Accumulation of radiolabeled anti-CEA antibody (mT84.66) in the case of multiple LS174T tumors in a nude mouse model

A comparison was made between labeled antibody accumulations in nude mice having either single or multiple human xenografts. The LS174T tumors were implanted subcutaneously. All animals were given 2 micrograms of labeled murine anti-carcinoembryonic antigen (CEA) monoclonal antibody 111In-mT84.66. Some animals were also given specific antibody pretreatment (SAP) of 200 micrograms of unlabeled mT84.66 to reduce liver accumulation of activity. In order to represent these multiple tumor examples, a simple initial-phase pharmacokinetic model was first fitted to each of the two groups (SAP and PBS treated) of single-tumor animals. Using the resultant six non-adjustable parameters as constants, the n = 1 uptake model was then used to represent tumor, liver and blood accumulations (%injected dose/organ) in the multiple-tumor animals. The model was found to be a good representation; in particular, it had far better agreement than single tumor predictions in the PBS mice. Differences between the single-tumor accumulations and those seen in multiple tumor examples were generally between two- and three-fold. The model also demonstrated that the result of SAP was to essentially eliminate the effect of liver targeting of tumor-secreted CEA. We conclude that an initial-phase one-tumor model can describe the decrease of accumulation of activity in the case of multiple tumors in nude mice in both untreated (PBS) and pretreated conditions. Implications for clinical imaging and therapy with monoclonal agents are discussed.     

Radiologic features of “adult type” polycystic kidney disease in the neonate

Two cases are reported of adult type polycystic renal disease (autosomal dominant) presenting in the newborn as a unilateral abdominal mass. The radiographic findings in the involved kidney simulated the ectatic tubules of infantile polycystic disease, yet histologic examination was consistent with the adult variety and both infants had other family members with adult type polycystic kidneys. These cases emphasize some of the ambiguities that exist in the definition and classification of polycystic renal disease.     

Cytomegalovirus retinitis in patients with acquired immune deficiency syndrome

Cytomegalovirus (CMV) retinitis is the most common intra-ocular infection in patients with acquired immune deficiency syndrome (AIDS), and a leading cause of AIDS-related morbidity. Untreated CMV retinitis in AIDS patients is a progressive and potentially blinding disorder. The diagnosis of CMV retinitis is a clinical one and it is important for physicians to be familiar with the clinical features of the disease. Ophthalmic screening of AIDS sufferers should be undertaken at regular intervals, and this is dictated, in part, by the patient's CD4+ T-lymphocyte (CD4) counts. CMV retinitis may be treated with systemic ganciclovir, foscarnet or cidofovir, or with local (intravitreal) therpy. CMV-related retinal detachment is treated surgically. In some patients with quiescent CMV retinitis receiving highly active anti-retroviral therapy, anti-CMV maintenance therapy may be discontinued in favour of close ophthalmologic observation and CD4 count monitoring.     

Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.     

Resident work hours and working environment in otolaryngology. Analysis of daily activity and resident perception

OBJECTIVE.--To analyze the working environment and work hours of a cohort of otolaryngology--head and neck surgery residents. DESIGN.--Environmental analysis questionnaire and a log of daily activities. SETTING.--Residents were on a clinical rotation system. PARTICIPANTS.--Fifty-nine residents from six programs, including three public and three private institutions, from geographically diverse regions of the country were involved in the study. Residents were equally distributed from their second year through their fifth year of postgraduate work. All eligible residents participated in and completed the study. INTERVENTION.--The environmental analysis survey was designed to elicit resident perception of different aspects of their working environment. The daily activity log required the resident to report on activities for each half-hour period for 7 consecutive days. RESULTS.--Residents were on call an average of 52.8 hours (2.2 days) and worked 79.4 hours per week. Seventy-five percent believed that the level of faculty supervision and the degree of resident responsibility was about right. Two major inefficiencies were the time involved in completion of paperwork and the lack of nonmedical support services. Thirty-one percent of the residents responded that fatigue resulted in substandard patient care 10% of the time. Forty-seven percent responded that their educational experience was substandard 25% of the time secondary to fatigue. Two thirds responded that the demands of residency training had a negative impact on their family and personal life. CONCLUSIONS.--Seventy percent of the otolaryngology--head and neck surgery residents surveyed at six institutions believe that an 80-hour workweek, including being on call every third night with no more than 24 hours of continuous work without sleep, approximates a reasonable, maximum work schedule. Residents working the longest hours expressed concern about rendering substandard care and developing negative attitudes toward patients. Noneducational inefficiencies were identified and solutions were proposed. Demands of residency training, even within guidelines established as reasonable, can have detrimental effects on residents' educational activities and personal life.     

Cognitive disturbances in patients with relapsing remitting multiple sclerosis

The performance of 42 patients with relapsing remitting (RR) multiple sclerosis was compared with that of 24 age-, education-, and gender-matched control subjects on a battery of neuropsychological tests known from previous studies to be sensitive to the impairments of patients with chronic progressive (CP) multiple sclerosis. Like CP patients, RR patients exhibited deficits on tests of information-processing speed, verbal fluency, and problem solving, and on recall measures of anterograde and remote memory. Although a few patients were mildly dysnomic, the RR patients were not generally impaired on visual confrontation naming and they did not exhibit perseverative responding on verbal fluency measures. The pattern of neuropsychological deficits exhibited by RR patients closely approximates the profile observed in other subcortical dementias and does not contain the features of cortical dementia evident in some CP patients. The impairment of RR patients on cognitive tests were less severe than those observed in CP patients in our previous studies. Differences in the age of patients in the CP and RR groups did not account for group differences in the severity of cognitive impairments, but differences in disease duration or severity of disability, as well as disease course, could explain why CP patients exhibit more serious cognitive disturbances than RR patients.     

The extra work of breathing through adult endotracheal tubes

A sinusoidal flow generator was connected to adult endotracheal tubes of sizes 5-10 and was used to simulate human ventilation. Measurement of the changes in pressure and flow allowed calculation of the work imposed on breathing by endotracheal tubes. The work of breathing increased with increasing ventilatory rate, tidal volume, and decreasing tube diameter. We discuss the suggestion that the work imposed on breathing by an endotracheal tube is a more appropriate unit for comparison than resistance to air flow.     

Performance of children with ADHD on tests sensitive to frontal lobe dysfunction

The performances of 20 children with attention deficit hyperactivity disorder (ADHD) were compared with those of 20 matched normal controls on a battery of neuropsychological tests. The ADHD children exhibited impaired function in reading comprehension, verbal learning and memory, and on the Information, Arithmetic, Digit Span, Block Design, and Coding subtests of the Wechsler Intelligence Scale for Children-Revised, but they performed nearly normally on measures of verbal and design fluency and on the Wisconsin Card Sorting Test. The hypothesis that disturbances in frontal lobe function related to impulse control may be responsible for the cognitive impairments observed in ADHD was not supported. Inability to control and direct attention appears to be more central to the pathophysiology of this disorder.