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Biomedical subjects

M O'Brien

Publications and source records attributed to M O'Brien.

At least 163 records · Page 9Linked to original sources
PubMed1995

Allograft heart valve sterilization: a six-year in-depth analysis of a twenty-five-year experience with low-dose antibiotics.

At the Prince Charles Hospital, from a 25-year experience with allograft heart valves (1969 to 1994), a 6-year analysis from March 1988 to August 1994 of the contamination rates and efficiency of a short-duration, low-dose antibiotic sterilization protocol was made. This analysis covered 642 collections and 680 aortic and pulmonary valve implants. Tissue samples obtained at collection, valve trimming, postantibiotic incubation, and implant provided the raw data. At collection, valves retrieved in open mortuaries produced the highest contamination rate of 54%. Minimal exposure to antibiotics during transport and trimming reduced the contamination rate to 11% (p < 0.05). This was similar to the contamination rate at trimming for valves collected in the "sterile" operating room from multiorgan donors (12%). Antibiotic incubation at 37 degrees C for 6 hours reduced the contamination rate to 4% (p < 0.05). Only valves that showed no contamination at cryopreservation were implanted. However, at implant, resected tissue from valves that had been incubated in antibiotics showed a contamination rate of 3%, presumably from the theater environment, compared with 15% (p < 0.05) for tissue from valves that had not been incubated. A residual antibiotic effect appears present at the time of implant in valves that have been incubated in antibiotics and may assist in the reduction of and resistance to infection in the immediate postoperative period. This is supported by the low incidence of endocarditis in the first 3 postoperative months. The simple and effective protocol of collection within 24 hours of death combined with low-dose antibiotic sterilization is sufficient to produce pathogen-free valves in the majority of cases (> 95%).

Anti-Bacterial Agents↗
PubMed1995

Challenges for the future: the nurse's role in weaning patients from mechanical ventilation.

Weaning patients from mechanical ventilation and extubating them following cardiothoracic surgery has traditionally been the responsibility of medical staff. Within critical care settings some nurses, with the appropriate experience, actively take part in this process under the direction of an anaesthetist. In the Adult Intensive Care Unit (AICU) of Royal Brompton Hospital, a policy was developed to enable nurses to wean and extubate postoperative patients without the need for consultation with anaesthetic staff. It was envisaged that following the implementation of the policy other areas for nursing development and research would be highlighted. Issues relating to accountability, quality and practice are discussed.

Clinical Protocols↗
PubMed1995

Adjuvant chemotherapy for oesophagogastric cancer with epirubicin, cisplatin and infusional 5-fluorouracil (ECF): a Royal Marsden pilot study.

Previous trials of adjuvant chemotherapy for oesophagogastric cancer have shown only modest or no improvement in survival. However, the regimens used in these studies produce low response rates in patients with advanced disease. ECF is a new regimen which results in higher response rates and may therefore be more effective in the adjuvant setting. Twenty-nine patients who had undergone a potentially curative resection for oesphagogastric carcinoma were treated with ECF [epirubicin 50 mg m-2 and cisplatin 60 mg m-2 for 18 weeks]. The median age was 52.5 years. Three patients had oesophageal tumours, 14 had tumours of the oesophagogastric junction (OGJ) and 12 had gastric tumours. All were adenocarcinomas apart from one undifferentiated carcinoma. One patient had stage I disease, nine stage II, 17 stage II and two stage IV. The mean number of chemotherapy cycles per patient was 5.2 (range 2-8). The median follow-up was 8.4 months (1.5-36.3 months). Eleven patients relapsed during follow-up (38%). One patient had an anastomotic recurrence and ten patients distant metastases. Overall 3 year survival was 61.5% (95% confidence interval 42-79); 3 year survival in stage II was 50% (21.2-86.3) and in stage III 65.6% (40-86). Chemotherapy was well tolerated, with grade 3/4 toxicity as follows: leucopenia 13.5%, nausea and vomiting 10%, diarrhoea 3.5%, infection 3.5% and thrombocytopenia 3.5%. There were no treatment-related deaths. We conclude that ECF can be administered safely as adjuvant treatment to patients with surgically resected gastro-oesophageal carcinoma. The results, especially in patients with stage III disease, are encouraging and support the investigation of this regimen within a prospective randomised trial.

Adenocarcinoma↗
PubMed1995

Inhibin as a marker for ovarian cancer.

Inhibin is a polypeptide hormone produced by the granulosa cells of the ovary, and is present in body fluids as dimers of various sizes each comprising an alpha- and beta-subunit. Free forms of the alpha-subunit also circulate, and the presently available radioimmunoassay (Monash assay) cannot distinguish these from biologically active dimeric inhibin. Recently we described a new two-site enzyme immunoassay able for the first time to measure the levels of dimeric inhibin throughout the human menstrual cycle. The sensitivity limit of this assay is 2 pg ml-1 in human serum with cross-reactivity against activin of 0.05%. The normal range of inhibin in post-menopausal women is < 5 pg ml-1, in pre-menopausal women 2-80 pg ml-1 (2-10 pg ml-1 in the follicular phase, 40-80 pg ml-1 in the luteal phase). This assay was used to determine inhibin levels in sera from 15 (five pre-menopausal and ten post-menopausal) patients with granulosa cell tumours of the ovary. It was raised in a pre-menopausal patient preoperatively (261 pg ml-1), in six post-menopausal patients (32, 43, 54, 66, 24 and 58 pg ml-1) and one pre-menopausal patient with recurrent tumour, (237 pg ml-1), all confirmed clinically. Inhibin was normal in six patients in remission. Oestradiol levels were normal in all patients. Serial levels of inhibin predicted recurrence before overt clinical relapse in two patients. In 29 patients with malignant epithelial ovarian tumours inhibin levels were modestly elevated in nine and normal in the rest. Three patients with endometrioid histology, two with undifferentiated tumours, three with mucinous adenocarcinoma and one with clear cell carcinoma had elevated inhibin levels. Functional inhibin is secreted by all granulosa cell tumours of the ovary studied and can be used as a tumour marker to determine response to therapy and predict recurrence and is superior to oestradiol. A more detailed analysis of the levels of inhibin, and its subunits in epithelial ovarian cancer is needed to identify the molecular forms of the immunoreactive material before optimised assays can be applied to this more common tumour.

Adult↗
PubMed1995

Postoperative toxic shock syndrome.

We conducted a retrospective review of all cases of postoperative toxic shock syndrome (PTSS) occurring in two community hospitals from 1981-1993, during which time 390,000 surgical procedures were performed. The incidence was 0.003% (12 cases). All wounds in these 12 cases, from those with scant superficial exudates to those with gross purulence, yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Patients had a mean maximal temperature of 40 degrees C. All patients had a rash, most in a truncal, "sunburn" pattern. Eleven patients had desquamation. Mean time from surgery to onset of symptoms was 4 days. All patients required vigorous fluid resuscitation. No correlation could be demonstrated between the development of toxic shock syndrome and a patient's age, sex, preoperative skin preparation or administration of antibiotics, members of the surgical team, or duration of procedure. All patients with PTSS survived. PTSS should be considered in the differential diagnosis for the acutely febrile, systemically ill postoperative patient, even when surgical wounds are deceptively benign in appearance. Early recognition and treatment of PTSS is essential for successful outcome.

Adolescent↗
PubMed1995

The prognostic value of CEA, beta HCG, AFP, CA125, CA19-9 and C-erb B-2, beta HCG immunohistochemistry in advanced colorectal cancer.

BACKGROUND: Evaluation of the prognostic significance of a group of tumour markers and their ability to predict response to chemotherapy may allow better targeting of palliative treatment in advanced colorectal cancer. PATIENTS AND METHODS: Using a prospectively acquired database of 377 patients (pts) with advanced colorectal adenocarcinoma, the prognostic significance of serum CEA (342 pts), beta HCG (203 pts), AFP (208 pts), CA125 (150 pts), CA-19-9 (76 pts) as well as C-erb B-2 (197 pts). Serum markers were taken prior to 5-FU based chemotherapy and immunohistochemistry was performed on diagnostic samples RESULTS: Tumour markers of poor prognostic significance in the univariate analysis were CEA > or = 5 micrograms/l (p = 0.006; median survival (MS 59 weeks vs 38 weeks) and CA125 > or = 35 U/ml (p = 0.01 MS 51 weeks vs. 30 weeks). Tumour markers elevated at greater than 10 times the normal value which correlated with a poor prognosis were CEA (p = 0.001; MS 47 weeks vs. 35 weeks), Serum beta HCG (p < 0.0001; MS 44 weeks vs. 7 weeks) and CA125 (p < 0.0001; MS 38 weeks vs. 15 weeks). Poor performance status ( > 2) and poorly differentiated tumour histology were also correlated to poor survival. In the multivariate analysis, tumour markers of independent poor prognosis were CEA > or = 5 micrograms/l (Hazard Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA > or = 50 micrograms/l (HR 1.6; CI 2.1-1.2), CA125 > or = 35 U/ml (HR 1.5; CI 2.3-1.0), CA 125 > or = 350 U/ml (HR 5.0; CI 9.6-2.6) and serum BHCG > or = 0 IU/l (HR 11.7; CI 30-4.5). Poor performance status (HR 6.7-5.0) and poorly differentiated histology (HR 2.8-1.0) were the other important factors in the model. No pretreatment tumour marker correlated with response to chemotherapy. CONCLUSIONS: This is the largest prognostic study of each tumour marker in advanced disease and it clarifies previous conflicting reports. Serum AFP, CA19-9 and immunohistochemical stains beta HCG and C-erb B-2 have no prognostic significance. Serum CEA, beta HCG, CA125 in advanced colorectal cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.

Adenocarcinoma↗
PubMed1995

Cisplatin and protracted venous infusion 5-fluorouracil (CF)--good symptom relief with low toxicity in advanced pancreatic carcinoma.

PURPOSE: The combination of protracted venous infusion (PVI) 5-FU with moderate dose cisplatin was evaluated in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Sixty-three patients with locally advanced or metastatic disease were treated with cisplatin (60 mg/m2 every 21 days) and PVI 5-FU (300 mg/m2/day) for a maximum of 24 weeks. All patients had histologically/cytologically confirmed tumour. Radiological response was assessed by CT scanning and toxicity, performance status and symptomatic response were assessed 3 weekly. RESULTS: The objective response rate was 16% with two radiological complete responses. The median survival was 7.6 months with a 1-year survival of 33% and a median progression-free survival of 6.6 months. Patients who had local disease only had a median survival of 14.8 months with a 1-year survival of 52%. Thirty-four percent of patients had an improvement in performance status on treatment and specific symptom response rates were weight loss 71%, dysphagia 100%, nausea and vomiting 70%, pain 60%, anorexia 50%, and reflux 81%. Chemotherapy was well tolerated with grade 3 or 4 toxicity being nausea/vomiting 5%, diarrhoea 7%, infection 4%, stomatitis 2%, plantar palmar syndrome 2%, anaemia 14%, leucopenia 5, neutropenia 10% and thrombocytopenia 8%. CONCLUSIONS: The CF regimen provides good symptomatic palliation with low toxicity in patients with advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1995

The plantar flexor muscle attachments on the tibia. A cadaver study.

Thirty-six tibiae from 11 female and 7 male cadavers were dissected. Anatomical and histological examinations of the plantar flexor muscle origins at the posteromedial border of the tibia were performed. Many individual variations in the type and size of muscle origin were observed. Muscle fibers and/or connective tissue in different proportions attached the muscle to the periosteum or directly to the cortical bone. The length of the attachments varied greatly and there was a considerable overlap of the muscles in some individuals. The attachments of the flexor digitorum longus overlapped the tibialis posterior and the flexor digitorum longus muscle was overlapped by the soleus muscle. In two cases the soleus muscle did not attach to the tibia at all. Our findings may shed some light on the question as to why some athletes sustain posteromedial tibial stress fractures and others develop shin splits or other posteromedial injuries from similar precipitating activity.

Aged↗
PubMed1995

Quantification of inhibin pro-alpha C-containing forms in human serum by a new ultrasensitive two-site enzyme-linked immunosorbent assay.

Precursor forms of the alpha-subunit of inhibin are abundant in human follicular fluid and possibly plasma, although their function is uncertain. We now describe the development of a new enzyme-linked immunosorbent assay to measure inhibin forms containing both the pro and alpha C regions of the alpha-subunit. The assay has a detection limit for purified human pro-alpha C of 0.5 pg/mL and less than 0.02% cross-reaction with recombinant forms of inhibin, activin, and follistatin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of follicular fluid extracts demonstrated that the assay is likely to detect pro-containing precursor forms of both the free alpha-subunit and intact dimeric inhibin. The serum concentration was measured in normal men (446 +/- 28 pg/mL), postmenopausal women (45.8 +/- 3.8 pg/mL), and women treated with FSH before in vitro fertilization (1827 pg/mL). Pooled human follicular fluid contained 488 ng/mL. The mean serum concentration in the female menstrual cycle rose from 150.6 +/- 26.1 pg/mL in the early follicular phase to 692.2 +/- 113 pg/mL in the midluteal phase. This assay offers a useful tool for investigation of the role of inhibin-related proteins in human reproduction. There may be particular clinical value under circumstances in which other assays for inhibin forms have insufficient sensitivity.

Activins↗
PubMed1995

Local reaction secondary to insulin injection. A potential role for latex antigens in insulin vials and syringes.

OBJECTIVE: To evaluate the possibility that latex antigens (natural rubber) can contribute to or cause local sensitivity at insulin injection sites. CASE: A subject with documented local cutaneous allergic reactions at the site of insulin injections and with systemic latex allergy manifested as anaphylaxis was tested with intradermal injections of insulin diluent from two manufacturers and with two brands of insulin syringes. RESULTS: The subject had high titer anti-latex Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE antibodies were absent. Erythema and wheals occurred at the sites of intradermal injection of insulin therapy components (insulin diluent and syringes) that contain natural latex rubber but not at the site of injection of insulin therapy components that do not contain natural latex rubber. CONCLUSIONS: Small quantities of natural latex rubber antigens in insulin injection materials can be sufficient to produce local cutaneous reactions at the site of insulin injection in individuals highly allergic to natural latex rubber.

Adult↗
PubMed1995

Postoperative toxic shock syndrome.

PURPOSE: To determine risk factors for postoperative toxic shock syndrome (PTSS), a rare, rapidly progressive, and potentially fatal syndrome associated with postoperative wound infections. Components of PTSS include fever, rash, desquamation, hypotension, and multisystem organ dysfunction. METHODS: We conducted a retrospective review of all cases of PTSS occurring in 2 community hospitals from 1981 to 1993, following 390,000 surgical procedures. RESULTS: There were 12 cases of PTSS among the procedures reviewed (0.003%). Orthopedic procedures included excision of accessory navicular and patellar realignment. Wounds ranged from those with scant superficial exudates to those with gross purulence; all cultures yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Mean time from surgery to onset of symptoms was 4 days. All patients had sudden onset of fever; mean maximal temperature was 40 degrees C. All patients displayed a rash, most in a truncal "sunburn" pattern. Eleven of 12 patients desquamated. All patients required vigorous fluid resuscitation. All patients survived. No correlation could be demonstrated between PTSS and patient age, sex, preoperative skin preparation or antibiotics, members of surgical team, or duration of procedure. CONCLUSIONS: Early recognition and treatment of PTSS are essential. No risk factors for PTSS have been identified. PTSS should be considered in the postoperative, acutely febrile, systemically ill patient, though surgical wounds may be deceptively benign in appearance.

Adolescent↗
PubMed1995

Safety and efficacy of increasing wintertime vitamin D and calcium intake by milk fortification.

We studied the safety and efficacy of milk fortified with vitamin D3 and calcium. Over the winter, we conducted a double-blind, placebo-controlled trial of fortified milk (12 micrograms vitamin D3 and 1525 mg calcium per litre) compared to unfortified milk (0.3 micrograms vitamin D3 and 1270 mg calcium per litre) in 102 adults (aged 17-54 years). Serum 25-hydroxyvitamin D [25(OH)D], ionized calcium, and creatinine were measured at baseline and after intervention. Fortification reduced the seasonal decline in serum 25(OH)D concentrations by > 50%. In the fortified group, serum 25(OH)D decreased by 15 nmol/l from 77 +/- 35 nmol/l to 62 +/- 26 nmol/l (p < 0.001). In the control group, serum 25(OH)D fell by 31 nmol/l from 85 +/- 38 nmol/l to 54 +/- 25 nmol/l (p < 0.001). We suggest that milk enriched with vitamin D be provided in high-latitude European countries to diminish the wintertime fall in serum 25(OH)D.

Adolescent↗
PubMed1994

The role of the lumbar facet joints in spinal stability. Identification of alternative paths of loading.

STUDY DESIGN: The role of the facet joints in spinal stability was analyzed using long-segment cadaver spines. OBJECTIVES: To establish the existence of alternate paths of loading when the facet joints and anulus are compromised. SUMMARY OF BACKGROUND DATA: It has been reported that facet arthrosis and degeneration never occur without the presence of adjacent disc degeneration. This suggests that intact discs protect the facets from severe loading and degeneration. Based on these studies of spinal mechanics, the authors devised an experiment to further explain the relationship of the disc and the facet in sharing compressive loads. METHODS: Ten human cadaver spines were placed unsupported in an Instron Model 4206 Tensile Testing Machine. Compressive loads of 1000 N then were applied to the specimens at a rate of 20 N per minute. The facet joints, anterior anulus, and lateral anulus then were destroyed sequentially at L3 and the loading cycles were repeated. The load-deflection curves for each cycle were evaluated and compared with the intact specimen. RESULTS: Unilateral and bilateral facetectomies had little affect on the ability of the specimen to support a physiologic load. Facetectomies in combination with anterior anulus destruction showed a significant change in the ability of the specimen to support a load with an extension moment applied. CONCLUSIONS: The facet joints of the lumbar spine are not the principle support structures in extension. With destruction of the facets, an alternate path of loading is established. The alternate path of loading transfers axial loads to the anulus and anterior longitudinal ligament to support the spine. Although facet joint destruction will not produce acute instability, it will transfer the loads to the adjacent disc and conceivably accelerate its degeneration.

Adult↗
PubMed1994

Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes.

This paper focuses on the relationship between the developmental programs that regulate nuclear and cytoplasmic maturation of mouse oocytes. As oocytes near completion of their growth phase, they become competent to resume meiosis when isolated from the small antral follicles and cultured, but the progression of meiosis in many of these oocytes stops at metaphase I (MI). With further growth and development at the germinal vesicle (GV) stage, however, these oocytes become competent to complete nuclear maturation and progress to metaphase II (MII). In this study, about 44% of the oocytes were arrested at MI after isolation from the small antral follicles of 18-day-old mice and culture for 16 to 17 hr. Upon insemination, these MI-arrested oocytes produced the first polar body, formed pronuclei, cleaved, and developed to the blastocyst stage. Seventy five percent of these blastocysts were triploid, the remainder were diploid. Treatment of MI-arrested oocytes with calcium ionophore resulted in the completion of the first meiotic division and parthenogenetic activation. Moreover, while the pattern of proteins synthesized in MI-arrested oocytes was quite different from that of normal MI oocytes as determined by [35S]methionine labeling and two-dimensional gel electrophoresis, it was similar to that of MII-arrested oocytes. It was therefore concluded that some critical aspects of cytoplasmic maturation can occur in oocytes whose nuclear maturation is arrested at MI. In addition, triggers that promote entry of MII-arrested oocytes into anaphase II are sufficient to drive MI-arrested oocytes into anaphase I and to produce the first polar body when the triggers are generated in mature cytoplasm. The developmental capacity of MII oocytes that matured in vitro after isolation from 18- or 26-day-old mice were compared. The frequency of fertilization and cleavage to the 2-cell stage was equal in both groups. In surprising contrast, the ability to complete the 2-cell stage to blastocyst transition occurred much more frequently when the oocytes were from the 26- than the 18-day-old mice (82 and 27%, respectively). Thus, even though both groups of oocytes had completed nuclear maturation by progressing to MII, oocytes from the smaller follicles of the younger mice were deficient in maternal factors essential for development of embryos beyond the 2-cell stage. Further differentiation of these GV-stage oocytes of small antral follicles is therefore required to produce eggs competent of completing preimplantation development.

Animals↗
PubMed1994

Perioperative creatine phosphokinase trends in elderly patients with hip fracture.

A prospective study of the serum levels of unfractionated creatine phosphokinase (CPK) in 69 consecutive elderly patients undergoing surgery for hip fracture is reported. Serum unfractionated CPK levels were measured on admission, on the evening following surgery and daily for the first five days post-operatively. All of the CPK levels measured on admission were within the normal range for this laboratory. A gradual rise in CPK levels followed surgery. On the evening following surgery 75% of values were greater than the upper limit of the normal reference range. The peak values were seen on day 1 post-operatively but 25% of values were still less than the reference maximum. A gradual decline was seen after this and at day 5 post operatively 50% of values were within the normal reference range. A single unfractionated CPK determination is not of diagnostic benefit in the post-operative period in elderly patients with hip fracture. However, patients with intracapsular and intertrochanteric fractures do not show elevation of unfractionated CPK levels prior to surgery.

Aged↗