Repair of severed peripheral nerves: Comparison of the “de Medinaceli” and standard microsuture methods

The return of function following transection of the rat sciatic nerve has been assessed after repair by either standard microsurgical techniques (i.e., the use of microsutures to coapt the severed ends) or the new repair technique introduced by de Medinaceli and coworkers. The regeneration after transection was compared with that following sciatic nerve crush, i.e., a lesion in which the return of function is near optimal. Return of function was monitored serially using walking track analysis (i.e., the sciatic functional index, which indicates overall functional performance), the ability to spread the toes (which indicates intrinsic function in the foot), and the determination of muscle twitch tension of the middle digit. Function in the nerve crush group returned to within the normal range by 53 days, but function in the transection and repair groups did not return to normal before the rats were perfused at 85 postoperative days. However, the function regained when nerves were repaired with the de Medinaceli technique was significantly superior to that regained after repair with microsutures. Histological examination of the repair site (at 85 days) revealed that the regenerated nerve fibers in the de Medinaceli group crossed the site of anastomosis in a relatively orderly fashion, whereas they were more randomly arranged when microsutures were used. However, there was no statistical difference between the two groups in the number of regenerated fibers present in the distal stump. The increase in function in the de Medinaceli group may therefore arise primarily from an increase in the proportion of regenerating fibers which reach appropriate targets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Status of an unpaired thiol group on the HLA-B27 epitope.

In a previous study we demonstrated that mitogen-stimulated CD8+ CD4-T cells from normal donors produce a suppressive lymphokine (PASL) of IgE-dependent platelet cytotoxicity. Here we demonstrate the production, after antigenic-stimulation, of this suppressive factor during ongoing infections by Schistosoma mansoni in man and in the rat. The T lymphocyte subpopulation producing this factor was also identified as expressing the marker of the suppressive subset. Because of the absence of species restriction, the relevance in vivo of PASL was determined in the rat model. In these conditions we observed a complete abolition of the protection normally conferred against a challenge infection by the passive transfer of platelets from immune to normal rats after treatment of transferred platelets with T lymphocyte supernatants.     

A physiological approach to surgery for acute rupture of the papillary muscle

There is controversy regarding the optimal management of patients in whom acute papillary muscle rupture develops. This study evaluates the effect of division of the anterolateral papillary muscle on left ventricular (LV) function and compares two methods of treatment--mitral valve replacement (MVR) and mitral valve repair. Thirteen pigs were placed on cardiopulmonary bypass, and interventions were performed in an isolated beating heart preparation. LV function was assessed with a compliant intraventricular balloon at baseline, after division of the anterolateral papillary muscle (Divided), after repair of the divided papillary muscle (Repair), and finally after MVR. Division of the anterolateral papillary muscle caused a significant deterioration in LV function. Function was maintained at this level after mitral valve repair but deteriorated with MVR. Developed pressure measured at baseline was 179 +/- 13 mm Hg; Divided, 148 +/- 11 mm Hg (p less than 0.05 versus baseline); Repair, 149 +/- 15 mm Hg; and MVR, 95 +/- 8 mm Hg (p less than 0.05 versus Divided) at a balloon volume of 20 ml. These results suggest that LV function is impaired by papillary muscle rupture. Repair of the ruptured papillary muscle is associated with better LV function than is MVR.     

N-methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines.

A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 microM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 microM). N-methylcarbamates of 9-methoxy-6H-pyrido[4,3-b]carbazole 1-,5-, and 11-methanols gave IC50 values ranging from 0.02 to 0.11 microM against N417, H460, and H358 and were only slightly less effective against H69.     

Lack of significant activity of 2'-deoxycoformycin alone or in combination with adenine arabinoside in relapsed childhood acute lymphoblastic leukemia. A randomized phase II trial from the Childrens Cancer Study Group.

Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children.     

Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN-DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN-DBS in influencing not only motor but also emotional behaviour.     

Maternal syphilis and congenital syphilis in Latin America: big problem, simple solution]

From the data submitted to the Pan American Health Organization (PAHO) by nationwide programs against sexually transmitted diseases (STD), HIV infection, and AIDS (2002), one can estimate the overall prevalence of syphilis among pregnant women to be 3.1% and to range from 1.00% in Peru to 6.21% in Paraguay. According to these data, the incidence of congenital syphilis ranges from 1.4 per 1000 live births in El Salvador to 12.0 per 1000 live births in Honduras. Among men who engage in sex with other men, who often classify themselves as heterosexual, as well as in female sex workers, the prevalence of syphilis ranged from 5% to 15%. Factors that determine the persistence of congenital syphilis as public health problem include a lack of awareness of the seriousness of the problem among politicians, health officials, and health care providers, difficult access to prenatal care, and screening services, a low demand for the test among users, and the stigma and discrimination that surround sexually transmitted diseases (STD). This paper seeks to focus the attention of health professionals on maternal and congenital syphilis so they will undertake actions, using an interprogrammatic approach, to eliminate congenital syphilis from Latin America and the Caribbean. Eliminating congenital syphilis will only become possible if interventions targeting vulnerable groups are also implemented. PAHO's role in eliminating congenital syphilis includes determining the baseline situation in the Region as a whole and in each country, developing communication and procurement strategies, supporting nationwide programs, promoting operational research, and facilitating interprogrammatic coordination.     

Role of cytokines and chemokines in prion infections of the central nervous system

Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.     

Second neoplasms in survivors of childhood and adolescent cancer are often treatable.

PURPOSE: To estimate the incidence and types of second neoplasms in survivors of childhood and adolescent cancer, as well as the characteristics of those who developed second neoplasms. METHODS: Survivors who were under age 21 years at initial diagnosis, off therapy, and in remission for 2 years are referred to the Long Term Survivors' Clinic (LTSC) at Children's National Medical Center (CNMC). This review includes patients entered in the clinic database from January 1, 1997 to August 30, 2002. RESULTS: Twenty-three (2.3%) of 987 childhood cancer survivors followed in the LTSC had 26 (2.6%) second and third neoplasms. The mean age was 6.7 years at initial diagnosis, 20.3 years at diagnosis of the second neoplasm, and 20.5 years at diagnosis of the third neoplasm. Of 10 female and 13 male patients, 15 were white, six black, one Hispanic, and one Asian. All but two of the patients received radiation. Nineteen neoplasms, including seven thyroid carcinomas, six central nervous system tumors (three meningiomas), three basal cell carcinomas, two breast cancers, and one soft tissue sarcoma, occurred at sites within or contiguous to radiation sites. Five patients died, but the majority of neoplasms were treatable and most patients had good outcomes. CONCLUSION: Indefinite follow-up in a long-term survivors' clinic is indicated for adolescent and adult survivors of childhood cancer, with routine examination and screening for recurrence of the initial cancer as well as late effects, including second neoplasms.