Summary report of observations, conclusions and recommendations.
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Computer Communication Networks↗
Biomedical subjects
E Hammond
Publications and source records attributed to E Hammond.
Fetal akinesia.
Normal fetal growth and development during pregnancy is highly dependent upon adequate fetal movement. Limitation of movement, regardless of the underlying cause, can result in a particular pattern of abnormal fetal morphogenesis. This phenotype is termed the fetal akinesia deformation sequence (FADS). The etiology of fetal akinesia may be generally classified into one of five categories: neuropathy, myopathy, restrictive dermopathy, teratogen exposure, or restricted movement due to intrauterine constraint. In this article, the differential diagnosis of fetal akinesia is systematically reviewed and information regarding prenatal diagnosis, prognosis, perinatal management, and recurrence risks are discussed.
Congenital Abnormalities↗
Benign pathologic responses of the larynx.
Benign laryngeal lesions were examined for patterns of injury indicated by deposition of fibronectin and collagen type IV. An immunoperoxidase technique was used to compare 33 fresh or paraffin-embedded tissues with regard to their staining of monoclonal antibodies directed against fibronectin and collagen type IV. Two types of patterns were recognized. One pattern showed intense fibronectin deposition in the superficial layer of the lamina propria, often coupled with basement membrane zone injury, indicated by thick collagen type IV bands. The other pattern showed rare basement membrane zone injury and very little fibronectin deposition. The first pattern correlated more with nodules, the second pattern more with Reinke's edema and some polyps. A better understanding of the effects of excessive deposition of structural glycoproteins such as fibronectin and of abnormal proteoglycan deposition may lead to a better characterization of vocal fold disease and its causation and, ultimately, better treatment.
Adult↗
Flow cytometric quantification of the proliferation-associated nuclear antigen p105 and DNA content in advanced head & neck cancers: results of RTOG 91-08.
PURPOSE: p105 is a proliferation-associated nuclear antigen which identifies proliferating but not resting cells. The objectives of this Radiation Therapy Oncology Group (RTOG) protocol (91-08) were: (1) to correlate tumor proliferative potential estimated using the p105 assay and deoxyribonucleic acid (DNA) analysis with treatment outcome in patients irradiated for advanced squamous cell carcinoma of the head and neck; and (2) to evaluate the potential of p105 labeling indices as a predictive assay. METHODS AND MATERIALS: Paraffin blocks of pretreatment biopsies of the primary tumor or metastatic neck nodes of patients with Stage III or IV squamous cell carcinoma of the head and neck treated with radiotherapy alone in three previous RTOG protocols (79-13, 79-15, and 83-13) were retrospectively obtained. From these paraffin blocks, areas of tumor were selected based on histological examinations and sectioned. Nuclei suspensions were then prepared and processed for p105 antibody and DNA staining and subsequent flow cytometric quantification of p105 labeling indices and DNA content and correlation with local-regional control and survival. RESULTS: Paraffin blocks of tumor biopsies from 148 out of a total of 598 eligible patients were available. Of these, 143 were analyzable. The median and (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (LI-S), and p105 antigen density (AD) were: 66.6 (3.85-99.5), 9 (1.55-36), and 93.2 (7.4-628.5), respectively. Deoxyribonucleic acid was diploid in 67 (47%), aneuploid in 22 (15%) and mixed aneuploid/diploid in 54 (38%) patients. There was a strong correlation between AD and DNA ploidy. Antigen density was above median in 91.5% of the aneuploid or mixed aneuploid/diploid tumors, but only in 8.5% of the diploid tumors. Patients with aneuploid or mixed aneuploid/diploid tumors had significantly greater local-regional failures than patients with diploid tumors (p = .0180). Those with p105 LI-C below the median or p105 AD above the median also had significantly greater local-regional failures (p = .0500 and p = .0167, respectively). Patients with p105 AD below the median had significantly better survival than those above the median (p = .0444), although there was no significant difference in survival with respect to DNA ploidy or p105 LI-C. Multivariate analyses showed that T-stage (p = .0001) and p105 AD (p = .0044) were significant prognostic factors for local-regional control, and T-stage (p = .0080), N-stage (p = .0021), primary site (p = .0110), and p105 AD (p = .0326) were significant prognostic factors for survival. CONCLUSION: These results suggest that flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content of pretreatment tumor biopsies may be a potentially useful predictive assay in patients irradiated for advanced squamous cell carcinomas of the head and neck.
Analysis of Variance↗
Relationship of clear cell oncocytoma to mitochondrial-rich (typical) oncocytomas of parotid salivary gland. An ultrastructural study.
Nosologically, the designation clear cell oncocytoma seems illogical and contradictory when the definition of an oncocytoma relies on mitochondrial-rich cells; its relationship to the granular (mitochondrial-rich) oncocytoma needs further clarification. Electron microscopy of six examples of oncocytoma from five patients allowed assessment of cellular features in three clear cell variants, two typical oncocytomas and one with a roughly equal proportion of clear and granular tumor cells. Ultrastructurally, in the clear cell types of oncocytoma, a considerable to extensive portion of the central cytoplasm was occupied by monoparticulate glycogen with margination of mitochondria and other organelles. The degree of extraction of the glycogen during fixation and processing accounts for variation in the extent of the clear cell component as phosphotungstic acid-hematoxylin staining reveals considerable mitochondria in many of the tumor cells in the clear cell variant of oncocytoma. Ultrastructural findings further support an interrelationship between clear and granular cells, as some typical oncocytes are evident in the clear cell variant of oncocytoma, and one oncocytoma in this series had a roughly equal number of glycogen-rich and mitochondrial-rich tumor cells both of which took part in the formation of microlumens. The designation clear cell oncocytoma is appropriate within the oncocytoma subgroup of salivary gland tumors.
Adenoma, Oxyphilic↗
Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12.
PURPOSE: This Phase II study was designed to test the tolerance and effectiveness of concurrent cisplatin-radiotherapy in the treatment of invasive bladder cancer. Objectives were to determine toxicity, complete response rate, bladder preservation rate, and survival. METHODS AND MATERIALS: Patients with invasive bladder cancer, clinical Stages T2-4, NO-2 or NX, MO were treated with pelvic radiotherapy 40 Gy in 4 weeks and cisplatin 100 mg/m2 on days 1 and 22. Complete responders were given an additional 24 Gy bladder boost plus a third dose of cisplatin; patients with residual tumor after 40 Gy were assigned radical cystectomy. RESULTS: The complete remission rate following cisplatin and 40 Gy for evaluable cases was 31/47 (66%). Acute toxicity was acceptable with only two patients not completing induction therapy. Patients with poorly differentiated tumors were more likely to achieve complete remission. Of fully evaluable patients, 28/42 (67%) achieved complete remission with induction therapy, 11 remain continuously in remission, and eight have relapsed with bladder as the only site of failure. Five of these eight cases relapsed with noninvasive tumor. Of the 14 patients who failed to achieve complete remission, only three remain disease-free. Median survival is not reached, with 17/42 (19/48) deaths reported. Actuarial survival is 64% at 3 years. CONCLUSION: This combined cisplatin-radiotherapy regimen was moderately well-tolerated and associated with tumor clearance in 66% of patients treated. Isolated bladder recurrences with invasive carcinoma are infrequent. Better definition of pretreatment selection criteria is needed if combined modality treatment is to achieve disease control and organ preservation for patients with bladder cancer.
Adult↗
A murine model of preterm labor: inflammatory mediators regulate the production of prostaglandin E2 and interleukin-6 by murine decidua.
Inflammatory processes may be important in the initiation and propagation of uterine contractions and preterm labor in human pregnancies. Recently, a murine model of preterm labor has been described. The purpose of our study was to determine whether murine decidua responds to inflammatory mediators, such as lipopolysaccharide (LPS) and the inflammatory cytokines interleukin (IL)-1 beta and tumor necrosis factor (TNF). Allogeneic pregnant mice (C3H/Hen females mated with C57/B6 males) were killed at 12-14 days of pregnancy, decidual tissue was isolated, and explants were placed on the polycarbonate membrane of Costar Transwell inserts. Initial validation studies of this explant system, including biochemical and histologic evaluations, indicated that the decidual tissue remained intact, viable, and responsive to IL-1 beta for at least 5 days in explant culture. Treatment of murine decidual explants with LPS, IL-1 beta, and TNF resulted in significant increases in the production of prostaglandin E2 (PGE2) and IL-6. Thus the regulation of PGE2 and IL-6 production from murine decidua by LPS and inflammatory cytokines is similar to findings previously reported for human decidua. Our findings are consistent with the view that the pathophysiology of infection-induced preterm labor in the mouse may be similar to that in human pregnancy and supports the continued development of murine models of preterm labor.
Animals↗
A human endometrial explant system: validation and potential applications.
OBJECTIVE: Our objective was to describe an in vitro explant system to study the regulation of prostaglandin production by human endometrium. STUDY DESIGN: Segments of late-luteal-phase endometrium were obtained aseptically at the time of endometrial sampling. The endometrium was cut into 1 mm3 pieces and applied to the polycarbonate membrane of tissue-culture-well inserts for 12-well plates (Costar Transwell cell culture chamber inserts, 0.4 microns pore size). After placing the well inserts, culture medium was carefully applied. The explants were incubated at 37 degrees C in 5% carbon dioxide in air, and the culture medium was changed daily. RESULTS: Electron microscopic examination and lactate dehydrogenase determinations of the explants revealed cellular viability for < or = 5 days of culture. Endometrial explants responded to treatment with interleukin-1 beta and tumor necrosis factor by a concentration-dependent increase in the production of prostaglandin E2. Costimulation of late luteal endometrial explants with interleukin-1 beta (10 ng/ml) and progesterone (10(-6) mol/L) resulted in variable production of prostaglandin E2, suggesting that the histologic examination of the endometrium does not necessarily reflect the functional properties of the endometrium. CONCLUSIONS: Our data show that when used with human endometrial tissue this explant system maintains tissue viability and responsiveness for < or = 5 days. This approach to explant methods is simple and provides a flexible model to study the regulation of the production of bioactive substances by human endometrial tissue.
Culture Techniques↗
Vasoactive intestinal peptide in canine hearts: effect of total cardiac denervation.
The effect of total cardiac denervation on the distribution of cardiac immunoreactive vasoactive intestinal peptide (IR-VIP) was determined in four groups of dogs. Denervated dogs killed at either 7 days (group 1) or 30 days (group 3) were compared with sham-operated dogs killed at either 7 days (group 2) or 30 days (group 4). The highest concentrations of IR-VIP were found in the left atrium and proximal left anterior descending and circumflex coronary arteries and were not affected by denervation. Concentrations of IR-VIP in the left ventricle were barely detectable. Only right ventricular IR-VIP concentrations were significantly lower in denervated compared with sham-operated dogs in both groups. Thus these data provide evidence of intrinsic VIP innervation of the atria and epicardial coronary arteries and localized extrinsic VIP innervation of the right ventricle of the canine heart.
Animals↗
Automated acuity scoring within a computer based medical record.
This paper describes the initial development of a completely automated acuity scoring system that resides within the TMR bedside computing system at the Duke University Medical Center, Surgical Intensive Unit. The scoring system is based upon the APACHE II acuity scoring system and provides for the recalculation of acuity scoring at 12 hour intervals through the patient's ICU course. When comparing hand calculated versus computer generated acuity scores for 19 patients, discrepancies fell into three broad categories: 1) data available to the application differed from that available to the human scorer. 2) apparent transcription errors 3) data items lost or absent from the paper record. It remains to be determined if computer generated acuity scoring provides for a more accurate representation of the patient's acuity.
Creatinine↗
Cobalt cardiomyopathy. A report of two cases from mineral assay laboratories and a review of the literature.
Two young men employed in the mineral assay industry developed non-inflammatory cardiomyopathy. By review of clinical findings, elicitation of occupational and environmental histories, work-site evaluations, and ascertainment of tissue cobalt levels, Nevada Public Health authorities confirmed these cases to be due to occupational cobalt exposure. Hair and heart cobalt levels were elevated for the cases, but control samples had no detectable cobalt. Excess ischemic heart disease mortality among cobalt-exposed workers may reflect misdiagnosis of cardiomyopathy.
Adult↗
A chorionic gonadotropin-secreting human pituitary cell.
Recent data from our laboratory show that hCG is secreted in a pulsatile manner in parallel with human LH (hLH) in nonpregnant normal humans. Furthermore, GnRH stimulates hCG and hLH release. Using a monoclonal antibody specific for the beta-chain of hCG and not reacting with hLH, we have identified a heretofore unknown cell type in human pituitaries which stains only for hCG. The light microscopic, immunocytochemical, and ultrastructural features are described. These data coupled to those from multiple earlier studies indicate that hCG is secreted by these cells in normal nonpregnant humans.
Chorionic Gonadotropin↗
Thermal laser probe angioplasty: influence of constant tip temperature, plaque composition, and probe/vessel diameter ratio.
Thermal laser angioplasty uses constant laser power, producing widely variable tip temperatures in vivo. Results have been suboptimal. We studied the effect of 50-400 degrees C tip temperatures on depth of ablation at 192 sites on plaqued and normal human aorta in vitro, and the angiographic and histologic response in vivo of 300-400 degrees C at probe/vessel ratios of 0.5-1.0, in 40 normal canine femoral artery segments. In vitro, there was a direct relationship between tip temperature and depth of ablation, r = 0.71 (all segments), r = 0.74 for fibrous plaque, but a poor correlation in fatty plaque r = 0.35. In fibrous plaque, there was proportionately more ablation at tip temperatures greater than 300 degrees C, mean depth 0.62 mm, than at 150-300 degrees C, mean 0.37 mm, (P less than .001). Ablation was similar in plaqued and normal aorta. In vivo, 300 degrees C, 350 degrees C, and 400 degrees C produced similar effects. At probe/vessel ratios less than 0.8, only disruption of internal elastic lamina was observed. At ratios greater than or equal to 0.8, spasm occurred in 39% (7/18), transmural damage in 28% (5/18), and perforation in one of 18. Ablation is not selective for plaque and is highly variable in fatty plaque. Tip temperatures above 300 degrees C produce greater ablation than at lower temperatures. In clinical applications, probe/vessel rations less than or equal to 0.7 may be most appropriate, and it appears that thermal remodeling may contribute more to outcome than plaque ablation.
Angioplasty, Laser↗
Frontal hypermetabolism and thalamic hypometabolism in a patient with abnormal orienting and retrosplenial amnesia.
A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally.
Adult↗
Inhibition of rat mesangial cell growth by heparan sulfate.
The ability of heparan sulfate, an endogenous component of the glomerulus, to regulate the growth of cultured rat mesangial cells was investigated. Heparan sulfate caused a dose-dependent inhibition of rat mesangial cell growth, 85% inhibition compared with controls at the highest dose (1,000 micrograms/ml). Chondroitin sulfate produced no inhibition. The low-sulfated fraction of heparan sulfate (9%) produced more inhibition than the high-sulfated fraction (13%), 90 +/- 1 vs. 71 +/- 2% (P = 0.002). The effects of the heparan sulfate were completely reversible. Treatment of heparan sulfate with heparitinase increased the degree of inhibition, 71 +/- 1 vs. 84 +/- 1% (P less than 0.001). Four different oligosaccharides derived from heparan sulfate and heparin were tested for their ability to inhibit growth. One of the oligosaccharides, low-sulfated (10%), caused significant inhibition, 76 +/- 2%. Heparan sulfate was also able to inhibit the growth of Swiss 3T3 fibroblasts (63 +/- 5%). This inhibition was less marked than that seen with mesangial cells. Thus heparan sulfate was able to significantly inhibit rat mesangial cell growth in culture. Alterations in glomerular heparan sulfate may play an important role in alterations in mesangial cell growth.
Animals↗
Hyperacute rejection of the transplanted mouse heart.
Mouse hearts transplanted heterotopically to MHC-disparate recipients can be hyperacutely rejected (HAR) after a single or 3 sequential donor type skin grafts, or a single intradermal injection of lymphoid cells. In the combinations tested, not all hearts are HAR; most of them are rejected in accelerated fashion. Our results with transplanted rat hearts are similar, even in a genetic combination for which HAR of all hearts has been reported. However, in rats, HAR tends to occur more rapidly and to be associated with more-intense vascular changes. Transfer of serum from mice or rats sensitized by 3 sequential skin grafts likewise resulted in occasional hyperacute but never accelerated rejection. Transfer of lymph node cells from mice sensitized with a single skin graft always resulted in accelerated but never in hyperacute rejection; transfer of cells after 3 sequential skin grafts caused neither accelerated nor hyperacute rejection.
Acute Disease↗
Platelet activation and prostacyclin supporting capacity in the loin pain hematuria syndrome.
The loin pain hematuria syndrome has been characterized as a constellation of severe recurrent flank pain and hematuria, occurring predominantly in young women. We studied a 17-year-old woman who had recurrent right flank pain, gross hematuria, and fever, without evidence of urinary tract infection. Her physical exam was remarkable for right costovertebral angle tenderness and a normal BP. Her urinalysis showed blood and protein but her creatinine clearance and 24-hour urinary calcium excretion were normal. A kidney biopsy was remarkable for arteriolar subintimal fibrous thickening and fibrin deposition, but no glomerulonephritis. Her peripheral hemostasis evaluation was normal except for circulating platelet aggregates and elevated fibrinopeptide A levels. On two occasions, her serum was unable to normally support prostacyclin (PGI2) production by cultured human umbilical endothelial cells, as measured by radioimmunoassay (RIA) of its stable metabolite 6-keto-PGF alpha. Blood samples from the right renal vein and inferior vena cava revealed a selective elevation of fibrinopeptide A in the right renal venous effluent. The presence of circulating platelet aggregates and elevated levels of fibrinopeptide A (a cleavage product of fibrin) suggests that platelet activation and fibrin deposition may play a role in the pathogenesis of this disorder. The inability of her serum to normally support the production of the potent antiplatelet and antithrombotic substance, PGI2, could represent a primary renovascular endothelial cell defect.
Adolescent↗
OKT3 monoclonal antibody in heart transplantation.
OKT3 monoclonal antibody (OKT3) has already proved to be a valuable edition to the immunosuppression armamentarium available in cardiac transplantation. It is highly effective in treating refractory rejection, where approximately 90% of subjects may be salvaged. It may be even more valuable in prophylaxis, where in combination with an antibody suppression strategy and low-dose, "delayed" cyclosporine it appears to afford near complete protection against rejection. Moreover, OKT3-based prophylaxis seems to impact favorably on the rejection rate after the prophylaxis course has been completed. Adverse reactions are common and generally manageable, although occasional serious clinical events do occur.
Antibodies, Monoclonal↗