Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn.

The present study investigated the regional distribution of the N-methyl-D-aspartate (NMDA) receptor containing the NR2B subunit protein in rat lumbar spinal cord and examined whether selective NR2B antagonists would exhibit antinociception with reduced side-effect liability than subtype non-selective NMDA antagonists and anticonvulsants. Immunocytochemical studies showed the NR2B subunit had a restricted distribution, with moderate labelling of fibres in laminas I and II of the dorsal horn suggesting a presynaptic location on primary afferent fibers and possible involvement in pain transmission. In the in vivo studies, the NMDA/glycine antagonists (MK-801, 0.02-1 mg/kg i.p., L-687,414 10-300 mg/kg i.p., and L-701,324 1-10 mg/kg i.p.) and the anticonvulsant, gabapentin (10-500 mg/kg p.o.), induced rotarod deficits at antinociceptive doses. In contrast, the selective NR2B antagonists, (+/-)-CP-101,606 (1-100 mg/kg p.o.) and (+/-)-Ro 25-6981 (3-100 mg/kg i.p.) showed a significant dose window. (+/-)-CP-101,606 caused no motor impairment or stimulation in rats at doses up to 100 mg/kg p.o., which is far in excess of those inhibiting allodynia in neuropathic rats (ID50 4.1 mg/kg, p.o.). (+/-)-Ro 25-6981 also showed a significant separation (ID50 allodynia 3.8 mg/kg, i.p.), however, some disruption of rotarod performance was observed at 100 mg/kg. The anticonvulsant lamotrigine (3-500 mg/kg p.o.) also showed a good dose window. These findings demonstrate that NR2B antagonists may have clinical utility for the treatment of neuropathic and other pain conditions in man with a reduced side-effect profile than existing NMDA antagonists.     

Educating allied health professionals to provide care for cancer patients and their families

From 1985 to 1988, a state-wide program of cancer education was offered to community-based allied health professionals (AHPs) at five different program sites in Pennsylvania. During this three-year period, 512 social workers, clergy, dieticians, physical therapists and others received training to increase their knowledge about cancer and counseling, improve their supportive attitude regarding cancer patients and families, and decrease stress related to their work with this population. Overall, the Program was successful in reaching AHPs working with cancer clients who had little formal training in the cancer field. At the beginning of training, it was observed that AHPs with initially higher levels of education and more years of work experience with cancer patients had higher levels of counseling knowledge. Those who were women, worked in hospitals, or had worked with cancer patients longer exhibited higher levels of cancer knowledge. Participants who were women and who had more education had reported lower levels of job stress. Among those AHPs who completed the training courses, cancer knowledge increased by 14 percent. In addition, knowledge related to counseling cancer patients and their families improved by 11 percentage points. Perceived job stress among the AHPs also declined by 10 percent. Finally, participant supportive attitude concerning cancer clients improved.     

Laparoscopic excision of ovarian neoplasms subsequently found to be malignant.

One hundred fifty-six members and candidate members of the Society of Gynecologic Oncologists responded to a survey concerning the "laparoscopic management of ovarian neoplasms subsequently found to be malignant." Twenty-nine responders (19%) reported a total of 42 cases of ovarian malignancy. The laparoscopic procedure was aborted or the cyst was aspirated in 38% of the cases, and partial or complete excisions were attempted in 33 and 29%, respectively. The characteristics of the masses were as follows: less than 8 cm 67%, cystic 62%, unilocular 48%, and unilateral 81%. All four "benign" characteristics were present in 31% of the cases found to be malignant, and three of four characteristics were present in 24%. Laparotomy was performed at the time of laparoscopy in 17% of cases, after laparoscopy in 71% with an average interval of 4.8 weeks, and not at all in 12%. Fifty-seven percent of the cases were invasive epithelial malignancies, whereas 29% were tumors of low malignant potential. At least 50% of the patients had stages II-IV. We conclude that attempted laparoscopic excisions of adnexal masses that are subsequently found to be malignant are not uncommon, and that the presence of so-called "benign" characteristics does not preclude malignancy. Attempts at partial or complete excision are common, as are delays in subsequent definitive surgery. The stage of disease is often advanced, and all histologic types of malignancy are encountered. We advocate careful evaluation of this practice, with development of strict guidelines to ensure optimal patient care.     

Acquired aphasia in children after surgical resection of left-thalamic tumors

Five children (three males, two females; four right-, one left-handed; age range 6 to 14 years) who developed aphasia after gross-total excision of left predominantly thalamic tumors are reported. Three patients had Broca aphasia, one had mixed transcortical aphasia, and one patient had conduction aphasia. In the months after surgery, three children improved while receiving radiation and/or chemotherapy, although none recovered completely. Two patients with malignant tumors developed worsening aphasia when the tumor recurred, and later died. Two of three patients tested had visuospatial difficulties in addition to language deficits. Attention and executive functioning were affected in three of three patients tested. Memory, verbal and/or visual functioning, were affected in four of four patients tested. Both patients who were tested showed transient right hemineglect. Two of two patients tested were probably apraxic. The wide range of deficits in these children highlights the importance of the thalamus and other subcortical structures in developing cognition.     

Complications of combined radical hysterectomy and pelvic radiation

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 48 women treated by radical hysterectomy (RH) and pelvic node dissection (PND) and in 25 women who received 5000–5400 rad of external pelvic radiation (RT) after RH-PND. No major complications developed in the surgery-only group, but the 5-year minor GI complication rate was 4% and the 5-year minor UT complication rate was 10%. In 9 patients receiving RT at 200 rad/day, one major GI complication (13%) and one major UT complication (14%) developed. In 16 patients receiving RT at 180 rad/day only minor GI complications (7%) and minor UT complications (13%) developed. The conclusion is that after RH-PND, adjunctive RT delivered at 180 rad/day through four ports results in acceptable, minimal complications.     

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD^50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD^50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD^50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.