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Biomedical subjects

L Calder

Publications and source records attributed to L Calder.

At least 19 recordsLinked to original sources

Tuberculosis in New Zealand, 1992-2001: a resurgence.

OBJECTIVE: To describe the recent epidemiology and clinical features of paediatric tuberculosis (TB) in New Zealand (NZ). METHODS: A retrospective review was conducted of clinical, laboratory, and radiology records of children <16 years old diagnosed with TB between January 1992 and June 2001 in nine NZ health districts. RESULTS: A total of 274 patients <16 years old were identified; the average annual TB rate was 4.8 per 100,000. Rates rose over time reaching a peak of 10.1 in 1999. Rates were highest in under-5 year olds, at 6.2 per 100,000, and varied by ethnicity: African 575.2, Pacific Island 15.2, Maori 6.4, Asian 5.6, and European 0.6. Seventy two cases (26%) were foreign born. Thirty six per cent of cases were not detected until they presented with symptoms and of these 44% had no known TB contact. Most cases were identified by contact tracing (48%) or immigrant screening (11%); 43% were part of outbreaks. Miliary TB or meningitis occurred in 8% of patients, two of whom died. Drug resistance was found in 7% of culture positive cases and no HIV co-infection was found. CONCLUSIONS: A resurgence of TB occurred among children in NZ between 1992 and 2001 predominantly involving non-European and immigrant groups. Despite established contact tracing and immigrant screening programmes, many cases were part of outbreaks, remained unidentified until symptoms arose, or had no known TB contact. These findings point to an unrecognised burden of adult disease, ongoing community transmission, and missed opportunities for prevention. Further study is required to confirm these hypotheses.

Adolescent↗

Isomerism of the right atrial appendages: clinical, anatomical, and microscopic study of a long-surviving case with asplenia and ciliary abnormalities.

This study describes a case of isomerism of the right atrial appendages (bilateral morphologically right atrial appendages associated with complex congenital cardiac lesions) with ciliary abnormalities. Detailed investigation included gross anatomic dissection, review of the clinical history, and light, confocal, and electron microscopy. Clinically, this 40-year-old, long-surviving male patient had relatively good health until 4 years before death, which was due to cardiac failure. Surgical intervention consisted only of a Blalock-Taussig shunt (anastomosis of the right subclavian artery to the right pulmonary artery) at 6 years of age. Despite the presence of complex cardiac malformations and asplenia, his longevity may be attributed to the connection of the pulmonary veins to the atrium without pulmonary venous obstruction, pulmonary valvar stenosis rather than atresia, no significant atrioventricular valve regurgitation, and no serious infections during his life. Microscopic examination of bronchial epithelium revealed a narrow, disorganized epithelium with abundant goblet cells and short, angulated cilia with a random orientation and possibly an abnormal central microtubule doublet. These abnormalities were not present in controls, and have been noted in primary ciliary dyskinesia (PCD) or Kartagener's syndrome. Because this syndrome has classically been thought to cause random lateralization resulting in a mirror-imaged arrangement of the organs, the occurrence of truly isomeric patterns is not widely recognized. Whereas polysplenia and left bronchial isomerism have been reported to occur in immotile cilia syndrome, this is the first report to present detailed postmortem anatomic evidence of isomerism of the right atrial appendages, right bronchial isomerism, and asplenia in association with microscopy suggesting ciliary abnormalities.

Adult↗

An outbreak of hepatitis A associated with consumption of raw blueberries.

This report describes the epidemiology, investigation and control of a hepatitis A (HAV) outbreak in New Zealand. Descriptive and analytical epidemiology, virology, product traceback and an orchard investigation were carried out. A case-control study revealed that 56% of 39 cases had consumed raw blueberries, compared with 14% of 71 controls (odds ratio 7.6; 95% confidence intervals 2.6-22.4). Traceback of product through retailers and wholesalers implicated a single commercial orchard. Hepatitis A virus was detected by reverse transcriptase polymerase chain reaction in faecal specimens from cases as well as a blueberry product from the orchard. Presence of hepatitis A virus was confirmed by DNA hybridization and sequencing of PCR products. Sanitary audit of the orchard revealed multiple opportunities for contamination of blueberries by pickers. This outbreak highlights the need for food safety programmes in the berry fruit industry.

Adolescent↗

A case of infectious tuberculosis on two long-haul aircraft flights: contact investigation.

AIM: During a five-week period in 1996, a passenger with highly infectious tuberculosis travelled on five long-haul aircraft flights. We investigated passengers and crew on two of these flights to identify whether transmission of Mycobacterium tuberculosis had occurred. METHODS: Crew and passengers were identified from airline and immigration records. Contacts were notified of their exposure and invited to attend their local public health clinic. At the clinic, a questionnaire was administered by a public health worker, and a Mantoux skin test was performed. When indicated, a second test was carried out twelve weeks later. Test positivity and conversion were defined according to the 1996 New Zealand tuberculosis control guidelines. RESULTS: Data were obtained on 206 (87%) of the 238 contacts. Twenty four contacts had a positive Mantoux test result, four of which were conversions. All of these contacts had at least one other major risk factor for a positive result, such as a previous BCG vaccination (n=17) or having lived in a country in which tuberculosis is endemic (n=15). To our knowledge, no contacts have subsequently developed tuberculosis disease. CONCLUSIONS: The investigation produced inconclusive evidence about the hypothesis that Mycobacterium tuberculosis was transmitted on one or both of these flights.

Adult↗

Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion.

Preparations of purified full-length fusion (F) protein of human respiratory syncytial virus (HRSV) expressed in recombinant vaccinia-F infected cells, or of an anchorless mutant (F(TM(-))) lacking the C-terminal 50 amino acids secreted from vaccinia-F(TM(-))-infected cells contain a minor polypeptide that is an intermediate product of proteolytic processing of the F protein precursor F0. N-terminal sequencing of the intermediate demonstrated that it is generated by cleavage at a furin-motif, residues 106-109 of the F sequence. By contrast, the F1 N terminus derives from cleavage at residue 137 of F0 which is also C-terminal to a furin recognition site at residues 131-136. Site-directed mutagenesis indicates that processing of F0 protein involves independent cleavage at both sites. Both cleavages are required for the F protein to be active in membrane fusion as judged by syncytia formation, and they allow changes in F structure from cone- to lollipop-shaped spikes and the formation of rosettes by anchorless F.

Amino Acid Motifs↗

Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New Zealand.

The aims of this study were to estimate carriage prevalence, identify factors predictive of carriage, and compare strains of Neisseria meningitidis isolated from patients with meningococcal disease and their household contacts. A total of 954 contacts of 160 patients had a nasopharyngeal swab and an interview relating to factors associated with carriage. The carriage prevalence was 20.4% for Neisseria meningitidis, 11.3% for serogroup B, and 2.6% for serogroup C. Age-standardised carriage was higher in Maori (36.8%) than in Pacific Island (21.5%) or European/other (11.1%) ethnic groups. Factors associated with carriage were smoking, with personal smokers (odds ratio [OR] 2.5) and passive smokers (OR 1.6) having a higher carriage risk than those in smoke-free houses; ethnicity, with Maoris having a higher carriage risk than those of non-Maori or non-Pacific Island ethnicity (OR 2.2); gender, with males at higher risk than females (OR 1.7); and age, with 0-4-year-olds less likely and 15-24-year-olds more likely to be carriers than those over 25 years. Strong patient-contact clustering by meningococcal strain (chi-square1 = 16.7, P=0.00004) suggested an important role for the household setting in transmission. The low carriage prevalence of serogroup B Neisseria meningitidis among household contacts may reflect its low transmissibility but high virulence. No direct relationship was found between prevalence of ethnic-specific carriage and the incidence of meningococcal disease.

Adolescent↗

Tuberculosis: reasons for diagnostic delay in Auckland.

AIMS: First, to quantify the interval between the onset of symptoms and the start of anti-tuberculous treatment in a series of Auckland tuberculosis patients. Second, to examine the help-seeking behaviour of the patients and the responses of the health-care providers whom they consulted about their symptoms. Third, to identify potentially modifiable reasons for delayed presentation or diagnosis. METHODS: 100 patients with tuberculosis (TB) were interviewed using a questionnaire which sought symptom duration and help-seeking behaviour. The doctors whom they consulted were surveyed about their diagnostic, therapeutic and referral responses. RESULTS: Delayed presentation by patients ('patient delay') was found in smokers, patients who reported cough, patients who hoped their symptoms would go away on their own, and patients reporting fear of what would be found on diagnosis. 'Doctor delay' (the interval from first consultation with a doctor to start of treatment) was longer than that found in most published series and was a more important component of total delay than delayed presentation by patients. Longer doctor delay was found if patients had pre-existing lung disease or consulted multiple doctors, and if doctors did not inquire into past exposure to TB or request a chest X-ray. CONCLUSIONS: Awareness programmes for high-risk communities are needed to encourage early reporting of symptoms. Continuing medical education for general practitioners is needed to encourage vigilance for TB and earlier use of diagnostic tests in patients who have symptoms of TB and are in high-risk groups.

Adolescent↗

Antibiotic prescribing for dental conditions: general medical practitioners and dentists compared.

OBJECTIVE: To compare the level of prescribing and types of antibiotics prescribed for dental problems by general medical practitioners and dentists. DESIGN: Secondary analysis of standard consultation data and prescription records from four different settings. SETTING: 30 participating general practices in the General Practice Morbidity Database for Wales in 1996. SUBJECTS: 1,185 attendances for tooth-related problems, at 30 participating practices in the General Practice Morbidity Database for Wales in 1996. Standard consultation records from a GDP emergency dental rota, and two weekend emergency dental clinics: one in a health centre, the other in a dental hospital. RESULTS: More than two thirds (68%) of attendances at general medical practices for tooth-related problems resulted in a prescription for antibiotics. In contrast less than a third (28%) of patients seen by a GDP rota, about half (52%) of patients at a weekend emergency clinic in a health centre, and just more than a third (38%) of patients attending the dental hospital clinic received antibiotics. General medical practitioners were also more likely to prescribe broad-spectrum antibiotics than dentists. CONCLUSION: For acute dental problems general medical practitioners are more likely to prescribe antibiotics than dentists. There also appear to be inter-professional differences in the tendency to prescribe broad spectrum antibiotics. Initiatives to rationalise prescribing for dental conditions may need to target doctors as well as dentists.

Anti-Bacterial Agents↗

A school and community outbreak of tuberculosis in Auckland.

AIM: To describe a school and community outbreak of tuberculosis in South Auckland in 1997/8. METHODS: Cases were diagnosed according to national guidelines at Middlemore, Green Lane and Starship Hospitals. Public health follow-up was conducted by Auckland Healthcare. RESULTS: Twelve cases were diagnosed during the outbreak. Nine cases were from the same South Auckland secondary school; six reported no association outside school. Three cases were in younger children who had close household contact with two of the school cases. Nine cases (including eight from the school) had identical Mycobacterium tuberculosis isolates on restriction fragment length polymorphism testing. No microbiological culture was obtained from the three remaining cases. Contact investigation detected five of the cases. Chemoprophylaxis was prescribed for twenty-six school students, two adult staff, and nine household contacts. CONCLUSION: This is the first published account of a tuberculosis outbreak in a New Zealand school setting for decades. Recognition of the outbreak was delayed. DNA fingerprinting played a valuable role in the investigation. The source case may have been a school student. The social impact of the outbreak and preventability with routine adolescent BCG vaccination are discussed.

Adolescent↗

Equivalence of ceftriaxone and rifampicin in eliminating nasopharyngeal carriage of serogroup B Neisseria meningitidis.

The efficacy of ceftriaxone in eliminating nasopharyngeal carriage of Neisseria meningitidis was compared with that of rifampicin during an epidemic of serogroup B meningococcal disease in Auckland, New Zealand. Household contacts of cases had a throat swab taken and were randomized to treatment. Carriers had a repeat swab taken 6 days later to determine efficacy of treatment. Ceftriaxone (98.2%) was equivalent to rifampicin (97.6%) in eliminating serogroup B N. meningitidis. It is cheaper than rifampicin and has the advantage of full compliance and fewer contraindications, but its acceptability by patients may limit its use as a first-line prophylactic agent.

Adolescent↗

Tuberculosis in immigrants and visitors.

Immigrants and visitors are a significant factor in the epidemiology of tuberculosis (TB) in New Zealand, accounting for an increasing proportion of notifications in recent years. At present screening of immigrants from countries with a high incidence of TB is inadequate. There are deficiencies in procedures, inadequate screening coverage, ineffectual coordination between the Ministry of Health and New Zealand Immigration Service, incomplete follow-up on those at risk of TB, confusion over financial responsibility, inadequate data to describe the problems and monitor interventions, and a lack of commitment to assistance with TB control in neighbouring countries from which some of our TB arises. We make recommendations in all of these areas. Timely screening of high-risk immigrants should be seen as health protection for ethnic minorities.

Emigration and Immigration↗

Variation in red cell transfusion practice in the intensive care unit: a multicentre cohort study.

OBJECTIVES: To determine the degree of interinstitutional transfusion practice variation and reasons why red cells are administered in critically ill patients. STUDY DESIGN: Multicentre cohort study combined with a cross-sectional survey of physicians requesting red cell transfusions for patients in the cohort. STUDY POPULATION: The cohort included 5298 consecutive patients admitted to six tertiary level intensive care units in addition to administering a survey to 223 physicians requesting red cell transfusions in these units. MEASUREMENTS: Haemoglobin concentrations were collected, along with the number and reasons for red cell transfusions plus demographic, diagnostic, disease severity (APACHE II score), intensive care unit (ICU) mortality and lengths of stay in the ICU. RESULTS: Twenty five per cent of the critically ill patients in the cohort study received red cell transfusions. The overall number of transfusions per patient-day in the ICU averaged 0.95 +/- 1.39 and ranged from 0.82 +/- 1.69 to 1.08 +/- 1.27 between institutions (P < 0.001). Independent predictors of transfusion thresholds (pre-transfusion haemoglobin concentrations) included patient age, admission APACHE II score and the institution (P < 0.0001). A very significant institution effect (P < 0.0001) persisted even after multivariate adjustments for age, APACHE II score and within four diagnostic categories (cardiovascular disease, respiratory failure, major surgery and trauma) (P < 0.0001). The evaluation of transfusion practice using the bedside survey documented that 35% (202 of 576) of pre-transfusion haemoglobin concentrations were in the range of 95-105 g/l and 80% of the orders were for two packed cell units. The most frequent reasons for administering red cells were acute bleeding (35%) and the augmentation of O2 delivery (25%). CONCLUSIONS: There is significant institutional variation in critical care transfusion practice, many intensivists adhering to a 100g/l threshold, and opting to administer multiple units despite published guidelines to the contrary. There is a need for prospective studies to define optimal practice in the critically ill.

Journal Article↗

A Canadian survey of transfusion practices in critically ill patients. Transfusion Requirements in Critical Care Investigators and the Canadian Critical Care Trials Group.

OBJECTIVES: To characterize the contemporary red cell transfusion practice in the critically ill and to define clinical factors that influence these practices. DESIGN: Scenario-based national survey. STUDY POPULATION: Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS: We evaluated transfusion thresholds before transfusion and the number of red cell units ordered, under the given conditions. Of 254 Canadian critical care physicians, 193 (76%) responded to the survey. The primary specialty of most respondents was internal medicine (56%). Internal medicine respondents were in practice for an average of 8.4 +/- 5.7 (SD) yrs, and worked most often in combined medical/surgical intensive care units. Baseline hemoglobin transfusion thresholds averaged from 8.3 +/- 1.0 g/dL in a scenario involving a young stable trauma victim to 9.5 +/- 1.0 g/dL for an older patient after gastrointestinal bleeding. Transfusion thresholds differed significantly (p< .0001) between all four separate scenarios. With the exception of congestive heart failure (p> .05), all clinical factors (including age, Acute Physiology and Chronic Health Evaluation II score, preoperative status, hypoxemia, shock, lactic acidosis, coronary ischemia, and chronic anemia) significantly (p< .0001) modified the transfusion thresholds. A statistically significant (p< .01) difference in baseline transfusion thresholds was noted across four major regions (with a maximum of five academic centers per region) of the country. Low physician numbers in two of the regions did not allow for further investigation of regional variations. CONCLUSIONS: There is significant variation in critical care transfusion practice, with many intensivists adhering to a 10.0-g/dL threshold, while other physicians described a much more restrictive approach to red cell transfusion. Also, many physicians opted to administer multiple units, despite published guidelines to the contrary. Additionally, the administration of red cells was strongly influenced by a number of clinical factors, many unique to intensive care unit patients. There is a need for prospective studies to define optimal practice in the critically ill.

Adult↗

An antibody which binds to the membrane-proximal end of influenza virus haemagglutinin (H3 subtype) inhibits the low-pH-induced conformational change and cell-cell fusion but does not neutralize virus.

A monoclonal antibody, LMBH6, was derived from mice which had been sequentially immunized with bromelain-cleaved haemagglutinin (BHA) from influenza virus A/Aichi/2/68, A/Victoria/3/75 and A/Philippines/2/82 (all H3N2). LMBH6 recognizes the haemagglutinin (HA) of all H3N2 influenza A strains tested, which were isolated between 1968 and 1989. HA in the low-pH-induced conformation is not recognized, and cleavage of the HA0 precursor to HA1 and HA2 is needed to obtain efficient binding. Compared to other monoclonal antibodies, binding of LMBH6 to virus and to virus-infected cells is weak, while binding to BHA is comparable. Electron microscopy demonstrates binding to the membrane proximal end of the stem structure. The antibody shows no haemagglutination-inhibition activity, but inhibits polykaryon formation and the low-pH-induced conformational change of BHA. However, LMBH6 cannot prevent infection of MDCK cells but slows the growth of virus when included in a plaque assay overlay.

Animals↗

One year of tuberculosis in Auckland.

AIM: To describe the recent epidemiology of tuberculosis in Auckland and the outcome of contact investigations. METHOD: Routine public health data were used to review the experience of tuberculosis (TB) in the Auckland region during a twelve month period in 1992-3. RESULTS: There were 152 cases, an age-standardised rate of 2.7 per 100,000 for Europeans, 37.8 for Maori, 70.9 for Pacific Island Polynesians and 131.3 for other ethnic groups. Fifty-two (35%) were born in New Zealand; 46 (31%) in Asia; 44 (30%) in the Pacific Islands. Forty-seven percent of foreign-born cases (28% of all cases) arrived in New Zealand in the 4 years preceding their notification. Forty-one per cent of cases appear not to have been diagnosed until 3 months or longer after the onset of their symptoms. Fifteen cases (including three sputum smear-positive cases) took 4 weeks or longer from diagnosis to be notified to the public health office. 12.5% of isolates were not notified. Two per cent of the 1079 contacts examined had tuberculosis. CONCLUSION: This review highlights the need for tuberculosis and the importance of timely comprehensive screening of immigrants from high incidence countries; reducing the interval between onset of symptoms and diagnosis; improving the notification rate of tuberculosis; and focusing contact investigation on those at highest risk.

Adolescent↗

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.

BACKGROUND: Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone. METHODS: The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol. RESULTS: Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion.

Abortion, Induced↗