SURVEILLANCE CAN BE THE STANDARD OF CARE FOR STAGE I NONSEMINOMATOUS TESTICULAR TUMORS AND EVEN HIGH RISK PATIENTS

PURPOSE: We investigate the results of a surveillance program for stage I nonseminomatous germ cell tumors to validate a surveillance policy, and furthermore improve it by analyzing diagnostic instruments and identifying prognostic factors for relapse. MATERIALS AND METHODS: From 1982 to 1994, 90 patients with stage I nonseminomatous germ cell tumors entered a surveillance protocol after orchiectomy. Patients with relapse were treated with cisplatin based chemotherapy. A statistical analysis of possible prognostic factors for relapse was performed. RESULTS: Relapse occurred in 23 (26%) patients. Disease specific survival was 98.9%, and 1 patient died of tumor. Most relapses were located in retroperitoneal lymph nodes only (78%). Tumor markers were the most important indicators of relapse. However, in 22% of patients with relapse abdominal x-ray of lymphangiographic contrast showed the first sign of relapse. Computerized tomography located all but 1 relapse. Vascular invasion (p = 0.0001), tumor size (p = 0.0341) and presence of immature teratoma (p = 0.0154) were significantly predictive of relapse with the multivariate analysis, percentage embryonal carcinoma only by univariate analysis (p = 0.032). The relapse rate was highest (52%) when vascular invasion was present. CONCLUSIONS: With surveillance for stage I nonseminomatous germ cell tumors, excellent treatment results can be achieved that are comparable to primary retroperitoneal lymph node dissection. Tumor markers and computerized tomography are highly reliable for detecting relapse. Lymphangiography is still of staging value. Pathological factors may influence the choice of adjuvant treatment. However, relapse risks of 50% to 60% are maximally achieved with presently available prognostic factors, and so sparing morbidity of adjuvant treatment by a surveillance protocol remains a feasible option even in these patients.     

ATP1A3 mutations in infants: a new rapid‐onset dystonia–Parkinsonism phenotype characterized by motor delay and ataxia

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid‐onset dystonia–Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre‐existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.     

Exercising attention within the classroom

Aim To investigate whether increased physical exercise during the school day influenced subsequent cognitive performance in the classroom. Method A randomized, crossover‐design trial (two weeks in duration) was conducted in six mainstream primary schools (1224 children aged 8–11y). No data on sex was available. Children received a teacher‐directed, classroom‐based programme of physical exercise, delivered approximately 30 minutes after lunch for 15 minutes during one week and no exercise programme during the other (order counterbalanced across participants). At the end of each school day, they completed one of five psychometric tests (paced serial addition, size ordering, listening span, digit‐span backwards, and digit‐symbol encoding), so that each test was delivered once after exercise and once after no exercise. Results General linear modelling analysis demonstrated a significant interaction between intervention and counterbalance group (p<0.001), showing that exercise benefitted cognitive performance. Post‐hoc analysis revealed that benefits occurred in participants who received the exercise intervention in the second but not the first week of the experiment and were also moderated by type of test and age group. Interpretation Physical exercise benefits cognitive performance within the classroom. The degree of benefit depends on the context of testing and participants’ characteristics. This has implications for the role that is attributed to physical exercise within the school curriculum.     

Factor structure of paediatric timed motor examination and its relationship with IQ

Aim Brain systems supporting higher cognitive and motor control develop in a parallel manner, dependent on functional integrity and maturation of related regions, suggesting neighbouring neural circuitry. Concurrent examination of motor and cognitive control can provide a window into neurological development. However, identification of performance‐based measures that do not correlate with IQ has been a challenge. Method Timed motor performance from the Physical and Neurological Examination of Subtle Signs and IQ were analysed in 136 children aged 6 to 16 (mean age 10y 2.6mo, SD 2y 6.4mo; 98 female, 38 male) attending an outpatient neuropsychology clinic and 136 right‐handed comparison individuals aged 6 to 16 (mean age 10y 3.1mo, SD 2y 6.1mo; 98 female, 38 male). Timed activities – three repetitive movements (toe tapping, hand patting, finger tapping) and three sequenced movements (heel–toe tap, hand pronate/supinate, finger sequencing) each performed on the right and left – were included in exploratory factor analyses. Results Among comparison individuals, factor analysis yielded two factors – repetitive and sequenced movements – with the sequenced factor significantly predictive of Verbal IQ (VIQ) (ΔR²=0.018, p=0.019), but not the repetitive factor (ΔR²=0.004, p=0.39). Factor analysis within the clinical group yielded two similar factors (repetitive and sequenced), both significantly predictive of VIQ, (ΔR²=0.028, p=0.015; ΔR²=0.046, p=0.002 respectively). Interpretation Among typical children, repetitive timed tasks may be independent of IQ; however, sequenced tasks share more variance, implying shared neural substrates. Among neurologically vulnerable populations, however, both sequenced and repetitive movements covary with IQ, suggesting that repetitive speed is more indicative of underlying neurological integrity.     

Late Gadolinium Enhancement of the Esophagus is Common on Cardiac MR Several Months after Pulmonary Vein Isolation: Preliminary Observations

Background: Pulmonary vein isolation (PVI) as a treatment for atrial fibrillation (AF) is commonly performed. This procedure can damage the esophagus. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) offers noninvasive assessment of scar. We sought to examine the prevalence of esophageal hyperenhancement on LGE‐CMR prior to and following PVI. Methods: Seventy‐four patients underwent LGE‐CMR prior to and 1.7 ± 1.9 months post PVI for AF. Transmural esophageal hyperenhancement was visually assessed. The pre‐ and post PVI esophageal position was measured, relative to the vertebral body. Results: Prior to PVI, 3% (2/74) of patients had esophageal LGE on CMR. At post‐PVI follow‐up, 30% (23/74) of the studies demonstrated new esophageal hyperenhancement adjacent to an ablation site. Most (74%, 17/27) positive esophageal LGE studies were performed >30 days after PVI, while no (0/9) studies performed >2 months post PVI were positive for esophageal hyperenhancement. The presence of post‐procedural esophageal hyperenhancement was not associated with longer ablation time (P = 0.42), use of an irrigated catheter (74% with LGE vs 47% without, P = 0.16), right‐sided esophageal location (56% with LGE vs 39% without, P = 0.17), size of left atrium cavity (58 ± 8 mm with LGE vs 61 ± 10 mm without, P = 0.15), or the timing of the LGE‐CMR study after PVI (36 ± 10 days with LGE vs 60 ± 66 days without, P = 0.09). Conclusion: Though rare before PVI, new esophageal LGE is seen in almost one‐third of patients after PVI. The clinical implications to remain to be explored, but clinicians should be aware of this frequent imaging finding. (PACE 2010; 33:661–666)     

Systolic Arterial Pressure Recovery After Ventricular Fibrillation/Flutter in Humans

Although the elective induction of cardiac arrest for implantable defibrillator insertion under general anesthesia is widely used, the hemodynamics of recovery of arterial blood pressure after cardiac arrest is not well-defined. Accordingly, the time course of recovery of systolic arterial pressure was studied in seven patients during the repetitive induction of ventricular fibrillation (n = 6) or ventricular flutter (n = 1). The mean number of episodes of cardiac arrest was 7 ± 2, and the mean drop in systolic pressure was 84 ± 16mmHg. The mean recovery time for systolic pressure was 10 ± 6 seconds, the average systolic pressure recovery rate was 13 ± 14 mmHg/sec, and the mean percent systolic pressure recovery was 94%± 9%. A negative logarithmic relation was found to exist between the rate of systolic arterial pressure recovery and the duration of ventricular fibrillation or flutter with a correlation coefficient of 0.68 to 0.97 (P < 0.05) in five of the seven patients. A linear relation between the time for systolic pressure recovery and duration of asystole was also defined. These results are consistent with the view that prolongation of ventricular fibrillation or flutter increases the duration of arterial pressure recovery through a negative effect on left ventricular contractility. Increased understanding of these relations may lead to increased safety of implantable defibrillator insertion.     

Atopic asthma: T lymphocyte subpopulations

Atopy is associated with diminished cell-mediated immunity and increased amounts of IgE, both of which may be caused by imbalances of T lymphocyte subsets. We compared the composition of highly purified peripheral-blood T cells of fifteen atopic asthmatics with ten non-atopic control subjects. Each subject was examined on five separate occasions. Indirect immunofluorescence using monoclonal antibodies was used to define T cell subsets. We examined the proportion of T cells with T3 (most T cells), T4 (helper/inducer), T8 (suppressor/cytotoxic), M1 (natural killer), and Ia (activated T cells) surface antigens. Blood was obtained at the same time of day to eliminate the effects of circadian rhythm. Subjects were taking no medications. We found no difference between the groups of the percentage of T cells with T4, T8, M1, and Ia antigens, nor the ratio of T4+ (helper) to T8+ (suppressor) cells. T3 percent was slightly (94.3 vs 92.5%) higher in the atopic group. We conclude that atopic asthma is not associated with imbalances of peripheral-blood T cell subsets.     

The kinetics of metaphase arrest in human psoriatic epidermis: an examination of optimal experimental conditions for determining the birth rate

The optimum experimental conditions have been investigated for the measurement of the birth-rate in human psoriatic epidermis using the vinca alkaloids vinblastine and vincristine. The dose response characteristics of the two drugs were assessed over a 2.5 h collection period; although the dose response characteristics differed between the two agents, a dose of 1μg injected intradermally was considered to be optimal for both. The linearity of metaphase correction was assessed for both agents, taking biopsies for up to 10 h after injection. It was found that there was a delay period for up to an hour which must be avoided during the analysis to prevent an underestimate of the birth rate. However, linearity was then demonstrated for up to 4 h after injection. Metaphase degeneration was assessed by isolating a cohort of unlabelled cells in the G₂ phase and tracing their fate over the next 10 h. It was found that the minimum life of an arrested metaphase was of the order of 4 h, and then metaphases degenerated at the rate of approximately 0.4% per hour. It is recommended that metaphase arrest experiments in psoriatic epidermis be confined to 4 h although, if required, correction factors are available to correct for experiments which are lengthened. Finally it is shown that flux into DNA synthesis exceeds the flux into mitosis by four or five times; several explanations are considered, and it is thought that the most likely explanation involves the death of psoriatic cells in the G₂ phase.