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Biomedical subjects

R Weaver

Publications and source records attributed to R Weaver.

At least 37 records · Page 2Linked to original sources

Possible mechanism for seeding of tumor during radical prostatectomy.

Prostatic adenocarcinoma sometimes recurs locally in the operative bed after radical prostatectomy. Having observed local recurrence in several patients who had a small tumor confined to the prostate on whole mount serial sections, we postulated that some instances of local recurrence could arise from malignant cells shed in prostatic secretions expressed during surgery. To evaluate whether prostatic secretions contain malignant cells and to estimate the frequency of this phenomenon, we collected fresh prostatic secretions from radical prostatectomy specimens immediately after removal. The secretions were analyzed by cytology for the presence of malignant cells. Of 76 samples collected from consecutive patients with clinical stages T1 and T2 prostate cancer at 3 institutions 11 (14%) contained malignant cells. Positive cytology results were most frequent in patients with poorly differentiated tumors. Of 11 cancers with a Gleason sum of 8 to 10 in the prostatectomy specimen 6 (55%) had a positive cytology result. However, of 63 tumors with a Gleason sum of 5 to 7 only 4 (6%) were positive (p < 0.0001). There was no significant correlation with either clinical or pathological stage of the tumor in this small series. Our findings suggest that malignant cells shed during prostatectomy may seed the surgical bed and could be responsible for some instances of local tumor recurrence. The rate of positive cytology results in our study is similar to the local recurrence rates reported in the literature. Surgeons should make prudent attempts to avoid seeding from this source.

Adenocarcinoma↗

Practice characteristics of graduates of postdoctoral general dentistry programs.

A mail questionnaire was sent to 900 dentists who completed a Postdoctoral General Dentistry (PGD) program in 1985 and 900 dentists who graduated from dental school in 1985 but did not participate in a PGD program. The response rate was 57 percent. Three-quarters of the PGD graduates trained in civilian programs with the remainder being equally divided between military and Veterans Administration (VA) programs. Graduates of military programs continued to be employed by the military five years after graduation in contrast to the VA where less than 2 percent of graduates were employed after five years. The percent of dentists who are specialists or are enrolled in specialty programs five years after graduation was approximately 13 percent and the rates were similar for PGD and non-PGD dentists. The patterns of care in private practice tended to be similar for both groups; however, in institutions GPR graduates provided more treatment for special care patients and patients who were economically disadvantaged. GPR graduates also were more involved in teaching and in hospital activities.

Community Health Centers↗

Early detection of prostate cancer.

Prostate cancer is unique among the potentially lethal human malignancies in the wide discrepancy between the high prevalence of histologic changes recognizable as cancer and the much lower prevalence of the clinical disease. Despite the availability of effective tests for early detection and of effective treatment for cancers so detected, the diagnosis usually is not established until the tumor is locally advanced or metastatic. Yet, physicians hesitate to use these tests for fear that many cancers found would be latent, of little threat to the life or health of the host, and treatment could introduce inappropriate morbidity. Latent or "clinically unimportant" cancers can be distinguished from those that are clinically important by the larger volume, higher grade, and greater invasiveness of the latter. The available tests can detect only those cancers large enough to be palpable, visible on ultrasound, or capable of elevating the serum level of prostate-specific antigen. Such cancers are clinically important and should be treated for cure if the life expectancy of the patient is sufficiently long and the morbidity rate of therapy is low. Early detection of prostate cancer using the tests that are available today may widen the window of opportunity so that treatment indeed becomes possible in those for whom it is necessary.

Antigens, Neoplasm↗

Software for analysis and manipulation of genetic linkage data.

We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.

Alleles↗

Meningococcal disease in the United States--1986. Meningococcal Disease Study Group.

Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons. The incidence of meningococcal disease was 1.3:10(5). The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5). Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease. Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma. Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N. meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there.

Adolescent↗

Analysis of clinical and food-borne isolates of Listeria monocytogenes in the United States by multilocus enzyme electrophoresis and application of the method to epidemiologic investigations.

To investigate the microbiology and epidemiology of the 1,700 sporadic cases of listeriosis that occur annually in the United States, we developed a multilocus enzyme electrophoresis (MEE) typing system for Listeria monocytogenes. We studied 390 isolates by MEE. Eighty-two electrophoretic types (ETs) were defined. Two distinct clusters of ETs, ET group A (ETGA) and ET group B (ETGB), separated at a genetic distance of 0.440, were identified. Strains of ETGB were associated with perinatal listeriosis (P = 0.03). All strains of H antigen type a were in ETGA, while all strains of H antigen type b were in ETGB. Among 328 clinical isolates from cases of literiosis, 55 ETs of L. monocytogenes were defined. Thirty-four ETs were identified among 62 isolates from food products. The mean number of strains per ET (5.2) was significantly higher among clinical isolates than among food-borne isolates. Examination of isolates from outbreaks further documented the link between cases and contaminated food products. In one investigation, we found 11 different ETs, ruling out a single common source as a cause of that outbreak. By examining a large number of isolates collected over a specified time in diverse geographic locations in the United States, we have begun to establish a baseline for the study of the epidemiology of listeriosis by MEE.

Bacterial Typing Techniques↗

Periodic alternating oscillopsia: a symptom of alternating nystagmus abolished by baclofen.

We describe an unusual patient with periodic alternating oscillopsia caused by periodic alternating nystagmus. A dramatic cessation of her symptomatology and disappearance of periodic alternating nystagmus was achieved with baclofen and has been maintained for a period of over nine months. The importance of proper diagnosis and therapy of patients with oscillopsia is described.

Baclofen↗

When headaches are good.

Occasionally patients with headache present with the complaint of "a really good one." This paper examines three cases of patients with migraine who often referred to their headaches as "good." When the patients were asked what made the headaches good, they immediately tried to clarify their terminology as "just a figure of speech" that really meant bad. Further exploration usually revealed the headache symptoms had indeed been "good" in a relative sense, in that it had somehow served to help the patient avoid a more unpleasant emotional situation. The headache may have allowed a "time out" or a forced period of rest in a hectic schedule, resolved a conflict for the patient in an acceptable way by becoming sick, or represented a suppressed or repressed affect, usually anger. When headaches are described as good, there may very well be something in the patient's life that is worse.

Adult↗

St. Anthony's fire: a medieval disease in modern times: case history.

Ergot intoxication is a syndrome recognized in the Middle Ages that was due to the effects of intense vasoconstriction upon the extremities. The authors present a patient with self-induced ergotamine poisoning who presented with vasospasm of the right lower extremity and had historical evidence suggestive of vasoconstriction involving other vascular systems. Excess ergot effect should be considered in the differential diagnosis of vascular insufficiency.

Drug Overdose↗

Spontaneous gallbladder perforation.

Acute gallbladder perforation is an infrequent, although not uncommon, complication of cholecystitis. It is rarely diagnosed preoperatively and the delay in making the definitive diagnosis usually accounts for the increased incidence of morbidity and mortality associated with this complication. A case of a 92-year-old patient in whom acute gallbladder perforation was suspected peroperatively at ultrasonography of the abdomen and confirmed by technetium-99m disofenin radionuclide biliary scan is reported.

Aged↗

Surveillance of listeriosis in Los Angeles County, 1985-1986. A first year's report.

After a large food-borne outbreak of listeriosis in Los Angeles County, California, in 1985, the California State Department of Health Services instituted mandatory reporting of Listeria monocytogenes by clinical laboratories. From September 1, 1985, through August 31, 1986, 94 cases of listeriosis were reported in Los Angeles County for an annual crude incidence rate of 12 cases per million persons. Of the 94 cases, 37 (39%) were in neonates and/or their mothers and 57 (61%) were nonperinatal. The overall case fatality rate was 31%, with a perinatal case fatality of 16% (6 fetal and 23 nonperinatal); this compares with an epidemic perinatal case fatality rate of 32%. No significant differences were observed in age-adjusted, race-specific incidence rates among nonperinatal cases or race-specific incidence rates among perinatal cases. All but 2 of the nonperinatal patients had a known predisposing risk factor for the development of listeriosis, the most common of which was a prior history of steroid therapy. A clustering of cases was not identified. No common food sources were apparent. Patients presenting as perinatal cases were more likely to have ingested Mexican-style cheese, ice cream, and yogurt than those presenting as nonperinatal cases. Improved case ascertainment through mandatory reporting and laboratory-based surveillance will establish meaningful baseline levels of listeriosis.

Adolescent↗

Epidemic listeriosis associated with Mexican-style cheese.

In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.

Adult↗

Valproic acid efficacy, toxicity, and pharmacokinetics in neonates with intractable seizures.

Six neonates with prolonged, intractable seizures were treated with valproic acid (VPA). Each patient had received maximum doses of phenobarbital (greater than 40 micrograms/ml), and five patients received at least two additional anticonvulsants, without success. Seizure activity was controlled in five of six (83%) cases. In four cases, all other anticonvulsants could be withdrawn, and seizures were controlled on VPA monotherapy. VPA was discontinued in three patients because of VPA-induced hyperammonemia. VPA pharmacokinetic measurements were as follows: for total VPA, volume of distribution (V) = 0.40 l/kg (range, 0.36 to 0.47 l/kg), serum clearance (Cl) = 14.4 ml/h/kg (5.5 to 18.2 ml/h/kg), half-life (T1/2) = 26.4 hours (8.6 to 48.5); for unbound VPA, V = 2.02 l/kg (1.14 to 2.44 l/kg), Cl = 108.9 ml/h/kg (42.0 to 252.0 ml/h/kg). T1/2 = 17.6 hours (6.7 to 34.2). VPA free fraction ranged from 11.3 to 31.6% (mean, 19.2%).

Absorption↗

Diphtheria in the United States, 1971-81.

After a decade-long resurgence, including a large cutaneous diphtheria outbreak in Washington State, the diphtheria incidence rate in the United States reached its lowest recorded level ever in 1980--two patients (0.01 case per million). Mortality paralleled the decline in incidence rate. Only 143 of the 3,141 US counties reported noncutaneous diphtheria patients during 1971-81; most were located in the West. The highest attack rates were experienced by children less than 15 years old (0.8 case per million) and by American Indians (22.6 cases per million). Persons immunized with three or more doses of diphtheria toxoid had a lower death-to-case ratio (1.3 per cent) than totally unimmunized persons (13.4 per cent). The reasons for the dramatic decline in diphtheria incidence rates are unclear, although it has been postulated that the gene for producing diphtheria toxin may be lost from organisms in highly immunized populations. Significant proportions of the adult and elderly populations are susceptible to diphtheria. Continuation of primary immunization with increased emphasis on the routine use of tetanus and diphtheria toxoids (Td) boosters in adults should ensure that diphtheria will remain largely a scourge of the past.

Adolescent↗

Metabolism of 2-acetylaminofluorene by two 3-methylcholanthrene-inducible forms of rat liver cytochrome P-450.

The present study examines the contribution of two major 3-methylcholanthrene (3-MC)-inducible forms of rat liver cytochrome P-450 (P-448MC and P-448HCB) to the metabolism of 2-acetylaminofluorene (AAF). In a reconstituted enzyme system, purified rat liver P-448MC metabolized AAF at a 10-fold greater rate than P-448HCB. The major metabolites produced by cytochrome P-448MC were 3-hydroxy (OH) (30%), 5-OH (24%), 7-OH (22%), and 9-OH (10%). N-OH-AAF (3%) was a minor metabolite. In contrast, P-448HCB catalyzed the N-hydroxylation of AAF preferentially (15% of total metabolites). The other primary metabolites formed by this isozyme were 7-OH-AAF (30%), 5-OH-AAF (29%), and 9-OH-AAF (25%). Cytochrome P-448HCB catalyzed the formation of less 3-OH-AAF (7%) than did P-448MC (30%). Since cytochrome P-448HCB is immunochemically related to P-448MC, specific antisera to both isozymes were made by immunoabsorption with the appropriate antigen bound covalently to Sepharose. Anti-P-448MC inhibited AAF metabolism approximately 43% in microsomes from 3-MC-induced male rats and 30% in microsomes from rats treated with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), another 3-MC-type inducer. Anti-P-448HCB inhibited total metabolism of AAF by only 22 and 38% in microsomes from 3-MC- and HCB-induced rats. However, anti-P-448HCB inhibited N-hydroxylation by 60% in both 3-MC- and HCB-induced microsomes. Anti-P-448MC did not inhibit N-hydroxylation. Neither antibody affected AAF metabolism in control microsomes. These data suggest that, in rat liver, two 3-MC-inducible izozymes of cytochrome P-450 metabolize AAF; however, N-hydroxylation is catalyzed primarily by one of these isozymes, cytochrome P-448HCB.

2-Acetylaminofluorene↗