Biomedical subjects

D Glover

Publications and source records attributed to D Glover.

At least 73 records · Page 4Linked to original sources

PubMed1976

Physiopathogenesis of subdural hematomas. Part 1: Histological and biochemical comparisons of subcutaneous hematoma in rats with subdural hematoma in man.

The dorsal subcutaneous injection in rats of 12 ml or more of autologous hemolyzed whole blood clotted in situ induced the formation of sterile, hemispheric lesions, 47% of which showed an initial decrease in volume followed by a progressive enlargement. The behavior, histology, and biochemical characteristics of the liquid contents of these lesions were found to be remarkably similar to those of subdural hematomas in man. To evaluate the role of the various blood components that may have influenced the formation and growth of these lesions, more than 150 clots composed of human platelet-free plasma, autologous hemolyzed blood, or autologous whole blood were implanted subcutaneously in rats by either surgical or injection techniques. The in vitro behavior of the different clots used was also assessed. This systematic approach led to the following conclusions: 1) the composition and volumes of the clots are critical variables; 2) plasma-fibrin provides the matrix shape of the lesions; 3) the breakdown products derived from erythrocytes, hemoglobin, leukocytes, and other solid blood elements induce neomembrane formation and contribute to the lesion's subsequent growth; and 4) inflammation mechanisms appear to be essential, while cerebrospinal fluid plays no discernable role in this process.

Animals↗

PubMed1976

Physiopathogenesis of subdural hematomas. Part 2: Inhibition of growth of experimental hematomas with dexamethasone.

A previously described experimental hematoma model, achieved by the subcutaneous injection of 12 ml of autologous hemolyzed blood clotted in situ, was made in 33 rats. Sventeen animals served as controls; the other 16 received daily intra-muscular injections of dexamethasone. After an initial decrease in size, 47% of the lesions in the control animals enlarged to a mean weight of 12.1 +/- 2.5 gm, while the lesions in the 16 steroid-treated rats weighted 3.2 +/- 0.70 gm (p less than 0.01). Histologically, lesions from the steroid group showed absence of neomembrane formation. These data offer further support to the theory that the neomembrane development and subsequent enlargement of subdural hematomas is due to inflammatory reactions of tissues in contact with large blood clots.

Animals↗

PubMed1976

Diethylstilbestrol in the treatment of rape victims.

Despite growing controversy surrounding its use as a "morning after pill," diethylstilbestrol (DES) is prescribed liberally for rape victims. Guidelines for its use in these patients is lacking. Of 150 consecutive rape victims treated at a university medical center, 63 (42 percent) received prescriptions for DES. Of the 55 (87 percent) on whom follow-up was obtained, in 40 (73 percent) there were substantial side effects-nausea or vomiting, or both. At least six (11 percent) did not complete therapy because of these side effects. The authors offer guidelines for use of DES for rape victims and a plan for patient education and follow-up.

Diethylstilbestrol↗

PubMed1975

The CLUE test. A multiparameter coagulation and fibrinolysis screening test using the platelet aggregometer.

Optical density measurements of plasma clot formation and lysis were recorded using a platelet aggregometer and strip chart recorder. It was discovered that, by adding standard solutions of ellagic acid-activated partial thromboplastin, urokinase, and CaCl2, and monitoring the reaction via the recorder, characteristic curves would be generated by normal human plasma. The curve segments were labeled Tc (clotting time), which correlated with the activated partial thromboplastin time, Fc (maximum optical density change), which paralleled fibrinogen concentration, and Tl (lysis time), which corresponded generally to plasminogen levels. Deviations from normal curve segments, observed in disseminated intravascular coagulation, hypo- and hyperfibrinogenemia, factor VIII deficiency, severe hepatocellular disease, juvenile rheumatoid arthritis, and neonates (normally low in plasminogen), indicated abnormalities which were substantiated by standard procedures. This new test, given the acronym "CLUE" for clotting and lysis, urokinase enzyme activated, appears to be sensitive, inexpensive and easily performed on a sample of 0.2 ml. of plasma in only 15 minutes.

Blood Coagulation↗

PubMed1975

Local alterations of hemostatic-fibrinolytic mechanisms in reforming subdural hematomas.

Multiple chemical and coagulation determinations were undertaken on the subdural hematoma fluid from the reformed effusions of two patients. It was found that plasma or blood repeatedly reentered the subdural cavity. Coagulation studies compared the in vitro effects of subdural fluid with those of cerebrospinal fluid, serum, and a buffer control. Despite some chemical differences, the subdural fluids from both patients behaved similarly by (1) accelerating the intrinsic clotting system, (2) producing defective clot formation, and (3) accelerating the fibrinolytic system. It is presumed that these continuous hemostatic-fibrinolytic alterations, acting in the subdural sac, may have important implications in the growth and reformation of subdural hematomas, and a hypothesis of the mechanisms involved is presented.

Aged↗

PubMed1974

Chronic subdural hematoma: concepts of physiopathogenesis. A review.

From the present review it seems clear that the physiopathogenesis of the chronic subdural hematoma is far from being completely understood. However, an analysis of the known data can be summarized as follows: The development of subdural hematomas most likely occurs following minimal trauma in those patients with predisposing factors. Experimental data substantiates the fact that an accumulation of clotted blood in the subdural or subcutaneous space induced the formation of the fibroplastic neomembrane. The hypothesis that blood must come in contact with cerebrospinal fluid in order for the growth to occur, is still controversial. It has been virtually disproven that osmosis, referring to the electrolyte gradient as measured by freezing point depression, has any significance as a growth inducing factor. The protein oncotic gradient theory, having been the most widely accepted explanation as to the progressive enlargement of the subdural hematoma sac, has little experimental data supporting it. A larger body of clinical evidence exists supporting the concept that plasma and/or erythrocytes continuously penetrate into the subdural cavity, where enhanced fibrinolytic activity is present. However, this chronic rebleeding cannot fully explain the observed growth, because the composition of the hematoma fluid is smoewhat different from serum or plasma, and the protein content is also progressively diluted by fluid arising from an unknown source. There is some clinical and experimental evidence to suggest that a production-reabsorption balance may be a significant growth variable. No work has been done to define the role, if any, of local inflammatory mechanisms in the chronic subdural hematoma. Sound clinical evidence has shown that after the initial formation of the subdural clot, growth follows, than a slow, complete reabsorption usually occurs. Aside from the plausible production-reabsorption balance concept, it is not known why the evolution proceeds in this manner.

Animals↗

PubMedDate not supplied

Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of drug hydrophilicity.

In attempting to account for the ability of most solid tumors to restrict the absorption of WR-2721, aminopropyl-aminoethylphosphorothioate, we examined a number of drug characteristics which might allow for this restriction, and observed that drug hydrophilicity was a major contributing factor. When the highly hydrophilic WR-2721 was dephosphorylated, the drug became less hydrophilic and could readily cross tumor cell membranes. In addition, conventional radioprotectants, such as cysteine and mercaptoethylamine, were shown to be less hydrophilic than WR-2721 and also to cross tumor membranes readily. Therefore, drug hydrophilicity would appear to be the factor underlying the ability of WR-2721 to selectively protect normal tissues while most other protectors alter the radiation resistance of normal and tumor tissue alike. A red blood cell model for studying this problem in greater detail is described.

Absorption↗

PubMedDate not supplied

Clinical trials of WR-2721 with radiation therapy.

The radioprotector with clinical potential, S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) is undergoing two Phase I trials. The objectives of these trials are 1) to determine the maximum tolerated dose (MTD) of WR-2721 in a single dose and 2) to determine the highest dose of WR-2721 that can be tolerated daily in the greatest number of fractions per week. A total of 65 patients have been treated. The single maximum tolerated dose has not yet been reached, though 740 mg/m2 is well tolerated. A single dose of 910 mg/m2 has been successfully administered to one patient. The multiple dose MTD is at an early stage with patients currently receiving 170 mg/m2 four times a week. Among the toxicities noted in both trials are hypotension, hypertension, emesis and somnolence. In addition, in the multiple dose trial there have been three patients who have had allergic reactions including one which was life-threatening. Phase II studies are planned and will begin when the maximum tolerated dose is established from each Phase I trial.

Amifostine↗

PubMedDate not supplied

Bone and joint infections caused by Kingella kingae: six cases and review of the literature.

Six cases of Kingella kingae arthritis, osteomyelitis, and diskitis were studied, and data were reviewed from an additional 23 cases in the English-language literature. K. kingae is a slow-growing, fastidious, gram-negative microorganism that colonizes mucous membranes of the upper respiratory tract. Infections were predominantly seen in infants and young children (86% of cases) and were preceded by an upper respiratory tract infection in 31% of patients. Low-grade fever (38 degrees C-39 degrees C) and pain or swelling involving the affected limb developed insidiously. However, 76% of the infections were diagnosed within 1 week after the onset of symptoms. The knee was involved in 47% and the hip in 33% of cases of arthritis. Osteomyelitis mainly involved the femur (36%); four cases of osteomyelitis (29%) were diagnosed as diskitis. The erythrocyte sedimentation rate was greater than 20 mm/h in all patients. Gram stains of aspiration fluid were positive in 19% of cases, whereas blood cultures yielded growth in only 5%. Radiographic signs indicating the presence of osteomyelitis were observed in 93% of patients. All patients recovered completely. K. kingae is an important causative agent in indolent bone, joint, and intervertebral disk infections.

Arthritis, Infectious↗

PubMedDate not supplied