid metastases had evidence of widespread metastatic disease elsewhere. Lymphoma was differentiated from anaplastic carcinoma on fine-needle aspiration cytology or surgical biopsy. Ultrasound was of value in differentiating between a benign haemorrhagic nodule and a malignant tumour. The various malignant tumours had similar appearances, however, and could not be distinguished on ultrasound.     

Lumbar facet joint tropism does not accelerate degeneration of the facet joints.

PURPOSETo study the relationship of lumbar facet joint tropism to degeneration of the cartilage and subcortical bone in the facet joints and the effect of tropism in intervertebral disk degeneration.METHODSThe orientation of 104 cadaveric lumbar facet joints with respect to sagittal plane was measured on CT scans, and the joints were classified as having no tropism, mild tropism, or severe tropism. On MR images, the severity of cartilage degeneration and bony sclerosis was measured. The correlation between tropism and degeneration was calculated, as was the relationship among age, spinal level, and degeneration.RESULTSWe identified four spinal levels with severe tropism, six with moderate tropism, and 94 without tropism. Cartilage degeneration was not significantly more severe in the joints with tropism than in the joints without. Sclerosis was slightly greater in the joints with tropism than in the joints without it. Sclerosis and cartilage degeneration were significantly related to age and spinal level.CONCLUSIONAge, spinal level, and overall facet joint angle are more important factors in facet joint degeneration than is tropism.