Clinical evaluation of eye movements in spinocerebellar ataxias: a prospective multicenter study.

BACKGROUND: Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6. METHODS: The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined. RESULTS: A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities. CONCLUSIONS: Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.

Evidence for the lateral intraparietal area as the parietal eye field.

It has long been appreciated that the posterior parietal cortex plays a role in the processing of saccadic eye movements. Only recently has it been discovered that a small cortical area, the lateral intraparietal area, within this much larger area appears to be specialized for saccadic eye movements. Unlike other cortical areas in the posterior parietal cortex, the lateral intraparietal area has strong anatomical connections to other saccade centers, and its cells have saccade-related responses that begin before the saccades. The lateral intraparietal area appears to be neither a strictly visual nor strictly motor structure; rather it performs visuomotor integration functions including determining the spatial location of saccade targets and forming plans to make eye movements.

Immunization in children with HIV seropositivity at birth: antibody response to polio vaccine and tetanus toxoid.

OBJECTIVE: To evaluate the humoral response to routine childhood immunization of HIV-infected children. DESIGN: Response rate, antibody titres and persistence after polio and tetanus vaccination were compared in 72 children with HIV seropositivity at birth and divided according to HIV infection status as determined by clinical and laboratory tests. METHODS: Polio antibodies were titred in a microneutralization test (positive titres, > or = 1:4), and antibody to tetanus toxoid with a passive haemagglutination method (protective titres, > or = 1:1024). RESULTS: The response rates to polio and tetanus vaccination (> 80 and > 75%) were similar in the HIV-infected and non-infected children, as were antibody levels. In the subgroup with sera obtained some months after the last dose of vaccine, polio antibody levels decreased in all four HIV-infected and in three of the seven non-infected children; protective tetanus antitoxin levels were detected in three of the six infected and in all three non-infected children. CONCLUSIONS: This study demonstrates the ability of children with HIV infection to respond adequately to the two vaccines considered, although tetanus antitoxin levels were inferior, compared with those in the seroreverted children. The unsatisfactory antibody levels observed in the admittedly few HIV-positive children studied some months after the last vaccination could be the result of a lower initial protective level and not necessarily an expression of severely impaired immunocompetence. The administration of booster doses in addition to the traditional immunization schedule could be useful in children with HIV infection.

Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenic patients have revealed structural brain abnormalities, with low volumes of gray matter in the left posterior superior temporal gyrus and in medial temporal lobe structures. However, the specificity to schizophrenia and the roles of chronic morbidity and neuroleptic treatment in these abnormalities remain unclear. METHOD: Magnetic resonance (1.5-T) scans were obtained from 33 patients with first-episode psychosis and 18 age-matched normal comparison subjects, all right-handed. Sixteen of the patients were diagnosed with affective disorder and 17 with schizophrenia. RESULTS: Quantitative volumetric analysis showed that the patients with first-episode schizophrenia had significantly smaller gray matter volume in the left posterior superior temporal gyrus than did the patients with first-episode affective psychosis or the comparison subjects, with a significant left-less-than-right asymmetry. The schizophrenic patients also showed a smaller gray matter volume of the left posterior amygdala-hippocampal complex than the comparison subjects. Both the patients with schizophrenia and those with affective psychosis had significant left-less-than-right asymmetry of the posterior amygdala-hippocampal complex. CONCLUSIONS: These findings suggest that temporal lobe abnormalities are present at the first hospitalization for schizophrenia and that low volume of the left posterior superior temporal gyrus gray matter is specific to schizophrenia compared with affective disorder.

Marked variation of thymidylate synthase and folylpolyglutamate synthetase gene expression in human colorectal tumors.

Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.

Flow cytometric analysis of DNA ploidy and cell proliferation activity in colorectal carcinoma.

The aim of this study was to evaluate the relationship between DNA ploidy, proliferative activity and other prognostic factors and the survival of patients with colorectal cancer. 45 patients were prospectively investigated for 6 years. Fresh multiple samples for flow cytometric analysis of DNA content were collected during surgical resection of primary tumor. A 42% frequency of aneuploidy was observed with a median DNA index value of 1.54. The proliferative activity (%S+G2M cells) was higher in the aneuploid cell sub-population (28.6%) compared to the diploid counterpart (22.7%)(p = 0.05). No significant relationship between DNA ploidy and tumor site, Dukes' stage, histological type, grading age or sex was observed. No correlation between DNA ploidy and survival was demonstrated, including in the analysis of patient subsets according to stage. No additive prognostic information was obtained from a breakdown analysis as a function of DI values, percentages of aneuploid cells and proliferative activity. This study suggests that flow cytometric content analysis lacks prognostic value in colorectal carcinoma.

Intracerebral aneurysms in human immunodeficiency virus infection: case report and literature review.

We describe a child with human immunodeficiency virus infection who presented with a large subarachnoid hemorrhage. She had multiple saccular and fusiform aneurysms in the proximal cerebral arterial circulation and no evidence of bacterial or fungal infection. The arteriopathy coincided with a high human immunodeficiency virus RNA load. Human immunodeficiency virus may cause cerebral arteriopathy with potentially life-threatening complications.

Amoxicillin/clavulanic acid versus cefotaxime for antimicrobial prophylaxis in abdominal surgery: a randomized trial.

Amoxicillin/clavulanic acid (amoxicillin 2 g/clavulanic acid 200 mg) has been administered in comparison to cefotaxime (2 g) for antimicrobial prophylaxis in 476 evaluable patients undergoing abdominal surgery at high risk of septic complications. Both antibiotics were administered as a single infusion. 205 evaluable patients (110 in amoxicillin/clavulanic acid group and 95 in cefotaxime group) underwent upper gastrointestinal surgery (including gastroduodenal and biliary surgery). The wound infection rate was 4.5% for amoxicillin/clavulanic acid and 7.4% for cefotaxime, with no significant differences. Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 1 patient in the cefotaxime group. 271 evaluable patients (135 in amoxicillin/clavulanic acid group and 136 in cefotaxime group) underwent lower gastrointestinal surgery (including colorectal surgery). The wound infection rate was 11% for amoxicillin/clavulanic acid and 13% for cefotaxime, with no significant differences. A purulent discharge was present in 3 patients in both groups. Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 4 patients in the cefotaxime group. No serious adverse events and no cases of diarrhea were observed. In conclusion, in our experience amoxicillin/clavulanic acid proved to be as effective as cefotaxime in protecting patients from surgical infections in abdominal surgery. Its use in surgical prophylaxis may help decrease the cost of treatment and reduce the risk of resistance to antibiotics and superinfections.

Tamoxifen and medroxyprogesterone therapy for advanced endometrial carcinoma.

We have studied the response rates and survival of a group of 93 patients with Stage III or IV endometrial adenocarcinoma after random allocation to therapy with tamoxifen (TAM) 20 mg twice daily (n = 45) or medroxyprogesterone acetate (MPA) 1 g/wk intramuscularly (n = 48). The patients were examined every 4 months. In the non-responders and in those who relapsed, combination therapy with TAM and MPA was given. Twenty-four of 45 (53.4%) responded to TAM alone, 27 of 48 (56.2%) responded to MPA alone. Of the responders 23 later relapsed in the TAM group and 24 in the MPA group and of these 14 (60.8%) and 15 (62.5%), respectively, responded to the combination therapy. Of the original 21 non-responders to MPA alone, 10 responded to the combination (47.6%) and 11 (52.4%) did not; the comparable figures for the TAM alone group were 13 (61.9%) and 8 (38.1%), respectively. Survival rates were much higher in the differentiated than in the undifferentiated carcinomas. In conclusion, we feel that the efficacy, and the few side-effects of these drugs used alone and particularly when used in sequential combination, make them a very attractive treatment for advanced endometrial adenocarcinoma.

[Experimental liver transplantation in pigs. Surgical technique and complications]. / Trapianto di fegato sperimentale nel maiale. Tecnica chirurgica e complicanze.

Only recently, in our laboratory of experimental surgery, we started with a protocol for orthotopic liver transplantation (OLT) in a pig model. This was felt as mandatory for experimental purposes as well as for future clinical applications at our center. We report herein our own experience with 41 OLTx. Intraoperative "lethal" complications occurred in up to 32% (14/41) whereas postoperative complications occurred in the remainders at different intervals of time with a maximum survival of 30 days. No attention was paid to prevent rejection-infection episodes. The main cause of death was the primary non-function (PNF) or dis-function (PDF) manifested either intra or postoperatively in 16 out the 41 OLTx (39%). Intraoperative technical errors accounted for up to 9% (4/41 OLTx). Acute hemorrhage gastritis and gastric perforations occurred postoperatively in 6 animals (14%) and represent one of the peculiar aspects of OLT in pig model.

[The prevention of the aorto-mesenteric compression syndrome in interventions for ileoanal anastomoses]. / Prevenzione della sindrome del compasso aorto-mesenterico negli interventi di ileo-ano-anastomosi.

Restorative proctocolectomy with ileal-anal anastomosis can induce a duodenal stenosis due to the compression between superior mesenteric artery (SMA) and aorta when the ileum is pulled-down to the anus stretching the SMA. This situation may require prolonged nasogastric intubation or even surgery. In our experience this occurred in 10% of pts. Aiming to avoid this complication we have performed an intestinal derotation just before ileal-anal anastomosis abolishing any possibility of duodenal compression. Comparing this latter group of patients to those who didn't receive intestinal derotation, we observed a significant reduction of nasogastric tube drainage and of the nasogastric intubation time. We think that intestinal derotation could be effective in preventing SMA syndrome after restorative proctocolectomy and ileal-anal anastomosis.

Historical underpinnings of the term essential tremor in the late 19th century.

BACKGROUND: The term essential tremor has been in regular use since the second half of the 20th century. To modern neurologists, the word "essential" may seem cryptic. The historical underpinnings of this term have not been examined. OBJECTIVES: To bring to attention early medical reports using the term essential tremor and examine the characteristics of the disorder that contributed to the proposed use of the term. METHODS: Review of 19th and early 20th century medical literature on essential tremor. RESULTS: The term tremore semplice essenziale (simple essential tremor) was first used by Burresi (Italy, 1874) to describe an 18-year-old man with severe, isolated action tremor. Several years later, Maragliano (Italy, 1879), Nagy (Austria, 1890), and Raymond (France, 1892) described similar cases and proposed the terms tremore essenziale congenito (essential congenital tremor), essentieller Tremor (essential tremor), and tremblement essentiel héréditaire (hereditary essential tremor) to define the illness. Mirroring contemporaneous views of constitutional and inherited disease, the key ingredients of the disorder were viewed as the constant presence of tremor in the absence of other neurologic signs and its heritable nature. By the early 20th century, the term began to appear in the medical literature with greater frequency. CONCLUSIONS: Toward the end of the 19th century, several clinicians attempted to provide a nosologic separation for a tremor diathesis that was often familial and occurred in isolation of other neurologic signs. This disorder, which was termed essential tremor, was later recognized as one of the most common neurologic disorders.