Monitoring of the effectiveness of ventilation is a significant problem during high-frequency ventilation (HFV). The time necessary to achieve equilibrium of the arterial tension of carbon dioxide (Paco2) following step changes in ventilation is appreciable, because of large body stores of CO2. Waiting for Paco2 to reach equilibrium is not only time-consuming but a potentially dangerous means of monitoring ventilator adjustments during HFV. Five kittens of mean +/- SD 1,082 +/- 383 gm weight were studied during HFV, both with normal lungs and lungs injured by saline lavage-induced surfactant depletion. The transcutaneous tension of carbon dioxide (Ptcco2) was monitored continuously to determine the time required to achieve equilibrium of Paco2 following a step change in ventilation. The rate of pulmonary CO2 elimination (VECO2) was measured immediately before and immediately after (less than 12 sec) step changes in ventilation and was used to predict the change in Paco2 achieved once equilibrium was reestablished. With normal lungs, equilibration time following step changes in ventilation was found to be approximately 20 minutes. After step decreases in ventilation of the injured lung, achieving equilibrium state took significantly longer, approximately 30 minutes. The Paco2 predicted was significantly related to the change in Paco2 achieved at equilibrium for both normal and injured lung studies. We concluded that direct monitoring of VECO2 during HFV may be a useful clinical monitoring technique, allowing rapid and accurate assessment of the efficiency of ventilation following step changes in ventilation and potentially assisting in optimizing ventilator settings.

Animals↗

PubMedDate not supplied

Scleroderma in South Australia: epidemiological observations of possible pathogenic significance.

BACKGROUND: Scleroderma is an autoimmune disorder of unknown cause. Previous epidemiological studies have suggested some regional clustering and associations with occupations involving exposure to silica dusts and hydrocarbons. AIMS: To determine: (i) prevalence and incidence of scleroderma in South Australia (SA), a state with a stable population living in well-defined urban, rural and industrial regions, (ii) hospital separation rates, (iii) cumulative survival rates, (iv) gender and disease subclassification, (v) geographical residency and occupations, (vi) familial associations and (vii) age at onset versus age-specific incidence rate. METHODS: Creation of the South Australian Scleroderma Register (SASR) to identify demographics and clinical and serological features of all scleroderma patients resident in SA. RESULTS: Scleroderma occurs in South Australia with a point prevalence of 23 per 10(5) and an incidence of approximately 1/15th of this. However, this prevalence is high compared with other regional world studies. Scleroderma is predominantly a female disease, with most patients having the limited form of scleroderma characterized by the presence of the anticentromere antibody and a mean survival of 27.6 years. In contrast, diffuse scleroderma is a less benign disease occurring at an early age of onset and has a mean survival of 9.6 years. Scleroderma occurs throughout SA without regional localization. Weak associations are seen in males, but not females, with occupations involving possible environmental exposure to silica or hydrocarbons. Scleroderma rarely occurs in families. CONCLUSION: No strong genetic or environmental influences were found to account for the relatively common occurrence of scleroderma in SA. The age at onset versus age-specific incidence curve suggests that scleroderma can be considered as a stochastic illness involving a number of random events occurring in a predisposed population. These random events may involve mutations of pivotal somatic genes.

Age of Onset↗

PubMedDate not supplied

Scleroderma renal crisis: poor outcome despite aggressive antihypertensive treatment.

BACKGROUND: Scleroderma renal crisis (SRC) is a rare but feared complication of scleroderma. Angiotensin--converting enzyme (ACE) inhibition has significantly improved survival, but it is unknown whether prophylactic ACE inhibitors will prevent this complication. AIMS: To determine: (i) the frequency of SRC in our cohort of well-characterized scleroderma patients resident in South Australia, (ii) any predisposing clinical and serological features, (iii) median disease duration at which SRC occurs, (iv) possible precipitants, (v) disease outcome, and (vi) whether patients were taking ACE inhibitors prior to onset of SRC. METHODS: Systematic review of the clinical course of all patients registered on the South Australian Scleroderma Register. RESULTS: SRC occurred in 16 patients. This constituted 2.8% of a total scleroderma cohort and 15% of the diffuse scleroderma cohort identified in South Australia. All 16 patients had diffuse cutaneous scleroderma. SRC occurred at a median disease duration of 15 months (range 1 week-11 years). Disease outcome was poor (five deaths, three requiring long-term dialysis and only two patients regaining a normal creatinine) despite aggressive antihypertensive treatment (including ACE inhibitors) in an intensive care or specialized renal unit. Two patients were later able to discontinue dialysis. Only two patients were taking small doses of ACE inhibitors prior to the onset of their SRC. The frequency of Scl-70 was decreased in the SRC group (P = 0.003). CONCLUSION: SRC is a rare event occurring in a small proportion of patients with diffuse scleroderma. The outcome of SRC was poor despite aggressive antihypertensive treatment. It is hypothesized that prophylactic ACE inhibition in susceptible patients might prevent or ameliorate this complication.

Adult↗

PubMedDate not supplied

Genomic instability in scleroderma.

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.

Adolescent↗