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Biomedical subjects

M Byrne

Publications and source records attributed to M Byrne.

At least 91 records · Page 5Linked to original sources

A case-control study of obstetric complications and later autistic disorder.

The precise etiology of autism remains unclear. Obstetric adversity has been described as one factor that may increase the risk for the disorder. We examined the contemporaneous birth records of 49 children satisfying DSM-III-R criteria for autistic disorder, at four Dublin maternity hospitals, using the previous same-sex live birth in that hospital as a control. Data were evaluated blind to subject status using two obstetric complication (OC) rating scales. No significant differences in obstetric adversity were found between index and control groups. Autistic individuals did not differ from controls in terms of previously described risk factors for this disorder (maternal age, maternal parity, birth order, and low birth weight) in autism. These data do not support the view that OCs increase the risk for later autism.

Adolescent↗

Prevalence and correlates of mixed-handedness in schizophrenia.

Increased rates of nonright-handedness have been reported in schizophrenia, but a clear distinction has not been made between left- and mixed-handedness. Handedness preferences in 96 patients fulfilling DSM-III criteria for schizophrenia and 43 normal comparison subjects were assessed with the Edinburgh Handedness Inventory. A 100% criterion was used to establish left- and right-handedness. Results were analyzed with mantel-Haenszel odds ratios adjusted for age and sex. The schizophrenic group showed a significant increase in the proportion of mixed-handers compared with the normal group. There was no increase in pure left-handedness in the schizophrenic relative to the normal group. Mixed-handedness in the schizophrenic patients was significantly associated with chronicity of illness. Mixed-handed patients were less likely to have a family history of psychotic illness than patients with strong right- or left-handedness. The results indicate a neurodevelopmental rather than a genetic origin for anomalous lateralization in schizophrenia.

Adult↗

Prediction of amputation wound healing with skin perfusion pressure.

PURPOSE: The purpose of this study was to determine whether laser Doppler skin perfusion pressure (LD-SPP) could accurately predict amputation wound healing. METHODS: We studied a total of 62 limbs in 52 patients (28 men and 24 women) with a mean age of 62.2 years (range 34 to 93 years). From this, 39 limbs underwent major amputation (15 above-the-knee, 24 below-the-knee), and 23 limbs underwent minor amputations (4 transmetatarsal and 19 toes). There were five postoperative deaths, leaving a total of 57 limbs available for analysis. RESULTS: Three of 13 above-knee amputations failed to heal. Twenty-one of 23 below-knee amputations healed. Three of four transmetatarsal amputations failed to heal and eight of 17 toe amputations failed to heal. Binary table analysis showed that an LD-SPP value of 30 mm Hg or greater had a negative predictive value (healing occurred) of 90%. An LD-SPP value of less than 30 mm Hg at the amputation site had a positive predictive value (healing failure) of 75%, (p < 0.001, chi square analysis). For major amputations, negative predictive value was 100%, and positive predictive value was 83%, (p < 0.001). For minor amputations, negative predictive value was 75% and positive predictive value was 66.7%, (p < 0.09). CONCLUSION: These data support the use of the LD-SPP test in the selection of major amputation level consistent with healing in ischemic limbs. Further study of the value of this parameter in the determination of minor amputation wound healing is necessary.

Adult↗

A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling.

Degradation of type I collagen, the most abundant collagen, is initiated by collagenase cleavage at a highly conserved site between Gly775 and Ile776 of the alpha 1 (I) chain. Mutations at or around this site render type I collagen resistant to collagenase digestion in vitro. We show here that mice carrying a collagenase-resistant mutant Col1a-1 transgene die late in embryo-genesis, ascribable to overexpression of the transgene, since the same mutation introduced into the endogenous Col1a-1 gene by gene targeting permitted normal development of mutant mice to young adulthood. With increasing age, animals carrying the targeted mutation developed marked fibrosis of the dermis similar to that in human scleroderma. Postpartum involution of the uterus in the mutant mice was also impaired, with persistence of collagenous nodules in the uterine wall. Although type I collagen from the homozygous mutant mice was resistant to cleavage by human or rat fibroblast collagenases at the helical site, only the rat collagenase cleaved collagen trimers at an additional, novel site in the nonhelical N-telopeptide domain. Our results suggest that cleavage by murine collagenase at the N-telopeptide site could account for resorption of type I collagen during embryonic and early adult life. During intense collagen resorption, however, such as in the immediate postpartum uterus and in the dermis later in life, cleavage at the helical site is essential for normal collagen turnover. Thus, type I collagen is degraded by at least two differentially controlled mechanisms involving collagenases with distinct, but overlapping, substrate specificities.

Amino Acid Sequence↗

Reproductive behaviour in schizophrenia relative to other mental disorders: evidence for increased fertility in men despite decreased marital rate.

Using case register data, the overall marital rate among 5158 patients with mental illness was found to be comparable to the general population. The proportion of those ever married was markedly reduced in the schizophrenic group relative to those with a manic or neurotic illness. Men with schizophrenia had a particularly low rate of marriage. The overall marital fertility of the 3 groups was comparable to each other and appeared to be higher than that in the general population. In the schizophrenic group only, married men, particularly those with a family history of mental disorder, produced more children than married women. Men might represent a more fertile group of schizophrenic patients with some biological advantage of increased fecundity, which may help to compensate for negative selection pressures.

Analysis of Variance↗

Oral sumatriptan compared with placebo in the acute treatment of migraine.

This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Urethane anesthesia reverses the protective effect of noncompetitive NMDA receptor antagonists against cocaine intoxication.

The present experiments examined whether pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 and dextrorphan, could antagonize cocaine-induced convulsions and lethality in conscious Sprague-Dawley (SD) rats and whether urethane anesthesia alters the observed interactions. Conscious, restrained male SD rats received continuous i.v. infusions of cocaine hydrochloride (1.25 mg/kg.min) until convulsions and death occurred. Cocaine doses of 21.2 +/- 1.8 and 29.5 +/- 2.5 mg/kg caused convulsions and death, respectively, in saline treated rats (n = 8). Convulsions were absent in MK-801 (1 mg/kg, i.v.; n = 8) pretreated rats; the lethal cocaine dose was 44.0 +/- 2.7 mg/kg (p < 0.05). In contrast, urethane anesthesia (1.2 g/kg, i.p.) decreased the dose of cocaine required to cause toxicity, compared to that in saline controls (24.8 +/- 0.8 mg/kg, n = 13), in MK-801 (2.0 +/- 0.3, n = 7; p < 0.01) and in dextrorphan mg/kg, n = 13), in MK-801 (2.0 +/- 0.3, n = 7; p < 0.01) and in dextrorphan (25 mg/kg, i.v.; 13.1 +/- 1.4, n = 6; p < 0.01) pretreated rats. Pressor responses with little change in heart rate were evident during cocaine infusion in vehicle pretreated rats. Bradycardiac responses were noted to cocaine in groups following NMDA receptor blockade. Reversal of the pressor response to cocaine was noted in MK-801 pretreated animals, while dextrorphan pretreatment moderated cocaine-induced increases in blood pressure. Ventilatory support protected against cocaine lethality in urethane anesthetized rats, indicating that respiratory failure is the proximate cause of death with cocaine infusion. However, artificially ventilated rats, pretreated with MK-801, were more sensitive (lethal cocaine dose, 76.6 +/- 8.0 mg/kg, n = 5) than vehicle pretreated rats (129.4 +/- 15.8 mg/kg, n = 6), indicating that MK-801 may increase both the respiratory and the cardiac toxicity of cocaine in urethane anesthetized rats. Interactions between NMDA receptors and cocaine are modified by urethane anesthesia.

Anesthesia↗

Further evidence for anomalies in the hand-prints of patients with schizophrenia: a study of secondary creases.

Finger and palm prints from 46 ICD-9 schizophrenic patients and 43 age and sex matched normal controls were examined independently and blind to diagnosis, by four raters. Seven prints were judged to have very high densities of secondary creases. These abnormal prints were all from the schizophrenic group. Patients with high densities of creases were more severely ill, having had more than five admissions to hospital and higher doses of neuroleptic medication. There was a trend for such patients to have had a complicated obstetric history and an earlier onset of their illness.

Adult↗

Meningococcal disease in childhood--a regional study in Ireland.

A retrospective study of microbiology laboratory records of culture-confirmed cases of meningococcal disease in children under 14 years of age, admitted to four Dublin hospitals, was conducted for the period 1981-1991 inclusive. The study aimed to describe the epidemiology of meningococcal disease in childhood and to assess the potential of meningococcal group A and C vaccine in preventing disease. There were 406 cases of meningococcal disease of which 319 (78.6%) were in children under 5 years of age. The meningitis to septicaemia ratio was almost 4:1 (320 vs. 86 cases). Of the 406 cases, 216 (53.2%) cases occurred during the period November to March. The age-specific annual incidence rates for the Eastern Health Board region served was 64.2 per 100,000 under 1 year of age and 24.6 per 100,000 under 5 years of age. A relative increase in disease caused by meningococcal serogroup C was observed during the period of the study. Only 15% all cases could have been prevented by a policy of universal meningococcal group A and C immunisation at 2 years of age. Such a policy, therefore, is not recommended. A vaccine for preventing disease caused by meningococcal group B is urgently required.

Adolescent↗

Immunological events in regressing genital warts.

Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract. The authors have studied 125 closely monitored patients with genital warts. Of these 125 patients, wart regression was seen in 28 patients. This study provides evidence that clearance of human papillomavirus from the genital tract is characterized by an active cell-mediated immune response. Regressing warts (n = 14) contained significantly more T lymphocytes (P < .05, Wilcoxon rank sum test) and macrophages (P < .01) than did nonregressing controls (n = 14). CD4-positive lymphocytes predominated in regression, both within the wart stroma and the surface epithelium, where there was a significant change in the ratio of CD4+ to CD8+ cells (P < .01). Lymphocytes in regression also showed greater expression of activation markers, and the majority were of the "antigen-experienced" phenotype. There was no difference in Langerhans cell numbers, although there was significant induction of the immune accessory molecules HLA-DR and ICAM1 (P < .05) on keratinocytes, and E-selectin and VCAM1 (P < .05) on endothelial cells in regressing warts. The changes in regression are consistent with a delayed-type hypersensitivity reaction to foreign antigen, and the ability to induce and mount such a response may be a critical determinant of effective natural immunity to the genital HPVs. Specific targeting of delayed-type hypersensitivity responsiveness may increase the efficacy of strategies for immuno-intervention against HPV infection in the genital tract.

Adult↗

The economic burden of unrecognized vasodepressor syncope.

BACKGROUND: The objective of this study was to describe the cost of prior diagnostic evaluation in patients referred for evaluation of syncope whose history was typical of vasodepressor syncope. METHODS AND RESULTS: Thirty consecutive patients who were referred for evaluation of syncope of undetermined origin and whose history was highly suggestive of vasodepressor syncope participated in this study. These 30 patients represented 19% of 158 patients referred for evaluation of syncope during the period of enrollment. All patients had positive results of an upright-tilt test, confirming the diagnosis of vasodepressor syncope. At the time of evaluation, the type and results of all diagnostic tests that had been performed prior to referral were recorded for each patient. The cost of diagnostic testing was then determined based on the 1991 cost of these tests at the University of Michigan Medical Center. A mean of 4 +/- 2 major diagnostic tests were performed before referral to the University of Michigan Medical Center. The mean and median costs of diagnostic testing per patient prior to referral were $3,763 +/- 3,820 and $2,678 (range: 0 to $16,606) respectively. Six patients underwent no major diagnostic tests prior to referral and, therefore, the cost of major diagnostic testing was zero in these patients. In the remaining patients, the mean and median costs of diagnostic testing per patient were $4,704 +/- 3,713 and $3,777 (range: $1,025 to $16,606) respectively. CONCLUSIONS: The results of this study demonstrate that a diagnosis of vasodepressor syncope can be established clinically in approximately 20% of patients referred to a university hospital for evaluation of syncope of undetermined origin. Failure to recognize the clinical features of vasodepressor syncope in these patients resulted in up to $16,000 of unnecessary diagnostic testing. A greater awareness of the clinical features of vasodepressor syncope may, therefore, result in significant economic savings.

Adolescent↗

Susceptibility of type I collagen containing mutated alpha 1(1) chains to cleavage by human neutrophil collagenase.

Two members of the matrix metalloproteinase family which can cleave native types I, II and III triple helical collagens are collagenases from fibroblasts and neutrophils. These enzymes are the products of different genes which share structural motifs but are only 57% identical. In this study, we determined the site of cleavage in the alpha 1(I) chains and showed that the neutrophil collagenase acted at the same site as the fibroblast collagenase. We also used collagens as substrates which were generated by site-directed mutagenesis of the murine Col1a1 gene and found that the pattern of susceptibility to cleavage by purified neutrophil collagenase was indistinguishable from that previously described for the fibroblast collagenase. Collagens containing substitutions of Pro for Ile-776 (P1) were not cleaved; whereas those containing substitutions of Met for Ile-776 were cleaved. Type I collagen which contained alpha 1(I) chains in which there were double substitutions of Pro for Gln-774 (P2) and Ala-777 (P2') were also not cleaved. These type I collagens contained wild type alpha 2(I) chains as well as mutant alpha 1(I) chains in the mixed helical trimers; the alpha 2(I) chain in the trimers containing the resistant alpha 1(I) chains were also not cleaved by the neutrophil collagenase.

Amino Acid Sequence↗

Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer.

BACKGROUND: The antioestrogen tamoxifen and progestins act via different receptors and may therefore have complementary effects against human breast cancer. This possibility was tested in a randomized study which compared the effects of tamoxifen, standard-dose megestrol acetate, and these two agents in combination, in patients with metastatic breast cancer. PATIENTS AND METHODS: 184 post-menopausal patients with metastatic breast cancer were randomized to initial treatment with either tamoxifen (TAM) 40 mg daily, megestrol acetate (MA) 160 mgm daily, or the combination of the two administered simultaneously. Patients crossed over to the alternative single agent on relapse or disease progression. Patients were evaluated for response, time to initial and ultimate treatment failure, and survival. RESULTS: There were no significant differences between the three groups with respect to response rates, nor the other parameters. Patient survival was significantly associated with age > 60 years, ER positive status, and the absence of visceral metastases. CONCLUSIONS: TAM and MA are both equally effective in response induction as initial treatments and the combination has no advantage. Sequential treatment is still optimal, TAM being the preferred initial agent in view of the reported side effects with MA.

Aged↗

A new method for the concentration of Cryptosporidium oocysts from water.

A novel method for the concentration of Cryptosporidium oocysts from water has been developed, based upon the precipitation of calcium carbonate. A 10 l water sample is treated by adding solutions of calcium chloride and sodium bicarbonate and raising the pH value to 10 with sodium hydroxide. Crystals of calcium carbonate form and enmesh particles in the Cryptosporidium oocyst size range. The crystals are allowed to settle, the supernatant fluid is discarded and the calcium carbonate precipitate dissolved in sulphamic acid. The sample can be concentrated further by centrifugation. Recoveries of oocysts from seeded samples of deionized, tap and river water were in excess of 68%.

Animals↗

Routine monitoring of Cryptosporidium oocysts in water using flow cytometry.

A flow cytometric method for the routine analysis of environmental water samples for the presence of Cryptosporidium oocysts has been developed. It uses a Coulter Epics Elite flow cytometer to examine water samples and to separate oocysts from contaminating debris by cell sorting. The sorted particles are then rapidly screened by microscopy. The method has been evaluated and compared with direct epifluorescence microscopy on 325 river, reservoir and drinking water samples. The technique was found to be more sensitive, faster and easier to perform than conventional epifluorescent microscopy for the routine examination of water samples for Cryptosporidium.

Animals↗

Interferon alpha and doxorubicin in malignant mesothelioma: a phase II study.

BACKGROUND: Malignant mesothelioma is a tumour which is generally resistant to chemotherapy. While the addition of interferon to chemotherapy improves response rates in some other malignancies, such a combination has not been evaluated in the treatment of mesothelioma. AIMS: To assess the anti-tumour effects and toxicity of interferon-alpha combined with doxorubicin in the treatment of pleural mesothelioma. METHODS: Twenty five patients (mean age 54 +/- 11 years) were enrolled in a phase II study. All patients had a confirmed histological diagnosis, measurable tumour, a life expectancy of at least three months, and no prior chemotherapy or interferon. Interferon alpha-2a, 9 x 10(6) U sc daily, was administered together with doxorubicin 25 mg per m2 i.v. weekly, for 12 weeks. Response status was assessed by tumour measurements on clinical examination and thoracic CT scans before and after treatment. RESULTS: A partial response was observed in four patients (16%; 90% CI, 8-30%), 11 remained stable, while six had progressive disease. Four patients withdrew within the first month because of toxicity. The median survival of all patients was 11 months (95% CI, 3-19). Dose modification as a result of toxicity was required in all patients. Lethargy, weight loss, leukopenia and vomiting were the most common side effects. CONCLUSIONS: The combination of interferon-alpha and doxorubicin showed only modest activity and was associated with significant toxicity. It cannot be recommended in the treatment of malignant pleural mesothelioma.

Combined Modality Therapy↗

Clinical features and management of recurrent balanitis; association with atopy and genital washing.

OBJECTIVE: To evaluate clinical features and diagnostic investigations in patients with recurrent or unresponsive balanitis in order to institute rational management. DESIGN: Forty-three patients presenting to a genitourinary medicine clinic with recurrent or persistent balanitis were studied. All patients were asked whether they had a history of atopic illness and about their practice of genital washing. All patients were investigated by taking a swab specimen from the preputial area for bacterial and viral culture and 30 underwent biopsy of the affected skin. Follow-up was between three and six months. SETTING: Outpatient genitourinary medicine clinic, St Mary's Hospital, London, UK. RESULTS: In 31 (72%) of the patients a diagnosis of irritant dermatitis was made. In comparison with the remaining patients, they had a greater lifetime incidence of atopic illness and more frequent daily genital washing with soap. For 28 (90%) of these patients, use of emollient creams and restriction of soap washing alone controlled symptoms satisfactorily. For the remaining 12 patients, a variety of diagnoses were made. Biopsy proved a well tolerated and diagnostic investigation, but the isolation of microbial pathogens from preputial swabs was irrelevant to management. CONCLUSION: A history of atopic illness and of the practice of penile washing are important aspects in the evaluation of patients with recurrent balanitis. Biopsy is an important investigation in the condition when it does not seem to be caused by irritant dermatitis.

Adult↗