PubMed HealthSearch

Biomedical subjects

S M White

Publications and source records attributed to S M White.

At least 19 recordsLinked to original sources

Early indications of monocrotaline pyrrole-induced lung injury in rats.

Monocrotaline pyrrole (MCTP), a putative metabolite of the naturally occurring plant toxin, monocrotaline (MCT), causes lung injury, pulmonary hypertension, and right cardioventricular hypertrophy when administered intravenously to rats. The lesions caused by MCTP administration are similar to those caused by MCT but appear to occur on a slightly accelerated time course. To explore the onset and development of lung lesions, male Sprague-Dawley rats were treated with a single, intravenous injection of MCTP, and several markers of lung injury were evaluated at early times after administration. Rats received 3.5 mg MCTP/kg or an equal volume of the vehicle, N,N-dimethylformamide (DMF), via the tail vein at time 0 and were killed at 4, 12, 24, 48, 72, or 120 hr after treatment. Beginning at 4 hr, MCTP-treated rats had increased wet lung-to-body-weight ratios (LW/BW). The LW/BW remained elevated at 12 hr, returned to baseline at 24 hr, then increased steadily over the next few days. At 24 hr, the protein concentration of cell-free bronchoalveolar lavage fluid (BALF) was slightly elevated. Lactate dehydrogenase activity in cell-free BALF samples was moderately increased 48 hr after MCTP. Changes in these markers were modest initially but became much more pronounced by 120 hr. Total nucleated cell counts in BALF were variable but were moderately elevated at 120 hr. Cytologic examination of the BALF samples revealed small but significant infiltrates of segmented neutrophils at 4 hr and relatively large infiltrates of segmented neutrophils and small lymphocytes at 120 hr post-treatment. Mature neutrophils had degenerate cytomorphologic characteristics at both 4 and 120 hr. These results confirm that pronounced lung injury is delayed for several days after a single, intravenous administration of MCTP, but they also indicate that subtle lung injury can be detected using quantitative markers quite early after MCTP administration.

Animals

Effects of serotonergic agents on isolation-induced aggression.

A series of serotonergic agents were assessed for their ability to antagonize isolation-induced aggression and their activity to disrupt performance in the rotorod motor coordination test. All compounds with 5-HT1A activity [buspirone, gepirone, ipsapirone, tandospirone (SM-3997), 8-OH-DPAT, Wy-48,723, BMY-7378, Wy-47,846] reduced aggression at doses below those which produced debilitation in the rotorod motor coordination test. In addition, the 5-HT3 antagonist zacopride failed to attenuate aggression or produce debilitation at any of the doses tested; however, the 5-HT2 antagonist ritanserin inhibited aggressive behavior at a high dose which was not debilitating. Benzodiazepines (chlordiazepoxide, diazepam and lorazepam), and antidepressant (desipramine) and an antipsychotic (haloperidol) reduced aggressive behavior only at debilitating doses. Activity at the 5-HT1A receptor, and possibly nonsedative anxiolytic activity, appears to be related to antagonism of isolation-induced aggression.

Aggression

Astigmatism after small incision cataract surgery. A prospective, randomized, multicenter comparison of 4- and 6.5-mm incisions.

Four surgeons evaluated induced astigmatism and postoperative wound stability in a randomized prospective study of 130 patients undergoing cataract extraction. After phacoemulsification through a scleral pocket, patients received either a 6.5-mm diameter silicone optic posterior chamber intraocular lens (PC IOL) folded for insertion through a 4-mm small incision or a 6.0-mm diameter polymethylmethacrylate (PMMA) optic PC IOL placed through an approximately 6.5-mm conventional incision. Vector analysis calculations of prism diopters (D) of mean postoperative-induced keratometric astigmatism for the small incision versus conventional incision groups were, at day 1, 1.54 D versus 3.07 D (P less than 0.0001); at weeks 1 to 2, 1.00 D versus 2.43 D (P less than 0.0001); at 1 month, 0.98 D versus 1.44 D (P = 0.004); and at 3 months, 0.82 D versus 1.03 D (P = 0.089). Subgroup analysis of the suturing technique for the 6.5-mm incision showed that the technique of wound closure, as well as the wound size, influenced the induced astigmatism. For all four surgeons using three methods of suturing the 6.5-mm wound, however, the variability in the amount of induced cylinder was least with the 4.0-mm wound closed with a horizontal mattress suture. Complications in the two groups were comparable.

Aged

Popliteal artery entrapment syndrome.

The purpose of this article was to describe popliteal artery entrapment syndrome, which is a cause of intermittent claudication in a young person, and to illustrate the importance of early diagnosis for successful treatment of this entity. A case report of a 28-year-old man with popliteal artery entrapment syndrome is presented. This patient had a classic history of calf pain that worsened with walking and was relieved by rest, running, or bicycle riding. Physical examination revealed evidence of ischemia in the distal extremity, and arteriography demonstrated signs of chronic occlusive disease. Early treatment might have included surgical release of the popliteal artery and arterial grafting. Due to extensive vascular disease, grafting was not possible and a below-knee amputation was performed. It is therefore essential to diagnose popliteal artery syndrome early for appropriate management.

Adult

Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats.

To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets.

Animals

Plasma membrane lipid organization and the adherence of differentiating lymphocytes to macrophages.

Changes in the packing of phospholipids in the plasma membrane of lymphocytes occur during differentiation within primary and secondary lymphoid organs. As they differentiate, lymphocytes interact with a variety of reticuloendothelial cells, including macrophages. To investigate a possible relation between these two phenomena, the strength of the interactions between lymphocytes and macrophages was measured in vitro as a function of the tightness of packing of phospholipids on the lymphocyte surface. Strength of adherence was measured by the ability of lymphocytes to remain adherent to macrophages when subjected to increasing centrifugal forces. Phospholipid packing was assessed using the fluorescent lipophilic probe merocyanine 540 (MC540), which preferentially binds to bilayers in which the lipids are more loosely packed. Three subpopulations of murine thymocytes were resolved with respect to strength of adherence to peritoneal or thymic macrophages. To determine whether these subpopulations corresponded with the three classes of cells distinguishable by MC540 fluorescence, populations enriched for staining or non-staining cells, and cells sorted on the basis of MC540 fluorescence intensity, were examined. The least fluorescent cells were the least strongly adherent; the most fluorescent cells were the most strongly adherent; and cells of intermediate fluorescence had intermediate adherence. When splenic lymphocytes were examined with respect to adherence to peritoneal or splenic macrophages, similar patterns of fluorescence and adherence were seen. These results suggest that the organization of the plasma membrane lipid bilayer of lymphocytes may be involved in their interactions with macrophages during primary and secondary differentiation. The adherence signal for lymphocytes thus may be similar to that proposed for other blood cells.

Animals

Pulmonary platelet sequestration is increased following monocrotaline pyrrole treatment of rats.

111In-labeled platelets were used to study the localization and survival of circulating platelets at various times after a single, intravenous administration of 3.5 mg/kg monocrotaline pyrrole (MCTP) to rats. Lung injury, assessed from elevated lung weight, lavage fluid total protein and albumin concentrations, and lactate dehydrogenase activity, was evident at Days 8 and 14. In addition, right ventricular hypertrophy was manifested by 14 days after MCTP administration. Pulmonary sequestration of 111In-labeled platelets was also elevated by Days 8 and 14, while circulating blood platelet number remained unchanged. Concomitantly, the hemoglobin concentration and total hemoglobin content of the lung homogenate supernatant in MCTP-treated rats on these days was decreased when compared to those in controls. A decrease in splenic platelet sequestration on Day 14 was accompanied by an increase in the combined radioactivity of the heart and kidneys. Platelet half-life and mean life span were increased only on Day 14. A higher dose of MCTP (35 mg/kg) caused moderate lung injury at 6 hr. However, this treatment did not result in increased platelet sequestration in the lungs, although a trend was observed. Data from this study support the hypothesis that platelets are involved in the development of the pulmonary hypertensive response following MCTP-induced lung injury.

Animals

Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia.

To elucidate further the role of the platelet in the development of monocrotaline pyrrole (MCTP)-induced lung injury and pulmonary hypertension, MCTP-treated rats were made thrombocytopenic by cotreatment with an anti-rat platelet serum (PAS). Lung injury was assessed from increases in lung weight, lavage fluid protein concentration, and lactate dehydrogenase activity and from accumulation in lung tissue of 125I-labeled albumin. These indexes of injury were not different in MCTP-treated rats with normal or reduced platelet numbers at day 4,8, or 14. In MCTP-treated rats not receiving the PAS, pulmonary arterial pressure was elevated by day 8. However, pulmonary arterial pressure was the same as controls at both day 8 and day 14 in MCTP-treated rats made moderately thrombocytopenic by cotreatment with PAS. More marked reduction of platelet number abolished the protective effect of thrombocytopenia against pulmonary hypertension. In a separate series of experiments, treatment with antibodies to platelet-derived growth factor (PDGF), a potential mediator in the response to MCTP-induced injury, did not protect rats from the cardiopulmonary effects of MCTP. These data indicate that moderate reduction of the number of circulating platelets prevents MCTP-induced pulmonary hypertension but not MCTP-induced lung injury, suggesting that the platelet is involved in the pulmonary hypertensive response to MCTP-induced lung injury by unknown mechanisms.

Animals

Effects of chlorphentermine and nitrogen dioxide on murine alveolar macrophages.

Male Swiss-Webster mice were treated daily for 14 days with either 120 mg/kg chlorphentermine (CP) to produce pulmonary lipidosis or an equal volume of water. Animals in each treatment group were then exposed by whole-body inhalation to either air or NO2 for 48 h. Immediately following exposure, alveolar macrophages (MPs) were collected from each animal by bronchoalveolar lavage. Assays performed on adherent viable MPs showed some changes in metabolic reduction, phagocytosis, and killing activity. 5'-Nucleotidase activity and yeast phagocytosis and killing assays suggested that CP elicited an increase in phagocytosis over control levels. Although the percentage metabolic reduction and microbicidal killing activities following CP were not increased when compared to controls, absolute reduction and killing (percentage values times total MPs) were significantly increased. These increased functions seemed to be highly dependent on the large increase in the total number of MPs induced by CP. It is possible that the large accumulation of MPs in the airways of the lipidotic lung may help protect the alveolar epithelium from NO2 by quenching free radicals produced during NO2-induced lipid peroxidation.

5'-Nucleotidase

Emergency obstetric surgery performed by nurses in Zaïre.

In rural northwestern Zaïre nurses at Karawa and Wasolo hospitals were trained to do caesarean sections, laparotomies, and supracervical hysterectomies. In Karawa 278 of 321 caesarean sections were done by nurse-surgeons in 18 months, with two deaths. In Wasolo all 32 caesarean sections in 13 months were done by the nurse-surgeons, with 1 death. Of the 37 laparotomies done in both centres, 16 were by nurse-surgeons, and there were two deaths. Four of the five deaths were attributable to protracted labour with septicaemia (1), postoperative infection (2), and protracted labour with no blood pressure on admission (1). Obstetric operations could safely be performed by specially trained nurses in rural areas of developing countries and the high maternal mortality rate in such areas could thus be reduced.

Cesarean Section

The effect of midazolam administration on the pharmacokinetics of antipyrine in the rat.

1. The clearance and elimination half-lives for i.v. doses of antipyrine were determined in 6 groups of 6 male CD rats with no prior treatment, then again following 7 days treatment with graded oral doses of midazolam, and finally after 3 i.p. doses of phenobarbitone. 2. Substantial increases in clearance and decreases in half-lives were observed following phenobarbitone treatment, demonstrating that antipyrine provides a reliable index of enzyme induction. 3. After treatment with midazolam, maximal induction was seen in animals dosed at 27 or 80 mg/kg per day; an intermediate effect was found with 9 mg/kg per day and no effect at 0.2 and 1.0 mg/kg per day. 4. The results indicate that there is a substantial margin of safety between the proposed human therapeutic doses (7.5 to 15 mg/day) and the minimum effective dose that leads to enzyme induction in laboratory animals.

Animals

Correlations between the human sperm-hamster egg penetration assay and in vitro fertilization results.

The human sperm-hamster egg penetration assay (SPA) has been used to evaluate male fertility under in vivo conditions. The test is not only unstandardized, but agreement does not exist as to the lower limits of normal penetration rates. Therefore, it is not surprising that there is considerable doubt as to whether any correlation exists between SPA results and the behavior of sperm in an in vitro laboratory situation. We investigated this question by examining the SPA results and the subsequent fertilization and cleavage rates in the in vitro fertilization program at Pennsylvania Hospital. The sperm from men whose SPA results were 11% or more fertilized 86% of the morphologically normal and mature human oocytes to which they were exposed. Men whose SPA scores ranged from 1% through 10% fertilized 65% of human oocytes, and men whose sperm failed to penetrate hamster eggs still were able to fertilize 41% of the human oocytes. The differences between these groups are statistically significant. This information can be of practical prognostic value during in vitro fertilization cycles in which the number of mature oocytes seen ultrasonographically appears to be at a minimum.

Animals

Early experience with the GIFT procedure.

Gamete intrafallopian transfer (GIFT) was performed in 19 cycles on 15 couples whose infertility had proven resistant to other treatments. Indications included infertility associated with immunologic factors, seminal deficiencies, endometriosis and infertility without a diagnosed etiology. Any history or finding of tubal disease served as an exclusion. Infertility was primary in ten couples and secondary in five, three of whom had conceived previously with a semen donor. Stimulation protocols included clomiphene citrate (CC) and human menopausal gonadotropins, CC alone and gonadotropins alone. Males were screened with the hamster egg sperm penetration assay. Four conceptions were recorded, and three are ongoing. Advantages of this procedure include acceptance by the major orthodox religions, avoidance of extracorporeal incubation and physiologic entry of the embryo into the uterine cavity. Disadvantages include the inability to determine if fertilization has occurred in the absence of pregnancy, the theoretical risk of increased ectopic gestation and tubal infection, and perhaps an increase in multiple gestations.

Adult

Tc-99m labeled leukocytes: preparation and use in identification of abscess and tissue rejection.

A simple and reproducible method for the preparation and labeling of leukocytes with Tc-99m has been developed. Leukocytes were separated from blood, incubated with stannous pyrophosphate, and then with 20-30 mCi (740-1110 MBq) of 99mTcO-4. In leukocytes separated from human blood, the labeling efficiency was 81% +/- 6% (n = 4). Experiments on dogs with abscesses showed accumulation of the Tc-99m-labeled leukocytes in the infected sites, indicating the viability of the labeled leukocytes. Additional studies showed that rat lymphocytes that were labeled with Tc-99m, using the same technique, localized in heart transplant tissue that was being rejected.

Abscess