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1. Isolated radular protractor muscles (RPM) of Busycon canaliculatum show a complex response to potassium-free solution. 2. While exposed to a bathing solution lacking K+, the RPM begins to respond with a hyperpolarizing phase. Within minutes, this gives way to a depolarizing phase (DP). After readmission of a bathing solution containing K+, there is an extra hyperpolarizing phase. 3. Acetylcholine over a range of concentrations from 10(-8)M to 10(-3)M progressively enhances the DP. 4. The action of acetylcholine is sodium dependent.

Activated T cells not only secrete interleukin-2 (IL-2) and express cell surface interleukin 2 receptor alpha (IL-2R alpha), but also shed IL-2R alpha. This soluble receptor is a truncated form of the membrane-bound p55 receptor with a similar binding affinity. It has been proposed that soluble IL-2R alpha (sIL-2R alpha) could negatively modulate local immune response. High levels of sIL-2R alpha have been found in the serum and ascites of ovarian cancer patients. The purpose of this investigation is to determine the amount of in vitro T cell inhibition seen in ovarian cancer ascites that is attributable to high levels of sIL-2R alpha. Purified sIL-2R alpha at levels up to 100,000 pg/ml was placed in lymphocyte proliferation assays. Soluble IL-2R alpha was removed from the ascites of three patients with advanced ovarian cancer. Lymphocyte proliferation assays utilizing phytohemaglutin (PHA) stimulation were carried out with this ascites. Untreated ascites from each patient served as control. Addition of purified sIL-2R alpha to lymphocyte proliferation assays failed to demonstrate significant lymphocyte suppression. Addition of ascites to the lymphocyte assays resulted in up to an 80% decrease in lymphocyte proliferation. Neutralization of ascites sIL-2R alpha as well as removal of sIL-2R alpha via a protein G column failed to reverse any of the observed lymphocyte suppression. We conclude that although sIL2R alpha is elevated in ascites of patients with ovarian cancer, it does not account for the profound ascites-induced T cell suppression observed in vitro.

Purpose: Privacy is of utmost concern to adolescents seeking advice regarding life-style and behavior choices. Lack of privacy and confidential health services are barriers to adolescents' access to health care. This study describes primary care physicians' practices with regard to inviting parent(s) to leave the room in order to interview the teen alone, and the factors associated with use of this technique., Method: A cross-sectional random survey of 1,630 pediatricians, internists, and family practitioners in a large metropolitan area was performed using a confidential mailed questionnaire., Results: The majority of the physicians were in private practice, male, board certified, Caucasian, and did not have a subspecialty. Forty-nine percent of the respondents "almost always" or "always" invite parent(s) to leave the room in order to interview the teen alone. Physicians who were female, board certified, and completed residency from 1974-94 were most likely to use this technique. Among physicians who frequently employ this strategy, the decision to interview the teen alone varied according to the clinical scenario. Using logistic regression analysis, only gender and board certification were significantly related to use of this interviewing method., Conclusion: A large proportion of physicians do not interview their adolescent patients alone, therefore, not affording them privacy to discuss confidential health concerns. Future research should focus on developing and validating methods to teach physicians skills to interview adolescents privately.

Births while on public assistance has been one of the central topics in the welfare debate in Maryland because the welfare grant increases with the number of children, and there is debate about whether or not to continue the increased income provision. Based on the Quality Control (QC) data for the period from July 1991 to June 1992, this study examined differentials in the incidence of births conceived and borne while the mothers were on welfare. The results indicate that about one-quarter of recipient children were born on welfare and that higher incidences of these births occur among mothers with less than high-school education, never-married, young, Baltimore residents, and with fewer children at entry on welfare. The presence of parents of welfare mothers or of any adults in the household is found to reduce the incidence of births. Disallowance of the increased welfare grant for additional children may increase the number of families in poverty and the number of children in foster care unless efforts are made to reduce unintentional births and school drop-outs and to fill the gap between mothers' schooling and the needs of the job market.

The basal metabolic rate (BMR), which accounts for 50-70% of total energy expenditure, is essential for estimation of patient and population energy needs. Numerous equations have been formulated for prediction of human BMR. Most equations in current use are based on measurements of Caucasians performed more than four decades ago. We evaluated 10 prediction equations commonly used for estimation of BMR in 76 Caucasian and 42 African-American girls between 8 and 17 yr of age against BMR measured by whole-body calorimetry. The majority of the prediction equations (9 of 10) overestimated BMR by 60 +/- 46 kcal/day (range, 15-176 kcal/day). This overestimation was found to be significantly greater (P < 0.05) for African-American (77 +/- 17 kcal/day) than for Caucasians (25 +/- 17 kcal/day) in six equations, controlling for age, weight, and sexual maturity. We conclude that ethnicity is an important factor in estimation of the BMR and that the current prediction equations are not appropriate for accurate estimation of the BMR of individual female children and adolescents.

1. The mean resting potential of 22 atrial preparations of Busycon heart was 42.5 mV, examined by the sucrose gap technique. Spontaneous action potentials of 8-18 mV amplitude occurred in repeated cycles of burst activity, generating burst patterned phasic contractile activity. 2. Isolated ventricles showed slow (1-3 beats min-1) constant myogenic contractile activity, suggesting that the primary driving pacemaker may reside in the atrium. 3. The atrial electrocardiogram commenced with a small prepotential leading to a plateau-like phase and terminated with a sharp spike potential. 4. Acetylcholine (ACh) at high concentrations depolarised the atrium by 5-8 mV and induced strong tonic contractures while suppressing spontaneous action potentials, suggesting an overall inhibitory role in downregulating cardiac intrinsic myogenic rhythms. 5. Serotonin (5-hydroxytryptamine, 5HT) was consistently excitatory, enhancing both action potential amplitude and rhythmic contractions by up to 50% at concentrations of 5 x 10(-7) to 10(-5)M. Neither methysergide nor metoclopramide affected atrial responses to 5HT and the 5HT1 antagonist metitipine simply increased action potential discharge in the rhythmic cycle. The vertebrate 5HT1-3 receptor classification is inappropriate to this molluscan preparation. 6. The atrium was very sensitive to the tetrapeptides FMRF- and FLRFamide, but the enhanced phasic contractions were not accompanied by alteration of resting potential or action potential amplitude, suggestive of neuromodulatory upregulation involving a secondary messenger. The related peptide SCP-B was without effect on the preparation, but GAPFLRFamide was excitatory, although much less so than FMRF- and FLRFamide. 7. Neither adenosine and ATP nor guanosine and GTP affected intrinsic atrial electrical or mechanical activity, suggesting that there was no noncholinergic, nonaminergic element to cardiac neuromodulation in this species. Only ACh, 5HT and FMRF/FLRFamide could be assigned clear roles in this respect.

1. Calcium-free media usually caused a cessation of all electrical and mechanical activity of the Busycon atrium. Where any electrical activity survived, the action potential consisted of a pre- and plateau-like potential devoid of the usual terminal spike. 2. High Ca salines induced tonic force, membrane depolarization and reduction in generation of spontaneous action potentials. The Ca ionophore A23187 enhanced contractions and the SR CaATPase inhibitor cyclopiazonic acid induced slight depolarization, tonic contractures and increased action potential firing. 3. The inorganic Ca antagonist Co2+ was without effect on the preparations, although the lanthanide Gd3+ inhibited contractions and spontaneous action potentials as well as inducing membrane potential depolarization. 4. The organic Ca entry-blocker nifedipine enhanced both spontaneous action potential amplitude and the phasic contractions they generated. 5. High K salines considerably depolarized atrial preparations with accompanying large tonic contractures and suppression of action potentials. The K channel-blocker 4AP enhanced action potential amplitude with slight increase in contractions, and TEA depolarized the atrium, and enhanced action potentials and rhythmic contractions. 6. Sodium-free salines strongly hyperpolarized atrial preparations and abolished spontaneous action potentials and, on washout, the membrane potential became temporarily unstable. In 2 preparations, low chloride and chloride-free media induced significant membrane potential hyperpolarization. 7. It is concluded that, in the atrium, the resting membrane potential is largely determined by the transmembrane K gradient, but with significant conductances to Na and Cl though probably not Ca. The action potential spike appears to be a Ca-dependent event and the plateau-like phase may be a Na-dependent event.

1. Isolated cannulated ventricles commenced spontaneous beating on application of perfusion pressure of 10 cm water. Complete hearts showed a fast patterned cyclical rhythm, whereas ventricles devoid of atrial material showed a continuous slow rhythm. 2. Perfused ventricles were inhibited by ACh with a threshold at 10(-8) mol l-1 and arrested at 10(-7) mol l-1, and ventricles under stimulation by 5HT could be arrested by ACh at this concentration. 3. Perfused ventricles were stimulated by 5HT, with threshold at 10(-9) mol l-1 and maximum at 10(-5) mol l-1. Metoclopramide was without affect on 5HT responses, but metitipine and methysergide did inhibit such responses suggesting that the 5HT receptor present possessed mixed properties of the vertebrate 5-HT1 and 5-HT2 receptor subtypes. 4. Ventricles were very sensitive to the excitatory actions of FMRFamide in the 10(-9) to 10(-5) mol l-1 range. Preparations were insensitive to GAPFLRFamide, but SCP-B was modestly excitatory (threshold 10(-7) mol l-1). 5. Preparations were not significantly affected by adenosine, ATP, and guanosine, but GTP was strongly excitatory at 10(-7) mol l-1. 6. 5HT and FMRFamide responses were additive. Preparations responded strongly to the adenylate cyclase activator forskolin and dibutyryl cAMP enhanced spontaneous contractions and 5HT responses, suggesting that the 5HT receptor may operate via a cAMP secondary mechanism. 7. The IP3 inhibitor lithium (10 mmol l-1), caused slight inhibition of FMRFamide responses, suggesting that the receptor to this peptide may operate via IP3 as a second messenger. 8. Neuromodulation in this preparation would appear to involve ACh as inhibitor, 5HT and FMRFamide as upregulators, with no clear roles for FMRFamide-related peptides and GTP.

A synthetic gene of 237 bases encoding the 77-residue acyl carrier protein (ACP) from Escherichia coli, along with two mutant genes, ACP-I54V and ACP-A59V, were subcloned into the pET11a-pLysS E. coli overexpression system under the control of the bacteriophage T7 promoter. This efficient expression system and a simplified purification protocol yielded more than 120 mg/l of pure protein. The construct produced a mixture of holo-ACP and apo-ACP and two HPLC procedures were developed to separate the two species. This overexpression system allows cost-effective growths of 13C- and 15N-labeled protein for structural and other studies on ACP. In the course of the work on the mutants of ACP, an apparent homologous recombination event led, in one case, to reversion to a wild-type protein, suggesting that precautions to prevent such reversion should be taken.

The acyl carrier protein (ACP) of Escherichia coli is a 77-amino acid, highly negatively charged three-helix protein that plays a central role in fatty acid biosynthesis. Previous NMR studies have suggested the presence of multiple conformations and marginally stable secondary structural elements. The stability of these elements is now examined by monitoring amide exchange in apo-ACP using NMR-based methods. Because ACP exhibits many rapid exchange rates, application of traditional isotope exchange methods is difficult. In one approach, heteronuclear correlation experiments with pulsed field-gradient coherence selection have reduced the time needed to collect two-dimensional 1H-15N correlation spectra to the point where measurement of exchange of amide protons for deuterium on the timescale of minutes can be made. In another approach, water proton selective inversion-exchange experiments were performed to estimate the exchange rates of protons exchanging on timescales of less than a second. Backbone amide protons in the region of helix II were found to exchange significantly more rapidly than those in helices I and III, consistent with earlier structural models suggesting a dynamic disruption of the second helix. Highly protected amides occur on faces of the helices that may pack into a hydrophobic core present in a partially disrupted state.

We report the 1H and 15N chemical shift assignments along with an NMR-derived preliminary structure for DnaJ(1-78), a highly conserved N-terminal domain of DnaJ, the Escherichia coli Hsp40 homolog. This 9 kDa domain is believed to cooperate with DnaK, the E. coli Hsp70 homolog, in regulating a variety of cellular functions. Heteronuclear 3D NMR experiments were carried out on a uniformly 15N-labeled DnaJ(1-78), which is a stable, folded fragment. Standard 15N-edited NMR techniques afforded complete assignment of the backbone amide 1H and 15N pairs and partial assignment of the side-chain 1H and 15N atoms. The secondary structure of DnaJ(1-78) was determined from NOE connectivities obtained from 3D 15N-separated and 2D homonuclear NOESY spectra as well as 3JHNH alpha coupling constants obtained from a DQF-COSY spectrum and a 15N-edited HNHA experiment. The stability of secondary structural elements was assessed by monitoring amide exchange rates, and a model for the three-dimensional fold of these elements was derived from a set of long-range contacts extracted from homonuclear 2D NOESY experiments. The analysis indicates that DnaJ(1-78) is comprised of four alpha-helices and no beta-sheet with a short unstructured loop between antiparallel helices II and III. The shorter N-terminal and C-terminal helices make contacts with helices II and III at points well removed from the central loop. A discussion of how this preliminary structural model may explain mutation data from other laboratories is presented.

We have shown previously that certain alkylation products, or alkylation derived lesions, which induce chromosome aberrations (abs) persist for at least two cell cycles in Chinese hamster ovary cells. The increase in abs in the second cycle after treatment contrasts with the classical observation of reduction in ab yield with successive mitoses following ionizing radiation. Here we present evidence that processing of lesions by mismatch repair is a mechanism for ab induction by methylating agents. Our previous studies implicated O6-methylguanine (O6MeG) as an important lesion in induction of abs, particularly in the second cell cycle after treatment. In the absence of repair of O6MeG by alkylguanine DNA alkyltransferase (AGT), new abs were induced in the second cycle after treatment with e.g. methylnitronitrosoguanidine (MNNG) and methylnitrosourea (MNU). Thus, we hypothesized that abs were produced not by O6MeG or its repair in the first S phase, but by subsequent processing of the lesions. We suggested that after replication proceeded past the O6MeG lesion in the first S phase, inserting an incorrect base on the newly synthesized strand, recognition and repair by mismatch repair in the second S phase led to a chromosome ab. Here we used MT1 cells, a human lymphoblastoid cell line that has a defect in strand-specific mismatch repair. MT1 cells are alkylation tolerant and have a mutator phenotype, compared with their parent line, TK6; both MT1 and TK6 cells lack AGT so do not remove the methyl group from O6MeG. While the initial levels of abs at the first metaphase were similar in MT1 and TK6 cells, ab levels in MT1 cells were greatly reduced in the second and third cell cycles following treatment with MNNG, dimethylnitrosamine and MNU, in contrast with the parent TK6 cells, which had more abs in the second cell cycle than in the first. This supports the hypothesis that repair of mismatched base pairs involving O6MeG is one mechanism for induction of chromosome abs. In contrast to the difference in response to methylating agents between TK6 cells and mismatch repair-deficient MT1 cells, the profile of ab induction by an ethylating agent, ethylnitronitrosourea, was similar in MT1 cells to those for TK6 cells and CHO cells.

All unexpected deaths in New Mexico from 1977 to 1988 were reviewed. By statute each such death must be reported to the Office of the Medical Examiner (OMI) and according to institutional policy autopsied even when death is presumed to be from natural causes. From this group the 650 index cases that form the basis of this report were obtained. The crude rate of sudden, unexpected death among New Mexico residents 5 to 39 years old during the study period was 6.6/100,000 persons at risk. As documented by autopsy, the underlying cause of death in a majority of these cases (53.4%) was related to cardiovascular disease and alcoholism. Male persons in general are at increased risk for sudden, unexpected death, and American Indian and black male persons are at greater risk than their Anglo and Hispanic counterparts. American Indians account for a disproportionate share of the unexpected deaths resulting from alcoholism, and black male persons are at particular risk for unexpected death resulting from cardiovascular diseases. This report emphasizes the importance of life style and diet in the well-being of persons 5 to 39 years old.

Haemophilus influenzae type b, Escherichia coli, Neisseria meningitis, Streptococcus agalactiae, and Streptococcus pneumoniae are classically the predominant meningeal pathogens of children. The Directigen latex agglutination test identifies these pathogens by detecting specific antigens in cerebrospinal fluid (CSF) and urine. The authors tested 1151 specimens from 791 children with suspected meningeal infections. They found that the sensitivity of the Directigen test for detecting the five classic CSF pathogens of children was 83.3% with CSF and 60% with urine specimens. In detecting all pathogens, however, the sensitivity was only 50% with CSF and 37.5% with urine. Thus, an increased prevalence of nonclassic pathogens in a pediatric population adversely affects the efficacy of the Directigen test for confirming a diagnosis of meningitis and emphasizes the diagnostic importance of the clinical history and other routine CSF tests.

Three commercial identification systems were evaluated as tools for biotyping coagulase-negative staphylococci. Emphasis was placed on the reproducibility of component tests and not on the ability of these kits to identify these bacteria accurately. Forty-seven clinical and reference strains of Staphylococcus were tested in duplicate with each system. The Staph-Ident profile of test results changed for 20 strains on repeat testing, the Staph-Trac profile changed for 10 strains, and the Vitek GPI profile changed for 14 strains. The component tests of each system that were responsible for these profile changes were identified.

RU486, a synthetic steroid receptor antagonist, has strong antiprogesterone and antiglucocorticoid properties. Chronic RU486 administration in two patients with ectopic secretion of adrenocorticotropin (ACTH) has been associated with decreasing plasma cortisol concentrations. One explanation of this finding is that RU486 may directly inhibit adrenal steroidogenesis. To test this hypothesis, we measured the effect of RU486 on specific steroidogenic enzymatic steps using an in vivo rat and an in vitro monkey model. Hypophysectomized-castrated-ACTH-replaced Sprague-Dawley rats were given RU486 i.p. at daily doses of 0, 0.0005, 0.005, 0.05, 0.5 and 5 mg/kg body weight per day for 7 days. The animals were sacrificed, and blood and adrenal glands collected. Adrenal cortical mitochondria and microsomes were purified from the rats and from two untreated Cynomolgus macaque monkeys. Specific steroidogenic enzyme activities were measured in the rat by the incorporation of 14C-labeled steroid substrates into products. A similar protocol was used to assay the steroidogenesis in the monkey adrenal fractions in the presence and absence of added RU486. Although rat adrenal weights decreased significantly at the highest RU486 dose, plasma levels of corticosterone were similar in control and treated rats. Rat adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase (3-HSD), 21-hydroxylase (21-OH) and 11-hydroxylase (11-OH) activities decreased with increasing RU486 doses, with 21-OH and 11-OH being most severely affected. Monkey adrenal 3-HSD, 21-OH, 11-OH, 17-hydroxylase and 17,20-desmolase similarly decreased in the presence of increasing in vitro concentrations of RU486.(ABSTRACT TRUNCATED AT 250 WORDS)

Once a cornerstone of medical education and medical practice, the autopsy has fallen into disuse and disregard in many circles in the USA. In this review of the autopsy today in the United States of America, I explore some of the values that should be exploited through autopsy study, the actual status of autopsy performance, and some of the initiatives that are being taken to counteract this trend.

A program for quality assessment of medical diagnostics is proposed, based on detailed, ongoing comparison of clinical diagnoses with autopsy diagnoses. The model requires that the autopsy service itself be subjected to quality control to assure the reliability of the autopsy findings, including the quality of diagnoses made postmortem, and the quality of autopsy reports. Discrepancies between premortem and postmortem diagnoses are classified as to cause and magnitude; for each disease, the total diagnostic experience is collected, and sensitivity and specificity of clinical diagnostics are computed. These are compared with control ranges of sensitivity and specificity, prospectively arrived at through analysis of thousands of cases. Statistically acceptable sampling for autopsy, and review of findings by an independent body are also discussed. The findings generated by this program would be of great value in programs for quality improvement of medical care. The model has the following advantages: (1) it recognises that there is an unavoidable baseline of diagnostic errors; (2) the control levels, based on current medical practice, are prospectively established; (3) it avoids placing blame in a single case; and (4) it provides a fairly high power scrutiny that can focus on diagnostics for single diseases rather than the entire spectrum of medical practice.

The study, which is based on data from a household level health survey conducted in 1990 in Freetown, Sierra Leone, examines the coverage of an Expanded Program on Immunization (EPI), infant mortality, and infant morbidity among children in Greater Freetown, capital of Sierra Leone. The results of the study indicate that there was a decline in infant mortality in the recent period of the survey, 1988-89, compared to earlier periods. This decline seemed to have been the result of immunization coverage, which considerably increased by 1989-90, reaching above 70% of the children under age 5. The study further reveals that the increased immunization coverage of children and their mothers might have considerably reduced the incidence of tetanus. While reduction of tetanus might have played the leading role in the latest reduction in infant mortality, the incidence of diarrhea, measles, and malaria continued to be high, suggesting that the increase in the quality and quantity of basic immunizations, oral therapy for diarrheal disease, and provision of chloroquine and improved drugs for malaria disease could further reduce most of the deaths from these prevailing diseases among children under age 5.

Tissue cultures of tumor cells are frequently utilized to characterize chromosomal changes when direct cytogenetic preparations on tumors fail. The present study demonstrates that chromosomal markers found in direct tumor preparations can become undetectable in cell culture at variable rates presumably because of overgrowth of normal cell components in the culture. Injection of cultured tumor cells into nude mice followed by direct chromosomal preparations on the resulting nude mouse tumors can be used to select cells with the original tumor karyotype. This is true even when the tumor cell frequency in the culture is so low that they are not found in routine chromosomal preparations of the cultured cells. This technique can thus complement tissue culture findings and provide additional useful information about the original karyotype in cases where direct chromosomal preparations from tumors have failed.

Autopsy practice today remains rooted in the fabric of medicine as it developed through the 18th and 19th centuries. Recent developments in medicine and society have left autopsy practice behind and have led to the decline of the autopsy. Potential new values of autopsies point strongly to the need for revitalized modern autopsy services, services focused on objectives and problems related to patients, their physicians, and the attendant societal issues. There are real values for pathology and pathologists, but only if major realignments in purposes and outcomes are forthcoming.

A nonradioactive, biotinylated herpes simplex virus (HSV) DNA probe, a shell vial (rabbit kidney cell) culture assay enhanced by a direct fluorescent (HSV monoclonal)-antibody stain at 16 to 20 h postinoculation, and conventional tube cultures with confirmation via HSV-specific (polyclonal antibody) immunoperoxidase assay were compared for 199 specimens. The predictive values of the positive results were 54.5% for the probe, 95.9% for the shell vial assay, and 100% for the conventional culture methods, while the predictive values of the negative tests were 68.1, 84.0, and 98.4%, respectively. We conclude that the DNA probe (sensitivity, 24.5%; specificity, 88.3%) and the shell vial assay (sensitivity, 66.2%; specificity, 98.4%) cannot be substituted for conventional tube culture techniques (sensitivity, 97.1%; specificity, 100%) in the routine identification of HSV in our laboratory.

A national meeting of pathology educators in 1989 provided the impetus for an exploration of new uses of autopsy in medical education. A month before the conference, the authors sent a questionnaire about the uses and value of autopsy in medical education to 120 persons registered to attend the conference. They used the 98 responses, representing 69 U.S. and Canadian medical schools, as the basis of a workshop on the place of autopsy in future medical education. The present article is a report of the authors' findings from the questionnaire and workshop. They found that the uses of autopsy go far beyond the traditional uses in teaching clinical pathophysiology, clinico-pathologic correlations, clinical anatomy, gross and microscopic anatomy of disease, and visual skills. Emphasis was placed on the potential role of autopsy in education regarding legal/judicial proceedings, vital statistics, epidemiologic investigations, and public health, and in the understanding of such complex matters as medical fallibility, medical uncertainty, and grief. These purposes were seen as congruent with current societal concerns about the need to reverse the trend toward dehumanization of medicine and physicians. The inability to realize these aims in the face of a precipitous drop in the autopsy rate is discussed.

The use of autopsy in medical practice in the United States has declined drastically over the past 25 years. Physicians conduct post-mortem examinations on less than 12 percent of persons who die in hospitals and on proportionally far fewer people who die at home. Without due assessment of causes of death, pathologists lose opportunities to conduct critical diagnostic exercises, and society fails to obtain accurate health statistics. Medical practitioners, legislators, insurers, and the public should consider diverse features of a national policy for assuring that sufficient numbers of autopsies are competently performed and their findings appropriately employed.

Hepatitis A virus (HAV) infection via the parenteral route is not common. To investigate this further, we obtained the fresh frozen plasma (FFP) component from a unit of whole blood provided by an HAV-infected donor and attempted to quantify and characterize the virus in this material. Despite repeated efforts at culture and cesium banding, HAV was not detected by these methods. However, a hepatitis-A-specific antibody capture assay did demonstrate an occasional HAV-like particle upon electron microscopic analysis of plasma-derived material. We conclude that the quantity of virus present in HAV-contaminated blood or products may be variable and therefore of insufficient numbers as to induce clinically apparent disease in all recipients.

The autopsy has been of great importance in educating students regarding medical uncertainty. The marked decline in the use of the autopsy in medical education and continuing education has contributed significantly to the current discomfort among physicians regarding medical uncertainty and medical errors, which, in turn, has furthered the decline of the autopsy. Inordinate guilt, denial, and other defensive behaviors that many physicians marshall in response to uncertainty and error prevent these individuals from learning from their mistakes. The autopsy experience during medical school, properly utilized, helps students to confront fallibility and sets the stage for later successful management of uncertainty and error.

The current state of death statistics in the United States would constitute a national embarrassment if it were not for the fact that the rest of the world seems to be similarly afflicted. This ubiquity of the issue does not, however, make it any less urgent. The etiology of the problem is multifaceted, and remediation will require a broad approach, designed to reach all of the several involved groups of people. The key to the solution, however, is accurate data on the underlying cause of death and contributory diseases, data generally best available through autopsy. More autopsies, more accurate autopsies, and more attention to proper completion of death certificates are needed.

The autopsy appears to be on the way to assuming an increasingly important role in patient care, continuing education, education of medical students and house staff, research in environmental pathology, and more fundamental aspects of disease. This trend needs to be nurtured. Not only pathologists but all physicians need to plan carefully to utilize autopsies to the fullest possible extent. Interest will continue to grow only if autopsies are performed or are closely supervised by highly motivated and experienced pathologists asking critical questions of current medical, scientific, and social concern. New, imaginative approaches are needed to develop the data necessary to address these questions.

Since the original description of solitary rectal ulcer by Cruveilheir in 1830, about 250 cases have been reported (1). The condition most frequently presents in adults between 30 and 50 years of age. There are very few pediatric case reports and none have come from North America. We report here a 13-year-old boy with solitary rectal ulcer syndrome and a review of the pediatric experience with this rare condition.

The cytodiagnosis of virus infected cells in the urine of immunosuppressed patients is a new and important aspect of exfoliative cytology. A case report is presented which demonstrates the detection of diagnostic viral inclusions in a renal allograft recipient with CID. Diagnostic cells with good cytologic detail are observed using a Cytocentrifuge technique.