Sports injury research. The numerator, denominator, and the population-at-risk.
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Athletic Injuries↗
Biomedical subjects
W R Clark
Publications and source records attributed to W R Clark.
Clearance of aerosolized 99mTc-diethylenetriaminepentacetate before and after smoke inhalation.
The pulmonary clearance of aerosolized 99mTc-diethylenetriaminepentacetate (DTPA) was studied in mongrel dogs immediately after exposure to wood smoke to see if a sensitive, objective way of assessing the degree of pulmonary injury might be found. Animals were studied in four groups as follows: control, following five minutes, two minutes, and 15 seconds of smoke exposure. Chest roentgenograms and 133Xe scans were taken before and after smoke exposure. The DTPA clearance was more sensitive in detecting injury than either of these imaging techniques. The DTPA clearance rates increased in a dose responsive way following smoke inhalation: 2.4 percent and 12.1 percent excreted per minute for control animals and those exposed to five minutes of smoke, respectively. Seven patients in a clinical trial of DTPA following smoke exposure are described; their DTPA clearance rates were all normal, although five were active cigarette smokers. Despite encouraging results in animal experiments, DTPA clearance studies may be of little practical value in the clinical setting of acute inhalation injury.
Aerosols↗
A calcium- and perforin-independent pathway of killing mediated by murine cytolytic lymphocytes.
Cytotoxic T lymphocytes have been thought to lyse cellular targets in the past by a calcium-dependent pathway. This notion was recently supported by the identification and purification of a pore-forming protein (perforin) from the granules of these cell types. Here, we show that perforin is absent from a number of cell lines that nevertheless display vigorous cytolytic activity toward target cells. The cytotoxic activity of eight murine CTL lines is completely or partially retained in the absence of calcium. The calcium-independent lytic activity is associated with two subcellular fraction peaks isolated by Percoll gradient centrifugation, e.g., a heavy density band migrating with granule markers and a lighter band corresponding to free cytosolic material. These results suggest a complex picture of lymphocyte-mediated killing involving probably multiple mechanisms and mediators that may operate in concert or independently in the delivery of the lethal hit.
Animals↗
The role of Ca2+ in activation of mature cytotoxic T lymphocytes for lysis.
We carried out a detailed analysis of the requirement for Ca2+ in the lysis of target cells by cloned cytotoxic T lymphocytes (CTL). In direct, antigen-specific lysis we always observed an influx of Ca2+ into the CTL concomitant with target cell binding. However, we never observed an increase in CTL Ca2+ content during lectin-mediated lysis, or nonspecific lysis by phorbol myristate acetate-induced CTL. We found that in all three types of lysis (direct, lectin-mediated lysis, C or phorbol myristate acetate-induced) the requirement for Ca2+ in lysis was dictated by the target cell used; the same CTL can kill one target cell in the absence of detectable Ca2+, and absolutely require Ca2+ for the lysis of another target cell. Target cell killing, when it occurred in the absence of Ca2+, was accompanied by microtubule organizing center reorientation in the CTL, showing that this function is not uniformly Ca2+ dependent. These results provide further evidence that Ca2+ is not always required for activation of the lytic pathway in CTL, although Ca2+ may be absolutely required for other CTL functions such as interleukin production or expression of the interleukin 2 receptor.
Animals↗
Resistance of cloned cytotoxic T lymphocytes to cell-mediated cytotoxicity.
Cloned CTLs show an unusually high resistance to lysis by effector CTLs. Several cloned CTL lines in our laboratories are absolutely refractory to lysis by other cloned CTLs, either (a) directly, (b) in the presence of lectin, or (c) by PMA-induced CTLs. They can be lysed to some extent by primary CTL, although they are less than 5% as sensitive as target cells normally used to assay primary CTL lytic activity. Lysis of cloned CTLs by primary CTL effector cells is not enhanced by the presence of lectin, and cloned T cells are also highly resistant to lysis by primary lymphokine-activated killer cells. Cloned CTLs are highly resistant to lysis by isolated CTL granules that contain the membranolytic pore-forming protein (PFP or perforin), while non-CTL targets are highly susceptible to granule-mediated killing, indicating that cloned CTLs resist lysis not only at the intact effector cell level but also when soluble effector proteins are used. This resistance mechanism may explain how CTLs kill but spare themselves from being killed during the cytolytic event.
Animals↗
Target cell recognition structures in LDCC and ODCC.
Cytotoxic T lymphocyte effector cells specific for a defined class I antigen can kill target cells displaying a wide range of different class I proteins in the presence of certain lectins and oxidizing agents. However, optimal lysis of the target cell (TC) still requires interaction of the CTL with the TC class I proteins. This raises the question of how the lectin or oxidizing agent alters the system in such a way that an "inappropriate" CTL-TC interaction takes place, in a class I-dependent manner. In this study we show that if papain-sensitive molecules are cleared from the TC surface and are allowed to regenerate in the presence of tunicamycin, the cells still serve as targets in direct, class I antigen-specific CTL killing, but not in LDCC or ODCC. Target cells treated in this way display N-linked carbohydrate-less class I proteins, and presumably other N-linked carbohydrate-less, papain-sensitive molecules as well. We present data showing that both types of molecules are important in nonspecific lytic reactions.
Animals↗
Cardiac transplantation: first-year experience in a community hospital.
The issue of decentralizing heart transplant services, formerly restricted to a few large medical centers, is currently under review by federal and state governments. We present the results of the first year of cardiac transplantation at a 385-bed community hospital. Twelve patients were selected according to generally accepted criteria from a pool of 24 referrals, all from within 75 miles of our institution. All patients were in New York Heart Association Class IV preoperatively. The one-year survival rate was found to be 82%, which is equivalent to that reported by established centers. All surviving patients were fully rehabilitated. Rates of infection and rejection were lower than expected, and costs were about half the national average. This series, in all likelihood, tests the limits to which the decentralization of cardiac transplant services can be taken. We conclude that cardiac transplantation can be accomplished at a community hospital with results, even for the first patients undergoing transplantation, comparable to those obtained by established programs at major medical centers.
Adult↗
Ureteropelvic junction obstruction. I. Observations on the classic type in adults.
A total of 111 adults underwent repair of congenital ureteropelvic junction obstruction during a 15-year period. A majority of the patients (77 per cent) presented with flank pain. In all patients established (89 per cent) or intermittent (11 per cent) hydronephrosis was demonstrated. In contrast with our former practice, a majority of the patients (86 per cent) underwent dismembered pyeloplasty with intubation. Of the 10 hypertensive patients 8 remained hypertensive postoperatively but only 3 of 22 patients with stones had recurrent calculi. The success rate was 95 per cent with 1 operation. Three patients required a second repair and 1 underwent nephrectomy. Therefore, the eventual success rate was 99 per cent.
Adult↗
Use of a balanced bowel preparation solution in urological surgery.
A balanced bowel preparation solution was used in 25 patients undergoing cystectomy and in 31 undergoing radical retropubic prostatectomy. No significant problems occurred during the preparation, intraoperatively or postoperatively. Metronidazole and neomycin were used for antibiotic coverage. Consistent with the findings of other studies no significant physiological shifts occurred and patient acceptance was good. Savings were noted in cost, duration of hospitalization, time needed for nursing care and nutritional status. The balanced bowel preparation solution is an attractive and equally effective alternative to the standard laxative-enema bowel preparations for urological operations.
Electrolytes↗
An improved cryopreservation procedure for human fetal pancreas tissues.
Improved viability and function of insulin-producing beta (B) cells of frozen-stored human fetal pancreatic tissue was obtained by a two-step method utilizing high concentrations of dimethyl sulfoxide (DMSO). Human fetal pancreata (14-23-week gestation) obtained from pathologic abortions were teased and cultured overnight. Prior to freezing the tissues were immersed in 0.9% saline containing 0.5 M DMSO for 30 min (room temperature) and then placed in 2.1 M DMSO on ice for 5 min. The tissues were frozen by the method previously developed in our laboratory and stored at -196 degrees C. The frozen-stored tissues were subsequently thawed at 24 degrees C and cultured overnight before viability testing. Viability and function of the B cells were assessed by several specific assay methods; glucose plus theophylline-induced insulin release during static incubation and perifusion, 3H-leucine incorporation into insulin, and insulin content of the tissue grown in athymic mice for 7 days. The response to glucose plus theophylline stimulation, measured on the frozen-thawed tissue one day after thawing, was 80% of the level measured in control tissue maintained in organ culture. Frozen-thawed tissues maintained in organ culture for 1 week responded comparably in the in vitro assay systems. The insulin content of frozen-thawed pancreatic tissue removed from athymic mice 1 week after transplantation was approximately 60% of the amount measured in the control grafts. These results demonstrate the utility of our procedure in the maintenance of the viability and function of frozen-stored human B cells both in culture and after transplantation.
Animals↗
Burn mortality. Experience at a regional burn unit. Literature review.
The burn patient population at a regional burn unit in Central New York State, from 1974 through 1980, (N = 507) is described completely in terms of age, total burn size, full thickness burn size, sex, race, etiology of burn, inhalation injury, referral pattern, distance from burn unit, interval to admission, length of hospitalization and causes of death. The interrelationship of these factors is examined to define their contribution to injury severity and identify variables useful in predicting death. Demographic profiles are compared to the population base, and the case-mix of patients is contrasted with that of other burn units. A logistic model to predict death is developed using the variables of full-thickness burn size, age, age 2, and the presence of inhalation injury. The power of statistical methods to predict death is discussed in relation to the 37 patients who died with emphasis on the outliers present in unscreened patient populations. The point is made that any clinically useful index of burn severity must include a factor reflecting the physiologic stress imposed on the individual patient. Clinical issues pertaining to the treatment of nonsurvivors are discussed in relation to the physician's responsibility, euthanasia, and resource consumption. Results of treatment are difficult to evaluate because of the variables of patient selection, injury severity, time, and the absence of a satisfactory measure of morbidity. Effective prevention is the only way to eliminate the deaths of victims who do not survive to enter the health care system and the morbidity that inevitably results from tissue loss. From the standpoint of public health, burn morbidity may have an economic impact far different from that of burn mortality. Supraregional burn units with access limited to seriously but not hopelessly burned individuals are proposed. Supraregional burn units would make the delivery of burn care more efficient and allow the selection of a patient sample homogeneous in terms of severity, thus increasing the reliability of treatment evaluations.
Adolescent↗
Class I MHC antigens in the generation and expression of promiscuous cytotoxic cell function.
In recent years investigators from a number of laboratories have described antigen nonspecific, lymphocyte-mediated cytotoxicity generated by TCGF alone, in the absence of antigen or mitogen. The exact origin of the cells mediating this cytotoxicity, in either mouse or humans, is unknown. We found that when mouse spleen cells are incubated with higher than normal concentrations of TCGF, good levels of cytotoxicity toward allogeneic, NK, and untransformed self target cells are generated by day 5 or 6 in culture. We were unable to block the lysis of any of these target cells with antibodies to target cell class I antigens. However, generation of this cytotoxicity from naive spleen cells was very strongly blocked by anti-class I MHC antibodies. When T cells from spleen were extensively purified, they did not respond to TCGF at any concentration unless adherent cells were added back. Generation of cytotoxicity under these conditions was also blocked by class I antibodies. Generation of promiscuous killing activity by PMA and ionomycin, on the other hand, was class I independent. Our data suggest that pre-CTL, under the influence of TCGF, can be activated to CTL and that under the continued influence of TCGF can be driven into a so-called "promiscuous" state of cytotoxicity. Possible roles for class I antigens in this process are discussed.
Animals↗
Multiple pathways for antigen-independent activation of a T helper hybridoma.
An important question in mitogen activation of T cells is whether the T cell must interact with a major histocompatibility complex product during the activation process. The T helper hybridoma AODH 7.1 is specific for human gamma globulin in the context of IEd, and when activated secretes interleukin 2. The mitogen concanavalin A (Con A) can activate AODH 7.1 cells directly, but two other standard T cell mitogens, phytohemagglutinin (PHA) and neuraminidase-galactose oxidase, cannot. However, Con A, PHA and neuraminidase-galactose oxidase could all activate AODH 7.1 when presented on various cloned class II+ cell lines. There was an absolute requirement for the presentor cell to be class II+, and the activation signal on mitogen-treated class II+ presentor could be blocked by monoclonal antibody to the class II antigens. To determine if class II molecules were absolutely required for the presentation of a mitogen activation signal we used class II- LtK- L cells and two LtK- cell class II gene transformants as presentor cells. Only the class II+ transformants, but not the class II- LtK- cells, could present either Con A or PHA. The class II requirement cannot be bypassed through provision of soluble factors. However, when Con A was used to activate AODH 7.1 cells directly, it appeared to be acting in a transmembrane fashion. It was not the case that AODH 7.1 cells were responding to Con A on a neighboring AODH 7.1 cell, and no class II antigens were involved. These results are consistent with the idea that different routes of activation exist for T cells, at least at the level of signal recognition.
Animals↗
Genital filariasis in Minnesota.
Genitourinary filariasis is a well-known entity in most tropical areas. However, filariasis cannot be eliminated from the differential diagnosis of testicular, epididymal, or spermatic cord masses in nontropical climes. We report a case of filariasis of the spermatic cord that manifested as an unexplained scrotal mass in a patient in Rochester, Minnesota.
Adult↗
Henoch-Schönlein purpura and the acute scrotum.
Scrotal involvement occurs in between 2% and 38% of patients with Henoch-Schönlein purpura. We report on a child in whom acute scrotal swelling was the initial presentation of this syndrome. In only four previous cases have the initial symptoms of Henoch-Schönlein purpura been suggestive of testicular torsion.
Acute Disease↗
Fetal pancreas as a donor organ.
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Animals↗
Carcinoma of the seminal vesicle.
Strict criteria were applied to 12 cases of carcinoma of the seminal vesicle in the Mayo Clinic tumor registry. Diagnosis was carcinoma of the seminal vesicle if the neoplasm was a papillary or anaplastic carcinoma localized primarily to the seminal vesicle and no other primary tumors were demonstrated. In addition, some degree of mucin production was required, especially when prostatic involvement was present. Only 2 of our cases and 35 cases reported previously were judged acceptable or probable cases of carcinoma of the seminal vesicle. Prognosis for patients with this tumor is poor. A combination of extirpative surgery and hormonal therapy appears to provide the best opportunity for extended survival, although this remains to be proved.
Adenocarcinoma↗
Detection of herpes simplex virus infection using glucose oxidase-antiglucose oxidase immunoenzymatic stain.
Herpes simplex virus (HSV) infected cells have been detected in tissue culture and human cell specimens by an immunoenzymatic staining method using the fungal enzyme glucose oxidase. Infected cells from culture or human specimens appear as dark blue, brown, or red, depending on the tetrazolium salt used in the disclosing reaction, with virtually no staining of uninfected cells. The specificity and sensitivity of this method and of the more commonly used immunoperoxidase method are comparable, but the immunoglucose oxidase method avoids the problems of nonspecific staining by the endogenous peroxidase present in mucosecretions and inflammatory cells. Staining time can be reduced up to 40% of that necessary for the unlabeled immunoperoxidase procedure without compromising the quality of staining results.
Animals↗