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Biomedical subjects

H L Davis

Publications and source records attributed to H L Davis.

At least 19 recordsLinked to original sources

Tuberculin skin test reactivity among adults infected with human immunodeficiency virus.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults.

Adult

External-beam radiation for carcinoma of the prostate.

Over 14 years 111 patients with prostatic cancer underwent attempted curative radiotherapy; full data was obtained on 105 patients. The 5-year actuarial survival rate was 62%, with 54 patients still alive at the time of review. The toxicity rate was 94%, and serious late complications occurred in 4%. 40% of the patients developed symptomatic recurrence, and only 4% of the patients had local recurrence.

Aged

Effects of tumor cell viability and inoculum density on growth parameters in the human tumor, soft-agar clonogenic assay.

Four hundred and forty-seven human tumor specimens were accessioned and processed for clonogenic assay, yielding 374 specimens, representing 23 different histiotypes, adequate for culture. Different levels of viable cell inoculum density produced contrasting effects between 255 solid tumors as compared to 72 malignant effusions and 47 bladder washings. All parameters for solid tumor growth were similar except plating efficiency; as inoculum density increased, plating efficiency decreased. For malignant effusions, no significant differences were noted for colony numbers or plating efficiency, but numbers of evaluable cultures increased significantly with increasing inoculum density. Bladder barbotage specimens followed a pattern similar to that of malignant effusions, but the only parameter significantly affected by increasing cell inoculum was colony number which increased proportionally to an increase in number of cells plated. The storage of 109 solid tumors at 4 degrees C, for culture at a later date, resulted in an overall decrease in cell viability (mean, 23.9%) as compared to 161 tumors processed on receipt (mean, 31.1%). This decrease in viability did not adversely affect growth parameters or culture evaluability rates. Based on a lower viable cell inoculum, the percentage of plating efficiencies of stored tumors was significantly higher (geometric mean, 0.127 compared to 0.079 for direct culture), colony numbers were similar for both groups, and culture evaluability rates did not differ greatly (80 and 76%).

Agar

Comparison of fiber size and phenotypic gene expression in muscles of dystrophic C57BL/6J DY2J/DY2J mice.

Considerable evidence has shown a correlation between fiber size and degree of necrosis in dystrophic muscles of hamster, X-linked muscular dystrophy (MDX) mice and humans. It has been proposed that small-caliber fibers have an immunity to the phenotypic expression of the dystrophic gene(s). The results from the present study show a discordance between fiber size and necrosis in dystrophic muscles of C57BL/6J dy2J/dy2J mice. Extensor carpi radialis longus and brevis muscles (ECRL and ECRB respectively) were compared in normal and dystrophic 2-week, 4-week and 12-month animals by measuring the mean cross-sectional area of type II fibers, determination of relative proportions of types IIA and IIB fibers and calculation of percentage of fibers exhibiting centronucleation in an entire cross-section of muscle (stained for haematoxylin and eosin or ATPase). The ECRL and ECRB muscles were found to have identical sizes of fiber at each of the 3 ages studied and similar proportions of fiber types, yet the former muscle developed and retained significantly more necrosis (manifest as centronucleation) than the latter.

Age Factors

Myotrophic effects on denervated fast-twitch muscles of mice: correlation of physiologic, biochemical, and morphologic findings.

Certain morphological, biochemical, and physiological parameters were assessed in fast-twitch muscles of 6-week-old mice with unilateral hindlimb denervation for 4 weeks. Some of the mice received daily injections (i.p.) of nerve extract throughout the period of denervation. Values from treated and untreated denervated muscles were compared with each other and with those from contralateral, innervated controls. The cross-sectional areas of denervated types IIA and IIATy muscle fibers were 45% and 28% greater, respectively, in muscles of treated than of untreated mice, which resulted in greater maximal tetanic tension. Injection with nerve extract did not influence the postdenervation reduction of phosphorylation of myosin light chain 2-fast nor the loss of posttetanic twitch potentiation, two parameters thought to be related. Denervation produced a significant decrease in relative content of cytosolic parvalbumin; however, this change was completely prevented by administration of nerve extract. This latter finding correlated with the amelioration of greater than 50% of the postdenervation prolongation of half-relaxation time of the twitch in treated than in untreated muscles. More than half of the prolongation of time-to-peak of the twitch was also prevented in denervated muscles of treated than of untreated mice.

Animals

Effect of denervation and nerve extract on ultrastructure of muscle.

Changes in denervated skeletal muscle result both from disuse and loss of neurogenic trophic substances. It had been shown that administration of nerve extract intramuscularly in rats or systemically in mice prevented the nondisuse component of atrophy in denervated muscle. Amelioration of atrophy was manifested as reduced losses of weight, protein, and cross-sectional areas of fiber in denervated hind-limb muscles. The present study assessed the effects of nerve extract on ultrastructural changes in different types of fiber (as classified by activity of ATPase) in mouse skeletal muscle denervated for 7 days. Denervated and contralateral innervated muscles of treated and untreated mice were examined by electron microscopy, and morphological parameters were quantitated by stereological techniques. Denervated muscles exhibited smaller reductions of several ultrastructural changes in treated than in untreated mice including sizes of mitochondria, and percentage volume per fiber of mitochondria, sarcoplasmic reticulum, and t-tubules. The magnitude of the myotrophic effects varied in the different types of fiber, with amelioration of between 50 and 95% of the postdenervation changes.

Animals

ECOG phase II trials of MGBG, chlorozotocin, COM multidrug therapy in advanced measurable colorectal cancer.

The Eastern Cooperative Oncology Group (ECOG) entered 326 patients with advanced measurable colorectal cancer into four phase II drug or drug combination trials. Previously treated and chemotherapy-naive patients were eligible. Chlorozotocin was administered to 83 patients (51 previously treated), methyl-glyoxal-bis-guanylhydrozone (MGBG) to 90 patients (58 previously treated), and two regimens of the three-drug combination of cyclophosphamide, vincristine, and methotrexate (COM) to 153 patients (120 previously treated). The multidrug regimen had been developed specifically for previously treated patients. In this trial, chemotherapy-naive patients were no more likely to respond than were members of the previously-treated group. Even among previously untreated patients, response rates did not exceed 10% in any of these phase II programs. They are not recommended for further trials in patients with colorectal cancers.

Adenocarcinoma

Sciatic nerve protein composition in normal and dystrophic C57BL/6J mice.

Proteins were extracted from homogenized sciatic nerves of normal C57BL/6J and dystrophic C57BL/6J dy2J/dy2J mice and were separated on SDS-polyacrylamide slab gel electrophoresis. Proteins visualized on Coomassie blue-stained gels were resolved into 43 bands. These were quantitated by densitometric scanning and continuous plotting of OD 595, then heights and areas of individual peaks were measured. The relative proportions of 5 proteins of intermediate molecular weight (37-92 kDa) were greater in dystrophic than normal nerves. These augmented proteins were not related to myelin or nuclear histone proteins.

Animals

Effect of denervation and injected nerve extract on soluble proteins of extensor digitorum longus muscles of rats.

Right extensor digitorum longus muscles of rats were denervated. After 7 days the soluble proteins were extracted from denervated and contralateral control muscles and fractionated into 32 bands by electrophoresis on polyacrylamide gels. The distribution of protein among the bands was calculated for each muscle. In denervated muscles the proportion of the total protein was increased in 11 bands and decreased in 6, relative to control muscles. Daily injection of denervated muscles with nerve extract, previously shown to offset postdenervation loss of muscle protein and shrinkage of muscle fibers, prevented the increased level of one protein and exaggerated the change in two others. Two bands, not affected by denervation, were decreased by the extract.

Animals

Myotrophic effects on denervation atrophy of hindlimb muscles of mice with systemic administration of nerve extract.

Atrophy was assessed in denervated hindlimb muscles of adult mice which either were not otherwise treated or received daily intraperitoneal injections of extract of rats' sciatic nerves. After 7 days, the denervated muscles of injected animals exhibited significantly smaller decreases in wet weight, total protein and cross-sectional areas of muscle fibers relative to innervated contralateral control muscles. The effects of denervation and nerve extract on different muscles varied.

Animals

Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, or mesothelioma.

Patients with objectively measurable soft tissue sarcoma, bone sarcoma, or mesothelioma who had failed at least one prior chemotherapy regimen received either bleomycin (20 U/M2 i.v. day 1 each week), chlorozotocin (150 mg/M2 i.v. q6 weeks), MGBG (500 mg/M2 i.v. each week, escalated in 50 mg/M2 weekly increments to a maximum dose of 700 mg/M2), or bruceantin (5.5 mg/M2 days 1, 8, 15, and 22, with cycles repeated every 6 weeks). One hundred eighty patients were evaluable: 53 on bleomycin, 51 on chlorozotocin, 38 on MGBG, and 38 on bruceantin. Two partial responses resulted from bleomycin, and one each from chlorozotocin and MGBG. Both responders on bleomycin had mesothelioma. Seventy-four percent of the patients were of ECOG performance status 0 or 1, and over half on each arm had moderate or worse toxicity. At these doses and schedules, none of the four drugs tested was active against previously treated sarcomas. Bleomycin, however, should be considered for further evaluation in mesothelioma patients.

Adolescent

Partial purification from mammalian peripheral nerve of a trophic factor that ameliorates atrophy of denervated muscle.

Atrophy in a denervated muscle results from the disuse caused by paralysis of the muscle, and from the loss of special nerve-derived trophic substances. Crude preparations of protein from rat or sheep sciatic nerves have been shown to prevent the nondisuse atrophy of the rat's extensor digitorum longus muscle when injected into the denervated muscle daily for 1 week. Aqueous extracts of sheep sciatic nerves were fractionated by gel-liquid chromatography. After each step of purification, the trophic activities of the various fractions were assayed in the rat. Cross-sectional areas of type IIB muscle fibers in the denervated extensor digitorum longus were measured to determine which injected fraction contained the active principle. Affinity chromatography on concanavalin A-agarose revealed that the trophic substance was a glycoprotein. Further fractionation by gel filtration indicated that the active substance had a molecular weight in the range of 90,000 to 130,000. Ion-exchange chromatography on DEAE-cellulose yielded an active fraction containing substances with isoelectric points between 7.0 and 7.2, determined by polyacrylamide gel isoelectric focusing. This active fraction was resolved into 15 bands on sodium dodecyl sulfate-gel electrophoresis. Two bands had apparent molecular weights of 91,300 and 127,400. The active factor was shown thus to be a glycoprotein, molecular weight approximately 100,000, isoelectric point approximately 7.0. It may be one of two protein bands that are similar to it in molecular weight.

Animals

Early use of oral theophylline in hospitalized chronic obstructive pulmonary disease patients: cost-containment through medical education.

This study measured the impact of an education program conducted by a clinical pharmacist on early conversion from intravenous to oral theophylline in hospitalized chronic obstructive pulmonary disease patients. Two separate two-month audit periods were conducted on the pulmonary medicine service (PMS) of a teaching hospital. During the first audit period (pre-ed), no education was provided. Prior to each month of the second two-month audit period (post-ed), an education program and handout outlining the rationale for early conversion from intravenous to oral theophylline was presented to medicine residents rotating onto the PMS. The results of this preliminary study suggest that the education program was responsible for a statistically significant decrease in intravenous aminophylline therapy from three days (pre-ed) to one day (post-ed). As a result of the reduction in length of intravenous therapy, both drug costs and patient charges were reduced by a statistically significant amount.

Administration, Oral

Prevention of denervation atrophy in muscle: mammalian neurotrophic factor is not transferrin.

Atrophy in a denervated muscle results from the disuse caused by paralysis of the muscle, and from the loss of special neurotrophic substances. Daily injections of proteins extracted from rats' sciatic nerves have been shown to prevent the non-disuse atrophy of rats' muscles denervated for 7 days. The trophic factor from chicken sciatic nerve which stimulates differentiation in aneural chick muscle in vitro has been purified and found to be closely similar to transferrin. We undertook to determine whether the trophic properties of mammalian nerve extract on denervated rats' muscles in vivo were due to the presence of serum transferrin in the extract. Atrophy was measured as the reduction in cross-sectional areas of type IIB fibers in the extensor digitorum longus muscle. Muscles denervated for 7 days and injected daily with 1 of several doses of iron-conjugated rat transferrin exhibited a rate of atrophy equivalent to that in denervated muscles that either were not treated or were injected with saline. Denervated muscles injected with crude extract of rats' sciatic nerves had significantly less atrophy than their controls. Removal of transferrin from the crude extract by immunoaffinity chromatography did not diminish its ameliorative effects on denervated muscle. Therefore, the trophic action of mammalian nerve extract on denervated rats' muscles in vivo is not due to the presence of serum transferrin in the extract.

Animals

Effect of nerve extract on number of acetylcholine receptors in denervated muscles of rats.

We have shown elsewhere that injection of an extract of peripheral nerves reduces the atrophy of denervated muscle fibers in vivo. Denervated muscle fibers exhibit supersensitivity to acetylcholine owing to the production of extrajunctional acetylcholine receptors. We sought to determine whether or not injection of nerve extract can influence the numbers of acetylcholine receptors in normal, immobilized, or denervated extensor digitorum longus muscles of rats. The receptors were assayed by measuring the binding of 125I-alpha-bungarotoxin. Normally innervated muscles injected with nerve extract exhibited slightly increased binding of the toxin, but this was due to the injections per se. Immobilization caused a small, transient increase in binding of alpha-bungarotoxin, whereas denervated muscles bound considerably more toxin than innervated controls. The nerve extract did not reduce or prevent the increase in acetylcholine receptors caused by denervation but instead caused an even greater increase. We concluded that the neurotrophic factor extracted from peripheral nerve that is responsible for the maintenance of the sizes of the fibers probably does not down-regulate extrajunctional acetylcholine receptors. The limitation of acetylcholine receptors to the end-plate regions is probably effected by a different mechanism which has yet to be elucidated.

Acetylcholine

Anticonvulsants in epileptic fowl.

The high seizure susceptibility in epileptic fowl is an autosomal recessive trait characterized in homozygotes by seizures that occur spontaneously and in response to photic stimulation or hyperthermia. Both of the latter stimuli can be used to evoke seizures in drug studies. Epileptic fowl have abnormal inter-ictal EEG activity. When exposed to photic stimulation spiking is apparent on the EEG at seizure onset. Phenobarbital, primidone, phenytoin, and valproic acid reduce seizure susceptibility at plasma concentrations approximating those used to control generalized and focal cortical tonic-clonic seizures in humans. Carbamazepine and the benzodiazepines also reduce seizure susceptibility. These data indicate that epileptic fowl provide a useful model for generalized and focal cortical tonic-clonic epilepsies. Ethosuximide was inactive in epileptic fowl. However, trimethadione had anticonvulsant activity indicating that this model is only relatively specific for the above seizure types. When seizures were evoked by hyperthermia phenobarbital but not phenytoin or valproate reduced seizure susceptibility. GABA (gamma-aminobutyric acid), AOAA (amino-oxyacetic acid) and THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c] pyridin-3-ole, a glial specific inhibitor of GABA uptake) all have anticonvulsant activity against seizures evoked by photic stimulation in young chicks. These data indicate that this model may be particularly useful for studies of the anticonvulsant activity of compounds designed to enhance GABAergic transmission.

Animals