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Biomedical subjects

A J Keller

Publications and source records attributed to A J Keller.

At least 19 recordsLinked to original sources

The efficacy of a malarial antibody enzyme immunoassay for establishing the reinstatement status of blood donors potentially exposed to malaria.

BACKGROUND AND OBJECTIVES: The two key objectives of the study were, first, to evaluate the sensitivity and specificity of a recombinant antigen-based malarial enzyme-linked immunoassay (EIA) and, second, to estimate the risk associated with implementing this test with a shortened cellular component restriction period (6 months rather than the standard 12-36 months) for blood donors with a malarial risk exposure. MATERIALS AND METHODS: Blood donors were recruited into four distinct groups [non-exposed (control), malarial area 'visitors', 'residents' and 'previous infection') and screened by using the Newmarket malarial antibody EIA. Assay specificity was evaluated in unexposed blood donors, and sensitivity was determined in acute clinical samples. RESULTS: No parasitaemic donors were detected amongst 337 malarial 'visitors' who had returned from a malaria-endemic area less than 6 months previously, or for 402 'visitors' or 'residents' who had returned from a malaria-endemic area more than 6 months previously. The incidence of malarial antibodies within the exposed blood donor groups was 1.33% (10/751). In acute clinical non-donor samples, the Newmarket EIA detected 106/108 (98.1; 93.5-99.5%) 'film' positive Plasmodium falciparum infections and 12/12 (100, 75.7-100.0%) P. vivax infections. The estimated additional risk exposure of the proposed new strategy was one infectious P. falciparum donation per 175 years or 1 per 4.2 years for P. vivax. CONCLUSIONS: The study findings support the efficacy and safety of a targeted screening strategy combining antibody screening with a 6-month cellular component restriction period for donors with a declared malarial risk.

Algorithms↗

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus.

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.

Australia↗

Variant Creutzfeldt-Jakob disease in Australian blood donors: estimation of risk and the impact of deferral strategies.

BACKGROUND AND OBJECTIVES: In Australia, a policy of deferring donors who have lived in the UK for longer than 6 months between 1980 and 1996 has been instituted to reduce the theoretical risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) through the blood supply. The objective of this report was to refine estimates of the possible risks and benefits of donor-deferral strategies that are aimed at avoiding transmission of vCJD. MATERIALS AND METHODS: Estimates of the effect of donor deferral on the blood supply in Australia were based on a 1998 survey of blood donors. The number of donations from donors potentially infected with vCJD and excluded by donor deferral was estimated based on published estimates of the size of the vCJD epidemic in the UK and assuming that the risk of vCJD in Australian blood donors was proportional to the time lived in the UK between 1980 and 1996. The possible increased number of blood donations that were infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) and made during a window period (as a result of increased donations from first-time donors) was estimated using published methods. RESULTS: A strategy of deferring donations in Australia from people who have lived in the UK for 6 months or longer, between 1980 and 1996, was estimated to result in exclusion of 5.3% of all blood donations, corresponding to 50 100 donations in 1998. It was estimated that the annual number of blood donations made by donors potentially infected with vCJD is 1.15 (range 0.02--31.1, based on the uncertainty in the UK prevalence estimate). Donor deferral was estimated to remove 0.92 (range 0.02--25.1) of these donations. Replacement of 33%, 50% and 100% of excluded donations by donations from first-time donors, was estimated to result in an increase of 0.0010, 0.0019 and 0.0044, respectively, of HIV-infected donations per year donated during the window period; in an increase of 0.021, 0.038 and 0.089, respectively, of HCV-infected donations per year; and in an increase of 0.18, 0.33 and 0.76, respectively, of HBV-infected donations per year. CONCLUSIONS: The large uncertainties involved in these analyses mean that estimates must be interpreted cautiously, but the data does suggest that donor deferral may exclude more donations from donors potentially infected with vCJD than the corresponding increase, caused by donor replacement, of window-period donations possibly infected with HIV, HCV or HBV.

Australia↗

Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey.

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of the type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.

Base Sequence↗

Zidovudine (AZT) therapy in children with HIV infection: the Australian experience.

Fifteen children (11 males and four females), on oral Zidovudine (AZT) for symptomatic HIV infection were studied retrospectively. Twelve acquired HIV via blood products, two from vertical transmission (maternal intravenous needle sharing) and one through breast feeding. Their mean age at the start of therapy was 8.6 years (s.d. 4.4 years, range 1.8-15.3 years). The main indications for therapy were failure to thrive (FTT) in 10, recurrent respiratory tract infections (RRTI) in eight, and developmental delay (DD) in one, with overlapping indications being Pneumocystis carinii pneumonia (PCP) in one and pulmonary lymphoid hyperplasia (PLH) in two. The mean commencement dose was 24 mg/kg per day orally in 3-6 divided doses (range 16-35 mg/kg per day). The duration of therapy was 2 weeks-2 1/2 years. Significant improvement in growth was observed by 2 months; at 6 months, growth was sustained in these otherwise ill children, with only two falling below pretreatment weight. Decrease in the frequency of RRTI based on subjective reports of the attending clinicians was observed in seven of the eight evaluable children still on therapy. Improvement in PCP and PLH occurred in two children and modest improvement was subjectively reported in PLH in one while still early in the course of therapy. Overall, AZT was well tolerated. Dose modifications were for neutropenia in three (of which only two were drug related), rapidly falling neutrophil count in one, anaemia in two (with concurrent history of chronic gastrointestinal tract blood loss in one), severe GIT irritation in one and transient sedation in one. Seven opportunistic infections were reported (three in the same patient) of which two occurred following cessation of therapy, one after only 2 weeks of therapy, and one had not been on primary prophylactic therapy. Three deaths occurred, one associated with opportunistic infections and two while off therapy (one respiratory failure, one PCP).

Adolescent↗

Population-based epidemiology of human immunodeficiency virus infection in Western Australia. Western Australian AIDS Advisory Committee.

A total of 328 cases of infection with human immunodeficiency virus (HIV) in Western Australia in 1983-1987 was studied with respect to demographic factors, the risk profile, the clinical progression of disease, the utilization of inpatient services and trends in incidence over time. The crude incidence rates were 8.8 cases/100,000 person-years in men and 0.4 cases/100,000 person-years in women. Age-specific rates peaked at 25 to 29 years of age in men. The risk of HIV infection was associated with metropolitan residence, low socioeconomic level, and two specific occupational groups. Homosexual and bisexual men constituted 86% of all cases; the incidence rate of HIV infection in such men was approximately 1000-times higher than was the incidence rate by apparent sexual transmission in heterosexual persons. However, the proportion of cases that occurred in women or that apparently was caused by heterosexual sexual transmission increased from zero in 1983-1984 to 7.5% and 5.4%, respectively, in 1987. After two years of follow-up, 71% of preclinical (category-C) patients had developed signs, symptoms or evidence of immune dysfunction, and 12% of those patients with lymphadenopathy or with other early clinical features of disease (category-B) had progressed to the acquired immunodeficiency syndrome (AIDS). At 21 months of follow-up, the survival rate with AIDS was 9%. Patients with AIDS utilized an average of 68.9 short-stay hospital bed-days per person-year, while category-B patients used 11.5 hospital bed-days per person-year. Notifications of HIV infection increased each year from 1983 to 1986, but fell by 22% in 1987. The latter may have been as a result of chance, a screening artefact or a real reduction in the incidence rate.

Acquired Immunodeficiency Syndrome↗

Increased complications and prolonged hospital stay in elderly cardiac surgical patients with low serum albumin.

Cardiac surgery in elderly patients is associated with acceptable operative mortality but an increased complication rate. Malnutrition is common in the elderly and may adversely affect surgical outcome. To determine the effect of hypoalbuminemia on postoperative complications, 92 patients greater than or equal to 75 years (range 75 to 90) undergoing a variety of major cardiac surgical procedures were evaluated. Thirteen patients (14%) had a serum albumin level less than 3.5 g/dl preoperatively. Compared to patients with normal albumin, hypoalbuminemic patients had an increased frequency of postoperative confusion, congestive heart failure, low cardiac output, renal dysfunction and gastrointestinal complications (all p less than 0.05). Mean postoperative length of stay was markedly prolonged in these patients (27 vs 12 days; p less than 0.001), and mortality also tended to be higher (31 vs 13%; p = 0.11). Using multivariate analysis, albumin less than 3.5 g/dl was the most powerful predictor of postoperative renal dysfunction (p less than 0.01), and was also an independent predictor of increased length of stay (p less than 0.01) and gastrointestinal disorders (p less than 0.05). Thus, hypoalbuminemia is a powerful indicator of an increased risk of perioperative complications in elderly patients undergoing cardiac surgery. Increased attention to nutritional factors is warranted in these patients.

Aged↗

Microvascular free flap reconstruction for head and neck defects.

In a three-year period, 53 microvascular free-tissue grafts were performed on 51 patients to repair defects following major head and neck ablative surgery or trauma. The vast majority were done at the time of tumor resection. The remainder were done as secondary operations after resection or injury. The choice of free flap was dictated by the reconstructive needs of the patient and donor site availability. Fifty-two (98%) of 53 free-tissue transfers were successful with one failure resulting from venous thrombosis. Complications were noted in 16 of 53 flaps. The majority of these complications were in flaps used to replace bony defects or oropharyngeal resections. Although free flaps may appear to be more risky than traditional forms of reconstruction, they offer the surgeon a greater spectrum of reconstructive options. Limitations of the use of free flaps result only from lack of technical skills and specialized equipment.

Adult↗

Evaluation of reconstructive techniques of oropharyngeal defects.

Despite recent advances in radiation therapy and chemotherapy, surgical procedures remain the primary modality of head and neck cancer therapy. Adequate surgical resection frequently requires the removal of significant amounts of tissue. The primary concern of the reconstructive surgeon is the restoration of a functional aerodigestive tract. In addition to the prolongation of life, the quality of that life should be taken into consideration. The records of 25 patients undergoing oropharyngeal reconstruction for tumors stage 3 or 4 in the 4-year period from 1983 to 1986 were reviewed. After surgical extirpation, reconstruction was performed using either a pectoralis major musculocutaneous flap or a microvascular free flap. Results were evaluated with emphasis on both the intraoperative and postoperative course. The length of the procedure, time of initiation of oral feedings, time of decannulation, postoperative complications, time of discharge, and quality of life after discharge were considered. Those patients reconstructed with microvascular free flaps were able to tolerate oral feedings sooner and were discharged sooner than those patients reconstructed with pectoralis musculocutaneous flaps. In addition, the patients with pectoralis flaps were twice as likely to have local complications (e.g., superficial wound infection, fistula) as those with free flaps. The quality of the patient's life with respect to deglutition and intelligibility of speech was likewise better for those patients reconstructed with microvascular free flaps. The explanation of these results is presented.

Abdominal Muscles↗

Voice restoration after laryngopharyngoesophagectomy.

Although various methods of alaryngeal communication after laryngectomy have been described, little attention has been given to voice restoration after laryngopharyngoesophagectomy. This article deals with our experience reconstructing the hypopharynx and cervical esophagus in five patients by the use of microvascular free tissue grafts. Voice restoration procedures with use of a Blom-Singer prostheses were used uniformly and resulted in the attainment of functional voice in each patient. It is our feeling that this method should be used equally in patients undergoing both traditional laryngectomy and laryngopharyngoesophagectomy.

Adult↗

Rigid internal fixation and vascularized bone grafting in mandibular reconstruction.

The technique of mandibular reconstruction utilizing rigid internal fixation and vascularized bone grafts has been described. This type of repair should be considered in all patients undergoing mandibular resection for head and neck malignancies. Although no ideal method of reconstruction has yet been described, it appears that rigid internal fixation combined with vascularized bone grafts most satisfactorily fulfills the requirements associated with reconstruction of jaw defects.

Aged↗

Morbidity and mortality of coronary bypass surgery in patients 75 years of age or older.

To determine factors associated with an increased risk of postoperative complications in elderly patients, 60 consecutive patients 75 years of age or older undergoing isolated coronary artery bypass grafting (CABG) were evaluated. Thirty-nine patients (65.0%) had at least one major postoperative complication, including 2 deaths (3.3%). Low body weight was the only univariate predictor (p less than 0.05) of an increased likelihood of complications overall. Prior cardiac operation, low serum cholesterol value, and prolonged cardiopulmonary bypass time were associated with increased bleeding. Electrocardiographic evidence of left ventricular hypertrophy was associated with prolonged postoperative confusion. Age of 80 years or more and increased cross-clamp time were predictive of pulmonary dysfunction. Low cardiac output occurred more frequently in patients with nonsinus rhythm, prior cardiac operation, recent congestive heart failure, or elevated level of blood urea nitrogen. Identification of risk factors for specific complications should prompt further studies to define ways of reducing morbidity and the resultant high cost associated with CABG in elderly patients.

Aged↗

Anatomic reconstruction and functional rehabilitation of oromandibular defects with rigid internal fixation.

Fifteen consecutive patients undergoing extensive surgery for head and neck cancer involving the oral cavity and oropharynx were reconstructed using the technique of rigid internal fixation combined with various vascularized flaps. The follow-up ranged from 6 to 18 months. Modifications in various myocutaneous or vascularized free flaps combined with an analysis of the radiation physics necessary to make this procedure a viable alternative for immediate and delayed mandibular reconstruction will be discussed. Consistently satisfactory functional and cosmetic results have been achieved.

Adult↗

Microvascular free-tissue transfer with rigid internal fixation for reconstruction of the mandible following tumor resection.

The authors described their experience using rigid internal fixation techniques in combination with free microvascular tissue transfer for the immediate reconstruction of mandibular defects following tumor ablation. The technique allows immediate return of jaw motion and limited function while assuring maintenance of occlusion and reasonable cosmesis.

Fracture Fixation, Internal↗

Hepatitis B markers in health care workers. The Newcastle study.

Health care workers in the Royal Newcastle Hospital, in surrounding hospitals and pathology services, and in a large mental institution were surveyed to determine the prevalence of hepatitis B markers. The aim of the study was to identify the groups of workers at particular risk of contracting hepatitis B in order to determine which workers would benefit most from a programme of vaccination against hepatitis B. Although the prevalence of hepatitis B markers in the Newcastle health care workers was higher than that in the control subjects, this rate did not approach the high rates previously reported in overseas studies.

Australia↗