Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Adenocarcinoma arising in a chondroid syringoma of vulva.

Chondroid syringoma of the vulva is an extremely rare tumor. Of the previously reported cases, only one was clinically malignant. The authors describe a case of chondroid syringoma of the right labium majus from which arose a papillary adenocarcinoma. A right inguinal lymph node was replaced with metastatic adenocarcinoma.     

Evaluation of anaerobic performance capacity by the isokinetic Ariel computerized exercise system-reliability and validity.

The present study examines the reproducibility and validity of computerized muscle strength and endurance evaluation protocols using the Ariel Computerized Exercise System (ACE). Since the ACE has only recently become commercially available, there are no published normative data for various exercises, nor are the measurements' accuracy and validity for the various exercise protocols documented. Twenty males (17 to 30 years old) performed a set of isokinetic maximal leg and arm exercises on the ACE Multi Function Unit twice on 2 separate days. Test-retest correlation coefficient ranged from 0.44 (bench press) to 0.91 (bench pull and leg extension flexion). Thirty additional male subjects (16 to 31 years old) performed, on 2 separate days, the Wingate Anaerobic Test (WAnT) (leg), and various force and endurance leg exercises (squat) on the ACE. Correlation coefficients of the various performance indices between the 2 test systems ranged from -0.02 to 0.23. The results obtained on the ACE indicate moderate to high reproducibility and low concurrent validity with WAnT.     

Ectodermal dysplasia,ectrodactyly and macular dystrophy (EEM syndrome) in siblings

We report a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy (the EEM syndrome). Both children had abnormalities of the hands and the hair, and bilateral macular degeneration. The clinical picture in both is similar to, but less severe than, that described in the previously reported cases of this rare syndrome. Even though the parents are not related, they are both of Jewish Yemenite origin, and the possibility of a common ancestor cannot be ruled out. This would suggest autosomal recessive inheritance. The clinical picture in these patients suggests either variable expression or genetic heterogeneity in the EEM syndrome and further delineates the clinical and genetic spectrum of this condition. © 2001 Wiley‐Liss, Inc.     

A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

Amputation of the lower limb as palliative treatment for debilitating musculoskeletal cancer

Limb sparing surgery has replaced amputation surgery for treating sarcomas of the lower limb in most cases. Wide resection followed by postoperative radiation therapy can achieve acceptable local control and survival rates in patients with bone and soft-tissue sarcomas of the lower limb. Recurrent or persistent disease constitutes a major oncological problem. Local symptoms such as agonizing pain, fractures, tumor fungation, inability to walk and inability to maintain daily activities, further impair the patient's quality of life. In this clinical set-up palliative amputation of the limb should be considered. Fourteen patients with soft-tissue or bone sarcomas underwent palliative major amputation. The procedures included: hemipelvectomy, hip disarticulation, knee disarticulation, above or below-knee amputation. Local control of the disease and pain, and improvement of the performance status were observed in 13 evaluable patients. The mobility was restored in 13/14 patients. The median survival following the procedure was 9 months. There was only one case of immediate post-operative death. Severe phantom pain was not reported by any of the patients. Quality of life was reported to be improved by two-thirds of the patients. We found palliative major amputation surgery worth-performing in low-performance status cancer patients with locally advanced disease of the lower limb.     

Endometrial carcinoma stage I

Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.     

Breast-cancer associated brachial plexopathy - still a diagnostic and treatment challenge

Brachial plexopathy (BP) in breast cancer patients is a rare event, attributed mainly to radiation damage or tumor infiltration of the plexus. Differentiation between these etiologies is a diagnostic challenge. We have studied retrospectively eight female patients with breast cancer who developed a clinical syndrome of brachial plexopathy following the treatment of the primary disease, out of more than 900 during the last 10 years. None of the available ancillary tests such as plain films, CT or MRI studies, EMG or tumor markers, provided reliable data regarding the cause of the plexopathy. Biopsy, on the other hand, was not always feasible. In our series, all the patients who developed BP did not have any blood-borne metastases before developing the syndrome. In 3 of the patients BP was the first sign of recurrence. In the other 5, only local or locoregional relapse preceded. In 7 of the 8 patients the left side was affected. Treatment should be tailored in each case according to course of the disease. The optimal treatment has not yet been defined.     

Inositol-Related Gene Knockouts Mimic Lithium's Effect on Mitochondrial Function

The inositol-depletion hypothesis proposes that lithium attenuates phosphatidylinositol signaling. Knockout (KO) mice of two genes (IMPA1 or Slc5a3), each encoding for a protein related to inositol metabolism, were studied in comparison with lithium-treated mice. Since we previously demonstrated that these KO mice exhibit a lithium-like neurochemical and behavioral phenotype, here we searched for pathways that may mediate lithium''s/the KO effects. We performed a DNA-microarray study searching for pathways affected both by chronic lithium treatment and by the KO of each of the genes. The data were analyzed using three different bioinformatics approaches. We found upregulation of mitochondria-related genes in frontal cortex of lithium-treated, IMPA1 and Slc5a3 KO mice. Three out of seven genes differentially expressed in all three models, Cox5a, Ndufs7, and Ndufab, all members of the mitochondrial electron transfer chain, have previously been associated with bipolar disorder and/or lithium treatment. Upregulation of the expression of these genes was verified by real-time PCR. To further support the link between mitochondrial function and lithium''s effect on behavior, we determined the capacity of chronic low-dose rotenone, a mitochondrial respiratory chain complex I inhibitor, to alter lithium-induced behavior as measured by the forced-swim and the amphetamine-induced hyperlocomotion paradigms. Rontenone treatment counteracted lithium''s effect on behavior, supporting the proposition suggested by the bioinformatics analysis for a mitochondrial function involvement in behavioral effects of lithium mediated by inositol metabolism alterations.The results provide support for the notion that mitochondrial dysfunction is linked to bipolar disorder and can be ameliorated by lithium. The phenotypic similarities between lithium-treated wild-type mice and the two KO models suggest that lithium may affect behavior by altering inositol metabolism.