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Biomedical subjects

D McKenna

Publications and source records attributed to D McKenna.

At least 37 records · Page 2Linked to original sources
PubMed1998

The platelet thrombin receptor and postoperative bleeding.

BACKGROUND: We hypothesized that small amounts of thrombin desensitize the platelet thrombin receptor during cardiopulmonary bypass (CPB), resulting in postoperative platelet dysfunction and bleeding. METHODS: Seventy-nine patients were entered into a study designed to measure changes in platelet thrombin receptor function during CPB and to correlate them to postoperative bleeding. In addition to measurements of clinical blood loss, platelet function tests of aggregation, activation, and cell-cell adhesion were used. The thrombin receptor agonist peptide (TRAP) was used to activate the platelets. Flow cytometry was used to measure various platelet surface markers and platelet-white cell interactions during CPB. RESULTS: Compared with preoperative values, both aggregometry and flow cytometry measured a significant reduction of TRAP-induced activation immediately and up to 24 hours after CPB. The response of other activating agents returned to normal by 24 hours. Postoperatively, 8 of 79 patients required excessive blood transfusion (> or = 10 units of blood products) and had significantly decreased TRAP-induced aggregation response. CONCLUSIONS: Our results show that (1) platelet activation, aggregation, and adhesion to leukocytes induced by TRAP are reduced after CPB, (2) decreased thrombin receptor responsiveness is associated with excessive postoperative blood loss, and (3) because the aggregation and activation responses are different for TRAP and thrombin, there may be a second thrombin receptor on platelets that is protected from damage during CPB. These results imply that prevention of the CPB-induced effects on the thrombin receptor will lessen postoperative morbidity associated with blood transfusion.

Blood Loss, Surgical↗
PubMed1998

The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy.

Endothelial cell association with vascular basement membranes is complex and plays a critical role in regulation of cell adhesion and proliferation. The interaction between the membrane-associated 67-kd receptor (67LR) and the basement membrane protein laminin has been studied in several cell systems where it was shown to be crucial for adhesion and attachment during angiogenesis. As angiogenesis in the pathological setting of proliferative retinopathy is a major cause of blindness in the Western world we examined the expression of 67LR in a murine model of hyperoxia-induced retinopathy that exhibits retinal neovascularization. Mice exposed to hyperoxia for 5 days starting at postnatal day 7 (P7) and returned to room air (at P12) showed closure of the central retinal vasculature. In response to the ensuing retinal ischemia, there was consistent preretinal neovascularization starting around P17, which persisted until P21, after which the new vessels regressed. Immunohistochemistry was performed on these retinas using an antibody specific for 67LR. At P12, immunoreactivity for 67LR was absent in the retina, but by P17 it was observed in preretinal proliferating vessels and also within the adjacent intraretinal vasculature. Intraretinal 67LR immunoreactivity diminished beyond P17 until by P21 immunoreactivity was almost completely absent, although it persisted in the preretinal vasculature. Control P17 mice (not exposed to hyperoxia) failed to demonstrate any 67LR immunoreactivity in their retinas. Parallel in situ hybridization studies demonstrated 67LR gene expression in the retinal ganglion cells of control and hyperoxia-exposed mice. In addition, the neovascular intra- and preretinal vessels of hyperoxia-treated P17 and P21 mice labeled strongly for 67LR mRNA. This study has characterized 67LR immunolocalization and gene expression in a murine model of ischemic retinopathy. Results suggest that, although the 67LR gene is expressed at high levels in the retinal ganglion cells, the mature receptor protein is preferentially localized to the proliferating retinal vasculature and is almost completely absent from quiescent vessels. The differential expression of 67LR between proliferating and quiescent retinal vessels suggests that this laminin receptor is an important and novel target for future chemotherapeutic intervention during proliferative vasculopathies.

Animals↗
PubMed1997

Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis.

In 10 consecutive patients with an acute febrile illness, human granulocytic ehrlichiosis was confirmed with specific polymerase chain reaction studies, serologic conversion, or both. Although no patients had the clinical features most suggestive of early Lyme disease (eg, erythema migrans or cranial nerve palsy), tests for antibody to Borrelia burgdorferi produced a reaction in most patients. In 6 of 7 patients (86%) with evaluable results, enzyme-linked immunosorbent assay yielded positive or equivocal findings, and an immunoblot technique yielded positive findings in 60% to 90% of patients, depending on the criteria used for interpretation. Inasmuch as approximately 25% of nymphal Ixodes scapularis ticks in Westchester County, New York, are infected with B burgdorferi, the probability that at least 9 of these patients were coinfected with B burgdorferi and human granulocytic ehrlichiosis by the same tick bite is estimated to be .00003. These observations suggest that serodiagnosis is insufficient to establish the presence of coinfection with B burgdorferi.

Adult↗
PubMed1995

Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans.

BACKGROUND: Doxycycline is widely used to treat Lyme disease associated with erythema migrans. Whether it is comparable to tetracycline is unknown. OBJECTIVE: We conducted a two-part retrospective analysis of (1) the safety and efficacy of doxycycline compared with tetracycline and (2) the safety and efficacy of a 14-day versus a 20-day course of doxycycline. METHODS: Twenty-seven patients given tetracycline (500 mg four times a day for 14 days [group 1]) were compared retrospectively with 21 patients who received doxycycline (100 mg two or three times a day for 14 days [group 2]). The results for group 2 were also compared with that of 38 patients who received doxycycline for 20 days (100 mg three times daily) in a prospective treatment trial (group 3). RESULTS: There was no significant difference in the incidence of adverse drug effects or in efficacy at 1 month, but at 1 year there was a trend toward a better outcome in the group treated with tetracycline (p = 0.08). A 14-day course of doxycycline was comparable to a 20-day course in the incidence of adverse drug effects and in clinical outcome. CONCLUSION: The principal advantage of doxycycline over tetracycline for the treatment of Lyme disease associated with erythema migrans is the convenience of less frequent dosing, not enhanced efficacy or safety. There appears to be no advantage in extending treatment with doxycycline from 14 to 20 days.

Administration, Oral↗
PubMed1993

Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study.

BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Adult↗
PubMed1992

Detection of human papillomavirus DNA in skin warts from immunocompromised patients but not in semen from men whose wives have abnormal cervical cytology.

The epidemiology of human papillomaviruses (HPV) was studied in 61 immunocompromised patients (e.g. renal and cardiac transplants; Bowen's disease; genital cancer) undergoing therapy at the University Hospital of Wales at Cardiff U.K. Warts from various sites of these patients were studied for the presence of HPV types 6, 11, 16 and 18 using the dot-blot DNA hybridization technique. Four HPV-16 and one HPV-11 was detected. The presence of HPV-16 in our study is quite significant since it suggests the potential occurrence of genital HPV types in skin warts in immunocompromised patients and hence the need for screening such patients against HPV types. HPV, mainly types 16 and 18 are usually associated with genital cancer, cervical malignancies and cervical intraepithelial neoplasia. The semen of the husband of 30 women with cervical abnormalities and the semen of 30 husbands (control) of wives with normal cervix were tested for HPV-6, 11, 16 and 18. No HPV-DNA could be detected in all of the 60 specimen. This suggests that specimens were either truly negative for any of those types or because virus DNA could present in a small amount less than 5 pg/microliters in some patients. Whether semen plays a role in transmitting HPV is still controversial.

Condylomata Acuminata↗
PubMed1992

Vesicular erythema migrans.

BACKGROUND: Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. OBSERVATIONS: Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. CONCLUSIONS: Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting.

Adolescent↗
PubMed1991

Reversing intravenous sedation with flumazenil.

This study was designed to evaluate the effects of flumazenil in reversing sedation from midazolam and meperidine after oral surgical procedures. Of the 35 patients entered, efficacy was evaluated in 33 and safety in 34. Patients were tested for sedation, psychomotor skills, and memory during a 3-hour period and at a 24-hour follow-up. Flumazenil almost totally reversed the effects of sedation for approximately 2 hours, after which some loss of effect was observed. A number of central nervous system-related side effects were observed in the flumazenil group, but none of these was considered serious. One patient in the flumazenil group had an episode of hypotension that precluded further testing.

Adolescent↗
PubMed1990

Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori.

Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single-blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer-healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice-daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients.

Anti-Ulcer Agents↗
PubMed1990

Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate.

Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori.

Amoxicillin↗
PubMed1988

Effect of treatment on Campylobacter pylori in peptic disease: a randomised prospective trial.

This study investigated the effect of colloidal bismuth subcitrate and cimetidine on Campylobacter pylori in peptic disease. In 74% of 135 patients with peptic disease diagnosed at endoscopy C pylori was detected before treatment. Compared with cimetidine, colloidal bismuth subcitrate significantly decreased the incidence of C pylori after six weeks of treatment (p less than 0.001). In the colloidal bismuth subcitrate group, subsequent healing of the lesion was correlated with the clearance of C pylori, unlike in the cimetidine group. C pylori was strongly associated with the presence of histological gastritis, which was decreased by colloidal bismuth subcitrate (p less than 0.001).

Adult↗
PubMed1988

Histological gastritis in duodenal ulcer: relationship to Campylobacter pylori and effect of ulcer therapy.

Antral gastritis has been described in up to 100% of patients with duodenal ulcer disease, and recently has been associated with Campylobacter pylori infection. The present study examines the effect of two ulcer therapies (cimetidine and colloidal bismuth subcitrate) on this lesion. Sixty-four consecutive patients with endoscopically diagnosed duodenal ulcer were randomized to treatment with either agent upon entry into the study. Antral biopsies were taken at both initial and final endoscopies for culture of C. pylori and assessment of degree of gastritis (as based on inflammatory cell infiltrate: grades 0 to 3). The organism was detected in 90% of the patients at initial biopsy, and grades 2 and 3 gastritis were documented in 76%. The presence of the organism and the gastritis were significantly correlated (p less than 0.001), and the bacterium was not cultured from histologically normal antral mucosa. Active chronic gastritis (grade 3) was seen in 65% of those with C. pylori, and was not found in any patient without the bacterium. Cimetidine had no effect on either the organism or the gastritis, whereas the bismuth preparation significantly (p less than 0.002) reduced the prevalence of both. The present study documents that therapy directed against C. pylori has a significant effect on the gastritis of duodenal ulcer disease and possible mechanisms for the observed effects are discussed.

Adult↗
PubMed1987

Campylobacter pylori and recurrence of duodenal ulcers--a 12-month follow-up study.

In 39 patients with endoscopically healed duodenal ulcers repeat endoscopy and two antral biopsies after 1 year showed a relapse rate of 59%. Only post-treatment Campylobacter pylori status was a significant predictor of endoscopic relapse. 79% of patients who remained culture positive had a relapse, compared with 27% of culture-negative patients. Relapse was more likely (66%) in patients with a recurrence of C pylori after apparent eradication of the organism than in those who remained negative for C pylori (10%). No patient who remained negative for C pylori had histological gastritis, whereas all with recurrence of C pylori showed histological gastritis. These findings suggest an important role for C pylori in duodenal ulcer relapse in the year after treatment.

Adult↗
PubMed1987

Uterine motility in the cow during the estrous cycle. I. Spontaneous activity.

This study describes a method for measuring intrauterine pressure (IUP) changes and uterine motility in cows. Spontaneous uterine motility was recorded during the estrous cycle in stanchioned, nonlactating dairy cows using a pair of miniature pressure transducers mounted 15 cm apart at the distal end of a dacron catheter placed in one uterine horn via the cervix. Clinical examination of ovarian status and determination of the peripheral plasma levels of estradiol-17beta and progesterone were used to determine the stages of the cycle. The pressure sensors recorded variations in muscular resting tension (tone) and the occurrence, spatial distribution, and force of the uterine contractions. Both tone and uterine activity varied significantly during the cycle. They were minimal during diestrus, increased during proestrus, reached maximal values at estrus, and then decreased. The highest synchronized motor activity with presence of peristaltic-antiperistaltic movements occurred during estrus. The prevailing direction of the uterine contractions during late estrus (immediate preovulatory period) was cervico-tubal.

Journal Article↗
PubMed1987

Uterine motility in the cow during the estrous cycle. II. Comparative effects of prostaglandins F(2alpha), E(2), and cloprostenol.

Intrauterine pressure (IUP) changes were recorded in nonlactating, cyclic dairy cows using transcervically placed intraluminal pressure microtransducers. Spontaneous activity was recorded for the first 30 min. Prostaglandins (PG) F(2alpha) (5 mug/kg), E(2) (5 mug/kg), or cloprostenol (0.1 mug/kg) were then injected intravenously (i.v.) at diestrus, proestrus, estrus, and metestrus, and their effects were recorded. The drug administrations did not alter the duration of the estrous cycle of the cows. Single doses of PGF(2alpha) and E(2) significantly increased uterine activity at all stages of the estrous cycle, while cloprostenol had no effect. PGF(2alpha) and PGE(2) increased IUP, frequency, and amplitude during all stages of the estrous cycle. The spontaneous pattern resumed within 20 min postinjection. Partial uterine refractoriness occurred with both PGs. The results indicate that low doses of natural prostaglandins stimulate uterine activity during the estrous cycle in cattle.

Journal Article↗
PubMed1987

Uterine motility in the cow during the estrous cycle. III. Effects of oxytocin, xylazine, and adrenoceptor blockers.

Intrauterine pressure (IUP) was recorded in nonlactating dairy cows using an intraluminal catheter with two micropressure transducers located 15 cm apart at the distal end. There was a significant increase (P < 0.05) in IUP following administration of xylazine and oxytocin at all four stages of the estrous cycle. The most significant increase in IUP occurred during proestrus for both drugs. The effect of pretreatment with adrenoceptor-blocking agents on IUP changes induced by xylazine and oxytoxin was evaluated. Alpha-1 adrenoceptor blockade (prazosin) had no effect on IUP following xylazine treatment. However, alpha-2 adrenoceptor blockade (yohimbine) resulted in a reduction (P < 0.05) in IUP compared to controls. Neither prazosin or yohimbine affected oxytocin-induced IUP.

Journal Article↗