Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum

The Mouse Models of Cancer Consortium of the NCI sponsored a meeting of neuropathologists and veterinary pathologists in New York City in November of 2000. A rapidly growing number of genetically engineered mice (GEM) predisposed to tumors of the nervous system have led to a concomitant need for neuropathological evaluation and validation of these models. A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve. The GEM tumors were found to have many similarities and some distinct differences with respect to human disease. After review of the biology and pathology for all models presented, participants were split into groups reflective of clinical expertise in human pathology, tumor biology, neuroimaging, or treatment/intervention. Recommendations were made detailing an extensive and complete neuropathological characterization of animals. Importance was placed on including information on strains, tumor clonality, and examination for genetic mutation or altered gene expression characteristics of the corresponding human malignancy. Specific proposals were made to incorporate GEM models in emerging neuroradiological modalities. Recommendations were also made for preclinical validation of these models in cancer therapeutics, and for incorporation of surrogate markers of tumor burden to facilitate preclinical evaluation of new therapies.     

Benign cervical thymoma masquerading as a malignant thyroid nodule

A thymoma in the neck region is a rare diagnosis involving a solitary neck nodule that moves with deglutition and is contiguous with the thyroid gland. The authors report an unusual case of a thymoma that accumulated both Tc-99m pertechnetate and Tc-99m MIBI. This is probably the first reported case of a benign neck thymoma concentrating these two radiopharmaceuticals. Thymoma should be added to the gamut of false-positive findings in the neck for thyroidal (with Tc-99m pertechnetate) and malignant (with Tc-99m MIBI) tissue.     

Study of sudden cardiac deaths in young athletes

Sudden cardiac deaths in athletes are usually due to underlying cardiovascular disease. The final pathway is usually ventricular fibrillation following hypertrophic cardiomyopathy and coronary artery anomalies in young persons below the age of 30 years. Sudden cardiac death in young is rare but remains as a source of concern. A postmortem study was conducted to ascertain the cardiac causes of sudden death in persons below the age group 30 years following exercise in games or otherwise. Out of 15 cases in autopsy finding, hypertrophic cardiomyopathy (n=7) was the commonest cause followed by coronary artery anomalies (n=4). Sudden unexpected death is a source of concern and careful screening of history and physical examination for potential athletes should identify majority of people at risk.     

RAPD & FINS (mitochondrial 16s rRNA gene sequence) in analysis of food contamination: detection of food poisoning by Lizard

In poisoning, detection of the nature of causative agent is important for management of trauma and forensic investigation. Most of the methods in clinical toxicology are developed for detection of toxins and poisons. A random amplified polymorphic DNA (RAPD)-based method has been described for detection of species of animal from its morphologically unrecognizable fragments, recovered from food substances, consumption of which caused even death. Pre-mixed RAPD reaction beads and six RAPD primers were used in polymerase chain reaction analysis. Among six RAPD primers used, any one of them was sufficient in resolving this practical forensic situation. To enhance the probability values for matching in the present study of fixing identity of an animal, six set of market available RAPD primers were used. This is the first report of a forensic application of RAPD DNA typing in identification of charred skeleton remnants of Lizard species in food material. Furthermore unique amplicons were generated for different reptilian species, which can be used as species specific markers for species identification in forensic situation, however, no variations among individuals of same species were observed.     

Effect of chitosan on lipid levels when administered concurrently with atorvastatin--a placebo controlled study

In a placebo controlled trialthe lipid lowering effects of chitosan, a unique dietary fibre, was assessed when given along with atorvastatin 10 mg in patients with chronic coronary heart disease. Altogether 100 patients were studied. They were randomly allocated in two groups of 50 patients each. Patients of group A received atorvastatin 10 mg before dinner plus 2 g/day chitosan in two divided doses. The groupB patients received atorvastatin 10 mg plus placebo. Patients were followed up for a period of 6 weeks. There was significant reduction in mean body weight in group A patients (3.14% versus 1,29% of body weight, p<0.05). There was also a significant rise in HDL cholesterol value (3.8% versus 1.07%, p=0.02) in group A patients. However, there was no significant reduction in the mean values of total cholesterol, LDL cholesterol and triglyceride in the two groups, although group A patients showed marginally lower values.     

RISUG (reversible inhibition of sperm under guidance)--an antimicrobial as male vas deferens implant for HIV free semen

HIV transmission from the male to the female is a major health problem. A hypothesis proposing an intra vas deferens implant of an antimicrobial compound to prevent the infection spread is presented. Mechanisms of action for the inhibition could include inactivating HIV in sperms passing through the vas deferens; drug release from the implant to destroy HIV entering into semen from genital structures distal to the vas deferens; and sperm acrosome released hyaluronidase mediated reabsorption of HIV. A subcomponent of the implant flowing along sperm pathway may have a role in reducing the entry of HIV from a positive female into penile tissue. A new drug RISUG (reversible inhibition of sperm under guidance) presently undergoing clinical trials for its contraceptive effect in the male (because it disrupts the sperm acrosome by an electrical charge and pH lowering effects) has also antimicrobial action. The drug being a combination of styrene maleic anhydride (SMA) and dimethyl sulfoxide (DMSO) on being injected into the lumen of the vas deferens produces styrene maleic acid thereby lowering pH; induces electrochemical action leading to a stable electrical charge generation; releases mandelic acid; and induces acrosome reaction in sperms with consequent release of hyaluronidase and sperm inactivation. Moreover, one time administration into the lumen of the vas gives long term action. All these phenomena very well match with the needs for HIV clearance of semen and hence RISUG is here proposed as a possible candidate material for the HIV inhibiting vas deferens implant when delivered in below contraceptive threshold dosage. For experimental validation, after obtaining data on the semen HIV load under control conditions in the HIV positive males inducted into the study, 30 mg of SMA in 120 microl of DMSO (contraceptive dose being 60 mg SMA+120 microl DMSO) is to be injected into vasa deferens bilaterally. Thereafter at intervals of one month the viral load needs to be determined in semen obtained either by masturbation or in lubricant free condom at intercourse - the method of collection remaining the same throughout for a particular subject. A significant reduction in the semen viral load following RISUG administration will validate the hypothesis. Speculated reduced female to male HIV transmission is more difficult to test. Nonspecific indications will come from a population study of the incidence of RISUG treated men becoming HIV positive as compared to that in the general population.     

Design for positive pressure respirators

This study deals with the design of a positive pressure respirator using a first order non-linear lung model. The non-linearities considered are non-linear airway resistance, effect of hysteresis and non-constant dead space. The analysis has been carried out using three different waveforms,viz., rectangular, sine and ramp. It is shown that the last two waveforms result in longer inspiratory periods making the actual respirators more reliable in operation.     

Irreducible acute anterior shoulder dislocation

Irreducible acute anterior dislocation of the shoulder has rarely been reported in the literature. This report describes a shoulder dislocation in a patient, which required open disimpaction of the humeral head from the glenoid before reduction of the glenohumeral dislocation could be achieved.     

Conservative management of vestibular schwannomas - second review of a prospective longitudinal study

Vestibular schwannomas have been traditionally managed with microsurgical removal and in recent years, stereotactic radiotherapy. However, there is a group of patients in whom a conservative management approach might represent a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. This is a prospective cohort review of a previously published group of patients [Clin. Otolaryngol. (2000) 25, 28-39] with unilateral vestibular schwannoma that were initially analysed at our institution in 1998 [Walsh R.M., Bath A.P., Bance M.L. et al., Clin. Otolaryngol. (2000) 25, 28]. The mean duration of follow-up was 80 months (range 52-242 months). All the patients in the study underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of rapid radiological tumour growth and/or increasing signs and symptoms, which necessitated active intervention. The mean tumour growth rate for the entire group at the second review was 1 mm/year (range -0.84-9.65 mm/year). The mean growth rate for cerebellopontine angle tumours (1.3 mm/year) was significantly greater than that of internal auditory canal (IAC) tumours (0 mm/year) (P = 0.005). The majority of tumours (87.14%) grew <2 mm/year. There was significant tumour growth seen in 38.9%, no or insignificant growth in 41.7%, and negative growth in 19.4%. Twenty-three patients (32%) failed conservative management at the second review. There was no difference in the outcome of these failed patients in comparison with patients who underwent primary treatment without a period of conservative management. The mean growth rate of tumours in patients that failed conservative management (3.1 mm/year) was significantly greater than that in patients who did not fail (0.2 mm/year) (P < 0.001). No factors predictive of tumour growth or failure of conservative management were identified. Hearing deterioration with pure tone averages (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred irrespective of tumour growth. This prospective study further emphasizes the role of conservative management in selected cases of vestibular schwannomas. Tumours in this study confined to the IAC typically demonstrated minimal or no growth on serial MRI scanning. Regular follow-up with interval scanning is mandatory in all patients.