Biomedical subjects

A Tucker

Publications and source records attributed to A Tucker.

At least 19 recordsLinked to original sources

PubMed2005

Heparin-induced thrombocytopenia and the use of r-hirudin during cardiopulmonary bypass.

We report the successful use of r-hirudin (lepirudin) for cardiopulmonary bypass in a 67-year-old man who developed heparin-induced thrombocytopenia type II during heparin treatment of an extensive deep venous thrombosis. Lepirudin was monitored by the modified ecarin clotting time in a "mobile laboratory" set up next to the cardiac theatre, aiming for lepirudin levels of 3.5 to 4.5 microg/ml during bypass.

Aged↗

PubMed2005

Organized tooth-specific cellular differentiation stimulated by BMP4.

Mammalian teeth develop on the oral surface of the first pharyngeal arch by a series of reciprocal interactions between epithelial and mesenchymal cells. The embryonic first pharyngeal arch oral epithelium is able to induce tooth formation when combined with mesenchymal cells from the second pharyngeal arch, a region devoid of tooth development. Second pharyngeal arch mesenchyme is thus competent to form teeth if provided with the correct signals. First-arch oral epithelium expresses several signaling molecules that could be potential inducers of tooth development, including BMP4. The addition of BMP4 to intact second-arch explants resulted in the development of organized structures containing layers of cells that express marker genes of tooth-specific cells, odontoblasts and ameloblasts. Thus, although overt tooth development did not occur, BMP4 has the ability to stimulate organized differentiation of epithelial- and mesenchymal-derived dental-specific cells from non-dental primordia.

Ameloblasts↗

PubMed2004

Direct ANP inhibition of hypoxia-induced inflammatory pathways in pulmonary microvascular and macrovascular endothelial monolayers.

Atrial natriuretic peptide (ANP) has been shown to reduce hypoxia-induced pulmonary vascular leak in vivo, but no explanation of a mechanism has been offered other than its vasodilatory and natriuretic actions. Recently, data have shown that ANP can protect endothelial barrier functions in TNF-alpha-stimulated human umbilical vein endothelial cells. Therefore, we hypothesized that ANP actions would inhibit pulmonary vascular leak by inhibition of TNF-alpha secretion and F-actin formation. Bovine pulmonary microvascular (MVEC) and macrovascular endothelial cell (LEC) monolayers were stimulated with hypoxia, TNF-alpha, or bacterial endotoxin (LPS) in the presence or absence of ANP, and albumin flux, NF-kappa B activation, TNF-alpha secretion, p38 mitogen-activated protein kinase (MAPK), and F-actin (stress fiber) formation were assessed. In Transwell cultures, ANP reduced hypoxia-induced permeability in MVEC and TNF-alpha-induced permeability in MVEC and LEC. ANP inhibited hypoxia and LPS increased NF-kappa B activation and TNF-alpha synthesis in MVEC and LEC. Hypoxia decreased activation of p38 MAPK in MVEC but increased activation of p38 MAPK and stress fiber formation in LEC; TNF-alpha had the opposite effect. ANP inhibited an activation of p38 MAPK in MVEC or LEC. These data indicate that in endothelial cell monolayers, hypoxia activates a signal cascade analogous to that initiated by inflammatory agents, and ANP has a direct cytoprotective effect on the pulmonary endothelium other than its vasodilatory and natriuretic properties. Furthermore, our data show that MVEC and LEC respond differently to hypoxia, TNF-alpha-stimulation, and ANP treatment.

Actins↗

PubMed2003

Assessing inhibitory control: a revised approach to the stop signal task.

The stop signal task (stop task) is designed to assess inhibitory control and is a frequently used research tool in clinical disorders such as ADHD and schizophrenia. Previous methods of setting stop signal delay and of assessing inhibitory control are problematic. The current study reports two modifications that improve the task as a measure of inhibitory control. The first modification was to set stop signal delays proportional to go mean reaction time (go MRT) to better account for inter-subject variability in go MRT. Twenty-eight normal children were tested, and all standard, stop task dependent measures were obtained when delays were set by this method. The second modification was to calculate a novel dependent measure called the area of inhibition (AOI) which provides a more complete measure of inhibitory control than the slope of the relative finishing time z-scores (ZRFT-slope). Implications for the assessment of inhibitory control in clinical populations are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems.

BACKGROUND: Ketamine has been found to exert antinociceptive effects in animals and to be analgesic at subanaesthetic doses in humans. This study was designed to investigate the involvement of spinal cord mechanisms in the potentiation of opioid analgesia by parenteral non-spinal administration of ketamine. METHODS: Thresholds for nociception were measured in an acute pain model in rats that allowed identification of antinociceptive effects due to drug action in the spinal cord. Dose-response curves for the antinociceptive effects of ketamine alone and ketamine in conjunction with the mu opioid fentanyl were constructed. RESULTS: Intraperitoneal ketamine up to 3.75 mg kg(-1) caused no sedative or antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally mediated antinociceptive effects. Injections of ketamine doses that caused no antinociceptive effects when given alone (intrathecal 25 microg and intraperitoneal 3.75 mg/kg) significantly increased spinally mediated antinociception produced by intrathecal fentanyl injections when assessed using noxious heat (tail-flick test) but not when assessed by noxious electrical current (electrical current threshold test). CONCLUSIONS: We conclude that ketamine can potentiate the effects of fentanyl by an interaction at the level of the spinal cord even when ketamine is given via a non-spinal route of administration.

Analgesics↗

PubMed2001

Evaluation of the early conception factor (ECF) test for the detection of nonpregnancy in dairy cattle.

The ability to detect conception and/or conception failure in cattle would be beneficial to producers in formulating reproductive management plans. A new diagnostic test, the early conception factor (ECF) test, has been developed forthis application yetthe accuracy of this test has not been adequately determined. The objectives of this study were to evaluate the effectiveness of the ECF test for detecting the nonpregnant cow, and to compare the reliability of serum versus milk ECF tests relative to actual pregnancy rates. In Trial 1, Holstein heifers were synchronized, the animals were bred (timed-AI), and serum ECF tests were performed 72 h later. Heifers exhibiting a negative ECF test after AI were re-synchronized, bred again, and re-tested for ECF for up to three services. Relative to actual pregnancy rates, a negative ECF test was correct (i.e., true negative) 38.5% of the time over the three services. In Trial II, Holstein heifers were bred (AI) after observed estrus and serum ECF tests conducted between Days 1 and 3 and Days 7 and 9 after AI. In this trial, only 44.4% and 55.6% of the confirmed nonpregnant heifers were identified correctly by serum ECF analysis at Days 1 to 3 and Days 7 to 9 post-AI respectively. In Trial III, 40 lactating cows were synchronized, the animals were bred (AI), and serum and milk ECF tests were performed on Days 3, 9, 15, 21 and 30 after AI. Pregnancy diagnosis (ultrasound on Day 30 and palpation on Day 51) confirmed that 50% of the cows were pregnant to AI, while serum and milk ECF analysis indicated a 100% and 37.5% predicted pregnancy rate, respectively, at 30 d post-AI. Moreover, results of the serum and milk ECF tests disagreed with one another 36.9% of the time overall, while agreement between ECF and actual pregnancy rates were 50.6% and 45.6% for milk and serum respectively. Additionally in Trial III, a negative ECF result only identified 5% and 28.8% of nonpregnant cows overall for serum and milk tests respectively (i.e., true negatives), with a high incidence of false positive ECF results noted (47.5% and 31.3% for serum and milk, respectively). Collectively, these data indicate that the current ECF test cannot accurately identify the nonpregnant cow with the precision needed by the dairy producer.

Animals↗

PubMed2001

Pecam-1 is a modulator of stat family member phosphorylation and localization: lessons from a transgenic mouse.

PECAM-1 (CD31) is a member of the immunoglobin (Ig) superfamily of cell adhesion molecules whose expression is restricted to hematopoietic and vascular cells. PECAM-1 can recruit adapter and signaling molecules via its immunoreceptor tyrosine activation motif (ITAM), suggesting that PECAM-1 plays a role in signal transduction pathways. To study the involvement of PECAM-1 in signaling cascades in vivo, we used the major histocompatibility (MHC) I gene promoter to target ectopic PECAM-1 expression in transgenic mice. We noted an attenuation of mammary gland development at early stages of virgin ductal branching morphogenesis. STAT5a, a modulator of milk protein gene expression during lactation, was localized to the nuclei of ductal epithelial cells of 6-week-old virgin PECAM-1 transgenics, but not in control mice. This correlated with decreases in ductal epithelial cell proliferation and induction of p21, an inhibitor of cell cycle progression. Using in vitro model systems we demonstrated PECAM-1/STAT5a association and found that residue Y701 in PECAM-1's cytoplasmic tail is important for PECAM-1/STAT5 association and that PECAM-1 modulates increases in STAT5a tyrosine phosphorylation levels. We suggest that by serving as a scaffolding, PECAM-1 can bring substrates (STAT5a) and enzymes (a kinase) into close proximity, thereby modulating phosphorylation levels of selected proteins, as previously noted for beta-catenin.

Animals↗

PubMed2001

Atrial natriuretic peptide blockade exacerbates high altitude pulmonary edema in endotoxin-primed rats.

High altitude pulmonary edema (HAPE) is associated with increases in pulmonary arterial and hydrostatic pressures and an increase in pulmonary vascular permeability. There is evidence to suggest that inflammatory mediators may cause some forms of HAPE, and Salmonella enteritidis endotoxin (ETX) is known to activate neutrophils and inflammatory mediators, such as TNF-alpha and IL1-beta. Since HAPE has been produced in rats primed with ETX, we hypothesized that ANP release and action may ameliorate HAPE and that ANP blockade may exacerbate HAPE in ETX-primed rats exposed to high altitude (HA). Plasma ANP, right atrial ANP mRNA, and indexes of lung injury were measured in rats primed with endotoxin (ETX) (0.1 mg/kg BW, i.p.) and exposed to simulated HA (4267 m; P(B) = 440 mmHg) for either 12 or 24 h. Catheters were chronically inserted into the right carotid artery, pulmonary artery, and jugular vein for assessment of hemodynamic parameters in response to ETX and/or HA. In addition, some rats were injected with an antibody against ANP (alphaANP) prior to normoxic (NX) or HA exposure. Pulmonary arterial pressure increased in the alphaANP group (50 +/- 20%; p < or = 0.05) and in the HA + alphaANP (51 +/- 15%; p < or = 0.05) group at 12 h compared to NX sham rats injected with normal rabbit serum. In addition, systemic arterial pressure was significantly lower in the HA + ETX rats compared to HA + ETX + alphaANP rats (p < or = 0.001). Plasma ANP levels were significantly higher at 12 and 24 h in ETX, HA, and HA + ETX groups (p <or = 0.05) compared to NX controls. There was an inverse relationship (p <or = 0.001) between plasma ANP levels and lung wet to dry (W/D) weight when data from NX, ETX, HA, and HA + ETX groups were pooled. The HA + alphaANP rats had significantly higher lung W/D ratios (p < 0.001) compared to sham rats. These results support the hypothesis that ANP, at physiological levels, modulates the development of pulmonary edema in HA-exposed ETX-primed rats.

Altitude Sickness↗

PubMed2001

Role of vascular smooth muscle in the development of high altitude pulmonary hypertension: an interspecies evaluation.

There is a marked variability in the degree of pulmonary hypertension induced by long-term exposure to altitudes above 3000 m among low altitude species, ranging from hyporesponders (sheep and dogs) to hyper-responders (cattle and pigs). The amount of inherent muscularization of small pulmonary arteries appears to be a determinant of this hypertensive response, as does the presence or absence of collateral ventilation. Hyper-responders also exhibit marked pulmonary vascular hypertrophy when exposed to long-term hypoxia. Humans exhibit similar inter- and intra-population variability. Animal species indigenous to high altitudes exhibit less variable, attenuated pulmonary hypertensive responses with little pulmonary vascular hypertrophy. This attenuated response is also apparent among human high altitude populations, particularly in Andean and Tibetan populations. Thus, successful adaptation to high altitudes is evident in species that do not sustain the acute cardiopulmonary compensations that occur upon initial exposure to high altitude.

Altitude↗

PubMed2001

Elevating dietary salt exacerbates hyperpnea-induced airway obstruction in guinea pigs.

Previous studies have indicated that increased dietary salt consumption worsens postexercise pulmonary function in humans with exercise-induced asthma (EIA). It has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of EIA) are mediated by similar mechanisms. Therefore, the purpose of this study was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential pathway of action of dietary salt was investigated by blocking leukotriene (LT) production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs were split into two groups. One group (n = 16) of animals ingested a normal-salt diet (NSD) for 2 wk; the other group (n = 16) ingested a high-salt diet (HSD) for 2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered either saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed for electrolyte concentrations and urinary LTE(4). The HSD elicited higher airway inspiratory pressures (Ptr) than the NSD (P < 0.001) postchallenge. However, after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was blocked in both diet groups (P < 0.001). Nonetheless, the HSD group continued to demonstrate slightly higher Ptr than the NSD group (P < 0.05). Urinary LTE(4) excretion significantly increased in the HSD group compared with the NSD group within treatment groups. This study has demonstrated that dietary salt loading exacerbated the development of HIAO in guinea pigs and that LT release was involved in HIAO and may be moderated by changes in dietary salt loading.

Airway Obstruction↗

PubMed2001

Intraoperative auditory assessments as predictors of hearing preservation after vestibular schwannoma surgery.

The purpose of this study was to determine the association of intraoperative auditory brainstem responses (ABRs) and near-field cochlear nerve action potentials (CNAPs) with postoperative hearing preservation in acoustic tumor surgery. Thirty-three consecutive patients undergoing middle fossa surgery had intraoperative surface ABR and direct CNAP assessments. Postoperatively, hearing was assessed. Hearing preservation was defined as any measurable hearing at any frequency and also by the American Academy of Otolaryngology--Head and Neck Surgery (AAO-HNS) hearing preservation classification system. The presence of an ABR or CNAP was associated with hearing preservation and the absence of an ABR, and CNAP was associated with no hearing preservation in 75.6 percent of the cases. The presence of either the ABR or CNAP was not related to AAO-HNS class outcome. ABR and CNAP had a useful rate of prediction of hearing preservation surgery outcome. However, in nearly one-quarter of the cases, no association between ABR or CNAP responses and hearing preservation was found. This finding must be taken into account when determining the clinical usefulness of these techniques.

Adolescent↗

PubMed2001

Anesthesia protocol for hyperpnea-induced airway obstruction in the guinea pig.

Guinea pigs (GP; Cavia porcellus) are used extensively as an experimental animal model in a wide range of disciplines including respiratory physiology. Guinea pigs are difficult to anesthetize, and many investigators use paralytic agents to eliminate spontaneous respiratory movements; however, strict federal regulations and institutional policies governing use of paralytic agents are few. We report an anesthesia protocol, using the injectable anesthetic agents sodium pentobarbital (SP) and xylazine (XYL) for the GP that induces consistent anesthesia while eliminating use of paralytic agents. Sixty percent of the calculated SP dose (45 mg/kg of body weight) was given for anesthesia induction, followed by 50% of the calculated XYL dose (7 mg/kg) 15 min later. Depth of anesthesia was monitored by response to toe pinch, ECG, and spontaneous respiratory movements. The animals were given additional boosts of SP (5 to 15% of the original dose, i.p. or i.v.) if a change in anesthesia depth was noted. Thirty-one animals completed the hyperpnea-induced bronchoconstriction (HIB) study with no fatalities. Using this protocol, we collected consistent, repeatable, and reliable data without use of propranolol or skeletal muscle paralytics. We believe that this protocol is not restricted to the GP and could be adapted for use in other terminal experiments.

Airway Obstruction↗

PubMed2000

Evolutionary stable strategy: a test for theories of retroviral pathology which are based upon the concept of molecular mimicry.

The genetic makeup of animal and plant populations is determined by established principles and concepts. Ecology and evolution provide a basic theoretical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknown. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a viral quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown that viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related peptide sequence found on certain immune cells. This related sequence, Gly-Thr-Glu-Arg-Val, is found on immune cells bearing a structure known as the major histocompatibility complex (MHC). The viral transmembrane sequence, Gly-Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-directed mutagenesis. This creates a viral clone devoid of the genetic similarity with the MHC. Chimpanzees progressing to AIDS contain both sequences of interest. Suppression of the chimpanzee quasispecies utilizing anti-retroviral drugs is proposed. This action serves to suppress the presence of the viruses containing the sequence Gly-Thr-Asp-Arg-Val. When viral load has been reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy predicts that a viable HIV clone with alanine residues can genetically dominate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alanine containing viral sequence should not recognize or bind to the MHC. Immunological parameters can then be measured to determine the physiological impact of eliminating a sequence responsible for molecular mimicry between virus and host.

Acquired Immunodeficiency Syndrome↗

PubMed2000

HIV+ patients have increased lymphocyte infiltrates in CIN lesions.

OBJECTIVE: The objective of our study was to analyze immunocyte infiltrates in CIN lesions from HIV+ patients to assess whether local immunosuppression, defined as a decrease in T cell infiltrates, could explain the aggressive nature of CIN in HIV-infected patients. MATERIALS AND METHODS: Cervical tissue was obtained from 6 HIV+ CIN patients, 6 HIV- CIN patients, who underwent LLETZ (large loop excision of the transformation zone) for CIN, and 17 normal patients who underwent hysterectomy for benign indications. The following cell surface markers were analyzed: CD20 (B cells), CD4 (T helper cells), and CD8 (T suppressor/cytotoxic cells). Each tissue section was visualized with a Leica microscope at 400x and the image was captured for analysis by Harmony Group image analysis software. RESULTS: A significantly higher number of lymphocytes (both B and T cells) was detected in the stroma of HIV+/CIN tissue compared to either HIV-/CIN or normal tissue. There was also a significant increase in CD8+ cells in the HIV+/CIN group compared to HIV-/CIN or normal tissue. There was a trend toward a decreased CD4+/CD8+ ratio in the HIV+/CIN compared to the other two groups; however, this did not reach statistical significance. CONCLUSIONS: This study indicates that HIV+/CIN cervical tissue has a greater number of tissue lymphocytes recruited to the neoplastic site compared to HIV- individuals. In addition, HIV+ patients may have a decreased CD4/CD8 ratio in locally infiltrating immunocytes in CIN lesions. The local immunomodulatory effects of HIV may be detectable early in infection and therefore may explain the aggressive nature of CIN in the HIV+ patient.

CD4-CD8 Ratio↗

PubMed2000

Placebo-controlled trial of indole-3-carbinol in the treatment of CIN.

OBJECTIVE: Most precancerous lesions of the cervix are treated with surgery or ablative therapy. Chemoprevention, using natural and synthetic compounds, may intervene in the early precancerous stages of carcinogenesis and prevent the development of invasive disease. Our trial used indole-3-carbinol (I-3-C) administered orally to treat women with CIN as a therapeutic for cervical CIN. METHODS: Thirty patients with biopsy proven CIN II-III were randomized to receive placebo or 200, or 400 mg/day I-3-C administered orally for 12 weeks. If persistent CIN was diagnosed by cervical biopsy at the end of the trial, loop electrocautery excision procedure of the transformation zone was performed. HPV status was assessed in all patients. RESULTS: None (0 of 10) of the patients in the placebo group had complete regression of CIN. In contrast 4 of 8 patients in the 200 mg/day arm and 4 of 9 patients in the 400 mg/day arm had complete regression based on their 12-week biopsy. This protective effect of I-3-C is shown by a relative risk (RR) of 0.50 ((95% CI, 0. 25 to 0.99) P = 0.023) for the 200 mg/day group and a RR of 0.55 ((95% CI, 0.31 to 0.99) P = 0.032) for the 400 mg/day group. HPV was detected in 7 of 10 placebo patients, in 7 of 8 in the 200 mg/day group, and in 8 of 9 in the 400 mg/day group. CONCLUSIONS: There was a statistically significant regression of CIN in patients treated with I-3-C orally compared with placebo. The 2/16 alpha-hydroxyestrone ratio changed in a dose-dependent fashion.

Administration, Oral↗

PubMed2000

Adenomyosis: symptoms, histology, and pregnancy terminations.

OBJECTIVE: To correlate symptoms of uterine adenomyosis with histopathologic features. METHODS: One hundred eleven specimens of uteri and cervices that weighed under 280 g were reevaluated. When adenomyosis was identified, assessment included depth of adenomyotic foci, graded as deep (above 80%), intermediate (40-80%), and superficial (under 40%), and number of adenomyotic foci. Clinical data were collected from patient records. RESULTS: Specimens were categorized in four groups, 17 with adenomyosis alone, 19 with adenomyosis with leiomyomas, 39 with leiomyomas alone, and 36 with neither. Among women with adenomyosis alone, 58.8% had pregnancy terminations and 47.4% of women with adenomyosis and leiomyomas had terminations, compared with 20.5% of women with leiomyomas alone (P <.01) and 22.2% in those with neither (P <.01). The number of foci correlated significantly with depth within the myometrium in specimens with adenomyosis alone (r =.46, P =.05) or combined with leiomyomas (r =.66, P <.001). The median number of foci associated with dysmenorrhea was 10 compared with 4.5 without it (P <.003); in menorrhagia the respective median numbers were 7 and 7 (P =.25). Menorrhagia and dysmenorrhea presented in 36.8% and 77.8% of deep, compared with 13.3% (P <.001) and 12.5% (P <.001) of intermediate depths, respectively. Superficial depth was not associated with menorrhagia or dysmenorrhea. CONCLUSION: Pregnancy termination might affect the pathogenesis of adenomyosis. The number of foci and their myometrial depths correlated to each other and to dysmenorrhea, but only myometrial depth correlated to menorrhagia.

Abortion, Induced↗

PubMed2000

Selective impairment of corticotropin-releasing factor1 (CRF1) receptor-mediated function using CRF coupled to saporin.

CRF is the main component in the brain neuropeptide effector system responsible for the behavioral, endocrine, and physiological activation that accompanies stress activation. Reduced CRF system activation plays a role in the etiology of a variety of psychiatric and metabolic disease states. We have developed a novel protein conjugate that joins native rat/human CRF to a ribosome-inactivating protein, saporin (CRF-SAP), for the purpose of targeted inactivation of CRF receptor-expressing cells. Cytotoxicity measurements revealed that CRF-SAP (1-100 nM) produced concentration-dependent and progressive cell death over time in CRF1 receptor-transfected L cells, but at similar concentrations had no effect on CRF2alpha receptor-transfected cells. The CRF-SAP-induced toxicity in CRF1-transfected cells was prevented by coincubation with the competitive CRF1/CRF2 receptor peptide antagonist, [D-Phe12]CRF-(12-41), or the selective nonpeptide CRF1 receptor antagonist, NBI 27914. Finally, in cultured rat pituitary cells that express native CRF1 receptors, CRF-SAP suppressed CRF-induced (1 nM) ACTH release. GnRH (1-10 nM) stimulated LH release was also assessed in the same pituitary cultures. Although there was a slight decrease in LH release from these cultures, this decrease was observed with CRF-SAP or SAP alone, suggesting that the response was nonspecific. Taken together, these results suggest the utility of CRF-SAP as a specific and subtype-selective tool for long term impairment of CRF1 receptor-expressing cells.

Adrenocorticotropic Hormone↗

PubMed2000

Vaccine preventable diseases and vaccination coverage in Australia, 1993-1998.

BACKGROUND: Since the introduction of childhood vaccination for diphtheria in 1932 and the widespread use of vaccines to prevent tetanus, pertussis (whooping cough) and poliomyelitis in the 1950s, deaths in Australia from vaccine preventable diseases (VPDs) have declined by more than 99%. It is important, however, that the downward trend in morbidity and mortality from VPDs is maintained and carefully monitored, and that changes are interpreted in relation to vaccination coverage. AIM: This report aimed to bring together three national sources of routinely collected data on the morbidity and mortality (notifications, hospitalisations and deaths) from VPDs during the period 1993-1998 for the 8 diseases then on the routine childhood vaccination schedule, and for 4 other diseases potentially preventable by childhood vaccination. It also examined vaccination coverage for the same period. METHODS: Data sources included notifications from the National Notifiable Diseases Surveillance System (NNDSS), hospitalisation data from the Australian Institute of Health and Welfare (AIHW) National Hospital Morbidity Database, deaths from the Australian Bureau of Statistics (ABS) Causes of Death Collection and vaccination coverage according to the Australian Childhood Immunisation Register (ACIR). All data sources were expected to have some limitations, the most important being under-reporting for notifications and vaccination encounters, and coding errors in the hospital morbidity data. RESULTS: Notifications for the 8 diseases covered by the routine schedule declined by 42%, from an average of 11,537 cases each year in 1993-1997 to 6700 in 1998, and hospitalisations fell by 12%, from an average of 1745 per year to 1536 in 1997/1998, while deaths remained unchanged at 7 each year over the period of review (Table 1). Tetanus caused 1 or 2 of the deaths each year. However, 6 of the 7 deaths in 1997 were in infants during a major outbreak of pertussis. Pertussis caused most of the notifications, hospitalisations and deaths during the review period. While most of these were in children, 46% of the notifications and 13% of the hospitalisations occurred in persons aged 15 years or more. There were notable declines in the numbers of notifications of invasive Haemophilus influenzae type b (Hib) disease in children under 5 years of age (77%), measles (87%) and rubella (75%), and there were no notifications of diphtheria or poliomyelitis. Vaccination coverage estimated using ACIR data increased during the review period. Coverage for the first 3 doses of diphtheria, tetanus, pertussis and Hib vaccines, assessed at 1 year of age, increased from 75% to 85%, while coverage for measles-mumps-rubella (MMR) vaccine, assessed at 2 years of age, increased from 83% to 86%. It is likely that these data underestimated coverage by 5-10%, and that the increase in coverage partly reflected better reporting to the ACIR by providers.

Adolescent↗