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Biomedical subjects

D S Smith

Publications and source records attributed to D S Smith.

At least 127 records · Page 7Linked to original sources

Rate of change in serum prostate specific antigen levels as a method for prostate cancer detection.

To examine prospectively the usefulness of measurement of rate of change in serum prostate specific antigen levels (PSA slope) in detecting prostate cancer in a PSA-based prostate cancer screening study, we evaluated 982 serially screened men whose initial screening was negative for cancer. All men had at least 1 PSA value greater than 4.0 ng./ml. and all ultimately underwent prostatic biopsy. For those who entered the study with normal PSA levels, a PSA slope cutoff point of 0.75 ng./ml. per year or more maximized sensitivity and specificity for predicting cancer (odds ratio 7.20, 95% confidence interval 4.52 to 11.47). This cutoff point was most predictive for men 70 years old or younger. For men who entered the study with elevated PSA levels (greater than 4.0 ng./ml.) a lower PSA slope cutoff point (0.4 ng./ml. per year or more) maximized sensitivity and specificity for predicting cancer (odds ratio 2.73, 95% confidence interval 1.82 to 4.07). We conclude that PSA slope is useful for serial prostate cancer screening, although its predictive value varies with patient age and initial PSA level.

Age Factors↗

Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values.

The objective of this study was to determine the need for repeat prostatic biopsies in men whose initial biopsy results revealed no evidence of cancer or atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a longitudinal prostate specific antigen (PSA) based prostate cancer screening study that called for biopsy if the serum PSA level was greater than 4.0 ng./ml. (Hybritech assay) and findings on rectal examination or ultrasonography were abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had negative initial biopsy results, a persistent serum PSA level of greater than 4.0 ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the cancers were detected through either biopsy 1 or 2. The median initial PSA level, followup PSA levels and the yearly rate of change in PSA were significantly greater in men whose cancer was detected compared with those of men whose cancer was not detected (6.4 versus 5.4 ng./ml., 7.4 versus 6.6 ng./ml. and 1.1 versus 0.7 ng./ml. per year, respectively). There was a trend for a higher percentage of tumors detected through serial screening to be pathologically organ confined with those detected through initial screening (73% versus 62%, p = 0.07). We conclude that men with a persistently elevated serum PSA value after an initial negative prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude adequately the presence of detectable prostate cancer.

Aged↗

The effectiveness of the confidential unit exclusion option.

BACKGROUND: The confidential unit exclusion (CUE) option is intended to reduce human immunodeficiency virus (HIV) transmission by excluding donors newly infected with HIV who have not yet developed HIV antibody (window-period donors); however, its efficacy in excluding window-period donors has not been evaluated. STUDY DESIGN AND METHODS: The use of the CUE option was studied among the donors of 3.7 million units at 18 American Red Cross blood services regions during 1991 and 1992 and among 322 previously HIV-1-seronegative donors who subsequently donated a seropositive unit between 1987 and 1990 at 40 United States blood centers. These seroconverting donors had previously been shown to be highly likely to donate during their window period. RESULTS: On the basis of data from these two populations, it was estimated that only 3 to 5 percent of units donated by window-period donors were not transfused because of the CUE option, that 0.4 percent of all donations were from donors who confidentially excluded their blood from transfusion, and that donors who confidentially excluded their blood were 21 times more likely to be HIV antibody-positive than donors who did not use the CUE option. It is estimated that, if all US blood centers used the CUE option, a total of 2 to 17 otherwise acceptable units donated by window-period donors would not be transfused annually. CONCLUSION: Although donors who confidentially exclude their blood from transfusion are 21 times more likely to have HIV antibody, the rarity of window-period donors and the infrequency of confidential exclusion by window-period donors cause the CUE option to have minimal impact on transfusion safety.

Acquired Immunodeficiency Syndrome↗

Laparoscopic pneumoperitoneum: impact of body habitus.

The purpose of this study was to determine the relationships among pneumoperitoneum pressure, CO2 insufflation volume, and patient height, weight, and body mass index. Forty-one male patients undergoing laparoscopic urologic procedures prospectively had a record made of the delivered volume of CO2 during insufflation to attain intraabdominal pressures of 5, 10, 15, 20, 25, and 30 mm Hg. The relationship of the delivered volume of CO2 insufflated and the intraabdominal pressure was compared statistically to the patient height, weight, and body mass index. In addition, six domestic female pigs underwent pneumoperitoneum, and the abdominal volume was calculated for intraabdominal pressures of 0, 5, 10, 15, 20, 25, and 30 mm Hg. Four different commercially available 10-mm trocars were tested for force required for placement at intraabdominal pressures of 15 and 30 mm Hg. There was a direct relationship between delivered volume of CO2 insufflated and the pneumoperitoneum pressure. There was no significant relationship between the delivered volume of CO2 insufflated at a given intraabdominal pressure and the patient height, weight, or body mass index. During insufflation, 94% of the abdominal volume is achieved by insufflating to 15 mm Hg. There is no significant difference in the force required for insertion of different ports at 15 mm vs 30 mm Hg pressure. Increasing the abdominal pressure to 30 mm Hg provides a 50% increase in the volume of CO2 insufflated vs a standard 15 mm Hg pneumoperitoneum. However, this additional volume does not significantly change the actual abdominal volume or diminish the pressure necessary to insert a trocar.

Abdomen↗

The clinical characteristics and infectious outcomes of febrile infants aged 8 to 12 weeks.

We reviewed 356 consecutive cases of febrile infants aged 8 to 12 weeks who received outpatient evaluation for sepsis over 4 years. Thirty-three infants (9.3%) had a serious bacterial infection (SBI), including bacterial meningitis, bacteremia, urinary tract infection (UTI), and Salmonella enteritis. The SBI rate, which was directly proportional to fever height, was significantly greater for infants with hyperpyrexia (35%) than those with lesser degrees of fever (7.7%) and for infants with peripheral blood leukocytosis (total WBC count > or = 15,000/mm3; 25%) than those with lesser total WBC counts (5.8%). An attending-level physician judged that 67% of infants with SBI appeared to be "well," including five or eight cases (63%) of bacteremia, 14 of 17 cases (82%) of UTI, and all three cases of Salmonella enteritis, whereas all five patients with bacterial meningitis appeared to be "ill." Urinalysis abnormalities indicative of UTI were present in 15 of 17 infants (88%) who had this infection. SBIs are not uncommon in febrile infants aged 8 to 12 weeks and occur significantly more often in those with either hyperpyrexia or peripheral blood leukocytosis.

Bacterial Infections↗

Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide.

Nitric oxide, a free-radical gas produced endogenously by several mammalian cell types, has been implicated as a diffusible intercellular messenger subserving use-dependent modification of synaptic efficacy in the mature central nervous system. It has been suggested on theoretical grounds that nitric oxide might play an analogous role during the establishment of ordered connections by developing neurons. We report here that nitric oxide rapidly and reversibly inhibits growth of neurites of rat dorsal root ganglion neurons in vitro. In addition, we show that exposure to nitric oxide inhibits thioester-linked long-chain fatty acylation of neuronal proteins, possibly through a direct modification of substrate cysteine thiols. Our results demonstrate a potential role for nitric oxide in the regulation of process outgrowth and remodelling during neuronal development, which may be effected at least in part through modulation of dynamic protein fatty acylation in neuronal growth cones.

Acylation↗

Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening.

OBJECTIVE: To determine whether prostate-specific antigen (PSA)-based screening alters the proportion of organ-confined prostate cancers detected. DESIGN: A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group. SETTING: General community outpatient screening program based at a university center. PATIENTS: The study group consisted of 10,251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE). MAIN OUTCOME MEASURE: Proportion detected with clinically or pathologically advanced prostate cancer. RESULTS: The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/129). Screened patients had a lower proportion of advanced cancers than the comparison group (chi 2 [2] = 12.3; P = .002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P = .08). CONCLUSION: Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone.

Aged↗

Pharmacological sensitivity of the articular capsule of the primary spines of Eucidaris tribuloides.

1. This paper describes the effects of several cholinergic agonists and antagonists, and of beta-phenylethylamine (PEA) and some of its derivatives, on the articular capsule, or ligament, of the primary spines of Eucidaris tribuloides. 2. Carbamylcholine (CCh), methacholine (MeACh), nicotine, and muscarine exert a stiffening effect similar to that of acetylcholine (ACh), although the time course of their actions varies widely. 3. Atropine induced stiffening and blocked and responses to muscarine and MeACh. The responses to MeACh were blocked also by 4-diphenylacetoxy-N-methylpiperidine, suggesting the presence in the ligament of type M3 muscarinic receptors, in addition to nicotinic ones. d-Tubocurarine induced stiffness of the ligament and failed to block the responses to ACh and nicotine. 4. While ACh induced only a slight desensitization, CCh caused a long-lasting blockade of the stiffening effects of the cholinergic agonists. This shows that the receptors for ACh have a site or sites that recognize the ester moieties of these molecules. 5. Eserine and neostigmine potentiate the responses to acetylcholine, indicating the presence of acetylcholinesterase in the ligament. 6. beta-Phenylethylamine, epinephrine, norepinephrine, and dopamine induce diphasic responses; usually a brief softening followed by a slow and irreversible stiffening of the ligament. 7. In contrast to the above, tyramine and octopamine elicit a simple softening of ligaments which are stiff as a result of handling or by exposure to cholinergic agonists. However, tyramine and octopamine do not soften ligaments which become stiff as a result of exposure to adrenergic agonists.

Acetylcholine↗

Contractile properties of the articular capsule or ligament, in the primary spines of the sea-urchin Eucidaris tribuloides.

1. The articular capsule or ligament, of the primary spines of the sea-urchin Eucidaris tribuloides behaves as a classical excitable tissue, responding with a shortening or contracture to a variety of stimuli including the cholinergic agonists acetylcholine (ACh), methacholine (MeACh), carbamylcholine (CCh) and nicotine. 2. d-Tubocurarine failed to decrease the amplitude of the acetylcholine-induced contractures, while the contractures elicited by methacholine were blocked by atropine. Neostigmine, but not eserine, increased the amplitude of ACh-induced contractures, suggesting the presence of AChE in the preparation. 3. The cholinergic agonists induced contracture of the ligament, but had quite different kinetics, the rate of rise of the contracture being fastest for ACh and decreasing in the following order: CCh, MeACh and nicotine. 4. Tyramine and octopamine exert an inhibitory action on "catch" and a relaxing effect on the contracting ligament. 5. The time courses of the contractures elicited in the same preparation were virtually identical to those of "catch". Therefore, we propose that "catch" and contracture are only two different aspects of the same phenomenon; namely the contracture of the muscle fibers present in the ligament.

Acetylcholine↗

Prevalence and pathological extent of prostate cancer in men with prostate specific antigen levels of 2.9 to 4.0 ng./ml.

Various authors have recommended different values for the upper limit of normal for the monoclonal prostate specific antigen (PSA) assay (for example 4.0 ng./ml. or less by the manufacturer Hybritech or 2.8 ng./ml. or less by others). To our knowledge, no studies have examined the prevalence and pathological extent of prostate cancer detectable by needle biopsy in ambulatory volunteers with PSA levels in the range of 2.9 to 4.0 ng./ml. We evaluated 121 volunteers by rectal examination and transrectal ultrasonography with PSA levels in that range. We performed ultrasound-directed needle biopsy of the prostate if abnormal findings were present on either examination. The prevalence of detectable prostate cancer in this group was 7.2% (8 of 111). All 8 patients had pathologically organ confined cancer, and only 2 had suspicious findings on rectal examination but all had abnormal or suspicious ultrasound findings. We believe that the 7.2% yield from ultrasonography and biopsy in patients with a PSA level of 2.9 to 4.0 ng./ml. is too low to justify further invasive evaluation. Rather, we recommend careful followup and monitoring of these patients with serial PSA measurements and rectal examination, and advise performance of ultrasonography and biopsy if the rectal examination becomes suspicious for cancer or the PSA level increases above 4.0 ng./ml.

Aged↗

Five-year experience in prehospital intraosseous infusions in children and adults.

STUDY OBJECTIVE: To evaluate the ability of emergency medical technician-paramedic (EMT-P) units to become and remain proficient in the performance of the intraosseous infusion procedure. DESIGN AND SETTING: Descriptive nonrandomized trial open to all patients meeting protocol criteria over a five-year period; prehospital urban and suburban area with a population of 951,000. PARTICIPANTS: One hundred fifty-two consecutive patients (age range, newborn to 102 years) who had intraosseous infusion line placement attempted by EMT-Ps. INTERVENTION: Jamshidi sternal intraosseous infusion needle placed in the proximal tibia bone marrow in patients requiring emergency vascular access for fluid and/or medication administration. RESULTS: EMT-Ps performed 165 attempts on 152 patients with a five-year success rate of 76% per patient and 70% per attempt. Success rates per patient age group were 78%, 0 to 11 months; 85%, 1 to 2 years; 67%, 3 to 9 years; and 50%, 10 years or older. Success rates were significantly higher in children 3 years old compared with children and adults 3 or more years old (P = .04). Proficiency was maintained over the five-year study period. Infiltration was the most common complication, occurring in 14 patients (12%). Errors in landmark identification and needle bending were the most frequent identifiable causes for unsuccessful attempts. Evidence of clinical response to fluid or medication infused was noted in 28 patients (24%). CONCLUSION: EMT-P units can successfully perform the intraosseous infusion line procedure in patients of all ages. Proficiency is maintained over time despite its infrequent use by individual EMT-Ps.

Adolescent↗

Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results.

Three investigators have applied different histopathologic methods (modified Bielschowsky silver methods, Congo red-gallocyanin) to differentiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild dementia and three with moderate to advanced dementia) neuropathology from brain changes associated with aging in three nondemented individuals who had been evaluated using a validated dementia severity staging instrument [Washington University Clinical Dementia Rating (CDR)] generally within a year of death. The presence of elevated numbers of neocortical (frontal and temporal) diffuse, mature, and total senile plaques (SP) was strongly correlated with the presence of clinical AD but did not equate with CDR dementia severity. Neocortical neurofibrillary tangle (NFT) density as well as hippocampal NFT and SP density in this small series did not differentiate statistically between AD and controls. NFT density appeared to correlate with CDR better than SP density. Quantitative histopathologic assessment of AD markers in only a few brain regions can accurately predict the presence of clinical AD, including the very mild form of the disease. This is especially true for SP in the neocortex.

Aged↗

Presence of paralytic shellfish poisoning toxins and soluble proteins in toxic butter clams (Saxidomus giganteus).

Butter clams obtained from a variety of locations along the northern British Columbia coast were assayed for the presence of individual paralytic shellfish poisoning toxins (PSPT) by HPLC and total PSPT toxicity using the mouse bioassay. Specific organs, namely the siphon, adductor muscle, foot and mantle were examined for soluble antigens that crossreacted with crab Saxitoxin-Induced Protein (SIP) using immunochemical (Western blotting) techniques. Butter clams containing high concentrations of PSPT also had several proteins that crossreacted with crab anti-SIP serum. In particular, soluble proteins with distinctly different molecular weights were found in the siphon and foot, respectively, in toxic shellfish. These proteins were absent in nontoxic butter clams. The concept of using PSPT-induced proteins in the butter clam as a screen for identifying toxic shellfish is introduced.

Animals↗

Agraphia in dementia of the Alzheimer type.

This study describes graphic errors made in writing a simple sentence in 368 healthy older adults and individuals in different stages of dementia of the Alzheimer type. Errors of agraphia were present in both healthy and demented people and, in general, increased with the severity of dementia. The errors of agraphia were not correlated with measures of aphasia or psychometric measures of language and motor performance. Writing skill may represent procedural memory, and agraphia errors indicate alterations in long-term memory in dementia of the Alzheimer type.

Aged↗

Cross-reacting antigens in the butter clam (Saxidoma giganteus) and their relationship to total paralytic shellfish poison toxicity.

A specific protein with an apparent mol. wt of 23,000 was identified in foot homogenate derived from paralytic shellfish poisoning (PSP) contaminated butter clams and was found to cross-react with crab-saxitoxin-induced protein (SIP) antiserum. Antiserum, once cross-absorbed against non-toxic shellfish material, was incubated with tissue homogenate derived from 52 butter clams with varying total PSP toxicities in a prototype ELISA. A significant (r = 0.83; P less than 0.001) correlation existed between soluble clam antigen content in foot homogenate and total PSP toxicity; the latter measured by the mouse lethality bioassay. From the ELISA results, a soluble antigen threshold of 0.1% total protein was successfully used to distinguish between PSP toxic and non-toxic butter clams. It is proposed that this type of screening assay could be used in conjunction with the standard mouse bioassay to increase PSP monitoring and potentially reduce unnecessary animal testing.

Animals↗