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Biomedical subjects

M W Riggs

Publications and source records attributed to M W Riggs.

At least 37 records · Page 2Linked to original sources

Significance of nondiagnostic fine-needle aspiration of the thyroid.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.

Adenoma↗

A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes.

Two mAb, C6B6 and 7D10, each significantly reduced infection of mice by Cryptosporidium parvum and reacted with a 23-kDa glycoprotein (p23) of geographically disperse C. parvum isolates. The antibodies were used to identify plaques in a cDNA library prepared from C. parvum sporozoite mRNA. cDNA insert sequences from positive plaques were determined and used to isolate additional clones encoding p23 coding sequences. A consensus open reading frame of 333 base pairs, encoding 111 amino acids, was identified in this collection of cDNAs. The predicted amino acid sequence contained one N-glycosylation site, but lacked hydrophobic membrane spanning regions. Epitope mapping revealed that mAb 7D10 defines the linear epitope QDKPAD which occurs twice in the C terminal region of the peptide encoded by the ORF. This same C terminal peptide region contains a non-linear epitope bound by mAb C6B6. Serum from mice immunized with synthetic C terminal peptide reacted with sporozoite p23. The occurrence of neutralization-sensitive epitopes encoded by defined regions of the C. parvum genome suggests that recombinant proteins or synthetic peptides containing these epitopes may prove useful for inducing immune responses that diminish infection.

Amino Acid Sequence↗

Evaluation of age-specific normal ranges for prostate-specific antigen.

OBJECTIVES: To compare the traditional normal range (TNR) of 0.0 to 4.0 ng/mL for serum prostate-specific antigen (PSA) to age-specific normal ranges (ASNRs). METHODS: An autopsy series of completely sectioned, clinically benign prostates from 171 consecutive Caucasian men over the age of 40 years was selected. These patients were divided into those having no prostate cancer at autopsy, prostate cancer less than 1 cc in volume, and prostate cancer at least 1 cc in volume. The PSA values of each group were compared using both the TNR and the ASNR. RESULTS: Twenty-three of 105 (21.9%) patients with no cancer had elevated PSA values by the TNR, whereas only 18 (17.1%) were elevated using the ASNR. Nine of 54 (16.7%) with cancer less than 1 cc were elevated using the TNR, and 7 of 54 (13.0%) using the ASNR. Of 12 patients with cancer at least 1 cc, all had elevated PSA levels using the TNR and 11 (91.7%) were elevated using the ASNR. All discrepancies between the TNR and ASNR occurred in the 60- to 79-year age range. CONCLUSIONS: Use of ASNRs appears helpful in increasing the specificity of PSA by eliminating some elevated values in patients in their 60s and 70s.

Adult↗

Neuroaxonal degeneration in sheep grazing Sorghum pastures.

During the fall of 1992, 250 (10%) of 2,500 Rambouilet cross feeder lambs grazing Sorghum bicolor developed neurologic signs including weakness, ataxia, head shaking, knuckling of the fetlocks, inability to rise, and opisthotonos. One hundred fifteen (46%) of the affected lambs died. Twenty of the surviving lambs exhibited residual neurologic signs of ataxia when stressed. At the same time, 275 (25%) of 1,100 ewes grazing a nearby sudex pasture (S. sudanese x S. bicolor) gave birth to lambs that were weak and unable to rise. Newborn lambs exhibited extensor rigidity and opisthotonos when assisted to a standing position. The dystocias that occurred were due to lambs with contracted limbs (arthrogryposis). All affected lambs died or were euthanized. Histologic examination of the brains of 3 feeder lambs and 9 newborn lambs revealed similar microscopic lesions. The predominant change was the presence of focal axonal enlargements (spheroids) in the proximal segments of axons, which were restricted to the nuclei of the medulla, cerebellum, and midbrain. In addition, the spinal cord contained spheroids in the ventral horn gray matter of the 6 newborns examined. Ultrastructurally, the spheroids were composed of aggregates of neurofilaments, mitochondria, vesicular bodies, and dense bodies bounded by a thin myelin sheath. There was mild gliosis in the more severely affected animals of both groups. There was minimal Wallerian degeneration in the white matter adjacent to affected nuclei in the brain and the ventromedial and dorsolateral funiculi of the spinal cord. This is the first detailed report of Sorghum toxicity in sheep.

Animal Feed↗

Bovine antibody against Cryptosporidium parvum elicits a circumsporozoite precipitate-like reaction and has immunotherapeutic effect against persistent cryptosporidiosis in SCID mice.

Control of cryptosporidiosis is currently hampered by the absence of drugs or vaccines proven consistently effective against Cryptosporidium parvum. On the basis of observations that anti-C. parvum antibody has therapeutic effect against cryptosporidiosis, cows were immunized with C. parvum to produce hyperimmune colostral antibody. An antibody-rich fraction was prepared and differentiated from control (nonhyperimmune) antibody by enzyme-linked immunosorbent assay, immunofluorescence assay, immunoelectron microscopy, and in vitro neutralizing titer against DEAE-cellulose-isolated C. parvum sporozoites. Oocyst, purified sporozoite, and merozoite antigens recognized by hyperimmune antibody were defined by Western blot (immunoblot). Hyperimmune antibody recognized antigens common to oocysts, sporozoites, and merozoites, as well as stage-specific antigens. Upon incubation with hyperimmune antibody, sporozoites underwent distinct morphologic changes characterized by progressive formation and eventual release of membranous sporozoite surface antigen-antibody complexes, similar to the malaria circumsporozoite precipitate reaction. The infectivity of sporozoites having undergone this reaction was neutralized. The reaction was minimal or absent on sporozoites incubated with control antibody. To determine therapeutic effect in vivo, persistent C. parvum infection was established in adult severe combined immune-deficient (SCID) mice by oral inoculation with 10(7) oocysts. At 5 weeks postinfection, infected mice were treated for 10 days with hyperimmune or control antibody by inclusion in drinking water and daily gavage. Fecal oocyst shedding and infection scores in the gastrointestinal tract and gall bladder/common bile duct in hyperimmune antibody-treated mice were significantly lower than those in the control antibody-treated mice. Hyperimmune bovine antibody prepared against C. parvum may provide a first-generation therapy for control of cryptosporidiosis. Additionally, the defined antigens can be evaluated as subunit immunogens to produce better-characterized polyclonal antibody for control of cryptosporidiosis or as targets for monoclonal antibody-based immunotherapy.

Animals↗

Computer-aided mammographic screening for spiculated lesions.

PURPOSE: To study the use of a computer vision method as a second reader for the detection of spiculated lesions on screening mammograms. MATERIALS AND METHODS: An algorithmic computer process for the detection of spiculated lesions on digitized screen-film mammograms was applied to 85 four-view clinical cases: 36 cases with cancer proved by means of biopsy and 49 cases with negative findings at examination and follow-up. The computer detections were printed as film with added outlines that indicated the suspected cancers. Four radiologists screened the 85 cases twice, once without and once with the computer reports as ancillary films. RESULTS: The algorithm alone achieved 100% sensitivity, with a specificity of 82%. The computer reports increased the average radiologist sensitivity by 9.7% (P = .005), moving from 80.6% to 90.3%, with no decrease in average specificity. CONCLUSION: The study demonstrated that computer analysis of mammograms can provide a substantial and statistically significant increase in radiologist screening efficacy.

Algorithms↗

Stage at presentation and survival of white and black patients with prostate carcinoma.

BACKGROUND: Black men are known to have a higher incidence and mortality from prostate carcinoma than white men and are more likely to have a more advanced stage or grade of disease diagnosed. METHODS: In a Veterans Administration Medical Center where black and white men have the same eligibility for medical care, the authors reviewed the stage at presentation of 861 consecutive cases of prostate carcinoma diagnosed from 1969-1990. In addition, survival, stratified by race, stage, and grade, was determined on all men in whom prostate cancer was diagnosed from 1969-1985 (525 patients). RESULTS: It was found that 26% of white and 52% of black men with prostate carcinoma presented with Stage D disease. Similar proportions of white and black men with prostate carcinoma presented with Stage D disease between 1969-73 as between 1986-90. The overall survival was poorer for black men because of their higher proportion of Stage D disease, but stratified for grade and stage, survival was similar in both races. CONCLUSIONS: This study suggests that factors other than eligibility for medical care may be responsible for the higher proportion of black men with prostate carcinoma presenting with Stage D prostate carcinoma.

Black or African American↗

Bilateral attachment of the vaginal cuff to iliococcygeus fascia: an effective method of cuff suspension.

OBJECTIVE: The objective of this study was to determine the anatomic success, defined as no persistent or recurrent support defects, of suspension of the vaginal cuff to iliococcygeus fascia. STUDY DESIGN: Forty-two women treated by suspension of the vaginal cuff to iliococcygeus fascia and repair of coexisting pelvic support defects between March 19, 1987, and June 11, 1992, had site-specific analysis of pelvic support performed preoperatively and at consecutive postoperative visits. The findings at the 6-week postoperative visit and subsequent visits were compared for support of the vaginal cuff and additionally for the urethra, bladder, cul-de-sac, and rectum. RESULTS: Two patients (5%) have had recurrence of their cuff prolapse during follow-up, one of whom required further surgery. She also had recurrence of an inguinal hernia that had been repaired at the original surgery. The other patient who had had five previous pelvic procedures developed asymptomatic prolapse of the cuff halfway to the hymen. Six additional patients have had loss of support at other sites in the follow-up period, one of whom had repeat surgery. CONCLUSION: Ninety-five percent of women experienced no persistence or recurrence of cuff prolapse 6 weeks to 5 years after the procedure.

Adult↗

Serum prostate-specific antigen levels in stage A1 prostatic cancer.

Quantitation of serum prostate-specific antigen (PSA) has recently come into widespread use. Controversy exists regarding its usage in screening for carcinoma of the prostate (CAP), based partly on concern that it may detect small foci of CAP that will not cause any significant morbidity or mortality. This study was conducted to evaluate serum PSA levels in stage A1 CAP. The authors identified 143 consecutive men who had PSA levels drawn within 8 weeks of transurethral resection performed for presumed benign prostatic hyperplasia. One hundred twenty-four of these (86.7%) had no cancer, 11 (7.7%) were found to have stage A1 CAP, and eight (5.6%) were found to have CAP beyond stage A1. The mean PSA level in patients with stage A1 CAP was 2.3 ng/mL, and the benign (no cancer) group had a mean PSA level of 3.8 ng/mL. Ten of the 11 patients in the stage A1 group had PSA values less than 4.0 ng/mL. Therefore, it was found that most patients with stage A1 CAP did not have elevated PSA levels. In the authors' experience, elevation of PSA levels caused by CAP is indicative of a tumor burden greater than that found in stage A1 CAP.

Adult↗

Preoperative and postoperative analysis of site-specific pelvic support defects in 81 women treated with sacrospinous ligament suspension and pelvic reconstruction.

OBJECTIVES: The objectives of this study were to identify factors that predict long-term success, defined as the absence of anatomic defects, in women undergoing pelvic reconstruction and to identify which defects most frequently persist or recur. STUDY DESIGN: Eighty-one women treated by sacrospinous ligament suspension and pelvic reconstruction between 1984 and 1990 had site-specific analysis performed preoperatively and at consecutive postoperative visits. The findings at the 6-week postoperative visit and subsequent visits were compared for each of five sites: urethra, bladder, cuff, cul-de-sac, and rectum. RESULTS: The Fisher exact test showed that patients with no support defects at the 6-week visit were less likely to require subsequent repair than patients who had any defect at that visit (p = 0.003). Thirteen patients with subsequent or persistent cystoceles had no bladder repair performed at the time of the study procedure. However, even with repair the bladder was the most likely site for persistence or recurrence. CONCLUSION: Absence of any pelvic support defect at the 6-week postoperative visit is associated with a 3% likelihood that the patient will require subsequent reconstructive surgery within 2 to 5 years. The anterior segment provides the greatest challenge to restoration of normal anatomy.

Adult↗

Ultrasound detection of prostate cancer in postmortem specimens with histological correlation.

Transrectal ultrasound detection of prostatic adenocarcinoma was correlated to 63 histological whole mount step sectioned prostatic specimens harvested from 148 consecutive autopsies at our institutions. No patient had known or palpably suspected prostatic adenocarcinoma on premortem digital rectal examination. Prostate specific antigen (PSA) was assayed in each case from premortem serum samples. Of 19 cancers 6 (32%) were detected by transrectal ultrasound and all were hypoechoic. Of the 13 nondetected cancers 7 were isoechoic, 3 were mixed hypoisoechoic, 2 were hypoechoic and 1 was mixed hyperisoechoic. PSA greater than 4 ng./ml. would have aided in cancer detection by suggesting the need for biopsy or further biopsy in 5 cancers with significant volume, which were missed by transrectal ultrasound. The sensitivity (32%) and specificity (64%) of transrectal ultrasound appear too low for use in clinical screening for prostatic adenocarcinoma. PSA and transrectal ultrasound together appear more effective than sonography alone in prostatic adenocarcinoma detection in this series.

Adenocarcinoma↗

Testosterone deficiency as a risk factor for hip fractures in men: a case-control study.

The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men. The study was a matched case-control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center. The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period, 11 men with a history of hip fractures in the preceding 25 months, and 28 randomly selected age-, race-, and living status-matched control subjects (mean age 73 years). Serum pooled total testosterone (9.2 +/- 5.5 nmol/L vs. 12.8 +/- 5.4 nmol/L; p less than 0.02) and free testosterone (37.9 +/- 18.8 pmol/L vs. 48.4 +/- 20.6 pmol/L; p less than 0.03) were significantly lower in hip fracture vs. control patients. Testosterone deficiency was found in 20 (71%) hip fracture men vs. 9 (32%) of the controls (p = 0.003; odds ratio 5.3). Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results. Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men (p less than 0.001). The conclusion is that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men. Prevention of hip fractures in men may involve early recognition and treatment of testosterone deficiency.

Aged↗

Neutralization-sensitive epitopes are conserved among geographically diverse isolates of Cryptosporidium parvum.

Isolates of Cryptosporidium parvum from New York, Florida, Brazil, Mexico, and Peru were examined for the presence of two sporozoite surface epitopes originally identified in an Iowa isolate by neutralizing monoclonal antibodies (MAbs) 18.44 and 17.41. Immunofluorescence microscopy and immunoblotting demonstrated the presence of both epitopes on all isolates. Incubation of DEAE-cellulose-purified sporozoites of the New York, Florida, Brazil, and Mexico isolates with MAb 18.44 or 17.41 significantly neutralized their infectivity for 4- to 6-day-old BALB/c mice. The results indicate that two neutralization-sensitive epitopes are conserved on geographically diverse C. parvum isolates.

Animals↗

CT-guided needle biopsy of the pancreas: a retrospective analysis of diagnostic accuracy.

The purpose of this study was to evaluate the accuracy of percutaneous needle biopsy of the pancreas and to compare its sensitivity with that of simple computerized tomographic (CT) prediction of malignancy. The records of 41 patients who underwent CT-guided percutaneous needle biopsies of the pancreas during a 4-yr period were reviewed retrospectively. Pre-biopsy CT scans were evaluated independently by two experienced radiologists in a blinded fashion. Needle biopsy yielded a correct diagnosis of cancer (sensitivity) in only 45% of patients ultimately found to have a malignancy, whereas the radiologic interpretation alone correctly predicted cancer in 76% of such patients. The negative predictive value of needle biopsy was no better (43%) than the radiologist's CT interpretation alone. Our findings confirm previous observations that percutaneous needle biopsy is an insensitive method of diagnosing pancreatic cancer. In our experience, needle biopsy proved less accurate than expert radiologic interpretation of CT scans alone.

Adenocarcinoma↗

Complete blood count indices in colorectal carcinoma.

Since carcinomas of the colon or rectum are associated with blood loss, we wondered if complete blood count data were suggestive of iron deficiency in cases of colorectal carcinoma. The mean corpuscular volume and especially the red blood cell distribution width are thought to be more sensitive to early iron deficiency than the hemoglobin value. These values were recorded from a series of 98 consecutive cases of colorectal carcinoma and compared with an age-matched control group consisting of patients with no history or clinical suspicion of malignant neoplasm. We found that the hemoglobin level, mean corpuscular volume, and red blood cell distribution width in patients with colorectal carcinoma do not generally show evidence of iron deficiency. The addition of the mean corpuscular volume and red blood cell distribution width to the hemoglobin value does not seem to increase the sensitivity of the complete blood count in the detection or clinical suspicion of colorectal carcinoma.

Blood Cell Count↗

Monoclonal antibody immunotherapy in nude mice persistently infected with Cryptosporidium parvum.

Three groups of congenitally athymic nude mice were persistently infected following oral administration of 2 x 10(7) Cryptosporidium parvum oocysts. Two groups were treated once daily for 10 days with either neutralizing monoclonal antibody (MAb) 17.41 or an isotype control MAb. The third group received no treatment. Intestinal-infection scores were significantly decreased in nude mice treated with MAb 17.41 compared with isotype control MAb-treated and nontreated control groups (P less than 0.005). Biliary and pancreatic cryptosporidial-infection scores were similar for the MAb 17.41-treated and isotype control MAb-treated groups (P greater than 0.05).

Animals↗

Cryptosporidium parvum merozoites share neutralization-sensitive epitopes with sporozoites.

Sporozoites and merozoites are stages in the life cycle of Cryptosporidium parvum that can cyclically infect intestinal cells, causing persistent infection and severe diarrhea in immunodeficient patients. Infection by sporozoites can be neutralized by surface-reactive mAb. We show that merozoite infectivity can also be neutralized by surface-reactive mAb. To do this, viable C. parvum merozoites were isolated by differential and isopycnic. centrifugation, and distinguished from sporozoites by transmission electron microscopy. Differential reactivity with a panel of seven mAb was used to determine the amount of sporozoite contamination in isolated merozoite preparations. The isolated merozoites were distinguished from sporozoites (p less than 0.0001) by four sporozoite-specific mAb (16.332, 16.502, 17.25, and 18.357) in an indirect immunofluorescence assay. Three mAb (16.29, 17.41, and 18.44) consistently reacted with both merozoites and sporozoites. Isolated merozoites were infectious for neonatal mice when administered by intraintestinal injection. Infectivity for mice was significantly neutralized (p less than 0.05) when 1 to 2 x 10(5) merozoites were incubated with sporozoite-neutralizing mAb 17.41 or 18.44, before inoculation. Merozoites incubated with an isotype control mAb remained infectious for neonatal mice. We conclude that C. parvum merozoites share neutralization-sensitive epitopes with sporozoites.

Animals↗

Kinetics of Cryptosporidium parvum sporozoite neutralization by monoclonal antibodies, immune bovine serum, and immune bovine colostrum.

Monoclonal antibodies, immune bovine serum, and immune bovine colostral whey neutralized infectivity of Cryptosporidium parvum sporozoites for mice in a time-dependent manner. Immune colostral whey neutralized sporozoites more rapidly and completely than immune serum, monoclonal antibody (MAb) 18.44, or a combination of MAb 18.44 and MAb 17.41. Mice were partially protected against oral challenge with C. parvum oocytes when treated with immune colostral whey, MAb 17.41, or a combination of MAb 17.41 and MAb 18.44.

Animals↗