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Biomedical subjects

W P Reed

Publications and source records attributed to W P Reed.

At least 19 recordsLinked to original sources

Neutrophil responses to intravascular pneumococcal sonicate.

Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.

Animals

Hip disarticulation for recurrent vulvar cancer in the groin.

A patient with squamous cell carcinoma of the vulva treated with a radical vulvectomy and bilateral inguinal and femoral lymphadenectomies utilizing separate groin incisions, subsequently developed a recurrence in the skin bridge between the vulvar and groin excisions. Following groin irradiation with chemosensitization, the tumor progressed to involve the superior public ramus and femoral vessels. A left hip disarticulation and resection of a portion of the superior pubic ramus was performed. The patient has been free of disease for 3 years. The advantages of this procedure over a hemipelvectomy include shorter operative time, reduced blood loss, better fascial closure of the abdomen, and the creation of a stump which is more amendable to prosthetic fitting.

Carcinoma, Squamous Cell

Differences in blood group B-specific mucinase activity between virulent and avirulent Shigella flexneri 2a strains.

Based on our previous findings we postulate that the production of blood group B-degrading mucinase by Shigella flexneri 2a is related to virulence. The virulent S. flexneri 2a strain M4243 produced a blood group B mucinase which decreased the blood group B reactivity of germ-free mouse mucins by a factor of 16 and the B reactivity of human saliva by a factor of 32. Avirulent S. flexneri 2a B-1, serologically similar, but not genetically identical to the M4243 strain, failed to degrade the blood group reactivity. The mucin-degrading ability of S. flexneri 2a M4243 harboring a large virulence-conferring 140 MDa plasmid was then compared with a genetically similar large plasmid-free avirulent S. flexneri 2a M4243A1. Virulent S. flexneri M4243 grew in human salivary mucins while the genetically identical avirulent M4243A1 did not. Supernatant of virulent M4243 culture decreased the blood B reactivity of salivary mucins by a factor of 32 while the avirulent M4243a1 had no effect. Eleven of 12 colonies of the transconjugant hybrid Escherichia coli K12 (7300-1-5) containing the shigella PWR 110 plasmid and chromosomal markers decreased the blood group B reactivity by a factor of 4-32, and two of four colonies of the E. coli strain 7262 containing only the plasmid reduced the B reactivity by a factor of 4-16. These findings suggest that blood group B-specific mucinase production may be related to S. flexneri virulence.

ABO Blood-Group System

Intravenous access devices for supportive care of patients with cancer.

Reliable long-term venous access is crucial as a pathway for the delivery of many current chemotherapeutic agents, as well as for the supportive measures needed to sustain patients during their recovery from the toxic effects of these drugs. Many access devices are now available, but all carry the risk of infection, thrombosis, and complications related to their insertion. Recent advances in technology and the use of antibiotics and anticoagulants offer the opportunity to reduce the rate of many of these complications.

Antineoplastic Agents

The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses.

Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma.

Adolescent

Correlation between mammography and the pathology of nonpalpable breast lesions.

One hundred consecutive needle localization biopsies were performed for nonpalpable breast lesions discovered on low-dose mammography of asymptomatic women between June, 1984, and August, 1986. Malignant disease was found on 21 biopsies. Four were carcinoma in situ, and 17 were infiltrating carcinomas. Only three of the infiltrating carcinomas had metastasized to regional nodes, as confirmed by subsequent axillary dissection. Two of these metastatic tumors involved two nodes and the third only one. The findings on the remaining 79 biopsies were benign. Forty-eight mammograms were read as "benign"; all (100%) were benign pathologically. Thirty-one mammograms were considered "malignant"; 19 (61%) were malignant pathologically. Only two of the 21 mammograms given "suspicious" interpretations were malignant. Microcalcifications correlated with malignancy only 30% of the time (12/42).

Adult

Ovarian carcinoma metastatic to breast: a case report and review of the literature.

Breast metastasis from ovarian carcinoma is a rare event, with only 26 cases being previously reported in the English literature. The twenty-seventh such case is presented herein, and the literature on this topic is reviewed. Metastases to the breast from the ovary signal widespread metastases and generally herald a rapid deterioration and death. Although rare, it is important that metastatic cancer to the breast be differentiated from primary breast carcinoma as both the treatment and prognosis differ significantly.

Adult

Use of frozen section analysis in the treatment of basal cell carcinoma.

Frozen section margin verification has been used in the treatment of basal cell carcinoma at our institution for the past 13 years. A review of the last 450 cases has shown frozen section to be most helpful in treating recurrent tumors where microscopic tumor foci extend beyond clinical margins in 45% of cases. Frozen section analysis may be of value in selected patients with primary tumors, but its routine use is not indicated for the majority of these lesions, since complete excision is possible without relying on frozen section in 90% of cases.

Basal Cell Carcinoma

Responses of isolated pulmonary arteries to the C5a anaphylatoxin.

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.

Anaphylatoxins

Pentoxifylline relaxes isolated pulmonary arteries after preconstriction with norepinephrine.

Pentoxifylline (PTX) is a methylxanthine derivative which improves systemic microvascular flow and tissue oxygen delivery, presumably through actions on platelet aggregation and erythrocyte deformability. Although PTX also improves pulmonary vascular flow, recent evidence suggests that part of this improvement may be due to pulmonary vasodilation. To evaluate these effects we studied isolated rabbit lobar pulmonary artery (PA) ring segments to determine if PTX had direct effects on PA tissues and whether these effects could be modulated pharmacologically or by endothelial disruption. PTX had no effect on PA at resting tension. However, if the PA tension was actively increased by norepinephrine (5 microM), subsequent PTX application caused concentration-dependent PA relaxation. Relaxation occurred promptly and was maximal within 45-60 s. The threshold PTX concentration necessary for relaxation was 1 microM. PTX-induced relaxation was not affected by pretreatment with the cyclo-oxygenase inhibitor indomethacin (1 microM). Endothelial disruption by gentle rubbing of the intimal PA surface abolished relaxation of preconstricted PA by acetylcholine, but had no effect on relaxation by PTX. Although PA at resting tension displayed no response to PTX, PA constriction by norepinephrine in the presence of PTX concentrations greater than 10 microM was significantly decreased. These data indicate that PTX has direct actions on isolated rabbit PA which are not blocked by indomethacin nor require the presence of intact endothelium. Furthermore, PTX can suppress norepinephrine-induced constriction of isolated PA.

Animals

Venous access devices utilized in association with intensive cancer chemotherapy.

Consistent and reliable venous access is a major component of the management of patients with cancer undergoing chemotherapy. Venous access devices such as the long-term right atrial catheter and the subcutaneous port have become a major aspect of the supportive care of such individuals, with resultant advantages which have improved their quality of life. Yet, the occurrence of infectious and non-infectious complications restricts the usefulness of these devices and warrants a standardized approach to device placement, patient education and the management of such complications. Infectious complications, including exit site and tunnel infections, as well as bacteremias requiring catheter removal occur at a rate of approximately two episodes for every 1000 catheter days, while non-infectious complications occur more frequently. Uniform patient education and catheter care, as well as placement by a single consistent surgeon will decrease the frequency of complications, improve the longevity and function of these venous access devices, while minimizing the associated morbidity.

Antineoplastic Agents

Choosing an appropriate implantable device for long-term venous access.

A variety of devices is now available for venous access in patients requiring long-term infusions of chemotherapeutic agents, hyperalimentation solutions, blood products or antibiotics. All have advantages and disadvantages which may make the selection of one type of device appropriate under a given set of circumstances but inappropriate in another. Experience has shown that patients needing intensive therapy for hematologic malignancies are best served by lines that require minimal dissection for insertion, such as the Hickman catheter. Patients who are unlikely to hemorrhage at the time of insertion and who need only intermittent therapy can take advantage of the greater convenience and cosmetic appearance of a totally implantable port. Peripheral vein cannulation by means of fine silicone rubber catheters can be performed by trained intravenous nurses to provide access of intermediate duration without the expense and inconvenience of surgical insertion in an operating room.

Catheterization, Central Venous

Responses of isolated pulmonary arteries to synthetic peptide F-Met-Leu-Phe.

The chemoattractant formyl-methionine-leucine-phenylalanine (FMLP) has recently been shown to possess spasmogenic properties in smooth muscle preparations from various organs. In this study we have investigated the actions of this peptide on isolated rabbit pulmonary artery (PA) ring segments. FMLP stimulated concentration-dependent constriction of PA at resting tension. However, in PA that had been preconstricted by norepinephrine, FMLP stimulated concentration-dependent relaxation. FMLP-stimulated PA constriction was inhibited by earlier exposure to indomethacin or to furegrelate, a thromboxane synthetase inhibitor, but not by earlier exposure to the H1 histamine receptor antagonist pyrilamine. FMLP-stimulated relaxation of PA was totally abolished by indomethacin but not by furegrelate or pyrilamine. Disruption of the endothelium in PA preparations decreased both the constriction and relaxation response to the peptide, suggesting that these cells were involved in these responses. These results indicate that the chemotactic factor FMLP can elicit constriction or relaxation of isolated PA, depending on the underlying active PA tension. In addition, both constriction and relaxation are dependent on cyclooxygenase products and intact endothelium.

Animals

Regionally variable pulmonary artery responses to C3a.

Products of the complement (C) cascade may have direct effects on pulmonary vascular tissue and contribute to pulmonary vasoconstriction in states of C activation. We studied the effects of C3a, a C-derived vasoactive peptide, on isolated rabbit hilar (HPA) and main pulmonary arteries (MPA). C3a elicited concentration-dependent constriction of HPA (10(7) M to 5 x 10(7) M) but minimal response in MPA at all concentrations tested. The difference between HPA and MPA responses was significant (P less than 0.05, paired t test). To evaluate HPA desensitization to C3a, the peptide was reapplied at 60 min in some tissues and at 120 min in others. All tissues consistently exhibited less constriction at 60 min than observed with previous exposures. Histamine contribution to the HPA response to C3a was determined by exposing the tissues for 30 min before C3a application to pyrilamine (1 x 10(-5) M), an histamine H1-receptor antagonist. Pyrilamine reduced the HPA response to C3a by 70-85%. We conclude that 1) isolated rabbit PA responses exhibit regional variability to C3a over a range of concentrations; 2) C3a desensitizes HPA for at least 60 min, but the tissue demonstrates variable recovery within 120 min; and 3) HPA responses to C3a are reduced by pyrilamine, an H1-receptor antagonist.

Animals

Long-term results and complications of preoperative radiation in the treatment of rectal cancer.

A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.

Adenocarcinoma

Outpatient dobutamine and dopamine infusions in the management of chronic heart failure: clinical experience in 21 patients.

Dobutamine (and dopamine) are potent positive inotropic drugs which are frequently given to treat decompensated congestive heart failure. This study reports on the use of ambulatory dobutamine (and dopamine) infusions in 21 outpatients with advanced congestive heart failure. Each patient was initially hospitalized, and hemodynamic and clinical efficacy to dobutamine (and dopamine) was assessed. These 21 patients were carefully selected from a larger population of approximately 40 patients referred for this therapy. Chronic venous access was established and a drug infusion pump was supplied. Patients and family members were trained in the use of these devices. Eleven patients were treated with intermittent dobutamine infusions for 48 consecutive hours weekly, six patients with continuous (i.e., 24 hours daily) dobutamine infusions, and four patients with continuous, daily dobutamine and dopamine infusions. Significant (p less than 0.001) increases in cardiac index (1.8 +/- 0.6 to 2.7 +/- 0.7 L/min/m2) occurred during the initial dobutamine titrations. Functional classification (3.8 +/- 0.4 to 2.8 +/- 0.7) also improved significantly (p less than 0.01) during the 1.8 to 24 (mean 7.8) months of outpatient infusion therapy with dobutamine (and dopamine). Complications during outpatient therapy included drug tolerance (two instances), infection (two with bacteremias, eight with exit site infections), drug extravasation (three instances), and pump malfunction (two instances). Twenty patients have died: eleven from heart failure, four suddenly (one of them 9 months after dobutamine was stopped), and five from noncardiac causes. Our data suggest that outpatient dobutamine (and dopamine) infusions may be an effective form of therapy for selected patients with severe congestive failure who are refractory to more conventional treatment or who are awaiting cardiac transplantation.

Adult

Endotoxin provocation of experimental renal cystic disease.

Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria; to Escherichia coli and Proteus mirabilis, endotoxin-containing bacteria; and injected E. coli endotoxin on peripheral leukocyte counts and renal morphology. Morphological changes were evaluated by light microscopy and scored blindly on a 0 to 4+ scale for 15 parameters of renal structure. Means of these renal "pathology scores" correlated with counts of polymorphonuclear leukocytes and lymphocytes in the peripheral blood. The highest counts and scores were found in rats given NDGA and exposed to endotoxin, either by injection or by oral feeding of endotoxin-containing bacteria. Counts and scores were lower in the absence of endotoxin and with non-endotoxin-containing bacteria, given alone or in combination with either NDGA or endotoxin. Results exclude bacterial colonization and intrarenal accumulation of NDGA as causes of nephropathy. They indicate that endotoxin and NDGA act synergistically to provoke renal damage in the germ free NDGA-fed rat and suggest that leukocytes are involved in the process.

Animals

Vertical rectus abdominis musculocutaneous flap for chest wall reconstruction after irradiation.

We have used a contralateral vertical rectus abdominis musculocutaneous flap based upon the superior epigastric vessels in six patients to provide coverage after resection of locally recurrent breast carcinoma in irradiated tissues. Primary healing of defects as large as 16 cm X 35 cm has been obtained using this technique. Although there is no evidence to suggest that such a procedure significantly lengthens survival, it was clearly beneficial to the quality of life in these patients. Our results suggest that older patients with relatively indolent disease receive the greatest benefit from this procedure.

Abdominal Muscles