Handcuff neuropathies

Compressive neuropathy due to tight application of handcuffs occurred in 5 patients. The superficial radial nerve was affected in 8 hands and the median nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing. Nerve conduction studies helped to exclude malingering and other diagnoses. All patients had been intoxicated when handcuffed or had been arrested with force. The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies.     

A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat

A Dose-Response Analysis of Methoxychlor-Induced Alterationsof Reproductive Development and Function in the Rat. GRAY, L.E., JR., OSTBY, J., FERRELL, J., REHNBERG, G., LINDER, R., COOPER,R., GOLDMAN, J., SLOTT, V., AND LASKEY, J. (1989). Fundam. Appl.Toxicol12, 92–108. In the present study rats were dosed fromweaning, through puberty and gestation, to Day 15 of lactationwith methoxychlor at 25, 50, 100, or 200 mg/kg/day. Morphologicallandmarks of puberty were measured, including the ages at vaginalopening, first estrus, and first estrous cycle in females andat preputial separation in males. In the female, estrous cyclicity,fertility, litter size, number of implantation sites, organweights, and ovarian and uterine histology were also measured.The viability of the offspring (F1) and their fertility wereevaluated using a continuous breeding protocol. Males were necropsiedafter breeding, the reproductive organs were weighed, and thecauda epididymal sperm counts were determined. One testis wasused for histopathology, while the other was used to quantifyinterstitial fluid (IF) content, IF testosterone concentration,and testicular sperm production. Testosterone and an drogen-bindingprotein were measured in the caput epididymis, and sperm motilityand morphology were evaluated from a caudal sample. The serumand pituitary were saved for hormonal determinations. Methoxychloraccelerated the age at vaginal opening and first estrus, andthe vaginal smears were cornified. Growth was retarded at 100and 200 mg/kg/day and fertility was reduced when the femaleswere bred with untreated or similarly treated males. In thehighest- dose group, the mated females went from constant estrusinto pseudopregnancy following mating, but they had no implants.In males, methoxychlor treatment markedly reduced growth, seminalvesicle weight, cauda epididymal weight, caudal sperm content,and pituitary weight. Puberty was delayed in the two highest-dosagegroups. Testicular sperm measures were much less affected thancaudal measures. Testis weight and histology were slightly affected,and testicular sperm production, sperm morphology, and motilitywere unaffected. Endocrine function of the testes and pituitarywas altered by methoxychlor administration. Leydig cell testosteroneproduction, in response to human chorionic gonadotropin challenge,was reduced and pituitary levels of prolactin, thyroid-stimulatinghormone (TSH), and follicle-stimulating hormone (FSH) were altered.In contrast, serum levels of prolactin, FSH, and luteinizinghormone were unaffected. Serum TSH was reduced by 50% of controlat 100 and 200 mg/kg/day, while pituitary levels were increased.Gonadotropin-releasing hormone concentration in the mediobasalhypothalamus was also elevated. In spite of the many reproductivealterations, the fertility of treated males was not reducedwhen they were mated with untreated females. Growth and viabilityof the offspring (F1) from the 50 mg/kg/day treatment groupwere normal, but in the females, vaginal opening was accelerated,estrous cyclicity was abnormal in the rats during middle age,and fecundity was reduced.     

Uveal melanoma radiation. 125I brachytherapy versus helium ion irradiation

The optimum radiation therapy for uveal melanoma is uncertain. Both helium ion irradiation and 125I brachytherapy have been used to treat this neoplasm. This investigation analyzed the control and complication rates of uveal melanomas treated with helium ions of 125I plaques. In both a retrospective and a prospective dynamically balanced study, the control rates appeared to be similar. There were more posterior segment complications after 125I plaques and more anterior segment complications, including neovascular glaucoma, after helium ion irradiation. The follow-up period is too short to draw definitive conclusions on the radiation complications. Overall, approximately 89% of eyes were retained and less than 4% of treated eyes were removed because of failure to control the tumor.     

Managing self-injection difficulties in patients with relapsing-remitting multiple sclerosis.

Difficulties with self-injection, including inabillity to self-inject, are common for individuals taking home-administered injectable medications. In relapsing-remitting multiple sclerosis (MS), all of the currently available disease-modifying medications are injectables marketed for self-injection. Problems with self-injection pose a barrier to treatment adherence for many patients. Clinicians at the University of California, San Francisco (UCSF) Multiple Sclerosis Center have developed a number of strategies to help patients who experience anxiety associated with self-injection. These strategies have been empirically tested and found to be effective and easily implemented by mental health professionals and nurses. This article offers case examples and discussion of the principles of the techniques developed at UCSF to remediate patients' difficulties with self-injection. Nurses are most often the healthcare providers responsible for training MS patients in self-injection and monitoring their compliance. Nurses who are familiar with these tools have the opportunity to have a significant positive impact on patient comfort, confidence, and, ultimately, successful long-term adherence to disease-modifying medications.     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Extranodal lymphomas presenting as soft tissue sarcomas to a sarcoma service over a two-year period.

Non-Hodgkin's lymphoma usually presents with lymphadenopathy at multiple sites but can also involve any part of the musculoskeletal system. Occasionally the presentation is with a soft tissue mass. The presentation of large, superficial lymphomatous masses is similar both clinically and radiologically to that of soft tissue sarcomas. The six cases of lymphoma presenting to the Exeter Sarcoma Service as suspected soft tissue sarcomas, over a two-year period (2002-2004), are presented. We describe the clinical and imaging characteristics of these tumours and their subsequent management. Our cases showed variability in presentation. Only one of the six cases presented with pain and one with tenderness. Four of the cases had no lymphadenopathy and the other two had lymphadenopathy restricted to one nodal basin. Overlying soft tissue swelling occurred in four cases and in distal limb swelling beyond the mass in one case. Radiologically, lymphomas are known to be likely to exhibit confluent lymphadenopathy that is rare in patients with soft tissue sarcoma. Confluent lymphadenopathy was demonstrated in only one case of this series of patients. It is thought that lymphomas infiltrate across anatomical fascial planes more readily than sarcomas and in four of our six cases this feature was present. Clinical history, examination and MRI are insufficient to differentiate between soft tissue sarcoma and lymphoma and the importance of obtaining a pathological diagnosis prior to surgery is clear. It is crucial to differentiate lymphoma from sarcoma in order to avoid unnecessary excisional procedures in lymphoma patients.     

Developmental Toxicity of Dimethylacetamide by Inhalation in the Rat

Developmental Toxicity of Dimethylacetamide by Inhalation inthe Rat. SOLOMON, H. M., FERENZ, R. L., KENNEDY, G. L., ANDSTAPLES, R. E. (1991). Fundam. Appl. Toxicol. 16, 414–422.Dimethylacetamide (DMAC) is a widely used industrial solvent.It has been reported to be teratogenic when given to rats byinjection or following dermal application. Most of these studiesemployed large single doses and did not examine both the fetaland the maternal response. In this study, groups of pregnantCrl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalationfor 6 hr/day from Days 6 through 15 of gestation (day on whichcopulation plug was detected was termed Day 1G). A control groupof chambered pregnant rats was exposed simultaneously to aironly. All female rats were euthanized on Day 21G. At 282 ppm,both maternal weight gain during the exposure period and fetalweight were significantly decreased and accompanied by a significantdose-response trend. These effects were not seen in rats inhalingeither 32 or 100 ppm. Fetal resorptions were not increased inany of the groups exposed to DMAC. Fetal incidences of external,visceral, or skeletal variations and malformations were similarbetween the test and control groups. Therefore, both fetal andmaternal toxicity were noted at 282 ppm and the no-observedadverse-effect level under these experimental conditions was100 ppm for both the dam and the conceptus. DMAC was not demonstratedto produce malformations in the rat fetus even at a level thatwas toxic to the dam.     

Defenses of the hamster lung against human neutrophil and porcine pancreatic elastase

Instillation of human neutrophil elastase (HNE) into hamster lungs produces milder emphysema but more pulmonary hemorrhage than an equivalent amount of porcine pancreatic elastase (PPE), whether equivalence is determined by elastolytic units or moles. We undertook a study of the mechanisms of these differences. 125I-HNE or 3H-PPE were instilled intratracheally into hamsters. The partitioning of radioactivity between bronchoalveolar lavage fluid (BAL) and lung tissue was similar for HNE and PPE as were the half-lives, 45 and 51 min, respectively, for uncomplexed, enzymatically active HNE and PPE. In BAL there was preferential binding and inactivation of HNE by the hamsters' alpha-1-protease inhibitor (a-1-PI) whereas PPE was preferentially bound by alpha-2-macroglobulin (a-2-M). This was also observed in vitro when HNE and PPE were incubated with plasma from untreated hamsters. Nevertheless, when the sum of the elastase binding capacity of a-1-PI and a-2-M was considered, hamster plasma had similar binding capacities for HNE and PPE. It is known that the enzymatic activity of elastases is inhibited by formation of a stable complex with a-1-PI. On the other hand, elastases bound to a-2-M are protected against a-1-PI inhibition but can free themselves by proteolysis and exhibit elastolytic activity. Preferential inactivation of HNE by a-1-PI may be one mechanism that accounts for the lesser emphysema-inducing potency of HNE than of PPE.