Biomedical subjects
P J Allen
Publications and source records attributed to P J Allen.
Surgical management of Merkel cell carcinoma.
OBJECTIVES: To characterize the natural history of Merkel cell carcinoma (MCC) and to analyze the influence of patient, tumor, and treatment-related variables on survival and recurrence. SUMMARY BACKGROUND DATA: Approximately 425 cases of MCC have been described in the literature. This study represents the largest experience reported. METHODS: A review was performed of patients who had been treated at Memorial Sloan-Kettering Cancer Center for MCC between 1969 and 1996. Follow-up data were available for 102 of the 109 (94%) patients identified. RESULTS: The overall 5-year disease-specific survival rate was 74%. The median follow-up was 35 months. For all patients, the only independent predictor of survival was the tumor stage at presentation. For patients with stage I disease, the tumor size at presentation was also an independent predictor of survival. Recurrence of disease occurred in 55 patients (55%), and the most common site of first recurrence was within the draining lymph nodes (n = 35). Elective lymph node dissection was the only parameter independently predictive of improved relapse-free survival. The overall disease-specific survival rate after recurrence was 62%. Predictors of improved disease-specific survival after recurrence included nodal as compared to local or distant recurrence, the ability to render the patient free of disease after recurrence, and a disease-free interval of >8 months. CONCLUSION: The prognosis for patients with MCC is favorable, and even after recurrence the majority of patients experience long-term survival. Incorporation of size into the staging system more accurately predicts survival in patients with stage I disease. Although elective lymph node dissection decreased the rate of recurrence, it was not associated with improved overall survival.
Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice.
BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene (Y-linked autoimmune accelerator). We studied the phenotype of disease in (B10 x BXSB)F1 and (BXSB x (B10 x BXSB)F1) backcross mice and genotyped 224 backcross animals to allow a microsatellite-based genome-wide linkage analysis to be conducted. In the backcross population, three intervals on chromosome 1 showed significant linkage to disease, suggesting that multiple loci contribute to the production of autoimmune disease. D1Mit5 at 32.8 cM was linked to development of nephritis (chi(2) = 15.68, p = 7.5 x 10(-5)), as was D1Mit12 at 63.1 cM (chi(2) = 20.17, p = 7.1 x 10(-6)). D1Mit403 at 100 cM was linked to anti-dsDNA Ab production (chi(2) = 17.28, p = 3.2 x 10(-5)). Suggestive linkages to antinuclear Abs and nephritis were identified on chromosome 3, to splenomegaly on chromosome 4, and to anti-ssDNA Ab production on chromosome 10. Chromosome 4 and the telomeric region of chromosome 1 have previously been linked to disease in other mouse models of systemic lupus erythematosus; however, the centromeric regions of chromosome 1 and chromosomes 3 and 10 are unique to BXSB. This implies that, though some loci may be common to a number of mouse models of lupus, different clusters of disease genes confer disease susceptibility in different strains of mice.
The effects of hepatic cryosurgery on tumor growth in the liver.
BACKGROUND: The effects of hepatic cryosurgery on residual hepatic tumor growth, and on tumor immunity, have not been determined. MATERIALS AND METHODS: Two experiments were performed. In both, animals (n = 10 per group) had solitary left lobe hepatomas established, and underwent left lobectomy, cryoablation, or control laparotomy. Experiment I: immediately after tumor treatment, intraportal challenge of hepatoma cells was performed to evaluate for the effects of treatment on residual hepatic tumor growth. Experiment II: animals were challenged 14 days after tumor treatment, and splenocyte cytotoxicity assays were performed to evaluate for tumor immunity. Hepatic tumor nodules were counted 3 weeks after challenge in both experiments. RESULTS: In animals challenged immediately after tumor treatment, the mean number of liver nodules at 3 weeks was similar between control and cryoablation groups (65 +/- 13 vs 115 +/- 38, P = 0.17). Animals that had undergone resection, however, had a significant increase in the mean number of nodules as compared to cryoablation (278 +/- 74 vs 115 +/- 38, P = 0. 04) and control (278 +/- 74 vs 65 +/- 13, P = 0.002) animals. In addition, only resection animals had elevation in serum levels of the growth factor FGF-basic, 48 h after treatment (mean = 30 +/- 14 pg/ml). In animals challenged 14 days following treatment, all groups had similar numbers of nodules (resection vs cryoablation, P = 0.8). Splenocyte cytotoxicity was not increased after cryosurgical treatment. CONCLUSIONS: Unlike partial hepatectomy, cryoablation of hepatomas in rats does not accelerate residual tumor growth in the liver or result in production of the growth factor FGF-basic. We did not find evidence for the development of tumor immunity following cryosurgery.
Identification of EEG events in the MR scanner: the problem of pulse artifact and a method for its subtraction.
Triggering functional MRI (fMRI) image acquisition immediately after an EEG event can provide information on the location of the event generator. However, EEG artifact associated with pulsatile blood flow in a subject inside the scanner may obscure EEG events. This pulse artifact (PA) has been widely recognized as a significant problem, although its characteristics are unpredictable. We have investigated the amplitude, distribution on the scalp, and frequency of occurrence of this artifact. This showed large interindividual variations in amplitude, although PA is normally largest in the frontal region. In five of six subjects, PA was greater than 50 microV in at least one of the temporal, parasagittal, and central channels analyzed. Therefore, we developed and validated a method for removing PA. This subtracts an averaged PA waveform calculated for each electrode during the previous 10 s. Particular attention has been given to reliable ECG peak detection and ensuring that the average PA waveform is free of other EEG artifacts. Comparison of frequency spectra for EEG recorded outside and inside the scanner, with and without PA subtraction, showed a clear reduction in artifact after PA subtraction for all four frequency ranges analyzed. As further validation, lateralized epileptiform spikes were added to recordings from inside and outside the scanner: PA subtraction significantly increased the proportion of these spikes that were correctly identified and decreased the number of false spike detections. We conclude that in some subjects, EEG/fMRI studies will be feasible only using PA subtraction.
Bilateral familial inferotemporal retinal dialyses.
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Automated blood pressure measurement at rest and during exercise: evaluation of the motion tolerant CardioDyne NBP 2000.
PURPOSE: The purpose of this study was to validate the use of a motion tolerant blood pressure monitor (CardioDyne NBP 2000, Luxtec, Worcester, MA) ) against standard manual auscultation at rest and during exercise. METHODS: Nineteen subjects (men, N = 9; women, N = 10) participated in the study (mean: age 21+/-1.2 yr; height 172.5+/-8 cm; mass 69.4+/-14.5 kg). Standard Bruce protocol treadmill exercise tests with 12-lead ECG and metabolic measures were administered to the subjects, with blood pressure measures taken at rest before, during, and after the exercise tests. Blood pressure by manual auscultatory sphygmomanometry and the CardioDyne NBP 2000 was recorded simultaneously in the same arm. Manual auscultatory blood pressure measures obtained by one experimenter were used as the criterion measure, and the data of two NBP 2000 audio reviewers were averaged for each data point recorded. RESULTS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) via manual auscultation and the NBP 2000 "automatic" values were not significantly different and were highly correlated at rest and during exercise. Resting intraclass correlation SBP values were high (range 0.95 to 0.98), as were DBP intraclass correlation values (range 0.83 to 0.95). Exercise intraclass correlation SBP values ranged from 0.94 to 0.99, and DBP intraclass correlation values from 0.88 to 0.93. CONCLUSION: We conclude that the NBP 2000 is simple to use at rest and during exercise stress testing and provides accurate and verifiable information.
Recording of EEG during fMRI experiments: patient safety.
The acquisition of electroencephalograms (EEG) during functional magnetic resonance imaging (fMRI) experiments raises important practical issues of patient safety. The presence of electrical wires connected to the patient in rapidly changing magnetic fields results in currents flowing through the patient due to induced electromotive forces (EMF), by three possible mechanisms: fixed loop in rapidly changing gradient fields; fixed loop in a RF electromagnetic field; moving loop in the static magnetic field. RF-induced EMFs were identified as the most important potential hazard. We calculated the minimum value of current-limiting resistance to be fitted in each EEG electrode lead for a representative worst case loop, and measured RF magnetic field intensity and heating in a specific type of current-limiting resistors. The results show that electrode resistance should be > or = 13 k(omega) for our setup. The methodology presented is general and can be useful for other centers.
Saphenous vein versus polytetrafluoroethylene carotid patch angioplasty.
BACKGROUND: The optimal material for carotid patch angioplasty after endarterectomy remains uncertain. This study compares the early outcome and recurrent stenosis rates between saphenous vein (SV) and expanded polytetrafluoroethylene (ePTFE) carotid patch angioplasty. METHODS: The results of 421 consecutive carotid endarterectomies performed over a 72-month period were reviewed. Postoperative complications and restenosis rates, defined as > OR = 60% narrowing measured by color flow duplex, were compared. RESULTS: Patch angioplasty was performed with SV in 287 and with ePTFE in 110 cases. Patients who had undergone primary closure (n = 20) or whose form of closure was unknown (n = 4) were excluded. The mean age of patients and length of follow-up was similar between groups. Women were more likely to be patched with ePTFE than were men (36% versus 23%, P = 0.02). One death occurred in each group (0.3% SV, 0.9% ePTFE, P = 0.47), and four strokes occurred in each group (1.4% SV, 3.6% ePTFE, P = 0.22). Cervical hematomas requiring operative evacuation occurred in five SV closures and in three ePTFE closures (1.7% versus 2.7%, P = 0.69). Vein harvest site complications occurred in 6 patients (2%) who had undergone SV patch angioplasty. Recurrent stenosis occurred in 3 patients with SV closure and in 3 patients with ePTFE closure (1.0% versus 2.7%, P = 0.35). The 60-month restenosis rates by life table analysis were 2.6% +/- 2.1% for SV and 10.7% +/- 7.9% for ePTFE (P = 0.17). CONCLUSIONS: The incidence of postoperative complications is similar with SV or ePTFE patch angioplasty; however, vein harvest site complications are avoided with the use of ePTFE. Recurrent stenosis at 5 years occurs infrequently with either SV or ePTFE.
Interspecific microsatellite markers for the study of pinniped populations.
Microsatellites have rapidly become the marker of choice for a wide variety of population genetic studies. Here we describe 20 pinniped microsatellite markers which have been tested across 18 pinniped species. The majority of these markers have broad utility in all pinnipeds and provide a strong base for detailed population genetic studies in the Pinnipedia.
Peripheral transscleral retinal diode laser for rubeosis iridis.
PURPOSE: To evaluate the results of peripheral transscleral retinal diode photocoagulation with or without transscleral cyclodiode therapy in patients with rubeosis iridis with or without elevated intraocular pressure and no fundal view. METHODS: Peripheral transscleral retinal diode photocoagulation was performed in 15 eyes of 13 patients in an attempt to promote regression of rubeosis. The fundus could not be seen in any of the 15 eyes, so conventional panretinal photocoagulation was not possible. Nine eyes had associated elevated intraocular pressure and were treated with concurrent transscleral diode cyclophotocoagulation. RESULTS: All eyes showed regression of rubeosis. Of the nine eyes treated with combination therapy, six had stabilized intraocular pressure, and three developed hypotony. None of the eyes developed a peripheral retinal detachment, and one eye lost the ability to perceive light. CONCLUSIONS: This method is effective in treating patients with rubeosis iridis when the view of the fundus is inadequate for conventional panretinal photocoagulation and more extensive intraocular surgery is precluded. It may be combined with transscleral cyclophotocoagulation therapy to manage concurrent high intraocular pressure in rubeotic glaucoma, but this involves a risk of postoperative hypotony.
Autoantibodies to the collagenous region of C1q occur in three strains of lupus-prone mice.
We have developed an ELISA to measure murine autoantibodies to the collagenous region (CLR) of C1q, using the whole human C1q molecule as the solid-phase ligand, in the presence of 1 M NaCl. The assay was validated by testing positive sera from 20 mice using purified mouse C1q, and from 10 mice using purified human C1q-CLR, as the solid-phase ligands. There were highly significant correlations between results obtained with human C1q (whole molecule) and: (i) mouse C1q (rsp = 0.73, P less than 0.001), and (ii) human Clq-CLR alone (rsp = 0.86, P = 0.001). Antibodies to Clq were measured in 53 MRL/lpr, 17 BXSB and 25 NZB/W lupus-prone mice. Median (range) anti-C1q (CLR) antibody levels in MRL/lpr, BXSB, and NZB/W autoimmune mice aged 3 months were 22 (16-66), 21 (17-39) and 19 (15-27) EU, respectively. The median anti-Clq antibody level in MRL/lpr mice aged 5 months was 76 (35-142) EU, significantly higher than that at 3 months (U = 558, P less than 0.0005). Median anti-C1q antibody level in NZB/W mice at 8 months was 37 (13-74) EU and in BXSB mice at 11 months was 62 (31-231) EU, significantly higher than corresponding values at 3 months (U = 326, and U = 4, P less than 0.001, respectively). This is the first demonstration of anti-C1q (CLR) antibodies in NZB/W and BXSB mice. The pathologic significance and the potential utility of these antibodies for monitoring disease in lupus-prone mice are under evaluation.
First seizures associated with playing electronic screen games: a community-based study in Great Britain.
Active surveillance by virtually all electroencephalographic departments throughout Great Britain identified 118 patients who had a first seizure while playing an electronic screen game during two 3-month periods. Patients were divided into Group A (46 patients)--those for whom there was thought to be a definite causal relationship (type 4 photoparoxysmal response); Group B (25 patients)--those for whom there was a probable causal relationship (types 1-3 photoparoxysmal response, clinical evidence of photosensitivity, subsequent recurrent seizures on repeat exposure to electronic screen games, and/or occipital spikes in the resting electroencephalogram); and Group C (47 patients)--those for whom there was no apparent causal relationship. The number of patients in Group C did not exceed that expected by the chance occurrence of two common events (playing electronic screen games and incidence of epilepsy). Most (103/118) of the patients were in the age range of 7 to 19 years. Within this age group the annual incidence of first seizures triggered by playing electronic screen games (Groups A and B combined) was estimated to be 1.5/100,000.
Incidence of photosensitive epilepsy: a prospective national study.
We undertook a prospective nationwide study to determine the incidence of photosensitive epilepsy (PE). Virtually all EEG departments in Great Britain (providing approximately 90% coverage of all EEGs performed on people with newly diagnosed seizures) screened cases referred to them over a 3 month period and identified all new cases of epilepsy (defined as one or more recognised seizures) whose first EEG showed a photoparoxysmal response (PPR) on intermittent photic stimulation (IPS). 191 cases were identified, 143 of whom had type 4 PPRs (generalised spike and wave on IPS) on their first EEG. The annual incidence of cases of epilepsy with type 4 PPRs on their first EEG was conservatively estimated to be 1.1 per 100,000, representing approximately 2% of all new cases of epilepsy. When restricted to the age range 7-19 years, the annual incidence rose to 5.7 per 100,000-approximately 10% of all new cases of epilepsy presenting in this age range. To ascertain if there was a significant seasonal variation in PE, 5 EEG departments (which together contributed 15% of cases in the first study period) were visited during a second 3 month study period to identify all new cases of epilepsy with type 4 PPRs on their first EEG. No significant seasonal variation in incidence between summer and winter was found.
Lower extremity lymphedema caused by acquired immune deficiency syndrome-related Kaposi's sarcoma: case report and review of the literature.
A case of severe lymphedema of the lower extremity caused by obstruction by human immunodeficiency virus-associated Kaposi's sarcoma is presented. A review of the signs and symptoms of obstructive lymphedema and Kaposi's sarcoma is provided. Early recognition of this clinical entity may allow use of simple preventative measures and help to avoid this life- and limb-threatening situation.
Microsatellite variation in grey seals (Halichoerus grypus) shows evidence of genetic differentiation between two British breeding colonies.
Eight highly variable microsatellite loci were used to examine the genetic variability and differentiation of grey seals (Halichoerus grypus) at two widely spaced British breeding colonies. Samples were collected from adults and pups on the island of North Rona, off the north-west coast of Scotland, and on the Isle of May, situated at the mouth of the Firth of Forth on the east coast. Highly significant differences in allele frequencies between these two sites were found for all eight loci, indicating considerable genetic differentiation. Thus, although grey seals are known to range over very large areas outside the breeding season, site fidelity of adults and philopatry of pups for these breeding colonies must be sufficiently common to have effects, through genetic drift, at the sub-population level. Migration rate was estimated using Wright's fixation index (FST), Slatkin's private alleles model and the new statistic, RST, which is analogous to FST but which takes into account the process of microsatellite mutation. An almost 8-fold discrepancy between the values we obtained provides cautionary evidence that microsatellite loci may contravene one or more of the assumptions on which these methods are based.
Partial purification and reconstitution of the sarcolemmal L-lactate carrier from rat skeletal muscle.
Purified sarcolemmal membranes from mixed rat hindlimb muscle were solubilized with octylglucoside and the extract subjected to hydroxylapatite (HA) chromatography. Following protein elution with a sodium phosphate gradient and detergent removal by dialysis, the HA eluate was reconstituted into asolectin liposomes using a freeze-thaw procedure. Specific L-[14C]lactate transport activity eluting from the 0.2 M sodium phosphate fraction was 30-fold higher compared with native sarcolemmal vesicles (31.64 versus 1.06 nmol/min per mg). The reconstituted carrier exhibited Michaelis-Menten saturation kinetics with Km and Vmax. values of 46.2 +/- 6.6 mM and 498.7 +/- 17.2 nmol/15 s per mg respectively. L-Lactate transport activity was inhibited 57% by preincubation of proteoliposomes with 10 mM alpha-cyano-4-hydroxycinnamate, a known inhibitor of lactate transport. Analysis of the HA eluates by SDS/PAGE showed the presence of a 34 kDa band corresponding to lactate transport activity. Reconstitution of lactate transport activity eluting from the HA column, together with SDS/PAGE analysis suggests the presence of a 34 kDa polypeptide mediating sarcolemmal lactate exchange in rat skeletal muscle.