Modeling intracranial second tumor risk and estimates of clinical toxicity with various radiation therapy techniques for patients with pituitary adenoma.

This study was designed to estimate the risk of radiation-associated tumors and clinical toxicity in the brain following fractionated radiation treatment of pituitary adenoma. A standard case of a patient with a pituitary adenoma was planned using 8 different dosimetric techniques. Total dose was 50.4 Gy (GyE) at daily fractionation of 1.8 Gy (GyE). All methods utilized the same CT simulation scan with designated target and normal tissue volumes. The excess risk of radiation-associated second tumors in the brain was calculated using the corresponding dose-volume histograms for the whole brain and based on the data published by the United Nation Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and a risk model proposed by Schneider. The excess number of second tumor cases per 10,000 patients per year following radiation is 9.8 for 2-field photons, 18.4 with 3-field photons, 20.4 with photon intensity modulated radiation therapy (IMRT), and 25 with photon stereotactic radiotherapy (SRT). Proton radiation resulted in the following excess second tumor risks: 2-field 5 5.1, 3-field 5 12, 4-field 5 15, 5-field 5 16. Temporal lobe toxicity was highest for the 2-field photon plan. Proton radiation therapy achieves the best therapeutic ratio when evaluating plans for the treatment of pituitary adenoma. Temporal lobe toxicity can be reduced through the use of multiple fields but is achieved at the expense of exposing a larger volume of normal brain to radiation. Limiting the irradiated volume of normal brain by reducing the number of treatment fields is desirable to minimize excess risk of radiation-associated second tumors.

Post-irradiation malignant fibrous histiocytoma of the larynx: A case report with an unusual metastatic spread pattern.

We report a case of a laryngeal malignant fibrous histiocytoma (MFH) that showed an uncommon clinical behavior. This tumor occurred in a 70-year-old male patient 5 years after radiation treatment for laryngeal squamous cell carcinoma, and unusual metastases were spread unusually to the pleural cavity. The interval between the end of radiotherapy and the onset of MFH can be justified by the development of laryngeal stenosis by fibrotic tissue as a late complication of radiotherapy. Laryngeal fibrosis after radiotherapy probably triggered the MFH. Neither computed tomography nor magnetic resonance imaging differentiate between fibrotic tissue and MFH, and only repeated biopsy was definitive to give us the correct diagnosis.

The AESOP robot system for video-assisted rigid endoscopic laryngosurgery.

Surgeons may occasionally encounter difficulty in visualizing the whole larynx with a direct laryngoscope. In such cases, rigid endoscopic laryngosurgery using a direct laryngoscope is an optimal solution. Multidirectional examination of the larynx using rigid endoscopes during direct laryngoscopy, leads to better control and management of the ventricle, inferior surface of the vocal fold and subglottis, and the anterior commissure. Currently, 0 degrees , 30 degrees , 70 degrees and 120 degrees angled rigid telescopes are used worldwide. Our experience in telescopic endolaryngeal surgery provided us the opportunity to work with AESOP 3000 (automated endoscope system for optimal positioning), coupling a robotic arm to a rigid endolaryngeal telescope. The use of this device allows the surgeon to control the field of view and operate with both hands. A total of 20 patients presenting a laryngeal lesion were randomly selected and included in this study undergoing a robot-assisted procedure. Three of 20 patients presented a difficult laryngeal exposure with direct laryngoscopy due to a rigid, short neck (1 male, 1 female) and prominent teeth (1 male). We used Karl Storz Hopkins II long rigid endoscopes having 0 degrees, 30 degrees and 70 degrees direction of view, a Storz Xenon 300 cold light, a Storz Tricam SL camera, the Kleinsasser direct laryngoscope. The instruments we used are all commercially available for microlaryngeal surgery and included upward curved instruments in case of difficult laryngeal exposure. The operative equipment was the same for all procedures. We evaluated the acquisition of skills in controlling the AESOP 3000, the feasibility of a single surgeon performing procedures with this machine, and any advantages that it might offer to endolaryngeal surgery. The use of robotic devices improves the precision of surgical procedures, offering surgeons a more comfortable working position, particularly for longer procedures, and without an assistant to hold the camera.

Experimental and clinical aspects of the efferent auditory system.

The discovery of active mechanisms in the cochlea and the efferent auditory pathways from the brain to the cochlea demonstrated the existence of a modulation of the auditory input in the central nervous system (CNS). Otoacoustic emissions (OAEs) are weak signals that can be recorded in the ear canal and are considered a byproduct of an active process from the outer hair cells (OHCs) to the basilar membrane. The efferent auditory system plays an inhibitory role on the activity of OHCs; its stimulation reduces auditory nerve response, basilar membrane motility and OAEs amplitude. Indirect stimulation by contralateral sound is also inhibitory; a reduction of OAEs amplitude can be recorded and such an effect disappears after olivocochlear bundle section. The efferent system seems to play a role in detection of signals in noise, protection in noise-induced cochlear damage, development of hearing and processing of complex auditory signals. With respect to clinical application, OAEs suppression after contralateral auditory stimulation seems to be the only objective and non-invasive method for evaluation of the functional integrity of the medial efferent system, and, therefore, for evaluation of the structures lying along its course, at least up to the level of inferior colliculi.

Variations of neck structures after supracricoid partial laryngectomy: a multislice computed tomography evaluation.

BACKGROUND: Surgery of laryngeal cancer used to profoundly alter the anatomy of the cervical region. Accurate anatomo-embryologic studies and repeated surgical trials allowed recognition of the cricoarytenoid complex as the smallest anatomofunctional unit able to maintain all the laryngeal functions. OBJECTIVES: The aim of this study was to determine whether significant variations of neck anatomical parameters exist after partial laryngectomy, and to analyze whether some of these parameters are associated with a positive functional outcome. METHODS: Out of 48 patients treated with a surgical technique according to Mayer-Piquet (cricohyoidoepiglottopexy, CHEP) over a 6-year period, 18 patients were enrolled in the study. Patients were all males with a mean age of 60 years. Cervical structures and their relationships were measured by computed tomography, and the measurements before and after surgery were compared. RESULTS: Our data showed that hyoid bone is modified, both in morphology and position during CHEP. More specifically the relation of the hyoid bone to other neck structures (identified by the alpha-angle) is modified. The neolarynx and trachea undergo a caudocranial shift. All diameters of the cricoid cartilage remain unchanged after surgery. The position of the epiglottis after CHEP, in particular its relation with the arytenoid cartilage, is closely related to swallowing function outcome and recovery time. CONCLUSIONS: Our study showed that these structures, and more specifically the relations among them, undergo significant variations after CHEP. Our results identify some parameters, i.e. the alpha-angle, width of the hyoid bone and position of the epiglottis, that may predispose to a positive functional outcome after surgery.

Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation.

Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.

Impaired postural control in patients affected by tension-type headache.

Sixteen subjects, affected by chronic tension-type headache (TTH) accordingly to the International Headache Society Classification (1988) criteria, in presence of tenderness in pericranial muscles,with a mean age of 37+/-11.8 years, and ten healthy volunteer subjects, age and sex matched, were submitted to postural analysis by Static Posturography (S.Ve.P. Amplaid). Aim of the study was to evaluate whether patients with TTH have disturbed postural control, as compared to normal subjects. Postural analysis considered all posturographic variables but focused on spectral frequency analysis of body sway. In both open (OE) and closed eyes (CE) condition, spectral frequency analysis showed a significantly increased body sway at low (OE= p < or = 0.01; CE= p < or = 0.01) and middle (OE= p < or = 0.01; CE= p < or = 0.01) frequencies on the antero-posterior (y) plane and at low frequencies (OE= p < or = 0.05; CE= p < or = 0.05) on the lateral (x) plane. Statistical analysis was performed using the Student's t test for unpaired data, p value 0.05 defined significant. The proprioceptive input seems to be predominant at middle and high frequencies in maintaining posture, our results seem then to suggest a proprioceptive disturbance in TTH patients. The disturbance is likely related to chronic pericranial muscle contraction and tenderness. Posturography and spectral analysis may help not only in the diagnosis of a postural disturbance but even more in the follow-up of TTH patients, during and after a medical and/or a rehabilitative treatment.

Nose: aesthetics and function. Rhinoplasty and functional problems related to anterior ethmoid.

Aesthetic nasal surgery has progressed in the last years, as concerning both surgical techniques and surgical instruments, which allowed the finding of new and more sophisticated surgical solutions. Clinical practice led to observe sometimes functional surgical failures, due rather than an inaccurate surgical technique, to an incomplete diagnostic approach to the patient. It has been observed that modifying the external conformation of nasal pyramidis inner-nose volumes and spaces will be subsequently reduced, giving as a result a condition which is only aesthetically but not functionally valid. 32 subjects, selected for a rhinoplasty and presenting nasal respiratory obstruction and anterior ethmoid abnormalities, confirmed by nasal endoscopy and nasal CT, were evaluated and subdivided into two groups: the first (A) group underwent only to an aesthetic rhinoplasty, the second group (B) was operated of a rhinoplasty combined with functional endoscopic sinus surgery (FESS) in order to correct the above mentioned anatomical abnormalities. The nasal airflow, and though the nasal cavities patency, was evaluated pre- and post-operatively in the two groups of patients, referring to rhinomanometric conductance values. Patients of group A reported decreased post-operative conductance values, patients of group B reported increased post-operative conductance values, showing though the functional involvement of anterior ethmoid in nasal obstruction and the necessity of correcting its anatomical abnormalities, in order to reach not only a new nasal profile, but also a better respiratory performance.

Nariz:estética y función. Rinoplastia y problemas funcionales relacionados con el etmoides anterior / Nose: aesthetics and function. Rhinoplasty and functional problems related to anterior ehtmoid

La cirugía estética nasal ha progresado en los últimos años tanto en cuanto a las técnicas quirúrgicas como en cuanto a los instrumentos, que permiten encontrar nuevas y más sofisticadas soluciones quirúrgicas. La práctica clínica nos permite observar a veces fallos quirúrgicos funcionales, debidos más que a una técnica quirúrgica inadecuada, a un abordaje diagnóstico incompleto del paciente. Se ha observado que modificando la forma externa de la pirámide nasal, el volumen y los espacios internos de la nariz se verán consiguientemente reducidos, dando así pues como resultado sólo una condición estética pero no válida funcionalmente. 32 pacientes, seleccionados para rinoplastia y que presentaban obstrucción nasal y anomalias etmoidales anteriores, confirmadas por endoscopia nasal y TC, fueron evaluados y subdivididos en dos grupos: Al primer grupo (A) sólo se le practicó rinoplastia estética y al segundo (B) se le practicó rinoplastia combinada con cirugía endoscópica funcional sinusal (FESS) par corregir las anomalías anatómicas más arriba mencionadas. El flujo nasal y asi pues la permeabilidad de las cavidades nasales, fue evaluado pre y posoperatoriamente en los dos grupos, referidos a los valores rinomanométricos. Los pacientes del grupo A tuvieron valores postoperatorios inferiores y los del grupo B superiores, mostrando así pues la relación funcional del etmoides anterior en la obstrucción nasal y la necesidad de corregir sus anomalías anatómicas, para no sólo conseguir un nuevo perfil nasal, sino también una mejor respiración (AU)

Numerical dose-compensated in vitro fertilization inseminations yield high fertilization and pregnancy rates.

OBJECTIVE: To evaluate in cases with morphologically abnormal sperm whether fertilization and pregnancy rates are increased by normalizing the number of sperm inseminated and whether biomarkers can identify cases of reduced or failed fertilization. DESIGN: Prospective studies of sperm morphology and function. SETTING: University hospital assisted human reproduction program. PATIENT(S): Partners of 308 women undergoing IVF. INTERVENTION(S): Motile sperm populations were assessed for sperm head morphology, for surface receptors for mannose and progesterone binding, and the ability to undergo a free mannose-induced acrosome reaction. Zinc in seminal plasma was determined by atomic absorption spectroscopy. MAIN OUTCOME MEASURE(S): Sperm morphology was associated with fertilization and clinical pregnancy rates. Biomarker analyses were correlated with fertilization rates using Kruskal-Wallis tests, chi2 tests, and Spearman rank order correlations. RESULT(S): Fertilization and pregnancy rates after numerical dose compensation inseminations were indistinguishable between men with differing percentages of normal sperm. Biomarker deficits were identified irrespective of sperm head morphology in 96% of cases of reduced or failed fertilization. CONCLUSION(S): Fertilization and pregnancy rates in cases of abnormal morphology are optimized by inseminating at least 25,000 sperm/mL with normal acrosomes. Reduced or failed fertilization can be predicted by testing for molecular deficits in mannose receptor expression and mannose-stimulated acrosome loss.

Electrophysiological changes in children with learning and attentional abnormalities as a function of age: event-related potentials to an "oddball" paradigm.

This study investigated age-related electrophysiological differences between children diagnosed with Learning Disabilities (LD), Attention Deficit Hyperactivity Disorder (ADHD), LD-ADHD and Conduct Disorder, using Event-Related Potentials recorded during a two-tone discrimination test. Although age-related (N1 and N2 amplitude), as well as diagnostic group-related (P3 latency and amplitude) ERP changes were found, there was no significant interaction between the diagnostic groups and age grouping. We conclude that: 1) Electrophysiological abnormalities in LD and ADHD do not significantly change with age during childhood. This study does not, therefore, support a hypothesis of age-related brain abnormalities in LD and ADHD. 2) Significant group differences for P3 latency and amplitude were found between normal children and the LD groups (LD and LD-ADHD), but not between normal children and those with ADHD alone, suggesting that main correlates of P3 abnormalities in these children are "processing" and not attentional problems.

Visual event related potentials and reaction time in normal adults, normal children, and children with attention deficit hyperactivity disorder: differences in short-term memory processing.

Visual Event Related Potentials were recorded during a memory search paradigm in 30 normal adults, 17 normal children, and 14 children with Attention Deficit Hyperactivity Disorder (ADHD). Group differences were found in P3 latency and amplitude, Reaction Time and number of errors. The findings indicate a different information processing pattern for ADHD children who possibly use a "self-terminating" as opposed to "exhaustive" search strategy.

24-hour blood pressure monitoring in patients with anterior ischemic optic neuropathy.

OBJECTIVE: To define parameters of ambulatory diurnal blood pressure in patients who had experienced anterior ischemic optic neuropathy (AION) in a case-controlled study. PARTICIPANTS AND METHODS: Twenty-four patients with AION and 24 control subjects who were matched for age, gender, medical diagnoses, and medications underwent ambulatory automated blood pressure monitoring for 24 hours. RESULTS: The overall diurnal pattern of blood pressure appeared to be normal in all subjects, showing lower blood pressures at night than during the day, an overnight nadir, and an ascending blood pressure curve in the morning to reach daytime levels. Also, patients with AION did not differ from control subjects with respect to the nighttime diastolic nadir or daytime peak systolic blood pressure. However, during the daytime, patients with AION had lower mean systolic and diastolic blood pressures than did matched control subjects. The widest difference between their blood pressure curves occurred after awakening in the morning, when patients with AION had a less steep and more irregular rise of blood pressure. Patients who had signs of vertebrobasilar insufficiency in addition to AION had lower mean diastolic blood pressure during both daytime and nighttime and a lower minimum daytime diastolic blood pressure. CONCLUSIONS: On ambulatory measurements of diurnal blood pressure, patients with AION consistently had a lower mean blood pressure than did control subjects and a lag in the usual rise in blood pressure in the morning to meet increasing daytime demands for perfusion. Chronic hypoperfusion of small end-arterial vessels that supply the optic nerve head may predispose to AION, and may be caused by relative hypotension owing to overtreated hypertension or to abnormal vascular autoregulation. Internists should be asked to monitor blood pressure carefully when treating hypertensive patients who are at risk for AION, to avoid hypotension, especially on awakening in the morning.

The impact of co-morbid risk factors at the start of dialysis upon the survival of ESRD patients.

By using a computerized database, we have catalogued the presence of 29 co-morbid risk factors in 683 patients with end-stage renal disease who started dialysis from 1970 through 1989, with follow-up through 1992. The authors hypothesized that current end-stage renal disease patients have more serious co-morbid risk factors impacting upon their mortality rate. Quantitation of dialysis patient co-morbidity, as a measure of patient illness, is lacking in the general nephrology literature. Seven co-morbid risk factors have been reserved for new dialysis patients: hypertension, low albumin, cerebral vascular disease, peripheral vascular disease, pre-existing cardiac disease, abnormal EKG/old myocardial infarction, and congestive heart failure. Except for low serum albumin, the proportion of patients with the six other co-morbid risk factors has increased significantly over this 20-year period (p < 0.0001, chi-square test for hypertension, peripheral vascular disease, pre-existing cardiac disease, abnormal EKG/old myocardial infarction, and congestive heart failure, and p < 0.006 for cerebral vascular disease). In addition, the co-morbid risk factors of hypertension, low serum albumin, and pre-existing cardiac disease at the start of dialysis were strongly prognostic of survival. The Cox proportional hazards regression model identified these three risks, among other factors, that were significantly associated with a decreased survival, with risk ratios ranging from 1.40-1.66. These results support the authors' hypothesis that incoming end-stage renal disease patients, who recently start dialysis, are sicker than in the earlier years of the authors' program. If the authors' patients reflect the national end-stage renal disease population, the presence of co-morbid risk factors may, in part, explain the continuing high mortality of dialysis patients.

Home hemodialysis: patient outcomes during a 24-year period of time from 1970 through 1993.

In the United States, from 1983 to 1993, home hemodialysis use has decreased from 6% to 1.3% of the dialysis population, whereas continuous ambulatory peritoneal dialysis (CAPD) has increased to 20%. Most home hemodialysis programs have withered away because of current patient mix, increase in CAPD, proliferation of outpatient centers, disinterest in nephrologists, and fear of self-cannulation by patients. From 1970 through 1993, 896 patients began dialysis at North Shore and were followed up through 1994. During this period, 687 patients were on in-center hemodialysis, 95 on CAPD, 74 on home hemodialysis, and 40 on in-center peritoneal dialysis. The home hemodialysis patients were younger, with a median age of 44 versus 59 years for in-center hemodialysis patients, and had less comorbidity. The home hemodialysis group had fewer diabetic patients and no renal vascular patients. The 5-year and median survival estimates were significantly better for the home hemodialysis patients versus other dialysis modalities. More home hemodialysis patients received transplants. Compared with the other dialysis modalities, home hemodialysis patients showed significantly improved survival rates. When matched by age, sex, and end-stage renal disease (ESRD) diagnosis to corresponding in-center hemodialysis, the home hemodialysis patients still had significantly better survival rates, but the home hemodialysis patients had less comorbidity. In conclusion, home hemodialysis patients survive longer and have better rehabilitation than other dialysis patients. Reasons for better survival in addition to a younger age and more favorable ESRD diagnosis may include less comorbidity, more patient involvement, and longer dialysis time. Because of these better outcomes, home hemodialysis should be offered to more ESRD patients.

Laboratory diagnosis of infection status in infants perinatally exposed to human immunodeficiency virus type 1.

Accurate and timely diagnosis of infection status in infants born to women infected with human immunodeficiency virus (HIV) is of paramount importance. The comparative accuracy of five diagnostic decision rules was evaluated in 208 HIV-exposed infants (32 infected, 176 uninfected) based on laboratory testing during the first 6 months of life. Diagnostic rules A and B, which required single blood samples analyzed by culture and polymerase chain reaction (PCR) (rule A) or culture, PCR, and p24 antigen detection (rule B) were more prone to incorrect diagnoses than were rules requiring 2 blood samples analyzed by a single assay (rule C) or combinations of culture and PCR (rules D and E). Rule D, which used PCR as the initial test, established the most useful algorithm: a positive PCR result followed by a positive culture in the second sample confirmed infected status, while two consecutive negative PCR results reconfirmed as negative at 6 months of age established uninfected status.

Unmet analgesic needs in cancer patients.

This study was designed to characterize unmet analgesic needs in a group of cancer patients. One hundred one inpatients were surveyed to document pain prevalence and intensity, satisfaction with pain control and factors associated with unmet analgesic needs during the week prior to admission. Forty-four percent had unmet analgesic needs, defined as pain of moderate or greater than moderate intensity. These patients had a significantly greater prevalence of bone and axillary node involvement, higher than pain intensity, and less satisfaction with pain control. Fifty-nine percent were satisfied with pain control. Dissatisfaction was associated with higher usual pain intensity, less satisfaction with physician information about pain etiology, less frequent attribution of pain to disease, sharp pain, constant and intermittent pain, patient perceptions of less physician concern about pain, patient and physician belief that the patient is receiving insufficient analgesic, and patient wanting more control over analgesic regimen. Patients may benefit from improved treatment of specific syndromes and by attention to communication.

Event-related potentials to an "oddball" auditory paradigm in children with learning disabilities with or without attention deficit hyperactivity disorder.

Event Related Potentials (ERP) were recorded during a two-tone discrimination task in 18 children with Learning Disabilities (LD) and 36 children with Learning Disabilities and Attention Deficit Hyperactivity Disorder (LD-ADHD). Twenty-seven normal children served as a control group. P3 wave amplitude was significantly smaller in the LD and LD-ADHD groups compared with normal children. There was no difference between the LD and LD-ADHD groups. It is suggested that the smaller P3 amplitude in children with LD-ADHD syndromes reflects cognitive and processing difficulties, which frequently coexist with ADHD in these children and is not specifically related to an attention deficit.

Renal vascular disease causing end-stage renal disease, incidence, clinical correlates, and outcomes: a 20-year clinical experience.

In the United States, the incidence of end-stage renal disease to hypertension has increased sharply over the last 8 years, especially in elderly white dialysis patients who demonstrate very poor survival rates. The 5-year survival rates were near 20% for patients 65 to 74 years old and 9% for those > or = 75 years of age. Our program experienced a sharp increase in cases of end-stage renal disease due to renal vascular disease after 1982. Renal vascular disease was characterized clinically in 83 of 683 dialysis patients either by angiography or asymmetric kidney size in patients with evidence of systemic atherosclerosis, hypertension, insignificant proteinuria, and a benign urinary sediment. The median age was 70 years, with 84% of the patients being older than 61 years. These patients had 56% 2-year, 18% 5-year, and 5% 10-year survival rates, which are quite similar to the 1992 US Renal Data System data. Patients with renal vascular disease have a significantly worse prognosis than other diagnostic groups, most likely due to their older age, underlying vascular disease, and coronary artery disease. We feel that a significant number of elderly white hypertensive patients described in the 1992 US Renal Data Service report have renal vascular disease as a cause of end-stage renal disease, highlighting the need to establish correct renal diagnoses. Hypertension should not be the end-stage renal disease diagnosis in elderly white hypertensive patients if clinical criteria suggest a diagnosis of renal vascular disease.

A comparison between two intermittent intravenous systems without needles.

Needle-stick injury remains the most dangerous exposure to blood and body fluids. Needleless intermittent intravenous devices are available to assist the health care professional in avoiding the risk of needle-stick injury. The i.v. team at North Shore University Hospital in Manhasset, New York designed a method to evaluate and compare different needleless systems. In this article, the method followed and results obtained in this study are discussed.